FitSugar

Being Thin Doesn't Mean You're Not Fat

FitSugar — Mon, 14 May 2007 14:30:00 -0700

I have talked about being TOFI (thin outside, fat inside) before, but it is back in the news more than ever right now.

New research has found that people who maintain their weight through diet rather than exercise are likely to have major deposits of internal fat, even if they are otherwise slim.

They eat too many fatty, sugary foods - and exercise too little to work it off - but they are not eating enough to actually be fat. Scientists believe we naturally accumulate fat around the belly first, but at some point, the body may start storing it elsewhere.

There is an increased risk of heart disease and Type 2 diabetes with anyone who has increased fat, no matter where it is. This means that normal-weight persons who are sedentary and unfit are at much higher risk for death than obese persons who are active and fit.

MRI's seem to be the only real way to tell if you're TOFI right now, so in order to keep your internal fat deposits at bay then a combination of diet and exercise is the way to go. If you just want to look thin, then maybe all you need to do is diet, but if you want to actually be healthy, then exercise has to be added as well.

Thanks to ccsugar for bringing this issue back to my attention.

Source

Who You Calling TOFI?

FitSugar — Wed, 03 Jan 2007 09:47:53 -0800

Do you hate your coworker because she eats whatever she wants and never works out yet still is thin? Well don't because chances are she is TOFI.

TOFI stands for "Thin on the Outside, Fat on the Inside." New studies are finding the fat deposits these so called Tofis carry are hidden in the white fat that lies around their vital organs, streaked through their underused muscles and wrapped around the heart. This hidden fat (rather than the fat lying in dimples underneath the skin) that can only be seen in high-tech MRI scanners is what sends out chemical signals, potentially leading to insulin resistance, Type 2 diabetes and heart conditions.

Consider this: Sumo wrestlers have a BMI of 56 and eat up to 5,000 calories a day, but they have very little internal fat. Surprisingly they also have low cholesterol, low insulin resistance and a low level of fatty acids. This seems to be due to the fact that their fat is all stored under the skin, on the outside.

Research is still being done on TOFI but as of now the best way researchers have discovered to combat the dangerous hidden fat is to eat a healthy diet with lots of dietary fiber. As always, exercising is always a good addition for anyone looking to be healthy, overweight or not.

Kidney stones

FitSugar — Wed, 08 Oct 2008 17:35:35 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

New Research:

Patients who have the most common type of gastric bypass surgery, the Roux-en-Y, are at increased risk for kidney stones, beginning 6 months after surgery, according to a study published in 2006.

Causes of Kidney Stones:

Calcium stones form when there is an imbalance in the urine substances that promote and block the formation of stones. Often, the cause of this imbalance is unknown.
Having acidic urine or too much uric acid in the body leads to the formation of uric acid stones.
Struvite stones are almost always caused by urinary tract infections due to bacteria that produce certain enzymes.
Other stones, including cystine and xanthine stones, are usually due to genetic abnormalities.

Treatments:

In about 85% of patients, the kidney stones are small enough that they pass through normal urination, usually within 2 - 3 days.
Certain medications can prevent recurrence of stones in people who are at high risk.
Extracorporeal shock wave lithotripsy (ESWL) is a technique that uses sound waves (ultrasound) to break up simple stones in the kidney or upper urinary tract. The shock waves are delivered from outside the body.
Surgery may be necessary if the stone or stones are too big to pass, and cannot be broken down through ESWL.
A change of diet and increased drinking of fluids, especially water, will help prevent a recurrence.

Introduction

Kidney stones are hard, solid rocks that form in the urinary tract. In many cases, the stones are very small and can pass out of the body without any problems. However, if a stone (even a small one) blocks the flow of urine, excruciating pain may result, and prompt medical treatment may be needed.

The process of urination begins in the kidneys. The kidneys filter out fluids and waste from the body, producing urine. The two kidneys are located deep behind the abdominal organs, below the ribs and toward the middle of the back.

Each kidney contains over a million nephrons. These are the tiny filtration units of the kidney.
Each nephron is composed of a tiny group of blood vessels (a glomerulus) enclosed in a funnel-like structure called Bowman's capsule.
Each glomerulus filters waste products, water, and salts out of the liquid part of the blood (plasma) that has entered the kidney.
About 1% of the plasma is converted into urine. The rest returns into the blood to prevent dehydration. Urine is primarily made of acids, urea, and creatinine (nitrogen compounds).
Urine passes from Bowman's capsule into tiny tubules, which lead to large collecting tubes in the center of the kidney. As the urine passes through this network, it becomes more concentrated.
Urine then flows from the kidney through thin tubes called ureters into the bladder.
The bladder's stretchy walls expand to store the incoming urine until it leaves the body through a tube called the urethra.

The kidneys are responsible for removing wastes from the body, regulating electrolyte balance and blood pressure, and stimulating red blood cell production.

Click the icon to see an image of the urinary tract.

Occasionally, various salts build up on the inside surfaces of the kidney and form crystals. Eventually these crystals become large enough to form stones in the kidney, a condition called nephrolithiasis. Kidney stones (renal calculi) may also form in the ureter or the bladder. Combinations of minerals and other chemicals, some derived from a person's diet, make up the salts in these stones.

Click the icon to see an image of the kidney stones.

Calcium Stones. About 70 - 90% of all kidney stones are made of calcium, usually combined with oxalate, or oxalic acid. A number of common vegetables, fruits, and grains contain oxalate.

About 6% of calcium stones are made of calcium phosphate (called brushite).

Uric Acid Stones. Uric acid is responsible for close to 10% of kidney stones. It is the breakdown product of purines, nitrogen compounds found in our bodies and in certain foods. The breakdown of purines to uric acid occurs in the liver, and from there uric acid enters the bloodstream, most of it passing into the kidneys. From the kidneys, uric acid leaves the body in the urine. Often, uric acid stones occur with calcium stones.

Struvite Stones. Struvite stones are made of magnesium ammonium phosphate. They are almost always associated with certain urinary tract infections. Worldwide, they make up to 30% of all kidney stones. In the United States, however, less than 15% of all stones are struvite. Most struvite stones occur in women. The rate of these stones may be declining in America, perhaps because of better control of urinary tract infections.

Cystine Stones. A build-up of the amino acid cystine, a building block of protein, causes 1% of kidney stones in adults and up to 8% of stones in children. The tendency to form these stones is inherited. Cystine stones are marked by rapid growth and recurrence, which, if not treated promptly, can eventually lead to kidney failure.

Xanthine Stones. Other kidney stones are composed of xanthine, a nitrogen compound. These stones are extremely uncommon and usually occur as a result of a rare genetic disorder.

Click the icon to see an animation about kidney stones.

Causes

The key process in the development of kidney stones is supersaturation.

The urine carries salts, including calcium oxalate, uric acid, cystine, or xanthine.
These salts can become extremely concentrated if there is not enough urine, or if unusually high amounts of crystal-forming salts are present.
When salt concentration levels reach the point at which they no longer dissolve, these salts form crystals.

Different factors may be involved in either reducing urine amount, or increasing the levels of the salts.

Deficiencies in Protective Factors. Normally, urine contains substances that may protect against stone formation, including:

Magnesium
Citrate
Pyrophosphate
Enzymes

These substances:

Allow salt in the urine to be at higher-than-normal concentrations without forming crystals
Prevent crystal formation
Coat the crystals and prevent them from sticking to the surface of kidney tubes

Not having enough of these protective substances can cause stones.

Changes in the Acidity of the Urine. Changes in the acid balance of the urine can affect stone formation.

Uric acid and cystine stones mainly form in acidic urine.
Calcium phosphate and struvite stones increase in alkaline urine.

Factors that Bind Crystals to the Kidney Tubules. Researchers are studying the cells lining the kidney tubules in order to understand how and why early crystals bind to the tubes long enough to form stones. Under investigation are elevated levels of substances that either cause crystals to stick to the tubes or deficiencies in those that prevent them from sticking.

In general, calcium stones form when there is an imbalance in the urine substances that promote and block the formation of stones. Often, the cause of calcium stones is not known, and the condition is then called idiopathic nephrolithiasis. Research suggests that nearly all stones result from problems in the breakdown and absorption of calcium and oxalate. Genetic factors may play a role in about half of these cases. A number of medical conditions and drugs can also affect digestion and intestinal absorption.

Excess Calcium in the Urine (Hypercalciuria). Hypercalciuria (too much calcium in the urine) is responsible for as much as 70% of calcium-containing stones. A number of conditions may produce hypercalciuria. Many are due to genetic factors, but most cases are idiopathic (due to unknown causes).

The following can lead to hypercalciuria and calcium stones:

Too much calcium absorption in the intestines: In most of these conditions, genetic factors lead to increased calcium absorption in the intestine. Researchers are investigating a possible defective gene that regulates calcitriol, a form of vitamin D, which, in excess levels, may increase intestinal absorption of calcium.
Excessive chloride: Chloride has a negative charge, and calcium has a positive one, so they balance each other in the body. Excess chloride may lead to excess calcium. A gene known as CLCN5, which regulates chloride in the urine, is defective in many patients with calcium stones.
Renal calcium leak: In this condition, the filtering processes in the kidney fail, causing an increase of calcium in the urine.
Excessive sodium: High urinary levels of sodium result in increased levels of calcium. Certain defects in the kidney tubules transport system, which cause imbalances in sodium and phosphate, can lead to high calcium levels in the urine. A diet high in salt can also produce this effect.

Excess Oxalate in the Urine (Hyperoxaluria). Oxalate is the most common stone-forming compound. Excessive oxalate in the urine (hyperoxaluria) is responsible for up to 60% of calcium stones and is a more common cause of stones than too much calcium in the urine.

Hyperoxaluria can be either primary or secondary.

Primary hyperoxaluria is an inherited disorder in which too much oxalate in the urine is the main problem.
Secondary hyperoxaluria results from specific conditions that cause high levels of urinary oxalate.

Secondary hyperoxaluria is usually caused by too much dietary oxalates (found in a number of common vegetables, fruits, and grains) or by problems in the body's breakdown of oxalates. Such defects may be due to various factors:

Severe vitamin B6 deficiencies (usually due to genetic disorders)
Deficiencies in Oxalobacter formigene, an intestinal bacteria that breaks down oxalate
Short bowel syndrome, a condition that makes the intestines unable to properly absorb fat and nutrients; calcium may bind to unabsorbed fat instead of oxalates, which causes a buildup of oxalate
Androgens (male hormones)

Female hormones (estrogens) actually lower the risk of hyperoxaluria. Estrogen may help prevent the formation of calcium oxalate stones by keeping urine alkaline, and raising protective citrate levels.

A study published in 2006 found that patients who undergo the most common gastric type of bypass surgery, the Roux-en-Y, were at increased risk for calcium oxalate kidney stones, beginning 6 months after surgery. The study found that patients who underwent the procedure developed hyperoxaluria, and the condition was common 12 months after surgery. The authors also noted an increased number of kidney stone incidents in this patient group.

Excessive Calcium in the Bloodstream (Hypercalcemia). Hypercalcemia generally occurs when bones break down and release too much calcium into the bloodstream. This is a process called resorption. It can occur from a number of different diseases and events:

Hyperparathyroidism: Overactive parathyroid glands cause about 5% of calcium stones. People with this disorder have at least a 20% chance of developing kidney stones. Women are more likely to have this disorder than men.
Immobilization: Lack of movement can lead to kidney stones.
Renal tubular acidosis: This disorder causes acidic and alkaline imbalance. Renal tubular acidosis not only increases calcium levels in the bloodstream but also reduces protective citrate levels.

Hyperuricosuria is a condition of high levels of uric acid in urine. It occurs in between 15 - 20% of people (mostly men) with calcium oxalate stones. Urate, the salt formed from uric acid, creates the center of a crystal (nidus), around which calcium oxalate crystals form and grow. Such stones tend to be severe and recurrent. They appear to be strongly related to a high intake of protein. (Hyperuricosuria also plays a major role in some uric acid stones.)

Low Urine Levels of Citrate (Hypocitraturia). Citrate is the main substance in the body that is responsible for removing excess calcium. It also blocks the process that turns calcium crystals into stones. Low levels of citrate in the urine (hypocitraturia) is a significant risk factor for calcium stones. In addition, hypocitraturia also increases the risk for uric acid stones. This condition most likely contributes to about a third of all kidney stones.

Many conditions can reduce citrate levels. Some causes include:

Renal tubular acidosis
Potassium or magnesium deficiency
Urinary tract infection
Kidney failure
Chronic diarrhea

Often, however, the cause of hypocitraturia-related stones is unknown.

Low Levels of Other Stone-Blocking Compounds. Several other compounds in the urine, including magnesium and pyrophosphate, also prevent the formation of calcium stones. If any of these compounds are lacking, stones may develop.

Nanobacteria Infection. Nanobacteria are tiny infectious organisms that can pass from the blood into urine. They coat themselves with mineral deposits that resemble the composition of kidney stones. Cells infected with these bacteria develop mineral deposits on the inside and outside. Researchers believe that nanobacteria may form the cores of the kidney stones in many people.

Human body tissues, certain foods, and certain alcoholic drinks contain substances called purines. Purine-containing foods include dried beans, peas, and liver. When the body breaks down purines, it produces uric acid. The presence of a certain level of uric acid in the body is normal.

The following conditions are usually seen in patients with uric acid stones:

Too much acid in the urine for a long period (the most important cause of uric acid stones)
Lower than normal amounts of urine produced.
Hyperuricosuria, a metabolic disorder that leads to high levels of uric acid in the urine

Note: Hyperuricosuria can also trigger calcium stones. Therefore, a combination of calcium and uric acid stones may be present in patients with hyperuricosuria.

A number of conditions and other factors may contribute to, or cause, uric acid stones:

Gout: Uric acid and other kidney stones develop in up to 25% of patients with primary gout, a painful form of arthritis that occurs when uric acid in the blood forms crystals in one or more joints.
Diabetes: New research has shown that people with type 2 diabetes have highly acidic urine that can lead to kidney stones, particularly uric acid stones. The findings were published in the May 2006 Journal of the American Society of Nephrology.
Insulin resistance: People with insulin resistance are at an increased risk for uric acid stones. The reason is unknown but may be related to the transport of certain salts through the kidneys. This transport changes in patients with insulin resistance.
Kidney abnormalities: Kidney problems that reduce the production of ammonia, particularly in people with diabetes or insulin resistance, may lead to uric acid stones.
Genetic factors: Genetic factors can increase a person's risk for uric acid stones.
Hypocitraturia: Hypocitraturia is a low amount of citrate in the urine.
Diet: Eating too much animal protein increases the risk of forming uric acid stones.

Other risk factors include:

Certain medications (chemotherapy drugs, diuretics, and salicylates)
Binge drinking
Not eating for long periods of time (fasting)
Lead poisoning
Blood cancers (leukemia, multiple myeloma, and lymphomas)
Some rare types of anemia (low levels of red blood cells in the blood)
Chronic diarrhea

Struvite stones are almost always caused by urinary tract infections due to bacteria that produce certain enzymes. These enzymes raise the concentration of ammonia in the urine. Ammonia makes up the crystals that form struvite stones. The stone-promoting bacteria are usually Proteus, but may also include Pseudomonas, Klebsiella, Providencia, Serratia, and staphylococci. Women are twice as likely to have struvite stones as men.

Other stones, including cystine and xanthine stones, are usually due to genetic abnormalities.

Causes of Cystine Stones. Cystine stones develop from genetic defects that cause abnormal transport of amino acids in the kidney and gastrointestinal system leading to a build-up of cystine, one of these amino acids. Researchers have identified two genes responsible for this condition: SLC3A1 and CLC7A9.

Causes of Xanthine Stones. In some cases, xanthine stones may develop in patients being treated with allopurinol for gout.

Risk Factors

Kidney stones are one of the most common disorders of the urinary tract. They are an ancient health problem. Evidence of kidney stones has been found in an Egyptian mummy estimated to be more than 7,000 years old.

An estimated 1.3 million Americans seek medical help for kidney stones each year. At this time, studies suggest kidney stones affect over 5% of Americans and that the rate has increased since the 1970s, perhaps because of increases in animal and dietary protein intake.

Men. The risk of kidney stones increases in a man's 40s and continues to rise until age 70. Caucasian men are at higher risk than other groups.

Women. The risk of kidney stones peaks in a woman's 50s. In younger women, stones are more likely to develop during the late stages of pregnancy. Pregnant women tend to have a higher calcium intake, but their kidneys do no handle the calcium as well as they did prior to pregnancy. Kidney stones are still a rare occurrence during pregnancy, however, affecting only 1 in 1,500 pregnancies.

Risk Factors in Children. Stones in the urinary tract in children are usually due to genetic factors. Most of the time, the cause is too much calcium in the urine (hypercalciuria). Deformities in the urinary tract pose a significant risk for kidney stones in children. Children with low birth weight who need to be fed intravenously are also at risk for stones.

Obesity and weight gain are both associated with an increased risk of kidney stones.

Men who weigh more than 220 lbs are 44% more likely to develop kidney stones than men who weigh less than 150 lbs.
Women who are obese are 90% more likely to develop kidney stones than women with a lower body mass index (BMI).

Higher BMIs and larger waist circumferences are both risk factors for kidney stones. Researchers think that there may be a link between fat tissue, insulin resistance, and urine composition. People with larger body sizes may excrete more calcium and uric acid, which increase the risk of kidney stone formation.

A family history of kidney stones increases one's risk for the condition. Researchers are looking into markers or other factors that might predict kidney stones in relatives, although none has yet been clearly identified. One report found that among the siblings of patients with calcium stones, sisters with higher urinary calcium levels and more acidic urine were more likely to develop stones. Brothers with high urinary calcium, low urinary potassium, and older age were more likely to have the problem. A family history of gout may also make a person vulnerable to stones.

According to a 2003 study of American ethnic groups, Caucasians have the highest incidence of kidney stones (5.9%) followed by Mexican Americans (2.6%). African-Americans have the lowest risk (1.7%).

Dietary factors, minerals in local water, or both may contribute to geographic differences that have been observed in the occurrence of kidney stones. Studies have reported the highest occurrence of kidney stones in the southern region of the United States and the lowest in the west. One study suggested that the higher risk may be due to a higher rate of high blood pressure in the southern states and certain dietary habits, particularly lower intake of magnesium and low use of calcium supplements.

Specific Foods. In general, certain foods increase the risk for stones only in people who have genetic or medical vulnerability. People whose diets are high in animal protein and low in fiber and fluids may be at higher risk for stones. A number of foods contain oxalic acid, but there is no proof that such foods make any major contribution to calcium oxalate stones in people without other risk factors. However, several studies have shown that increasing dietary calcium and restricting salt, animal protein, and foods rich in oxalate can help prevent calcium oxalate stones from returning.

Stress. One study reported that people who had a major, stressful life experience were more likely to develop stones than those who had not. Some experts speculate that this increased risk may be due to a hormone called vasopressin, which is released in response to stress. Vasopressin also increases the concentration of urine.

Sleep Position. Sleeping in the same position consistently may influence risk. A 2001 study reported that in people who had a history of kidney stones, recurrences tended to occur on the same side that people slept on. An earlier study suggested that people who had kidney stones were more apt to sleep on their stomachs. Movement during sleep did not appear to affect the risk.

Being Bedridden. Any medical or physical condition that keeps a person in bed or immobile increases blood levels of calcium from bone breakdown, thereby posing a risk for stone formation.

Gout. Patients with gout are at a high risk of uric acid stones. These patients have very acidic urine, and a 2002 study suggested that the two disorders may have a common source.

High Blood Pressure. Persons with high blood pressure are up to three times more likely to develop kidney stones. It is not entirely clear whether having high blood pressure increases the risk for a stone, whether stones lead to high blood pressure, or if there is an action linking both.

Inflammatory Bowel Disease: Crohn's disease and ulcerative colitis cause problems in absorption of substances in the intestines. These problems significantly increase the risk for kidney stones, particularly in men.

Urinary Tract Infections (UTIs): Urinary tract infections are almost always the cause of struvite stones.

Hyperparathyroidism: The parathyroid glands regulate calcium levels in the body through the parathyroid hormone. In hyperparathyroidism, one or more of these glands makes too much parathyroid hormone. Some people with hyperparathyroidism develop kidney stones. Surgery to remove the hyperactive parathyroid gland in such patients reduces the risk for stone formation, but the risk still remains high for some time after surgery.

Other Medical Conditions. Kidney disease, chronic diarrhea, certain cancers (such as leukemia and lymphoma), and sarcoidosis put people at higher risk for stones.

AIDS medications. Over 10% of persons with AIDS who take the medicine indinavir develop stones. The risk is even higher in patients with AIDS who also have hepatitis B, hepatitis C, or hemophilia, as well as those who are very thin or who take the antibiotic combination TMP-SMX. In one study of persons with AIDS who took a combination of indinavir, zidovudine, and lamivudine, 36% developed kidney stones.

Other Drugs. Kidney stones are a rare side effect of thyroid hormones and loop diuretics (drugs that increase urination). In fact, diuretics are also used to prevent calcium stones. Certain cancer chemotherapies can also cause kidney stones. Long-term use of medications, such as antacids, which change the acidic content of urine, may increase the risk for kidney stones.

Symptoms

In many cases, kidney stones do not produce symptoms. However, if a stone becomes stuck in the ureter (the thin tube between the bladder and the kidney), symptoms can be very severe. Often, they vary depending on the stone's location and its progress.

Kidney stone attacks tend to be most common late at night or in the early morning, possibly because of minimal urine output or constriction of the ureters during the early morning hours. Kidney stone attacks are least common during the late afternoon

Pain usually begins abruptly on one side and then usually continues as intense, constant pain. (In some cases it persists for a few minutes, disappears, and then returns after about 10 minutes.)
The patient cannot become comfortable and usually stands, sits, paces, or reclines in a vain search for a position that will bring relief.
If the stone is in the kidney or upper urinary tract, the pain usually starts in one flank area (to the side of the back near the waist). It typically moves to the groin as the stone passes down.
If the stone is too large to pass easily, the pain follows the muscle contractions in the wall of the ureter as they try to squeeze the stone along into the bladder.
Nausea and vomiting may occur.
Blood in the urine may be present.
As the stone passes down the ureter closer to the bladder, a person may feel the need to urinate more often or a burning sensation during urination.
If fever and chills accompany any of these symptoms, an infection may be present.

The size of the stone does not necessarily predict the severity of the pain; a very tiny crystal with sharp edges can cause intense pain while a larger round stone may not be as distressing. Struvite stones can often occur without symptoms.

Diagnosis

The doctor will perform a physical exam. This includes pressing against abdominal areas for tender locations that might indicate the presence of the stone.

The patient's age is a significant factor. Kidney stones that occur in children and young patients are more apt to result from inherited problems that cause cystine, xanthine, or, in some cases, calcium oxalate stones. In adult patients, calcium stones are most common.

A medical history may help predict which crystal has formed the stone. The doctor will need to know the following:

Any previous kidney stone attacks
Histories of cancer, sarcoidosis, or small bowel disease
Any medications being taken, including non-prescription substances, particularly high doses of vitamins D or C and calcium-containing antacids

Many conditions can cause symptoms similar to kidney stones. Usually the diagnosis is easily made because of the specific nature of the symptoms, but it is not always clear. Urinary tract infections can cause similar, but usually less intense, pain. In fact, infection may be present with a kidney stone. Other causes of pain that may mimic kidney stones include:

Gallstones
Diverticulitis (infection or irritation of abnormal pockets in the intestines)
Intestinal blockage
Blood clots
Irritable bowel syndrome
Appendicitis
Stomach ulcers
Hiatal hernia (when the upper part of the stomach bulges into the chest, through an opening in the diaphragm)
Pancreatitis (inflammation of the pancreas)
Hepatitis
Pelvic inflammatory disease
Inflammatory bowel disease (Crohn's and colitis)
Heart attack

Various imaging techniques are helpful in determining the presence of kidney stones. The best approach uses spiral (or helical) computed tomography scans. If it is not available, the patient will need ultrasound or standard x-rays. If no stones show up, but the patient has severe pain that suggests the presence of kidney stones, the next step is an intravenous pyelogram.

X-Rays. A standard x-ray of the kidneys, ureters, and bladder may be a good first step for identifying many stones, since many are visible on x-rays. Calcium stones can be identified on x-rays by their white color. Cystine crystals can also show up on x-rays.

Spiral (or Helical) Computed Tomography. A type of computed tomography (CT) scan, called a spiral or helical CT scan, is currently the best method for diagnosing stones in either the kidneys or the ureters. This test is fast, does not require instruments or foreign chemicals to enter the body, and provides detailed accurate images of even very small stones. If stones are not present, a spiral CT scan can often identify other causes of pain in the kidney area. It is better than x-rays, ultrasound, and intravenous pyelogram -- the previous standard test for detecting kidney stones. Experts hope spiral CT will eventually be able to identify the chemicals present in a stone.

Ultrasound. Ultrasound can detect clear uric acid stones and obstruction in the urinary tract. It is not useful for finding very small stones, but some research indicates that it may be a useful first diagnostic step in the emergency room to help predict the likelihood of a stone, including suspected stones in children.

Intravenous Pyelogram. With intravenous pyelogram (IVP), the doctor injects a special dye into the patient. A technician will then take x-rays as the dye enters the kidneys and travels down the urinary tract. IVP is invasive but, until recently, was the most cost-effective method for detecting stones. Where it is available, spiral CT is now preferred, since it gives a faster diagnosis, is more accurate, is safer, and is similar in cost.

In any case, IVP should not be used on patients with kidney failure. There is also a risk for an allergic reaction to standard dyes, although newer less allergenic ones are becoming available.

In the procedure intravenous pyelogram (IVP), the patient is injected with dye. X-rays are taken as the dye travels through the urinary tract. This procedure is done to confirm the presence of kidney stones, although some stones may be too small to see.

Magnetic Resonance Imaging. Magnetic resonance imaging (MRI) techniques are showing promise for diagnosing urinary tract obstruction but do not yet accurately reveal small stones, or ones that do not cause a blockage. Because no radiation is involved with MRI, however, it may prove to be a good option for pregnant women.

Urine samples are required to evaluate features of the urine, including its acidity and the presence of:

Red or white blood cells
Infection
Crystals
High or low levels of chemicals that inhibit or promote stone formation

Clean-Catch Urine Sample for Culturing. After determining that a kidney stone is present, the health care provider usually gives the patient a collection kit, including filters, to try to catch the stone or gravel as it passes out. The urine may also be tested (cultured) for the presence of infection-causing organisms. A clean-catch urine sample is almost always required for culturing. To provide a clean catch, do the following:

First, wash your hands thoroughly, then wash the penis or vulva and surrounding area four times with downward strokes, using a new soapy sponge each time.
Begin urinating into the toilet and stop after a few drops.
Position the container to catch the middle portion of the urine stream. Ideally, this urine will contain only the bacteria and other evidence of the stone.
Urinate the remainder into the toilet.
Tighten the cap on the container securely, being careful not to touch the inside of the rim.

Click the icon to see an image of a calcium urine test.

Twenty-Four Hour Urine Collection. A 24-hour urine collection may be needed to measure urine volume and levels of acidity, calcium, sodium, uric acid, oxalate, citrate, and creatinine.

You should not change any of your usual eating or drinking patterns when performing this test.
Discard the first urination on the day of the test.
Afterward all urine passed over the next 24 hours is collected, including the first urination on the morning of day two.
A second 24-hour urine collection may be needed to determine if treatment is working or if the first analysis was not conclusive and the doctor suspects a less common stone, such as a cystine or xanthine stone.

Click the icon to see an image of a uric acid urine test.

Urine tests that are used to determine the specific chemical and biological factors causing the stone should be performed about 6 weeks after the attack, since the attack itself may change the levels of such substances, including calcium, phosphate, and citrate. It should be noted that calcium levels in the urine may be abnormal even in many people without stones. In addition, high urinary concentrations of calcium may pose a greater or lesser risk depending on age. (In one 2001 study, middle-aged adults with high urinary calcium concentrations had a much greater risk than older adults with high levels.)

The kidney stones obtained from the urine sample are examined under a microscope. The crystal formations are often specific enough so that the doctor is able to identify the substance causing the stone.

Calcium oxalate crystals are eight-sided, while calcium phosphate crystals tend to have irregular shapes.
Uric acid stones are sometimes described as pear-shaped or diamond-shaped.
Some struvite stones have very specific shapes commonly described as "coffin lids." Struvite crystals may also occur in a formation known as a staghorn, which can be large and damaging to the kidney.

Testing whether urine is acidic or alkaline helps to identify the specific type of stone. The levels of acidity or alkalinity in any solution, including urine, are indicated by the pH scale:

A pH value of 7.0 is neutral.
A solution with a low pH (below 7.0) is acidic. (A low pH favors uric acid and cystine stones.)
A solution with a high pH is alkaline. (A high pH favors calcium phosphate and struvite stones.)

A dipstick test for blood in the urine (called hematuria) is typically performed when patients appear in the emergency room with flank pain (the primary symptom of kidney stones). About a third of kidney stone patients, however, do not show blood in the urine, so other tests may be needed.

Blood Tests for Stone Factors. Blood and urine tests help determine what substances form the crystals. This allows the doctor to determine the appropriate treatment and preventive measures.

Blood tests may help determine blood levels of urea nitrogen, creatinine, calcium, phosphate, and uric acid for patients with known or suspected calcium oxalate stones. Doctors will usually schedule these tests about 6 weeks after the attack, in order to measure these substances when the stone has been passed, and the patient has been stabilized. This is particularly true in patients with recurrent stones.

Parathyroid Tests. Tests to detect parathyroid hormone levels are given if the doctor suspects hyperparathyroidism, based on other signs and symptoms.

Tests for Infection. A test result that shows a high white blood cell count might indicate infection. Such results, however, could be misleading, since the number of white blood cells could also increase in response to the extreme physical stress of a kidney stone attack.

Tests for Metabolic Problems. About half of children with stones have an identifiable metabolic disorder, which increases their risk of stone recurrence five-fold. Experts argue whether tests for metabolic disorders are routinely needed once the stone composition has been determined. Studies suggest the following:

People with recurrent calcium stones have a wide range of irregular blood or urine test results, indicating a variety of possible metabolic disorders. For example, calcium stones in middle-aged women may be due to parathyroid abnormalities.
Calcium phosphate stones most likely result from renal tubular acidosis.
People with non-calcium stones generally have identifiable metabolic disorders.
Determining the stone composition may be sufficient for treatment, and may help avoid unnecessary metabolic tests.

Treatment

When tests show there is a kidney stone, the next step is to determine treatment. The patient should be admitted to the emergency room if they have severe vomiting, fever, or symptoms of infection.

Strong opioid painkillers, such as meperidine (Demerol), are often required for a severe kidney stone attack. However, doctors will usually not give such drugs until they confirm the presence of a kidney stone on an x-ray. In some cases, powerful nonsteroidal anti-inflammatory drugs (NSAIDs) may work just as well as opioids, and they have fewer side effects. However, they do take longer to work.

In about 85% of patients, the kidney stones are small enough that they pass through normal urination, usually within 2 to 3 days. In some cases, a stone may take weeks to months to pass, although pain usually goes away before that.

The patient should drink plenty of water (two to three quarts a day) to help move the stone along, and take painkillers as needed. The doctor usually provides a collection kit with a filter and asks the patient to save any passed stones for testing.

If the stone has not passed in 2 - 3 days, the patient will need additional treatments. In some severe cases, hospitalization may be necessary.

Specific procedures vary depending on the size of the stone or complexity of the situation. Noninvasive procedures are proving to be very beneficial in eliminating stones, and have largely replaced invasive surgeries.

For small stones that are lodged in the lower part of the ureter, ureteroscopy or shock wave lithotripsy are the procedures of choice.
For larger stones, ureteroscopy, percutaneous nephrolithotomy, and shock wave lithotripsy are all potentially useful. The choice of any of these procedures depends on a number of factors, including location of the stone and the presence of any problems that caused the stone in the first place.
In some complicated cases, standard open surgical procedures (called nephrolithotomy) may be required.

See "Other Treatments" section for more information on kidney stone surgery.


Stone Type	Diet and Lifestyle	Medications	Procedures
Calcium Oxalate	Plenty of fluids. (Choose water, lemon juice. Avoid grapefruit, apple, and cranberry juice.) Limit the amount of protein and salt in the diet. Increase fiber. Limit the amount of fats in the diet, particularly in people who have short bowel syndrome. Balance normal calcium intake with potassium- and phosphate-rich foods. Limit the amount of calcium in the diet (only in people who have genetic abnormalities that cause high intestinal absorption of calcium). Limit the amount of foods high in oxalates (only in patients with rare intestinal conditions that cause hyperoxaluria).	Diuretics ("water pills"), Citrate salts, phosphates, cholestyramine.	Lithotripsy, uteroscopy, percutaneous nephrolithotomy, open surgery.
Uric Acid	Plenty of fluids. (Choose water, blackcurrant juice. Avoid cranberry juice.) Increase calcium intake (be sure well-balanced with potassium and phosphates). Reduce protein and other foods with high-purine content.	Potassium citrate, sodium bicarbonate, allopurinol.	Lithotripsy, uteroscopy, percutaneous nephrolithotomy, open surgery.
Struvite stones	Plenty of fluids (water, cranberry juice). Reduce proteins.	Antibiotics to eliminate any infection. Acetohydroxamic acid (AHA) may be helpful in combination with antibiotics. In some cases, organic acids given through urinary tract.	May respond poorly to most lithotripsy procedures and require open surgery. Newer procedures may be helpful.
Cystine stones	Very high fluid intake (four quarts a day). Limit the amount of protein in the diet.	Alkalizing agents (such as bicarbonate). Sometimes d-penicillamine, tiopronine, or captopril useful for lowering cystine levels.	May respond poorly to most lithotripsy procedures and require open surgery. Newer procedures may be helpful.

Medications

Diuretics. Diuretics are medicines commonly used to treat high blood pressure and other disorders. They remove fluid and sodium from the body. Low doses of a class of diuretics known as thiazides are sometimes used to reduce the amount of calcium released by the kidneys into the urine. Thiazides include:

Hydrochlorothiazide (Esidrix, HydroDiuril)
Chlorothiazide (Diuril)
Trichlormethiazide (Metahydrin, Naqua)
Chlorthalidone (Hygroton)

However, thiazides also cause potassium loss, which reduces citrate levels and can increase the risk for stones. Patients taking thiazide pills should also take potassium citrate, to prevent citrate loss. Amiloride (Midamor) is a potassium-sparing diuretic, which may be used if a thiazide does not work.

Citrates. Citrate salts are often given to people with calcium oxalate or uric acid stones:

Potassium magnesium citrate is available over the counter. It is proving to be very beneficial in preventing kidney stones. In one study, potassium magnesium citrate reduced the risk for kidney stone recurrence by 85%.
Potassium citrate (K-Lyte, Polycitra-K, Urocit-K) is given as the only treatment to people with normal urine calcium levels. Between 70 - 75% of patients with recurrent stones have ongoing remission (no stone recurrence) with potassium citrate treatment. However, some people cannot tolerate potassium citrate because of side effects (stomach problems).
Magnesium citrate (Citroma, Citro-Nesia) may help people who develop calcium stones from impaired intestinal absorption due to short bowel disease.

None of these products should be used by people with struvite stones, urinary tract infections, bleeding disorders, or kidney damage. Patients who take citrate supplements containing potassium should not take any other medications that either contain this mineral or prevent its loss (such as so-called potassium-sparing diuretics). People with peptic ulcers should avoid citrate supplements, or discuss using non-tablet forms with their doctor.

Phosphates. Phosphates help reduce the breakdown of bone that releases calcium into the bloodstream. They are also involved in the kidney's reabsorption of calcium from the urine.

Phosphate compounds:

Neutral (nonacidic) sodium or potassium phosphate (K-Phos, Neutral, Neutra-Phos) is usually taken four times a day after meals to prevent kidney stones unless otherwise directed by the doctor. Diarrhea is a possible side effect.
Cellulose phosphate (Calcibind) is recommended only for severe hypercalciuria that is associated with recurrent calcium stones and is caused by excessive absorption of calcium from the intestines. However, this drug may increase oxalate levels and decrease magnesium levels, which can lead to different stones. Taking magnesium supplements and reducing dietary oxalates, calcium, and ascorbic acid may help offset these risks. Cellulose phosphate may also cause bloating.

Avoid acidic forms of phosphate, since they increase the risks for both hypocitraturia and hypercalciuria.

Cholestyramine (Questran, Questran Light) is a drug used to reduce cholesterol levels. However, it also binds with oxalate in the intestine, so it is also used to reduce high oxalate levels in urine (hyperoxaluria). The drug usually comes in a powder that is dissolved in liquid.

Bloating and constipation are common side effects of this drug. Cholestyramine also interferes with other medications, including digoxin (Lanoxin) and warfarin, and may contribute to calcium loss and osteoporosis. In order to prevent such interactions, take other drugs 1 hour before, or 4 - 6 hours after, taking cholestyramine.

Long-term use of cholestyramine may cause deficiencies of vitamins A, D, E, and K. Vitamin supplements may be necessary.

Sodium Bicarbonate. Patients whose persistently acidic urine causes uric acid stones may take sodium bicarbonate to reduce urine acidity. Patients taking sodium bicarbonate must test their urine regularly with pH paper, which turns different colors depending on whether the urine is acidic or alkaline. Too much sodium bicarbonate can cause the urine to become too alkaline. This increases the risk for calcium phosphate stones. Patients who need to reduce the amount of sodium they take in (as a result of other medical conditions) should not use sodium bicarbonate.

Potassium Citrate. Potassium citrate, which restores citrate to the urine, is useful for patients with high levels of uric acid in the urine.

Allopurinol. Allopurinol (Lupurin, Zyloprim) is very effective in reducing high levels of uric acid, and may be helpful for patients with uric acid stones. Allopurinol will not prevent calcium stones from forming. There is also a slight risk for the formation of xanthine stones with this drug. Side effects include diarrhea, headache, and fever. More severe complications include blood disorders that may produce fatigue, bleeding, or bruising. The drug may also increase the risk for cataracts.

About 2% of patients experience an allergic reaction to allopurinol that causes a rash. In rare cases, the rash can become severe and widespread enough to be life threatening. Allergic individuals who have experienced only a mild rash to sodium bicarbonate may be able to build up their tolerance for allopurinol by undergoing a desensitization process. In this process, patients start with small doses of allopurinol and gradually increase them, if no reaction develops.

Allopurinol reduces uric acid levels rapidly, so it may trigger an attack of gout in vulnerable people. To prevent this problem, patients taking allopurinol should also take a nonsteroidal anti-inflammatory drug (NSAID) for 2 or 3 months. Aspirin should not be taken, since it increases uric acid levels. Patients should discuss the appropriate NSAID choice with their doctor.

Before patients can receive any medical treatment for struvite stones, they must have surgery to completely remove the stones.

Antibiotics for Eliminating Infection. Persons with struvite stones receive ongoing treatment with antibiotics to keep the urine free of the bacteria that cause urinary tract infections. Careful follow-up and urine testing is extremely important. A high-pH urine indicates low acidity and an increased risk of infection.

Acetohydroxamic Acid (AHA). Acetohydroxamic acid (AHA or Lithostat) is beneficial when used with long-term antibiotics. AHA blocks enzymes that bacteria release, and has been effective in preventing stones even when bacteria are present. Side effects, however, can be severe. The drug reduces iron levels in the body, so anemia is a common problem. Patients may need to take iron supplements. Other side effects include nausea, vomiting, depression, anxiety, rash, persistent headache, and, rarely, small blood clots in the legs.

Experts recommend this drug only for patients with healthy kidneys who have chronic diseases caused by specific struvite-causing organisms.

Patients taking this medicine should avoid alcohol. Pregnant women should not take acetohydroxamic acid.

Organic Acids. Medical treatments to dissolve stones may be useful in patients who do not respond to other medications, or in combination with surgeries. Acidic urine dissolves struvite stones, so the doctor may wash the urinary tract with a solution of organic acids (such as Renacidin). Candidates for such washes must have sterile urine (no bacteria or other organisms in the urine) and healthy kidney function. In surgical patients, the wash is performed 4 or 5 days after the operation. The wash starts with saline (salt solution) for 1 - 2 days and, if there are no problems, the organic acid solution follows for another 1 or 2 days, until all stones dissolve. Regular urine tests are necessary to ensure that the bacteria do not return.

Aluminum Hydroxide Gel. An aluminum hydroxide anti-acid gel may reduce phosphate levels that are important in struvite stone formation, but it has a long-term risk of causing aluminum toxicity. Long-term reduction of phosphorus can also increase the risk for calcium oxalate stones. Experts recommend limiting phosphorus through a low-protein diet, rather than through the use of this gel.

The first-line treatment for cystine stones is increasing the alkalization of urine so the stones can dissolve. If alkalization fails, drug treatments may include d-penicillamine, alpha-mercaptopropionylglycine (tiopronine), or captopril. These medications lower cystine concentration.

Patients with cystine stones must drink plenty of fluids, much more than patients with other stones. The patients should drink at least four quarts of water over a 24-hour period.

Other Treatments

Surgery is usually needed if the stone is too large to pass on its own, if there are signs that the stone is growing, or if the stone is blocking the urine flow and causing a urinary tract infection or kidney damage.

Until recently, the procedure to remove a stone was a very painful, major surgery, requiring 4-6 weeks of recovery. Today, treatments for stones are much less invasive. Major surgery is performed in less than 2% of patients.

Stone removal procedures:

Extracorporeal shock wave lithotripsy (ESWL) is used for small stones (less than one centimeter, or slightly less than half an inch) that occur in the upper part of the ureter and do not pass on their own. One study indicated lithotripsy might even be safe and effective for patients whose stones are associated with malformed kidneys, although such patients are at higher risk for stone recurrence and should be carefully monitored.
Percutaneous nephrolithotomy (PNL). PNL can be used for very large stones in the upper urinary tract, when ESWL fails, for kidney transplant patients, or when the kidneys or surrounding areas are malformed. PNL is the preferred procedure for drug-resistant cystine stones, which are usually also resistant to shock wave therapy.
Ureteroscopy. For stones in the lower tract, ureteroscopy is generally the best procedure, although lithotripsy is also usually feasible and patients ordinarily prefer it.
Standard open surgery (nephrolithotomy) may be required if any of these procedures fail or are not appropriate, or in special cases, such as when the patient is very obese.

Most procedures are more effective for calcium and uric acid stones and less effective for struvite and cystine stones, although new techniques may be improving their effects on all stones.

Extracorporeal shock wave lithotripsy (ESWL) is a technique that uses sound waves (ultrasound) to break up simple stones in the kidney or upper urinary tract. ("Extracorporeal" means "outside the body," and "lithotripsy" means stone-breaking.) ESWL is not used for cystine stones. The procedure generally does not work for stones larger than three centimeters in diameter (which is slightly over an inch). There are several variations of ESWL. The following is a typical procedure:

Most ESWL procedures use some anesthesia, although they are often done on an outpatient basis.
The patient is positioned in a water bath. (In some procedures the patient lies on a soft cushion.)
The procedure uses ultrasound to generate shock waves that travel through the skin and body tissues until they hit the dense stones. (The doctor pinpoints the stone during treatment by using x-rays or ultrasound.)
The shock waves crush the stones into tiny sand-like pieces that usually pass easily through the urinary tract.
The shattered stone fragments may cause discomfort as they pass through the urinary tract. In such cases, the doctor may insert a small tube called a stent through the bladder into the ureter to help the fragments pass. This practice, however, has not proved to speed up passage of the stones in most cases and is not used routinely.

Extracorporeal shock wave lithotripsy (ESWL) is a procedure used to shatter simple stones in the kidney or upper urinary tract. Ultrasonic waves are passed through the body until they strike the dense stones. Pulses of sonic waves pulverize the stones, which are then more easily passed through the ureter and out of the body in the urine.

Success rates of ESWL range from 50 - 90%, depending on the location of the stone and the surgeon's technique and level of experience. Recovery time is short, and most people can resume normal activities in a few days.

Complications. Complications may include the following:

The most common complication is blood in the urine, which lasts for a few days after treatment. To reduce the chances of bleeding, doctors usually tell patients to avoid taking aspirin and other NSAIDs, which can promote bleeding, for 7 - 10 days before the treatment.
Bruising and minor discomfort due to the shock waves are common in the back or abdomen.
Sometimes the stone does not completely break up with one treatment, and additional treatments may be required. Inability to pass stone fragments may also be a particular problem in patients who have cysts or other kidney problems.
Higher risk for diabetes later. A 2006 study published in the journal Urology found that 17% of patients who received shock-wave lithotripsy developed diabetes later in life. The diabetes risk was related to the number and intensity of shocks.
Higher risk for hypertension (high blood pressure). The same study that linked ESWL to diabetes also showed that people who received shock-wave lithotripsy treatment were 47% more likely to develop high blood pressure than those who had their stones treated without surgery.

ESWL appears to be safe for children, although a 2001 study reported temporary damage in the kidney tubules after treatment. It is unclear if this complication has any long-term consequences. Experts recommend using the least amount of shocks and impact possible in young people. If more than one treatment is needed, there should be a waiting period of at least 15 days between treatments.

Percutaneous nephrolithotomy may be used when ESWL is not available or effective (such as if the stone is very large, in an inaccessible location, or is a cystine stone). It is also preferred over ESWL for stones that have remained in the ureter for more than 4 weeks.

It is more effective than ESWL for patients with severe obesity, and appears to be safe for the very elderly and the very young. Success rates are nearly 98% for kidney stones and 88% for ureteral stones. They may vary by the technique used and the specific patients. For example, success rates are slightly lower in children, although the procedure can be done safely in young patients. Long-term effects are unknown.

A typical procedure is as follows:

The surgeon makes a tiny incision in the back and creates a tunnel directly into the kidney.
The surgeon then inserts an instrument called a nephroscope through the tunnel.
The stone is located and removed. If it is large, it is destroyed using ultrasound, lasers, or other devices. The surgeon then removes the fragments. An advantage of percutaneous nephrolithotomy over ESWL is that the surgeon is able to remove the stone fragments directly, instead of relying on their natural passage from the kidney.
Generally, patients stay in the hospital for 5 or 6 days and may need a small device called a nephrostomy tube left in the kidney during the healing process.

Devices Used to Destroy Stones. For large stones, some type of energy-delivering device may be needed to break the stone into small pieces. They are referred to as intracorporeal lithotripsy devices (meaning stone breakers within the body). The device may be one of the following:

Ultrasound is currently the preferred method. It results in a stone-free rate of 94%. A rigid nephroscope delivers the ultrasound waves.
Pneumatic (compressed air) lithotripsy uses a probe that comes in direct contract with a stone. Compressed air causes a piston to collide rapidly with the probe, and the result is a "jackhammer" action against the stone, causing the stone to break up. This method, however, can send stone fragments into other parts of the urinary tract.
A more recent device uses a combination pneumatic probe and ultrasound, with stone-free rates of 80 - 89%. It may prove to be superior to ultrasound alone and be effective against stones of all types.
The holmium laser literally melts the stones and destroys up to 100% of stones of any composition. It uses a flexible nephroscope and has an excellent safety record. It should be used sparingly, however, with particular caution against large uric acid stones until more is understood about its effect. Another device, the erbium: YAG laser, although showing promise in lithotripsy, is not currently practical.

Complications. Complication rates are about 3%. Major complications occur in about 1% of cases. These complications may include scarring of the tissue, but studies indicate that it does not impair kidney function, even if the patient requires repeat surgery. There is also a risk for blood loss during and after the procedure, which, in some cases, can be significant.

Because the procedure requires large volumes of fluid, fluid overload is a potential problem, particularly in children or patients with heart disease.

In some cases, infection may result. Other complications may include a collapsed lung and injuries to areas outside the kidney (but within the operative area), such as the abdomen or chest.

Ureteroscopy may be used for stones in the middle and lower ureter. With the arrival of smaller instruments, this procedure can be done successfully in children as well. The procedure involves the following:

The patient receives a general anesthetic, though no incision is required for the procedure.
The surgeon passes a small fiberoptic instrument called a ureteroscope through the urethra and bladder into the ureter.
The surgeon locates the stone or stones.
The surgeon can remove smaller stones by grasping them with small forceps. A laser or pneumatic device breaks up large stones.
The surgeon may decide to leave a small tube, or stent, in the ureter for a few days after treatment, to help the lining of the ureter heal.

Complication rates range from 10 - 20%, with major problems occurring in up to 6% of patients. In some cases, large stones are not broken up into small enough pieces. This can result in blockage of the urinary tract and possible kidney damage.

Imaging tests, such as ultrasound or spiral CT, are useful within 3 months to check for residual stones, and a second procedure may be required. The risk of complications is highest when the procedure is performed by less experienced surgeons, or if stones are found in the kidney. The risk for perforation of the ureter increases the longer the procedure takes.

Open surgery involves incisions through the patient's flank and into the kidney. The surgeon will cool the kidneys using ice. X-rays during the procedure help locate the stone. At the beginning of the surgery, the surgeon will isolate the arteries supplying the kidneys, ensuring they are not harmed during the surgery. The surgeon will then locate and remove the stone. The surgeon will also correct any blockage in the affected area. The surgery, called nephrolithotomy, is very invasive and is restricted to the following:

Patients with very large or complex stones that cannot be removed using less invasive measures
Very obese patients

Some centers report success with extracorporeal shock wave lithotripsy, however, in patients who would normally be nephrolithotomy candidates. Therefore, even these patients should discuss other options with their surgeon.

The procedure is not appropriate for patients with:

Bleeding or clotting disorders
Untreated widespread infection
Severe and chronic kidney insufficiency (unless removing the stone will improve kidney function)

Complications

Between 70 - 90% of crystals remain tiny enough so that they can travel through the urinary tract and leave the body in the urine without being noticed. When they do cause symptoms, however, kidney stones have been described as one of the most painful disorders to afflict humans. The pain they cause is sometimes called renal colic. ("Renal" means "kidney.")

Obstruction and Infection. Although kidney stones often lead to obstruction (blockage) of the urinary tract, the blockage is usually temporary and causes no lasting damage. In some cases, however, particularly if the obstruction progresses with no symptoms, infection may occur, which can be serious and need immediate attention.

Kidney Failure. It is very rare for kidney stones to cause kidney failure, although some people have risk factors that make them more vulnerable to this serious complication. Risk factors include the following:

Very frequent recurrences (such as in people with cystine stones or other inherited forms of kidney stone disorders)
Accompanying episodes of urinary tract infections with obstruction, a particular risk with struvite stones
A history of multiple urologic procedures for kidney stones
Greater size of the kidney stone gravel

Without preventive treatment, calcium stones recur in 10% of patients within a year of the first attack, and in half of patients within 5 - 7 years. Individual risk for recurrence, however, varies depending on the stone and the underlying condition. For example, a 15-year-old with inherited cystine stones has a very high risk for recurrence, while a middle-aged man with a first calcium oxalate stone has a good chance of never passing another.

Prevention

All individuals who have experienced kidney stones should take some specific preventive measures to prevent recurrence. The following are some general observations:

The most important dietary recommendations for reducing the risk for calcium stones are increasing fluid intake, restricting sodium, and reducing protein intake.
A lower risk for calcium stones is also associated with higher potassium intake.
A high calcium diet does not appear to increase the risk for kidney stones as long as it also contains plenty of fluids and dietary potassium and phosphate. (Increasing calcium alone may pose a modest risk for stones.)
Patients should try to correct any dietary habits that cause acidic or alkaline imbalances in the urine, which promote stone formation.

Because different kidney stone types may require specific dietary changes, patients should work with their doctors to develop an individualized plan. It is important to note that nutritional considerations are very important in preventing recurrence, and patients should be vigilant in complying with the proper diet.

Good voiding habits, particularly frequent urination, are important. Therefore, of all the preventive recommendations, drinking enough fluids is the most important guideline for people with any type of kidney stones.

In general, patients with calcium or uric acid stones should drink at least 10 full glasses of fluid each day (at least half should be water). This includes one with each meal and drinking fluids at night, even if it means getting up from sleep. Fluid intake should produce at least two and a half quarts of urine each day.
To prevent cystine stones, patients should drink even more water -- over a gallon, or 16 8-ounce cups, every day. Patients should drink this amount at regular intervals throughout the night and day.

In all cases, patients need more fluid after exertion and during times of stress. If they drink enough, the urine should be pale and almost watery, not dark and yellow.

Water. Although water is best, it may vary depending on its source. Variations in water itself may have different impacts. One study reported that drinking hard tap water increased urinary calcium concentration by 50% compared to soft bottled water. On the other hand, mineral water containing both calcium and magnesium may reduce several risk factors for both calcium and uric acid stone formation.

Juices and Specific Effects. Other beverages have various positive or negative effects, depending on the type of stone:

Lemon Juice: Drinking one-half cup of pure lemon juice (enough to make eight glasses of lemonade) every day raises citrate levels in the urine, which might protect against calcium stones. (While orange juice also increases citrate levels, it does not lower calcium and it raises oxalate levels. Therefore, it is not recommended.)
Cranberry and Apple Juice: Apple and cranberry juice contain oxalates, and both have been associated with a higher risk for calcium oxalate stones. Cranberry juice has properties that may increase the risk for both calcium oxalate and uric acid stones. On the other hand, cranberry juice helps prevent urinary tract infections and so may be helpful for reducing the risk for struvite and brushite stones. (These stones are far less common, however.)
Black Currant Juice: In one study, black currant juice reduced urine acidity and was associated with protection against uric acid stones.
Grapefruit Juice: A number of studies have found a risk for stones from drinking grapefruit juice. In one study, just one 8-ounce cup of grapefruit juice per day increased the risk for forming stones by 44%.

Other Beverages and Their Effects on Stone Formation.

Soft Drinks. Patients with stones should avoid cola drinks, since they can severely reduce citrate levels in the urine. Many soft drinks contain phosphoric acid, which increases the risk for stones. Some research shows that drinking one quart (less than three 12-ounce cans) of soda per week may increase a person's risk of developing stones by 15%.
Alcohol. Wine may be protective against kidney stones. A study conducted in Finland, suggests that the risk of developing stones also decreases with beer consumption. However, it is important to remember that beer is high in oxalates. Beer and other alcoholic beverages also contain purines, which may increase the specific risk for the less common uric acid stones in susceptible people. Binge drinking, in any case, increases uric acid and the risk for stones.
Coffee and Tea. Some research reported a lower risk for stones in people who drink tea and both regular and decaffeinated coffee.

A long-term 2002 study followed men with calcium oxalate stones and high levels of urinary calcium. The study found that a low-sodium, low-protein diet, containing normal levels of calcium, dramatically reduced the recurrence of stones compared to a diet that was simply low in calcium.

Salt Restriction. Because salt intake increases the amount of calcium in urine, patients with calcium stones should limit their sodium intake. Sodium may also increase levels of urate, the crystalline substance that can trigger formation of recurrent calcium oxalate stones. Although the relative contribution of limiting sodium intake has not been confirmed, some researchers believe that restricting sodium along with increasing fluid intake is the most important dietary measure for preventing stones.

Protein Restriction. Protein increases uric acid, calcium, and oxalate levels in the urine, and reduces citrate levels. Diets high in protein, particularly meat protein, have been consistently connected with kidney stones. (Meat protein has a higher sulfur content and produces more acid than vegetable protein.) A 2002 study of those following a high-protein, low-carbohydrate diet (such as the Atkins diet, for example), found dramatically increased levels of urinary uric acid and calcium after just several weeks. These effects put patients at higher risk for not just kidney stones, but possibly osteoporosis as well. According to Swiss studies, about a third of people at risk for calcium stones may have a sensitivity to meat proteins that causes mild hyperoxaluria.

Whether restricting meat protein alone has any protective value without restricting sodium as well is unknown. Most studies to date have found no difference in stone development between people with low and normal meat protein diets over four years. A 2000 study reported that only dramatic reductions in meat protein had any preventive effect against stone recurrence.

Although the precise role of dietary protein in kidney stones needs further clarification, it is reasonable for everyone to consume meat protein in moderation. People with struvite stones, who need to reduce phosphates in their diets, should also cut down on proteins.

Calcium from Foods. Dietary calcium recommendations for kidney stone prevention need to be determined on an individual basis. A doctor will suggest calcium guidelines based on a patient's age, gender, body size, and type of stone. Most studies indicate that dietary calcium (found in milk, yogurt, and cheese) protects against many types of calcium oxalate stones. Large studies of both men and women found that those with the highest intake of calcium from foods had a much lower risk for stones than those who had little calcium in their diets. A diet containing a normal amount of calcium, but reduced amounts of animal protein and salt, may protect against stones better than a low-calcium regimen. However, calcium metabolism changes as people age. Some studies suggest that a high calcium intake protects against kidney stones in men younger than age 60, but not in older men.

Dietary calcium may actually bind the oxalate in foods, preventing it from being absorbed into the blood and excreted into the urine. In a normal healthy diet, dairy products supply almost 80% of the daily calcium requirement. For people who have calcium stones associated with resorption (the breakdown of bone that releases calcium into the bloodstream), limiting calcium intake could cause further bone loss.

Calcium Supplements. Evidence on calcium supplements is mixed, although in general many studies suggest that they reduce oxalate levels and so help prevent calcium oxalate stones. One study suggested that taking 500 mg of calcium supplements a day regularly may "reprogram" the intestines to absorb less calcium and may therefore be protective. Experts generally agree that calcium supplementation within dosage recommendations (about 1,200 mg per day) remains safe. In one study, however, women who took calcium supplements had a 20% higher risk for stones. Research indicates that dosages of calcium above 2,000 mg per day are clearly associated with the formation of stones. Some experts speculate that this higher risk may occur because supplements are often taken in the morning, either without food or with breakfast, which is typically low in oxalates. Taking supplements with later meals may not produce the same risk.

Calcium Restriction in Certain Cases. Some patients, such as those whose stones are caused by genetic defects in which the intestine absorbs too much calcium, may need to limit calcium intake. More studies are needed to define this group precisely.

Fiber may be beneficial for people with kidney stones. In addition, some fiber-rich foods may contain compounds that help protect against kidney stones. A wide variety of high-fiber plant foods contain a compound called phytate (also called inositol hexaphosphate, InsP6, or IP6), which appears to help prevent crystallization of calcium salts, both oxalate and phosphate. Phytate is found in legumes and wheat and rice bran. (Soybeans are also rich in phytate but they are also very high in oxalates, so the overall effects of soy on kidney stones are not clear.)

A high intake of purines can increase the amount of uric acid in the urine. Those at risk for uric acid stones should reduce their intake of foods and beverages that contain purines. These include beer and other alcoholic beverages, anchovies, sardines, yeast, organ meats (such as liver and kidneys), legumes (including dried beans, peas, and soybeans), mushrooms, spinach, asparagus, cauliflower, and poultry.

Most people with calcium oxalate stones should not avoid oxalate-rich foods unless the doctor specifically recommends a restrictive diet. Oxalate binds with calcium in the intestine, which may actually reduce calcium absorption. Some studies, in fact, indicate that eating foods containing oxalates and calcium together may reduce the risk of stones. Most of the foods that contain oxalates are very important for good health. Limiting oxalates may be particularly harmful in people with bowel disorders marked by malabsorption.

Foods high in oxalic acid include beets, soy, beet tops, black tea, chenopodium, chocolate, cocoa, dried figs, ground pepper, lamb, lime peel, nuts, parsley, poppy seeds, purslane, rhubarb, sorrel, spinach, and Swiss chard.
Foods containing moderate amounts of oxalates include beans (green and wax), blackberries, blueberries, carrots, celery, coffee (roasted), concord grapes, currants, dandelion greens, endive, gooseberries, lemon peel, okra, green onions, oranges, green peppers, black raspberries, strawberries, and sweet potatoes.

Certain fats may play a beneficial or harmful role in specific cases of kidney stones.

Restricted Fats in Patients with Stones Associated with Bowel Disease. Patients who have stones associated with short-bowel syndrome should eat foods with lower amounts of fats and oxalates. If patients with short-bowel syndrome eat too much fat, calcium may bind to unabsorbed fat instead of to oxalates. This increased oxalate levels, resulting in increased risk of stone formation.

Fish Oil. Omega-3 fatty acids, found in oily fish like mackerel, salmon, and albacore tuna, have many health benefits, but the most current evidence suggests they do not help prevent kidney stones. A 2005 study of over 200,000 adults found that increased omega-3 fatty acid intake did not reduce kidney stone risk.

Vitamin B6. Vitamin B6, or pyridoxine, is used to treat people with primary hyperoxaluria, a severe inherited disorder. Patients should not try to treat themselves with vitamin B6. Very high doses (500 to 2,000 mg daily over long periods) can cause nerve damage, with loss of balance and numbness in the feet and hands. Food sources of vitamin B6 include meats, oily fish, poultry, whole grains, dried fortified cereals, soybeans, avocados, baked potatoes with skins, watermelon, plantains, bananas, peanuts, and brewer's yeast.

Vitamin C. Ascorbic acid (vitamin C) may change in the body to tiny crystals, called oxalates. These crystals do not dissolve. People with hyperoxaluria (too much oxalate in the urine) should avoid vitamin C supplements. Even for men with normal oxalate levels, higher consumption of vitamin C (more than 1,000 mg a day) may increase kidney stone risk.

Magnesium and potassium may help reduce the risk for kidney stones in men.

Because of an association between stress and kidney stones, relaxation and stress management techniques may also be beneficial.

Dietary Considerations. People with kidney stones appear to be more sensitive to certain foods than people who do not form kidney stones. Therefore, vulnerable people should make specific changes in their diet. They should work with their doctors to develop a dietary plan that fits their individual situation. Drinking plenty of fluids is important for preventing recurrence of any kidney stone.

Indications for Drug Treatments. If dietary treatments fail, drug therapy may be helpful. A number of drugs are available to prevent recurrences of calcium oxalate and other stones. Medications that inhibit the formation of stones include allopurinol, thiazide, potassium citrate, and potassium-magnesium citrate. In addition, drug treatments can sometimes also help prevent other complications related to stones, such as osteoporosis.

Correcting Underlying Conditions Known to Cause Kidney Stones. It is also important to treat and correct, if possible, any underlying disorder that may be causing stones to form. Such disorders include distal renal tubular acidosis, hyperthyroidism, sarcoidosis, and certain cancers. To prevent calcium stones that form in hyperparathyroid patients, a surgeon may remove the affected parathyroid gland (located in the neck). In most cases, only one of the glands is enlarged. Removing it ends the patient's problem with kidney stones.

Resources

www.kidney.niddk.nih.gov -- National Kidney and Urologic Diseases Information Clearinghouse
www.urologyhealth.org -- American Urological Association
www.kidney.org -- National Kidney Foundation
www.ohf.org -- Oxalosis and Hyperoxaluria Foundation

References

Cameron MA, Maalouf NM, Adams-Huet B, Moe OW, Sakhaee K. Urine composition in type 2 diabetes: predisposition to uric Acid nephrolithiasis. J Am Soc Nephrol. 2006 May;17(5):1422-8. Epub 2006 Apr 5.

Curhan GC, Willett WC, Knight EL, Stampfer MJ. Dietary factors and the risk of incident kidney stones in younger women: Nurses' Health Study II. Arch Intern Med. 2004;164(:885-891.

Finkielstein VA. Strategies for preventing calcium oxalate stones. CMAJ. 2006;174(10); 1407-1409.

Krambeck AE, Gettman MT, Rohlinger AL, Lohse CM, Patterson DE, Segura JW. Diabetes mellitus and hypertension associated with shock wave lithotripsy of renal and proximal ureteral stones at 19 years of followup. J Urol. 2006;175(5):1742-7.

Sinha MK, Collazo-Clavell ML, Rule A, et al. Hyperoxaluric nephrolithiasis is a complication of Roux-en-Y gastric bypass surgery. Kidney International. 2007;72:100-107.

Straub M, Hautmann RE. Developments in stone prevention. Curr Opin Urol. 2005;15(2):119-126.

Taylor EN, Stampfer MJ, Curhan GC. Dietary factors and the risk of incident kidney stones in men: new insights after 14 years of follow-up. J Am Soc Nephrol. 2004;15(12):3225-3232.

Taylor EN, Stampfer MJ, Curhan GC. Fatty acid intake and incident nephrolithiasis. Am J Kidney Dis. 2005;45(2):267-274.

Taylor EN, Stampfer MJ, Curhan GC. Obesity, weight gain, and the risk of kidney stones. JAMA. 2005;293(4):455-462.

Taylor EN, Stampfer MJ, Curhan GC. Diabetes mellitus and the risk of nephrolithiasis. Kidney Int. 2005 Sep;68(3):1230-5.

Wasserstein AG. Nephrolithiasis. American Journal of Kidney Diseases. 45(2);2005:422-28.

Review Date:
7/24/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial policy, editorial process and privacy policy. A.D.A.M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www.hon.ch).

A.D.A.M. Copyright

The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-2009 A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.

adam.com

Cervical cancer

FitSugar — Wed, 08 Oct 2008 17:34:57 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Prognosis
Symptoms
Prevention
Diagnosis
Treatment for Cervical Intr...
Treatment for Cervical Canc...
Treatment for Invasive Cerv...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Human Papilloma Virus (HPV) Prevalence

About 25% of women age 14 - 59 are infected with the human papilloma virus (HPV), indicates a 2007 study in the Journal of the American Medical Association (JAMA). HPV prevalence is highest (45%) among women age 20 - 24. HPV is the main cause of cervical cancer.

Immunization Guidelines

In 2006, the FDA approved the first vaccine to prevent cervical cancer. Gardasil protects against human papilloma virus (HPV) 16 and 18, the strains most likely to cause cervical cancer, and HPV 6 and 11, the strains most likely to cause genital warts. In 2007, several expert groups released immunization guidelines for the cervical cancer vaccine. Guidelines from the U.S. Centers for Disease Control’s Advisory Committee on Immunization Practices recommend:

Routine vaccination for girls age 11 - 12 with a vaccine series of 3 doses. Girls as young as 9 years old may be vaccinated at their doctors’ discretion.
Catch-up vaccination for girls and women age 13 - 26 who have not been previously vaccinated or who have missed doses.

Vaccine Effectiveness

The vaccine prevents human papilloma virus (HPV) infection caused by four HPV strains but cannot treat pre-existing HPV infection, confirms a 2007 JAMA study
The vaccine is nearly 100% effective in preventing cervical cancer and genital warts when it is administered before females become sexually active, indicate several 2007 studies.

HPV and Throat Cancer

Human papilloma virus (HPV) 16 increases the risk of oropharyngeal cancers of the throat, tonsils, and back of the tongue, according to several 2007 studies. HPV can be transmitted during oral sex, causing infection in the mouth. (However, not all people who engage in oral sex or who have oral HPV infection will develop throat cancer. The virus usually goes away on its own.) Previously, alcohol and tobacco use were considered the main risk factors for oropharyngeal cancer.

Introduction

The cervix is the lower third portion of the uterus (womb). It serves as a neck to connect the uterus to the vagina. The opening of the cervix, called the os, remains small and narrow, except during childbirth when it widens to allow a baby to pass from the uterus into the vagina.

The uterus is a hollow muscular organ located in the female pelvis between the bladder and rectum. The ovaries produce the eggs that travel through the fallopian tubes. Once the egg has left the ovary it can be fertilized and implant itself in the lining of the uterus. The main function of the uterus is to nourish the developing fetus prior to birth.

Cervical cancer develops in the thin layer of cells called the epithelium, which cover the cervix. Cells found in the this tissue have different shapes:

Squamous cells (flat and scaly). Most cervical cancer arises from changes in the squamous cells of the epithelium (squamous cell carcinoma).
Columnar cells (column-like). These cells line the cervical glands and cancers here are known as adenocarcinomas.
In rare cases, cancer can occur in cells that form the supportive tissue around the cervix (the stroma).

Cervical cancer usually begins slowly with precancerous abnormalities, and even if cancer develops, it generally progresses very gradually. Cervical cancer is the most preventable type of cancer and is very treatable in its early stages. Regular Pap tests and human papilloma virus (HPV) screening can help detect this disease early.

Dysplasia. Dysplasia is a term that refers to a precancerous condition. It may become cancerous, but not always. In the case of cervical cancer, dysplasia indicates that the layer of cells that covers the cervix (squamous epithelial cells) are abnormal in size and shape and are beginning to grow.

Cervical Intraepithelial Neoplasia. Dysplastic changes seen on a Pap smear may indicate the presence of cervical intraepithelial neoplasia (CIN). This means precancerous changes are found within the lining of the cervix. The changes are categorized according to severity: CIN I, CIN II, and CIN III.

With CIN I, there are mild abnormalities that rarely develop into cervical cancer. This condition may progress if untreated but often goes away without treatment.
In CIN II, the lesions often appear more aggressive under the microscope and may turn into cancer unless treated.
CIN III is the most aggressive form of dysplasia. If not removed, there is a high chance that it will turn into invasive cancer. CIN III includes carcinoma in situ (CIS). CIS is an early stage of non-invasive cancer -- the cells are confined within the tissue where they grew and have not yet invaded surrounding tissue. However since CIS can progress to invasive cancer, this condition should be treated as soon as possible.

Click the icon to see an image of cervical dysplasia.

The cells of the epithelium rest on a very thin layer called the basement membrane. Invasive cervical cancer occurs when cancer cells in the epithelium cross this membrane and invade the stroma, the underlying supportive tissue of the cervix.

In later stages, the original cancer may spread to areas surrounding the uterus and cervix or near organs such as the bladder or rectum. It may also spread to distant sites in the body through the bloodstream or the lymph nodes.

Causes

The human papillomavirus (HPV) has been detected in virtually all invasive cervical cancers and has been confirmed as the major cause of this cancer.

How HPV Is Transmitted. HPV is spread primarily by having sex with an infected partner. Most sexually active young women become infected with this virus, but only 10% remain infected for more than 5 years. Only those infected for longer than 5 years have a higher risk (about 50% above normal). Other factors are then needed to trigger the disease.

How HPV Contributes to Cervical Cancer. Researchers believe that most cervical cancers develop when various aggressive genetic HPV strains activate certain oncogenes (cancer-causing genes). Oncogenes called E6 and E7 are particularly important because they interfere with certain protective proteins, such as p53 and pRb, respectively. Under normal conditions, these proteins limit cell growth. Once they are blocked, cell growth can run rampant, leading to tumor development and cancer.

HPV Genetic Types. More than 30 genetic variants of human papillomaviruses can be passed through sexual contact form one person to another. The severity, however, varies widely according to genetic type. (Women initially infected by one type of HPV are still at risk for infection from other types.)

In women with cervical intraepithelial neoplasia I , the HPV viruses that are present are often types 6 and 11, which are low risk. Other low-risk HPV genetic types are 40, 42, 43, 44, 54, 61, 70, 72, and 81. These viral types often produce genital warts (condylomata) that rarely lead to cancer. (These warts usually affect the woman's genitals, the vagina, and vulva, rather than the cervix.)

Of the high-risk types, HPV types 16 and 18 have long been known to be particularly dangerous. These two genetic types and six others (31, 33, 35, 45, 52, and 58) account for 95% of HPV-related cervical cancers. Other high-risk types are 39, 51, 56, 59, 68, 73, and 82. All are associated with moderate cervical intraepithelial neoplasia II and cervical intraepithelial neoplasia III. Types 26, 53, and 66 are also considered high-risk.

In 2007, several studies indicated that HPV-16 infection in the mouth is associated with increased risk for oropharyngeal cancer. (Oropharyngeal cancer develops in the throat, just behind the mouth. It includes the base of the tongue, soft palate, tonsils, and side and back walls of the throat.) Prior to this research, alcohol and tobacco were thought to be the main risk factors for this type of cancer. According to the studies, oral sex (both fellatio and cunnilingus) significantly increases the risk of HPV-16 transmission and, therefore, the risk of developing oropharyngeal cancer. While the risk of HPV-16 causing oropharyngeal cancer is lower than the risk of it causing cervical cancer, experts think that the HPV vaccine may help reduce the incidence of throat, tonsil, and tongue cancers, as well as cervical cancer.

High-risk types of HPV have also been associated with an increased risk for other cancers, including other genital and lung cancers. The high-risk viruses generally produce flat and nearly invisible growths, compared to the usually harmless warts caused by low-risk HPV viruses.

Herpes viruses. Certain herpes viruses, including herpes simplex virus 6, 2, 7, and cytomegalovirus, have been detected in women with cervical cancer. herpes simplex virus 6 is under particular suspicion for playing a role in activating the papilloma virus gene. The presence of these very common viruses, however, may simply be coincidental, and they may serve no purpose other than being bystanders.

Chlamydia Trachomatis. Studies are finding an especially strong association between the incidence of Chlamydiatrachomatis, a sexually transmitted infection, and HPV. (Chlamydia trachomatis should not be confused with Chlamydia pneumoniae, a common cause of mild pneumonia in young adults. Chlamydia pneumonia e is not associated with cervical cancer.)

Other Sexually Transmitted Diseases. Other sexually transmitted diseases that have been associated with cervical cancer include HIV and gonorrhea. These infections, however, also may only be markers of increased sexual activity and may not themselves cause cancer.

Risk Factors

According to the American Cancer Society, about 11,150 new cases of invasive cervical cancer will be diagnosed in the U.S. in 2007. However, the number of new cervical cancer cases has been declining steadily over the past decades. Fifty percent of cervical cancer diagnoses occur in women ages 35 - 55, and slightly more than 20% occur in women over 65 years of age.

Some women (15%) develop cervical cancer before the age of 30. Although cervical cancer is rare in women under age 20, cancer rates in younger women are on the rise. Many young women are infected with multiple types of human papillomavirus, which can increase their risk of getting cervical cancer. Young women with early abnormal changes who do not have regular examinations are at high risk for localized cancer by the time they are age 40, and for invasive cancer by age 50.

Although it is the most preventable type of cancer, cervical cancer is ranked as the second most common cause of female death. Each year it kills an estimated 3,700 women in the U.S. and nearly 300,000 women worldwide.

In the United States, cervical cancer mortality rates plunged by 74% from 1955 - 1992 thanks to increased screening and early detection with the Pap test.

Although the rate of cervical cancer has declined in both Caucasian and African-American women over the past decades, it remains much more prevalent in African-Americans -- whose death rates are twice as high as Caucasian women. Hispanic American women have more than twice the risk of invasive cervical cancer as Caucasian women, also due to a lower rate of screening.

These differences, however, are almost certainly due to social and economic differences. Numerous studies report that high poverty levels are linked with low screening rates. In addition, lack of health insurance, limited transportation, and language difficulties hinder a poor woman’s access to screening services. Researchers are investigating programs that provide screening and treatment for women with abnormal Pap smears in a single visit.

The human papilloma virus (HPV) is the primary cause of cervical cancer. According to a 2007 study in the Journal of the American Medical Association, about 1 in 4 U.S. females ages 14 - 59 are infected with HPV. The prevalence of HPV is highest (45%) in women age 20 - 24.

The risk for cervical cancer in infected women appears to be highest in those infected with HPV for more than 6 months. In most people, the virus goes away within a year. However, it persists in about 10% of infected women.

High Sexual Activity. In adults, the most important risk factor for HPV is sexual activity with an infected person. Women most at risk for cervical cancer are those with a history of multiple sexual partners, sexual intercourse at 17 years or younger, or both. A woman who has never been sexually active has a very low risk for developing cervical cancer. Sexual activity with multiple partners increases the likelihood of many infections in addition to human papilloma virus.

Douching. Women who douche on a weekly basis are more likely to contract cervical cancer than those who do not. Douching may destroy the natural antiviral substances normally present in the vagina, making women more susceptible to HPV.

Pessaries. Use of a pessary (a ring-shaped plastic device that keeps the vagina and uterus from collapsing) increases the risk of chronic inflammation and viral infection at the insertion site and therefore may increase the risk for cervical cancer.

Risk Factors for HPV in Children and Infants. HPV also can occur in children and even newborns. The virus may also be transmitted by an infected mother. In children, HPV is usually the harmless form that cause skin warts.

In one analysis, 15 - 20% of women with cervical cancer had at least one close relative with the disease. Two studies have also reported that in families with cervical cancer there have also been higher rates of other human papilloma virus-related and smoking-associated cancers. Inherited factors in such cases most likely cause changes in the immune system that make such people more susceptible to human papilloma virus or other viruses.

Several studies, including a major analysis, have reported a strong association between cervical cancer and long-term use of oral contraception (OC). Women who have taken OCs for more than 10 years have a much higher risk of human papilloma virus (HPV) infection (up to four times higher) than those who do not use OCs. (Women taking OCs for fewer than 5 years have no significantly higher risk.) The reasons for this risk from OC use are not entirely clear. Women who use OCs may be less likely to use a diaphragm, condoms, or other methods that offer some protection against sexual transmitted diseases, including HPV. Some researchers also suggest that the hormones in OCs might help the virus enter the genetic material of cervical cells.

Studies indicate that having many children increases the risk for developing cervical cancer, particularly in women with human papilloma virus.

Smoking is associated with a higher risk for precancerous changes (dysplasia) in the cervix and for progression to invasive cervical cancer. Smoking may cause human papilloma virus (HPV) to grow faster and increase its likelihood of causing cancer. According to a 2006 study, women smokers who have HPV-16 are 14 times more likely to develop cervical pre-invasive cancer than smokers who do not have the virus. By contrast, non-smokers with HPV-16 were only 6 times more likely to develop cancer than those who were not infected.

Secondhand smoke is also linked to increased risk for cervical cancer tumors. It is not clear if this association is due to cigarette smoke’s direct cancer-causing effects or general damage to the immune system. Cigarette smokers are also deficient in folate, a B vitamin. Folate deficiency may play a role in the development of dysplasia.

Diethylstilbestrol. From 1938 - 1971, diethylstilbestrol, an estrogen-related drug, was widely prescribed to pregnant women to help prevent miscarriages. The daughters of these women face a higher risk for cervical cancer, genital tract abnormalities, and miscarriage.

Environmental Chemicals. Long-term exposure to certain types of agricultural and industrial chemicals may increase the risk for cervical cancer.

Prognosis

The following are some examples of the time it takes for early stages of cervical dysplasia to progress to the next stage:

Only about 1% of untreated mild cervical dysplasia (CIN I) cases progress to severe dysplasia or cancer each year.
In women with untreated moderate dysplasia (CIN II), 16% will progress to the next stage in 2 years, while 25% will progress after 5 years.
Most untreated pre-invasive cancer will develop into invasive cancer over a period of 10 - 12 years.

Over the past 30 years, the death rate from cervical cancer has declined significantly. In general, 71% of women with invasive cervical cancer survive for 5 years or more. African-American women tend to have poorer 5-year survival rates than Caucasian women, although survival rates have significantly increased in African-American women in recent years.

The outlook for specific women varies depending on different factors:

In women who receive treatment when cervical cancer is still local, the cure rate is about 90%. Experts say universal screening could essentially reduce the cervical cancer death rate to zero. Still, only 12 - 15% of women have routine Pap smears. As a result, only 55% of Caucasian women and 44% of African-American women are diagnosed at early stages.
If the cancer cells have spread beyond the cervix, the average 5-year survival rates may drop to 50% and below, depending on how much it has spread and the type of cancer cell.

Identifying what type of human papilloma virus (HPV) a woman has may help determine outlook and the severity of cervical cancer. For example, HPV-18 and HPV-16 are associated with severe cases. HPV-16 has also been linked to a rare form of cervical and uterine cancers.

Other biochemical markers in the body may also help predict outcome and treatment. For example, women with cervical cancer who have high levels of an enzyme called cyclooxygenase (COX-2) may need more aggressive treatments than those with low levels.

The treatments for advanced cervical cancer also add to the emotional burden in premenopausal women, because they nearly always prevent future childbearing.

Symptoms

Most women with dysplasia or pre-invasive cancer have no symptoms. Screening tests, therefore, are very important.

When the cancer becomes invasive, unusual bleeding can occur. Bleeding may stop and start again between regular periods or there may be bleeding after menopause. Unexpected bleeding can also occur after intercourse or a pelvic exam. Periods sometimes last longer or are heavier than usual. Increased vaginal discharge may be noticeable as well. Pelvic pain can occur, but it is not common.

These symptoms are not exclusive to cervical cancer. Sexually transmitted diseases, for instance, can cause similar symptoms.

Prevention

The best way to prevent cervical cancer is to avoid getting infected with human papilloma virus (HPV). Because HPV is sexually transmitted, practicing safe sex and limiting the number of sexual partners can help reduce risk. A vaccine can protect against the major cancer-causing HPV strains. Regular Pap tests remain the most effective way of preventing the development of invasive cervical cancer.

In 2006, the FDA approved the first human papilloma virus (HPV) vaccine to prevent cervical cancer. Gardasil has been tested in more than 12,000 uninfected girls and women in 13 countries. Studies show it provides nearly 100% protection against HPV-16 and HPV-18, the viruses that cause 70% of cases of cervical cancer. Gardasil also protects against HPV-6 and HPV-11, which cause 90% of cases of genital warts.

Gardasil is approved for girls and women ages 9 - 26. Current immunization guidelines recommend:

Routine vaccination for girls ages 11 - 12 years. The vaccine should be administered in 3 doses, with the second and third doses administered 2 and 6 months after the first dose. The HPV vaccine can be given at the same time as other vaccines.
Girls as young as age 9 can receive the vaccine at their doctors’ discretion.
Girls and women ages 13 - 26 who have not been previously immunized or who have not completed the full vaccine series should get vaccinated to catch up on missed doses. [The U.S. Advisory Committee on Immunization Practices (ACIP) and the American Academy of Pediatrics (AAP) recommend catch-up doses for ages 13 - 26. The American Cancer Society (ACS) recommends catch-up for ages 13 - 18. The ACS suggests that women ages 19 - 26 discuss with their doctors the relative risks and benefits of vaccination.]
Women should not get the vaccine during pregnancy.

The HPV vaccine can only prevent -- not treat -- HPV infection, genital warts, and cervical cancer. Because the vaccine cannot protect females who are already infected with HPV, doctors recommend that girls get vaccinated before they become sexually active. Several 2007 studies indicated that the vaccine is nearly 100% effective in preventing cervical cancer and genital warts when given prior to HPV exposure. However, young women who are sexually active may still derive some benefit from the vaccine, at least for protection against any of the four HPV strains that they have not yet acquired.

The FDA is considering approving another type of cervical cancer vaccine (Cervarix). Cervarix protects against HPV-16 and HPV-18, as well as the cancer-causing strains HPV-31 and HPV-45. It does not protect against genital warts.

The FDA is not yet sure how long Gardasil’s protection lasts or when patients may need a booster shot. A 2006 study of the Cervarix vaccine found that protection lasted for at least 4.5 years.

These vaccines do not protect against all types of cancer-causing HPV. The FDA still recommends that women receive annual screening to detect any early signs of cervical cancer. For girls and women who have been sexually active before they receive the vaccine, screening still provides the best protection against cervical cancer.

Use of barrier contraceptives such as condoms is associated with a reduced risk of cervical cancer, even in women already infected with human papilloma virus (HPV). HPV can exist outside the area protected by the male condom, so this method is not foolproof in preventing an initial infection. However, a 2006 New England Journal of Medicine study found that when men used condoms every time they had sexual intercourse, their female partners had less than half the rate of HPV infection as women whose partners used condoms less than 5% of the time. The female condom is becoming increasingly popular in developing countries. It may prove to be particularly effective against sexually transmitted diseases in these regions.

A 2002 study reported that men who are circumcised have a lower risk for carrying human papilloma virus (HPV) and therefore reduce the risk for cervical cancer in their female partners.

Some studies have suggested possible protective benefits against cervical cancer from certain vitamins.

High blood levels of vitamins E and C have been linked with lower rates of some cancers, including cervical cancers.

Although vitamin E is a fat-soluble vitamin, there are no known toxic effects of megadoses.

Click the icon to see sources of food which contain vitamin E.

Click the icon to see the benefits of vitamin C.

Click the icon to see sources of food which contain vitamin C.

Folic acid, a B vitamin, prevents birth defects and may also lower the risk for development of dysplasia (precancerous changes) leading to cervical cancer. It is not clear how strong this association is, or why this would occur. Some evidence points to its actions in reducing levels of homocysteine, a compound associated with a higher risk of cervical cancer.

There is no definitive evidence, however, that taking vitamins can prevent any cancer. Eating healthy foods rich in such vitamins and other important nutrients is, in any case, the best approach for overall good health.

Diagnosis

The changes that lead to cervical cancer develop slowly. Screening tests performed during regular gynecologic examinations can detect early changes.

Every year in the U.S. about 50 million women have a Papanicolaou test (the Pap smear). Use of the Pap smear has reduced the annual death rate from cervical cancer from 26,000 in 1941 to 3,700 in 2005.

Forty percent of women who have a Pap smear fail to follow-up for retesting and treatment. Most cases of cervical cancer occur in women who have not had regular Pap tests.

The Procedure. The most accurate test results are obtained 12 - 14 days after menstruation begins. Women should not douche or have intercourse within 48 hours of the test. Douches and spermicidal creams may clean out abnormal cells and interfere with the results of a Pap smear. (In general, douching is not recommended at all.) A Pap smear is usually painless, although some women may have some discomfort.

The test is done in a doctor's office. The woman removes her clothes from the waist down and puts on a medical gown. She lies on her back on the examination table, bends her knees, and puts her feet in supports (called stirrups) at the end of the table.
A doctor inserts a metal device into her vagina to widen it.
Using a spatula, brush, or both, the doctor gently scrapes the surface of the cervix, and sometimes the upper vagina, to gather living cells. The doctor will also obtain cells from inside the cervical canal. Such cells include squamous and glandular cells and those that lie higher up in the cervical canal (known as the endocervix). Using both a brush and spatula helps gather better samples to detect the presence of cancer.
The cells are preserved, stained for microscopic viewing, and then analyzed under a microscope by a specialist known as a cytopathologist.

A Pap test is a simple, relatively inexpensive procedure that can easily detect cancerous or precancerous conditions.

Reliability and Accuracy. Over the course of a lifetime of regular screening, a woman faces a 40% chance of being told her Pap smear is abnormal. The Pap smear is not, however, a perfectly reliable measure of a woman's risk for cervical cancer.

In general, about 10% of Pap smears have abnormal results, but only about 0.1% of the women who have these results actually have cancer. In most cases, abnormal cells are low grade and not likely to progress to cancer or are due to benign conditions, including natural cell changes after menopause.

No test is 100% accurate, and it is possible for the Pap smear to miss the presence of cancer. However, if abnormal cells are missed on one test they are likely to be spotted during the next one without a significant danger.

Newer, thin-layer liquid based tests (ThinPrep, SurePath) use the original cervical sample, which is rinsed in a special solution to thin the mucus (rather then dried). The result is a clear, clean sample that may be able to accurately reveal abnormal cells. The fluid can also be examined for evidence of human papilloma virus (HPV) and other early abnormalities. Some -- but not all -- studies have found this test to be more accurate than the standard Pap smear. A rigorous 2006 review of 56 studies found that liquid-based tests were no more accurate than conventional Pap smears.

The U.S. Preventive Service Task Force (USPST), the American Cancer Society (ACS), and the American College of Obstetricians and Gynecologists (ACOG) have all released guidelines for cervical cancer screening. ACOG and ACS have established separate screening criteria for women below and above 30 years of age. Although there are some small differences between these three sets of guidelines, they generally make similar recommendations as summarized below:

Recommendations for Initial Screening. Women should begin to undergo Pap tests within 3 years of onset of sexual activity or at age 21 (whichever comes first).

Women with no history of sexual activity should still have Pap smears. They are at low risk for squamous cell carcinoma, but adenocarcinoma (cancer that occurs in cervical glands) can occur, although this is very uncommon.

Women Up to Age 30. Women under age 30 should receive annual screening with the conventional Pap smear. The American Cancer Society (ACS) offers the alternative of screening every 2 years using the newer liquid-based testing. HPV testing is not recommended for this age group because HPV infections in women under age 30 tend to resolve on their own.

Women Age 30 and Over. Women in this age group who have received three consecutive negative (normal) annual Pap tests have two screening options:

Screening with standard or liquid-based Pap tests every 2 - 3 years. Women in high-risk groups (DES exposure, HIV infection, weakened immune system, or previous diagnosis of cervical cancer) should continue to receive annual tests.
Screening with Pap test plus HPV DNA test. If a woman tests negative on both of these tests, then she can be rescreened no more frequently than once every 3 years. If one of the tests is positive, she will need to be screened more frequently.

Elderly Women. In its 2003 guidelines, the U.S. Preventive Service Task Force recommended against routine screening in women over age 65 with low or no risk factors. (The ACS recommends stopping at age 70, while the American College of Obstetricians and Gynecologists declines to set an upper age limit.) Such women have had at least three previous normal screenings and have had no abnormal results for at least 10 years. According to the guidelines, older women should be screened if they have not been screened before or if there is a possibility that they have not been screened (for example, if the woman is from a country that does not do routine screening). However, a 2006 study of more than 15,000 postmenopausal women recommended continued screening for elderly women who are sexually active but not monogamous. (Women in the study had a uterus.) The researchers note that about 25% of new cervical cancer cases, and 41% of cervical cancer deaths, occur among women 65 years and older.

After a Hysterectomy. The 2003 guidelines recommend against routine screening for women who have undergone a total hysterectomy for benign causes. Women who have had a hysterectomy that preserves the cervix (called a supracervical hysterectomy) should continue with Pap screening.

If Pap smear results are normal for 3 consecutive years, most expert groups recommend a Pap test every 2 - 3 years thereafter in most women over 30 years of age. (The American Cancer Society suggests that such women wait until they are 30 before extending the interval to 3 years.)

Both the American Cancer Society and the American College of Obstetricians and Gynecologists recommend that annual screening should continue in women in high-risk categories. High risk categories may include the following, depending on the medical group:

Women who have had multiple sexual partners or whose male sexual partners have had multiple partners.
Women who engaged in sexual activity at a young age.
Women whose male sexual partners have had other sexual partners with cervical cancer.
Women with current or prior HPV infection.
Women who are HIV-positive or who are immunosuppressed.
Women with a history of sexually transmitted diseases.
Smokers and substance or drug abusers.
Women who have a history of cervical dysplasia or cervical, endometrial, vaginal, or vulvar cancer.
Women in lower socioeconomic groups, particularly if they have not been able to obtain regular gynecologic screening and care.

Any abnormal result, even a mild abnormality, requires follow-up visits and additional tests. The extent of these tests depends on the degree of abnormalities.

New tests and methods have been developed to improve the accuracy of the Pap smear in detecting cancer cells. For example, there are several computerized Pap test systems (FocalPoint, PAPNET) that are used to rescreen the original smear. These systems are either used to detect abnormal samples that may have been missed by manual review methods or are used in place of a human cytotechnologist. According to the U.S. Preventive Services Task Force (USPSTF), there is not yet enough evidence to know whether or not computerized methods are superior to conventional Pap testing.

There are tests for identifying the high-risk types of human papilloma virus (HPV) that are known to cause cervical cancer. The presence of these types is a strong predictor of high-grade aggressive abnormalities or cancer itself. Testing for HPV does not replace the Pap smear, but when used adjunctively with the Pap test this screening combination may help to more accurately detect cervical cell abnormalities than either test alone.

In 2003, the FDA approved the Hybrid Capture 2 (HC2) HPV DNA test for use with the Pap test for cervical cancer screening in women over 30 years of age. The HPV DNA test can identify 13 types of the high-risk HPV that are most frequently implicated in the development of cervical cancer. At this time, the test is recommended as an adjunct to the Pap test but not as the sole method for primary screening.

Other screening tests are being investigated for use in combination with the Pap smear for improving accuracy. For example, combinations with human papilloma virus (HPV) DNA tests or cervicography may prove to be more effective for detecting cervical intraepithelial neoplasia I and II dysplasia (potentially invasive cells) than Pap smears alone.

Cervicography. Cervicography uses a photograph of the cervical region (a cervigram), which is then highly magnified and examined. It may prove to be a useful companion to a Pap test, particularly in high-risk younger women. It is painless, easy to use, provides documentation of the area, and is highly sensitive to abnormal changes. (It also, however, picks up abnormalities that are not cancerous.)

Acid Test. A diluted solution of acetic acid (similar to vinegar) is applied to the cervix. When viewed through a special green lens, this solution makes abnormal cells look white, whereas normal cells appear pink. Skilled doctors may also be able to spot abnormal blood vessel patterns indicative of cancer areas on the cervix. This is an inexpensive and simple test.

Fluorescence Spectroscopy. Small noninvasive probes that can be swept across the surface of the cervix to detect cancer are showing promise as an effective screening tool for cervical cancer. One probe emits a laser light. The head of the probe catches the return signals from the woman's cervical cells and compares them with a computer library of cancer cells. In one comparison test, fluorescent spectroscopy was more accurate than the Pap smear but not as effective as other screening methods.

Other Investigative Tests. Experts are working on an antibody-based method for improving the identification of true cancerous cells in a cervical smear, which could significantly reduce the need for expensive and distressing tests in women who do not actually have cancer. In addition, they are looking for biologic markers to improve diagnosis, such as specific proteins that indicate the presence of cancer cells.

The cells viewed in a cervical smear sample are classified on a scale representing the spectrum of cell changes from normal to cancerous. The smear is first characterized as either "normal" or "abnormal."

Once abnormal cells are identified, the doctor must decide whether the patient needs only repeat Pap smears, a test for the human papilloma virus (HPV) virus, or colposcopy (a procedure used to magnify the cervix and permit detection of lesions for biopsy). To help the doctor make the decision, the abnormal cells are divided into categories, depending on the degree of abnormality. These classifications are based on the 2001 Bethesda System (TBS), which is formulated to standardize the reporting of Pap test results.

Atypical Squamous Cells. Atypical squamous cells (ASC) are mildly abnormal cells on the surface of the cervix. They may simply represent inflammation. Over 80% of these cells normalize, but unfortunately, between 5 - 17% of these women have a chance for having cervical intraepithelial neoplasia II and III dysplasia (potentially invasive cells). Researchers have further categorized atypical squamous cells as the following:

ASCUS. These atypical squamous cells of undetermined significance are the lowest risk abnormal cells. Women with these cells should be tested for human papillomavirus infection (HPV). If results indicate they are infected with HPV, they should receive colposcopy, a more invasive diagnostic procedure, to determine if the condition is actually at a more aggressive stage. If they do not have HPV they are simply monitored with repeat Pap smears.
ASC-H. This category refers to the presence of atypical squamous cells, but a doctor cannot exclude possible high-grade squamous intraepithelial lesions. Such women have a 24 - 94% chance of having cervical intraepithelial neoplasia II and III. All are referred for colposcopy.

Among those with atypical squamous cells, immunosuppressed women and those with high-risk human papilloma virus infections are at higher risk for cervical intraepithelial neoplasia II and III and should always be given colposcopy. Postmenopausal women with normal immune systems have a lower risk than younger women. It should be strongly noted, however, that actual risk for cervical cancer in general in women with atypical squamous cells is only 0.1 - 0.2%.

Low Grade Squamous Intraepithelial Lesions. Low-grade squamous intraepithelial lesions (LSIL) are typically associated with human papilloma virus changes, with or without early dysplasia. Between 15 - 30% of women with LGIL, however, may have cervical intraepithelial neoplasia II or III on biopsy. Women with LSIL are either monitored with repeat Pap smears or given colposcopy. Doctors recommending colposcopy argue that these are high-risk women who risk delaying a diagnosis of cancer using only repeat Pap smears.

High-Grade Squamous Intraepithelial Lesions. High-grade squamous intraepithelial lesions (HSIL) are associated with moderate dysplasia and other cervical intraepithelial neoplasia II or III. Such women are always referred to colposcopy for biopsy. Even if colposcopy results report only cervical intraepithelial neoplasia I, over a third of these women are likely to have cervical intraepithelial neoplasia II or III. Experts, therefore, recommend a careful review of the tests in such cases. Pregnancy poses a problem since it increases the chance in HSIL for both normal and abnormal results. In nonpregnant women, particularly when fertility is not an issue, immediate treatment with loop electrosurgical excision procedure may be appropriate.

Atypical Glandular Cells. Atypical glandular cells are uncommon, but pose a higher risk for cancerous changes than atypical squamous cells or low-grade squamous intraepithelial lesions. Between 9 - 54% have some cervical intraepithelial neoplasia, 0 - 8% have pre-invasive cancer, and 1 - 9% have invasive cancer. Doctors recommend that the next step should be a colposcopy (rather than a repeat Pap smear).

The Pap smear shows only the presence of abnormal cells. It is useful simply as a screening test that identifies women who may have preinvasive or early cancerous changes. For a definitive diagnosis, the next step is usually colposcopy, during which the cervix is visualized under low power magnification. The surgeon takes samples of suspicious cells for biopsies. A biopsy will determine the stage of the precancerous growth or whether invasive cancer is present.

The Procedure. Colposcopy can be performed in a doctor's office without anesthesia in 10 - 15 minutes. It causes about as much discomfort as mild menstrual cramps:

First, using a speculum to keep the vagina open, the doctor aims a light at the cervix.
The doctor then looks through the eyepiece of a special microscope, known as a colposcope, to view the cervix. (Some colposcopies include a TV attachment that transmits the picture to a nearby monitor for easier viewing.)
A biopsy (a sampling of the tissue) is taken of suspicious areas, of the endocervical canal (the inner part of the cervix and uterus), and any abnormal-looking areas. This may cause cramping or pinching.

Click the icon to see an image of a colposcopy-directed biopsy.

After the colposcopy, the woman may have a brownish discharge from an iron solution called Monsel's solution, which the doctor applies to prevent bleeding. The doctor usually advises sexual abstinence for 1 - 2 weeks.

Follow-Up Procedures. Women with evidence of cervical intraepithelial neoplasia (CIN) or cervical cancer require treatment. Women with biopsies that show low-grade abnormal cells (LGSIL), but whose cervix is otherwise normal, are generally given follow-up colposcopies.

Treatment for Cervical Intraepithelial Neoplasia and Pre-invasive Cancer

Treatment of cervical intraepithelial neoplasia (CIN), including pre-invasive cancer, depends on the type and extent of abnormal changes. Some of the treatments for CIN are also used for early-stage cancer.

CIN I often goes away on its own. Careful follow up is required to make certain that the Pap smear and colposcopic exam return to normal.
CIN II or CIN III may turn into invasive cancer if the suspicious area is not removed. This is often done using an outpatient technique called loop electrosurgical excision procedure (LEEP). [See next section.]
If doctors cannot see extensive areas of CIN II or III with colposcopy or if they sthese areas pread into the mucous membrane in the cervical canal, a more aggressive procedure called conization (cone biopsy) may be required.

The cold cone biopsy is a surgical procedure that requires general anesthesia. It is performed when there are severe precancerous changes in the cervix.

Treatment for Adenocarcinoma. An adenocarcinoma is cancer inside tissue that looks like or functions as a gland. (A gland is a group of cells that secretes a substance to be used by or removed from the body.) Adenocarcinomas tend to be more aggressive than the more common pre-invasive cancer, which grows in the lining of tissue (mucous membrane). Some evidence suggests that adenocarcinomas develop in numerous sites rather than a single location. Hysterectomy is generally recommended. For women who wish to retain fertility, a docotor may perform a cone biopsy, although this procedure sometimes causes sterility and it does not always remove all adenocarcinomas.

Follow-Up. Patients treated for CIN need to be monitored. Testing for human papilloma virus (HPV) may prove to be useful in determining whether repeat colposcopies may or may not be needed. One study strongly suggested that if both HPV and Pap smear tests are normal on two consecutive visits, treatment most likley was successful. If either the HPV or Pap smear is abnormal, it may be reasonable to consider another colposcopy.

Loop electrosurgical excision procedure (LEEP), also called large loop excision of the transformation zone (LLETZ), uses a high frequency electrical current to cut away diseased tissue.

A local anesthetic is applied to the cervix, and a wire loop is inserted into the vagina.
A button-sized slice of tissue is removed from the cervix for examination.
A deeper slice is used to evaluate the endocervical canal.

The procedure is done in one office visit. Extensive and deep sections of damaged tissue can be effectively removed in this visit. Disease can be cured in one treatment. When used for dysplasia, it appears to be as effective as more invasive procedures.

The only downside of LEEP may be its simplicity. Doctors may be tempted to use it for more serious conditions best treated by a procedure called conization. It also may impair the ability to detect hidden invasive cancer. Patients should be monitored closely if the biopsies on the cervical tissue removed by LEEP suggest that the cells may become invasive.

LLETZ is becoming increasingly popular as a treatment for cervical intraepithelial neoplasia. However, women of child-bearing age should be aware that it may later cause pregnancy problems, such as preterm delivery and low birth weight. Women who have this procedure may also be more likely to break their water too early (premature rupture of membranes).

Conization is a surgical procedure that removes suspicious sections of cells covering an abnormally large area, or those extending into the cervical canal. Conization is preferred over Loop electrosurgical excision procedure (LEEP) or large loop excision of the transformation zone (LLETZ) for lesions that are so big they require a larger biopsy for their complete removal. As in LEEP, patients should be monitored closely if patients are infected with human papilloma virus (HPV) virus or the biopsies on the cervical tissue removed show aggressive-grade cells.

The surgery can be performed under general anesthesia in the operating room with either traditional surgical instruments or lasers.

A technique called frozen section examination (FSE) freezes the margins of the area being removed. Studies suggest that FSE allows immediate and precise evaluation of areas that may harbor invasive cancer cells, and may be an important addition to this procedure in women with high-grade cervical intraepithelial neoplasia.

With conization, the ability to become pregnant can be preserved in many (but not all) cases. In women who do become pregnant, some studies have indicated that this procedure increases the risk for low-birth weight infants, so careful prenatal care is essential. Conization can also increase the risk for preterm delivery and Cesarean section. Patients who have this treatment must have follow-up evaluations.

Cryosurgery is not usually feasible for large abnormal areas. The procedure removes abnormal, but noncancerous, tissue by freezing it. Cryosurgery can be performed in a doctor's office in 15 minutes without medication.

The vagina is opened with a speculum and a probe transmits gas (either nitrous oxide or carbon dioxide), which freezes the surface of the cervix.
The gas is applied for 3 minutes or until ice crystals form on the targeted tissue.
After waiting 3 minutes, freezing can be repeated for another 3 minutes.

Click the icon to see an image of cervical cryosurgery.

Side effects from this procedure include cramping, sometimes painful, for a few hours or days and a heavy, watery discharge for 2 - 4 weeks. The discharge can be irritating, have a bad odor, and may be blood-tinged. Symptoms that may indicate serious complications are fever and chills, heavy clotted bleeding, or extreme pain in the abdomen or back.

The patient may have a temporary change in menstrual periods. The menstrual periods may be heavier or lighter, or come later or earlier. Tampons, douching, bathing, swimming, and intercourse should be avoided for several weeks after cryosurgery to prevent infection.

Patients who have this treatment must be willing to commit to regular follow-up examinations.

Treatment for Cervical Cancer

In contrast to cervical intraepithelial neoplasia, cervical cancer represents true invasion of cells beyond the epithelium into surrounding tissue. Cervical cancer may be detected in a biopsy performed during colposcopy for an abnormal Pap smear, or it may be visible to the naked eye when the doctor performs a speculum exam.

Imaging Tests to Determine Extent of Tumor Spread. If a biopsy detects invasive cancer, the patient will need additional tests to find out how far the cancer has spread. How fart the cancer has spread determines whether the cancer is operable.

An abdominal computed tomography (CT) scan is commonly used to check for spread of the disease to lymph nodes and areas around the pelvic area.

In computed tomography (CT), a thin x-ray beam rotates around the area of the body. Using very complicated mathematical processes called algorithms, a computer is generates a 3-D image of a section of the body.

Other procedures may be used to find out if cancer has spread to areas around the uterus. X-ray images are taken of the bladder and urinary system (known as intravenous pyelography, or IVP) or of the lower intestinal tract (known as a barium enema).

Click the icon to see an image of intravenous pyelography.

Click the icon to see an image of a barium enema.

If these tests detect cancer in any of these surrounding sites, the patient will need more tests :

Cystoscopy is performed to examine and take tissue from the bladder for biopsy.

Click the icon to see an image of cystoscopy.

Sigmoidoscopy is used to evaluate the rectum. (In this procedure and a cystoscopy, a tube with a lighting device is inserted to view internal areas.)

Click the icon to see an image of sigmoidoscopy.

Magnetic resonance imaging (MRI) is a sensitive and noninvasive procedure that is occasionally useful for finding tumors in the tissues surrounding the uterus.

Click the icon to see an image of a MRI.

Sentinel Node Biopsy. One technique is called a sentinel node biopsy. It has been used in patients with breast cancer to help determine if cancer has spread beyond the lymph nodes. It is now being investigated for patients with early cervical cancer and may be helpful in determining which patients need to have lymph nodes removed in their pelvic area:

The procedure uses an injection of a tiny amount of a blue dye, into the tumor site.
These substances then flow via the lymphatic system into the sentinel node. This is the first lymph node to which any cancer would spread.
The sentinel lymph node and possibly one or two others are then removed.
If these nodes do not show signs of cancer, the rest of the lymph nodes may be cancer-free, making further removal of lymph nodes unnecessary.

After making a diagnosis, the doctor will classify the stage of the cancer according to how far the disease has spread into the lining of the cervix, throughout the cervix, or beyond. Doctors use these classifications to determine treatment and outlook.

Patients who have been diagnosed with cervical cancer need to know the normal treatments for their particular stage, so they may compare their doctor's suggestions with these norms.

Stage 0 is pre-invasive cancerconfirmed by biopsy and confined to the first layer of cervical tissue (the epithelium). Treatment options include loop electrosurgical excision procedure (LEEP), laser therapy, conization, and cryotherapy.

Stage I is invasive cancer, but the tumor is confined to the cervix. This stage is further categorized as IA and IB.

Stage IA. Five-year survival rates for stage IA can be 95% or more.

In stage IA1 cancer cells are microscopic, there is minimal invasion (less than 3 mm) into the supportive tissue around the cervix (the stroma), and the horizontal extent of the tumor is less than 7 mm. Treatment is usually a simple hysterectomy. Conization is sometimes possible for women who want to remain fertile and who have a nonaggressive tumor that has spread less than 3 mm, with no lymph or blood vessel involvement. Trachelectomy has been investigated for women who want to preserve fertility. More research is needed.
In stage IA2 there is deeper invasion (greater than 3 mm but less than 5 mm) and the horizontal extent of the tumor is less than 7 mm. Radical hysterectomy with surgical lymph node removal (lymphadenectomy) is a common treatment.

Note on Stage IA2 through IIA: Postoperative concurrent radiation and platinum-based chemotherapy may be considered for stages IA2 through IIA tumors if the following high risk features are found at the time of primary surgery: lymph node involvement, cancerous cells found in the margins of the tumor, and involvement of the parametrium.

Stage IB and Locally Advanced Cancer. Five-year survival rates for stage IB can be 80 - 90% with either radiation or surgery. Survival rates are lower if the cancer has spread to the lymph nodes.

In stage IB1 the tumor is typically visible (not usually microscopic), and the diameter may be up to 4 cm. Radical hysterectomy with pelvic lymph node removal (lymphadenectomy) is the recommended treatment. Primary radiation can be used instead of surgery in patients who eitehr are poor surgical candidates or do not plan on being sexually active.
In stage IB2 the tumor is more than 4 cm and considered "bulky." Relapse rates after surgery are higher than in stage 1B1. Primary treatment with radiation therapy with concurrent platinum-based chemotherapy is reasonable. Some women in stage IB may receive combinations of radiation and surgery, although the benefits of such combinations are unclear for most women, particularly given a higher risk for severe side effects.

Note on Locally Advanced Cervical Cancer: Stages IB2 through IVA are often referred to collectively as locally advanced cancer and are frequently treated similarly. Standard treatment includes radiotherapy with concurrent platinum-based chemotherapy. Experimental approaches for some women with locally advanced cervical cancer use radiation therapy with hyperthermia (high heat often provided by ultrasound) and neoadjuvant (preoperative) chemotherapy and radical surgery. More research is necessary.

Stage II invasive cancer has spread beyond the cervix, but it has not spread to the pelvic side wall. This stage is further categorized as IIA and IIB.

Stage IIA. Cure rates for stage IIA can be as high as 75 - 80% with either radiation or radical hysterectomy. Survival rates are lower if cancer has spread to the lymph nodes. In stage IIA, cancer has spread to the upper two thirds of the vagina but not to the parametrium (the connective tissue between the pelvic floor and upper part of the cervix). Radical hysterectomy with pelvic lymph node removal (lymphadenectomy) is the recommended treatment. Primary radiation can be used instead of surgery in patients who eitehr are poor surgical candidates or do not plan on being sexually active. If the tumor is bulky, however, primary treatment with radiation therapy with concurrent platinum-based chemotherapy is reasonable. Some women in stage IB may receive combinations of radiation and surgery.

Stage IIB. For stage IIB 5-year survival rates are about 60%. In stage IIB the cancer has spread to the parametrium. Recommended treatment is radiation therapy with concurrent cisplatin-based chemotherapy.

In stage III, the cancer is invasive, extending to the lower third of the vagina (stage IIIA) or to the side walls of the pelvis (stage IIIB). The kidney may be affected. Recommended treatment is radiation therapy with concurrent cisplatin-based chemotherapy. Five-year survival rates are about 40%.

In stage IV, invasive cancer has spread beyond the pelvis or to the mucosal lining of the bladder or rectum. Five-year survival rates are less than 20%.

Stage IV. In stage IVA, the cancer has spread to the inner lining of the bladder or rectum. Recommended treatment is radiation therapy with concurrent cisplatin-based chemotherapy.

Stage IVB. In stage IVB, the cancer has spread beyond the pelvis. Recommended treatment is radiation therapy to relieve symptoms and chemotherapy (usually cisplatin or carboplatin combined with other drugs such as topotecan). Platinum-based chemotherapy yields short-lived response in 20% of patients. Clinical trial participation is reasonable.

Cervical cancer may recur locally in the lymph nodes near the cervix, it may spread to distant sites, such as the lung or bones, or it may appear both locally and in distant locations.

Recommended treatment is pelvic exenteration if cancer has spread to only local areas. (This involves removal of the cervix, uterus, vagina, and perhaps the bladder, lower colon, or rectum. It is an aggressive surgical approach that may lead to cure in a small percentage of patients with recurrent cervical cancer.) Radiotherapy is another option if it is technically possible -- generally if patients did not have it previously. If cancer has spread, platinum-based chemotherapy is reasonable. Other drugs may be useful under certain circumstances.

Only 1% of cervical cancers occur during pregnancy or shortly afterwards. To diagnose the condition, a cervical biopsy, in which a small amount of tissue is removed for diagnosis, can be performed anytime during the pregnancy. However, a cone biopsy, which removes larger amounts of tissue, is typically delayed until after the first trimester to reduce the risk of abortion. Treatment options may be as follows:

If the abnormality is diagnosed as dysplasia or even pre-invasive cancer, treatment is sometimes delayed until a few weeks after the mother gives birth, and vaginal delivery may still be possible. The pregnant woman should discuss the risks and benefits of this approach, however, with her doctor.
If early-stage cancer is diagnosed in the late second or third trimester, a woman may sometimes be able to delay treatment until the baby is delivered. A Cesarean section is the preferred delivery method. The cancer treatment of choice is started shortly afterward.
More locally advanced invasive cancer is nearly always treated, particularly if is diagnosed within the first 20 weeks of the pregnancy.

Treatment for Invasive Cervical Cancer

Radiation therapy and surgery are about equally effective as a single option for treating very small cervical cancers in their earliest stages. Survival rates in the appropriate patients can be about 85 - 90%. Factors influencing the choice between radiation therapy and surgery in women with invasive cancer include the patient's age and health and the amount of cancer. Both surgery and radiation therapy eliminate the possibility of having children in premenopausal women.

Although treatments for cervical cancer have several potentially severe side effects, they are usually well-tolerated. Women undergoing any of these treatments should feel free to seek support groups and counseling, which can be as important for their outlook as medical therapies.

Surgery. Surgery almost always involves a hysterectomy, an operation that removes the uterus and sometimes other areas in the pelvic region as well. It does not, however, usually impair sexual activity.

In general, surgery is the better choice when small cancers are confined to the cervix in women who wish to remain sexually active.

Radiation. Radiation treatments to the pelvis often inhibit ovarian function. Early menopause often occurs. Radiation also may cause vaginal scarring. Treatments are available that may reduce these problems, and women should not be shy about discussing them with their doctor. Radiation therapy is usually the choice under the following circumstances:

Cancers have spread beyond the cervix to the pelvis, lower vagina, and urinary tract.
When certain tumor features indicate a high risk for recurrence after surgery.

Important studies now strongly suggest that radiation along with chemotherapy can improve survival rates improve in patients with stages IB to IVA compared to radiation alone. The benefits are greatest in stages I and II.

In the early stages of cervical cancer, surgery is often the preferred primary treatment approach since it preserves normal sexual function. Some patients desiring fertility who have early stage I cancer may be candidates for cervical cone biopsy.

Hysterectomy. A hysterectomy attempts to eliminate the cancerous tissue by removing the uterus. There are several variations of this operation, depending on the location of the tumor. In women of childbearing age, the ovaries can usually be left intact. Although a woman who has a hysterectomy but retains her ovaries cannot bear children, she will not go into premature menopause. (Studies indicate that leaving the ovaries intact is safe for most women and does not pose any greater risk for cervical cancer recurrence.)

A simple hysterectomy involves the removal of the uterus and the cervix, but leaves the parametrium (tissue surrounding the uterus) and vagina intact. Lymph nodes in the pelvis are not usually removed.

Click the icon to see an illustrated series detailing a hysterectomy.

A radical hysterectomy removes not only the uterus and the cervix but also the parametrium, the supporting ligaments, the upper vagina, and some or all of the local lymph nodes (a procedure called lymphadenectomy).

If the cancerous tumor recurs within the pelvis after primary treatment, the patient may need a more extreme procedure called a pelvic exenteration, which combines radical hysterectomy with removal of the bladder and rectum. (In such cases, plastic surgery may be needed afterward to recreate an artificial vagina.) Patients undergoing this procedure are physically and psychologically screened in advance to determine whether it is an appropriate choice. The success rate for pelvic exenteration in halting the progression of the disease is about 25 - 45%.

Any form of hysterectomy is major surgery and requires at least a 3 - 5 day hospital stay. Although hysterectomy typically uses a wide abdominal incision, less invasive techniques that allow shorter recovery time may be possible for some women with early stage cancers if performed by experienced surgeons.

Side effects include difficulty emptying the bladder or bowels and a painful lower abdomen. Urinary tract infections are very common. Complications include fistulas (abnormal channels within the pelvis, which in this case are a result of surgery), bladder dysfunction, and cysts.

Normal activity, including intercourse, can be resumed in about 4 - 8 weeks. Once the uterus is removed, menstruation will cease. If the ovaries are removed, the symptoms of menopause will begin. These symptoms are likely to be more severe in surgical menopause than in natural menopause. The pateint should discuss the benefits and risks of hormone replacement therapy with her doctor.

Trachelectomy. An experimental procedure called trachelectomy is being investigated for preserving fertility in certain women in early-stage cervical cancer, but it is highly controversial and appropriate in only about 5% of patients. In the procedure, only the cancerous portion of the cervix is removed, while the uterus and the rest of the cervix are left intact. The cervix is closed with a suture.

The procedure is primarily performed outside the U.S., and few American surgeons are skilled in this surgery at this time. Throughout the world, in fact, only about a few hundred of these procedures have been performed to date. Larger and longer-term studies are needed to confirm its long-term safety.

Radiation therapy is an alternative approach for early stage cervical cancer. Radiation with concurrent cisplatin-based chemotherapy is now the standard treatment for locally advanced cervical cancer. Radiation therapy uses high-energy rays aimed at the body from an outside machine (external beam radiation) and radioactive materials placed inside the body against the cervix (intracavitary radiation).

External beam radiation is given first and aimed at the lymph nodes along the pelvic wall. It usually involves a short period of direct-radiation 5 days a week for about 6 weeks in an outpatient setting.
Intracavitary radiation (also called brachytherapy) follows and is designed to deliver high doses of radiation to the local tumor area. Radioactive material, typically cesium-137, is encapsulated in both gold and platinum. These capsules are inserted in a long stainless steel tube called a tandem, which is inserted in the uterus. and in small stainless steel cylinders, called colpostats, which are placed against the cervix as close to the cancerous cells as possible. Commonly, two or more radiation treatments are administered for about 35 hours each time. Radiation implants may also be inserted directly into the tumor using a needle.

In order to be effective, radiation therapy must be powerful enough to destroy the cancer cells' capacity to grow and divide. This means that normal cells are also affected, which may cause significant side effects. Fortunately, healthy cells usually recover quickly from the damage, whereas abnormal cells do not.

Advanced methods that target radiation more precisely and limit the damage to healthy tissue are now available. They include 3-D conformal radiation and intensity-modulated radiation therapy (IMRT):

3-D conformal techniques use computers and a three-dimensional image of the cervix to provide precise targeting of the tumor using multiple high-dose radiation beams.
IMRT also uses 3-D techniques and employs very thin and precise beam at various intensities.

Side Effects. Side effects of radiation therapy include fatigue, redness or dryness in the treated area, diarrhea, frequent or uncomfortable urination, and vaginal dryness, itching, or burning. After treatment, side effects usually disappear.

Long-Term Complications. Complications include proctitis (inflammation of the rectum) and cystitis (inflammation of the bladder). Bowel obstruction is an uncommon complication. Radiation therapy may also cause vaginal scarring, sexual difficulties, and premature menopause in younger women. Occasionally an abnormal tunnel between the bladder and the vagina, known as a vesicovaginal fistula, will develop and may require surgery.

Click the icon to see an image of the female anatomy.

Investigative temporary silicone implants or a noninvasive device called the belly board may protect the small intestine during radiation therapy and help reduce complications.

Radiation itself may increase the risk for later development of cancer in the area surrounding the treated tissue. Although newer more precise radiotherapy approaches should reduce this risk, there is some concern that IMRT may double the incidence of secondary cancers over time compared to 3-D conformal techniques. This is of particular concern in younger patients.

Radiation and Hyperthermia. Investigators are studying hyperthermia (use of high heat often provided by ultrasound) in combinations with radiation therapy. This approach has shown some promise in achieving significant response rates in small studies. Comparison studies are important to determine if this approach would be as beneficial with radiation therapy as concurrent chemotherapy.

Chemotherapy uses cell-killing drugs called cytotoxic drugs to destroy widespread cancer cells that have spread from the primary tumor and can no longer be treated with surgery or radiation.

For many years, chemotherapy was only used to reduce symptoms in women with very advanced disease. Today, platinum-based chemotherapy drugs (see below) are being used in many situations for cervical cancer, such as:

In combination with radiation therapy to improve survival rates in certain women, including some with locally advanced cancer.
In some women with locally advanced cancer to reduce tumors to the point where the cancer may be operable.
When cancer has spread (metastasized), mostly to reduce symptoms such as pain.

Platinum-Based Drugs. Platinum-based drugs cisplatin and carboplatin are often used for treating various stages of cervical cancer. These drugs are usually used in combination with radiation therapy or other chemotherapy drugs. In 2006, the FDA approved a combination of cisplatin and topotecan (another type of chemotherapy drug) for treatment of late-stage cervical cancer in women who are unlikely to be helped by surgery or radiation therapy. Women with stage IVB cervical cancer who received the combination treatment survived around 3 months longer (9.5 months versus 6.5 months) than women who received only cisplatin.

Other drugs. Other drugs, mostly used in combinations, have also been investigated with some promise. They include epirubicin, irinotecan, paclitaxel, bleomycin, mitomycin, vinorelbine, gemcitabine, and doxifluridine.

Administration. Chemotherapy may be given by mouth or as an injection. This may be done at a medical center, doctor's office, or even a patient's home. Some patients receiving chemotherapy may need to remain in the hospital for several days so the effects of the drugs can be monitored. The drugs are often given in cycles with a period of rest following a period of treatment, to allow recovery from the side effects.

Side Effects. Chemotherapy affects all fast-growing cells, including healthy ones. So, side effects are inevitable. Side effects occur with all chemotherapeutic drugs. They are more severe with higher doses and increase over the course of treatment.

Common side effects include the following:

Nausea and vomiting. Drugs known as serotonin antagonists, especially ondansetron (Zofran), can relieve these side effects in nearly all patients given moderate drugs and in most patients who take more powerful drugs.
Diarrhea
Temporary hair loss
Weight loss
Fatigue
Anemia
Depression

Complications. Serious short- and long-term complications can also occur and may vary, depending on the specific drugs used. They include:

Increased chance for infection. Chemotherapy suppresses the immune system.
Severe drop in white blood cell count (neutropenia). Certain drugs, such as taxanes, pose a higher risk for this than other chemotherapeutic drugs. White blood cell count may be improved with the addition of a type of drug called granulocyte colony-stimulating factor (either filgrastim or lenograstim).
Liver and kidney damage.
Abnormal blood clotting (thrombocytopenia).
Allergic reaction, particularly to platinum-based drugs. (A simple skin test that may identify people with a potential allergic response is under investigation .)
Menstrual abnormalities. These are common. Premature menopause occurs in about 30% of women, particularly in those over 40.
Secondary cancers such as leukemia (rare).
Problems in concentration, motor function, and memory, which may be long-term. Between a quarter and a third of women report such problems. This may be due to a drop in estrogen levels after treatments.

Resources

www.cancer.gov -- National Cancer Institute
www.cancer.org -- American Cancer Society
www.acog.org -- American College of Obstetricians and Gynecologists
www.ashastd.org -- American Social Health Association
www.arhp.org -- Association of Reproductive Health Professionals
www.nccc-online.org -- National Cervical Cancer Coalition
www.cervicalcancercampaign.org -- Cervical Cancer Public Education Campaign
www.fda.gov/womens/getthefacts/hpv.html -- FDA HPV Fact Sheet
www.thegcf.org -- Gynecologic Cancer Foundation
www.wcn.org -- Women's Cancer Network
www.plwc.org -- People Living with Cancer
www.gothpv.net -- HPV Support Site

References

Ault KA; Future II Study Group. Effect of prophylactic human papillomavirus L1 virus-like-particle vaccine on risk of cervical intraepithelial neoplasia grade 2, grade 3, and adenocarcinoma in situ: a combined analysis of four randomised clinical trials. Lancet. 2007 Jun 2;369(9576):1861-8.

Committee on Infectious Diseases. Prevention of human papillomavirus infection: provisional recommendations for immunization of girls and women with quadrivalent human papillomavirus vaccine. Pediatrics. 2007 Sep;120(3):666-8.

Davey E, d'Assuncao J, Irwig L, Macaskill P, Chan SF, Richards A, et al. Accuracy of reading liquid based cytology slides using the ThinPrep Imager compared with conventional cytology: prospective study. BMJ. 2007 Jul 7;335(7609):31. Epub 2007 Jun 29.

D'Souza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C, Koch WM, et al. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 2007 May 10;356(19):1944-56.

Dunne EF, Unger ER, Sternberg M, McQuillan G, Swan DC, Patel SS, et al. Prevalence of HPV infection among females in the United States. JAMA. 2007 Feb 28;297(:813-9.FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med. 2007 May 10;356(19):1915-27.

Garland SM, Hernandez-Avila M, Wheeler CM, Perez G, Harper DM, Leodolter S, et al. Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. N Engl J Med. 2007 May 10;356(19):1928-43.

Gunnell AS, Tran TN, Torrang A, Dickman PW, Sparen P, Palmgren J, et al. Synergy between cigarette smoking and human papillomavirus type 16 in cervical cancer in situ development. Cancer Epidemiol Biomarkers Prev. 2006 Nov;15(11):2141-7. Epub 2006 Oct 20.

Hildesheim A, Herrero R, Wacholder S, Rodriguez AC, Solomon D, Bratti MC, et al. Effect of human papillomavirus 16/18 L1 viruslike particle vaccine among youngwomen with preexisting infection: a randomized trial. JAMA. 2007 Aug 15;298(7):743-53.

Markowitz LE, Dunne EF, Saraiya M, Lawson HW, Chesson H, Unger ER; Centers for Disease Control and Prevention (CDC); Advisory Committee on Immunization Practices (ACIP). Quadrivalent human papillomavirus vaccine: Recommendations of the AdvisoryCommittee on Immunization Practices (ACIP). MMWR Recomm Rep. 2007 Mar 23;56(RR-2):1-24.

Ronco G, Cuzick J, Pierotti P, Cariaggi MP, Dalla Palma P, Naldoni C, et al. Accuracy of liquid based versus conventional cytology: overall results of new technologies for cervical cancer screening: randomised controlled trial. BMJ. 2007 Jul 7;335(7609):28. Epub 2007 May 21.

Saslow D, Castle PE, Cox JT, Davey DD, Einstein MH, Ferris DG, et al. American Cancer Society Guideline for human papillomavirus (HPV) vaccine use to prevent cervical cancer and its precursors. CA Cancer J Clin. 2007 Jan-Feb;57(1):7-28.

Sturgis EM, Cinciripini PM. Trends in head and neck cancer incidence in relation to smoking prevalence: an emerging epidemic of human papillomavirus-associated cancers? Cancer. 2007 Aug 27; [Epub ahead of print]Weller SC, Stanberry LR. Estimating the population prevalence of HPV. JAMA. 2007 Feb 28;297(:876-8.

Review Date:
9/1/2006
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Coronary artery disease

FitSugar — Wed, 08 Oct 2008 17:35:07 -0700

In This Report

Highlights
Introduction
Prognosis
Risk Factors
Diagnosis
Managing Heart Disease
Anti-Clotting Medications...
Other Medications
Surgery
Coronary Artery Bypass Graf...
Angioplasty and Stents
Other Treatments
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Angioplasty Versus Drugs

Angioplasty works no better than drug therapy (high blood pressure, cholesterol, anti-platelet, and other medication) in preventing heart attack and stroke in patients with stable coronary artery disease (CAD), according to an important New England Journal of Medicine study. Experts still recommend angioplasty for patients with unstable or severe CAD.

Stents

Stents coated with drugs may have a slightly higher risk of causing blood clots than bare metal stents, according to FDA meetings held in late 2006. Researchers still need to conduct more research before reaching final conclusions.
Drug-coated stents work well when they are used for patients with specific types of heart conditions, indicate several studies published in the New England Journal of Medicine. However, problems may develop when these stents are used for “off-label” purposes. Experts are also concerned that both bare metal and drug-coated stents may be used too frequently.
Patients who receive a drug-coated stent must take both aspirin and an anti-platelet thienopyridine drug (usually clopidogrel) for at least 1 year after the stent is inserted, advises an important statement from the American Heart Association. Patients who cannot take a thienopyridine drug should receive a bare metal stent instead of a drug-coated stent.

Anti-Bleeding Drugs for Coronary Artery Bypass Graft (CAGB)

Aprotinin (Trasylol), a drug used to control bleeding during CABG, is more dangerous than other types of anti-bleeding drugs, according to a 2007 study in the Journal of the American Medical Association. Many experts now recommend against its use.

Diagnosis

Blood tests for biomarkers do not provide much more predictive information than standard disease risk factors, suggest several recent studies. In a 2006 study published in the New England Journal of Medicine, researchers found that risk factors such as high blood pressure, high cholesterol, and diabetes are still the best methods for predicting the likelihood of heart disease and heart-related death.

Introduction

The heart is the human body's hardest working organ. Throughout life it continuously pumps blood enriched with oxygen and vital nutrients through a network of arteries to all parts of the body's tissues.

The external structures of the heart include the ventricles, atria, arteries, and veins. Arteries carry blood away from the heart while veins carry blood into the heart. The vessels colored blue indicate the transport of blood with relatively low content of oxygen and high content of carbon dioxide. The vessels colored red indicate the transport of blood with relatively high content of oxygen and low content of carbon dioxide.

In order to perform the difficult task of pumping blood to the rest of the body, the heart muscle itself needs a plentiful supply of oxygen-rich blood, which is provided through a network of coronary arteries. These arteries carry oxygen-rich blood to the heart's muscular walls (the myocardium).

Click the icon to see an image of the anterior heart arteries.

If blood flow to the myocardium is interrupted, an injury known as an infarct occurs. This is also known as myocardial infarction or, more commonly, a heart attack.

Click the icon to see an animation about coronary artery disease.

Coronary artery disease is the end result of a complex process called atherosclerosis (commonly called "hardening of the arteries"). This causes blockage of arteries (ischemia ) and prevents oxygen-rich blood from reaching the heart. There are many steps in the process leading to atherosclerosis, some not fully understood.

Click the icon to see an image of atherosclerosis.

Increasingly, however, researchers are studying the interactions between cholesterol and processes known as oxidation and the inflammatory response.

Cholesterol and Lipoproteins. The story begins with cholesterol and sphere-shaped bodies called lipoproteins that transport cholesterol.

Cholesterol is a white, crystalline substance that is found in all animal cells and in animal-based foods. It is critical for many functions, but under certain conditions cholesterol can have harmful effects.
The lipoproteins that transport cholesterol are referred to by their size. The most commonly known are low-density lipoproteins (LDL) and high density lipoproteins (HDL). LDL is often referred to as the "bad" cholesterol and HDL as the "good" cholesterol.

Click the icon to see an image of cholesterol inside an artery.

Oxidation. The damaging process called oxidation is an important trigger in the atherosclerosis story.

Oxidation is a chemical process in the body caused by the release of unstable particles known as oxygen-free radicals. It is one of the normal processes in the body, but under certain conditions (such as exposure to cigarette smoke or other environment stresses) these free radicals are overproduced.
In excess amounts, they can be very dangerous, causing damaging inflammation and even affecting genetic material in cells.
In heart disease, free radicals are released in artery linings and oxidize low-density lipoproteins (LDL). The oxidized LDL is the basis for cholesterol build-up on the artery walls and damage leading to heart disease.

Inflammatory Response. For the arteries to harden there must be a persistent reaction in the body that causes ongoing harm. Researchers now believe that this reaction is an immune process known as the inflammatory response. The following is one theory about how the inflammatory response contributes to heart disease:

The injuries to the arteries during oxidation signal the immune system to release white blood cells (particularly those called neutrophils and macrophages) at the site. These factors initiate the inflammatory response.
Macrophages literally "eat" foreign debris, in this case oxidized LDL cholesterol.
The process converts LDL cholesterol into foamy material that attaches to the smooth muscle cells of the arteries. The cholesterol becomes mushy and accumulates on artery walls.
Over time the cholesterol dries and forms a hard plaque, which causes further injury to the walls of the arteries.
In response to this additional harm, the immune system releases other factors called cytokines. These are powerful inflammatory molecules that attract more white blood cells and perpetuate the whole cycle, causing persistent injury to the arteries.

Click the icon to see an image of atherosclerosis.

Evidence is growing that the inflammatory response may be present not only in local plaques in single arteries but also throughout the arteries leading to the heart.

Blockage in the Arteries. Eventually these calcified (hardened) arteries become narrower (a condition known as stenosis).

As this narrowing and hardening process continues, blood flow slows and prevents sufficient oxygen-rich blood from reaching the heart.
Such oxygen deprivation in vital cells is called ischemia. When it affects the coronary arteries, it causes injury to the tissues of the heart.
Injured inner vessel walls also fail to produce enough nitric oxide, a substance critical for maintaining blood vessel elasticity. (Nitric oxide has complex effects and may increase inflammation in the arteries.)
These narrow and inelastic arteries not only slow down blood flow but also become vulnerable to injury and tears.

Click the icon to see an image of coronary artery blockage

The End Result: Heart Attack. Heart attack can occur as a result of one or two effects of atherosclerosis.

(1) If the artery becomes completely blocked and ischemia becomes so extensive that oxygen-bearing tissues around the heart die.

(2) If the plaque itself develops fissures or tears. Blood platelets adhere to the site to seal off the plaque, and a blood clot (thrombus) forms. A heart attack can then occur if the formed blood clot completely blocks the passage of oxygen-rich blood to the heart.

Click the icon to see an image of the developmental process of atherosclerosis.

Angina is the primary symptom of coronary artery disease and, in severe cases, of a heart attack. It is typically experienced as chest pain and occurs when the heart muscle does not get as much blood (hence as much oxygen) as it needs for a given level of work (ischemia). Angina is usually referred to as one of two states:

Click the icon to see an image about angina.

Stable Angina (which is predictable)
Unstable Angina (which is less predictable and a sign of a more serious situation)

Angina itself is not a disease. Much evidence indicates that onset of angina less than 48 hours before a heart attack may be protective, possibly by conditioning the heart to resist the damage resulting from the attack. Angina may be experienced in different ways and can be mild, moderate, or severe.

Click the icon to see an image of angina.

Specific factors are typically considered in determining whether symptoms indicate angina:

Quality of the pain. Angina pain is typically described by patients as squeezing, heavy, suffocating, or griplike. It is rarely described as stabbing or burning. Changing one's position or breathing in and out does not affect the pain. The intensity of the pain does not always relate to the severity of the medical problem. Some people may feel a crushing pain from mild ischemia, while others might experience only mild discomfort from severe ischemia. In some cases, the patient experiences shortness of breath, fatigue, or palpitations instead of pain. In others, the ischemia is entirely asymptomatic ("silent ischemia").
Duration. A typical angina attack lasts minutes. If it is more fleeting or lasts for hours, it is probably not angina.
Location. Pain is usually in the chest under the breast bone. It often radiates to the neck, jaw, or left shoulder and arm. Less commonly, patients report symptoms that radiate to the right arm or back.
Triggers of Angina. Angina is usually triggered by physical exertion, emotional stress, or exposure to cold.
Factors that Relieve Angina. Angina is usually relieved by rest or by taking nitroglycerine under the tongue.

Stable Angina. Stable angina is predictable chest pain. Although less serious than unstable angina, it can be extremely painful. It is usually relieved by rest and responds well to medical treatment (typically nitroglycerin). Any event that increases oxygen demand can cause an angina attack. Some typical triggers include:

Exercise
Cold weather
Emotional tension
Large meals

Angina attacks can occur at any time during the day, but most occur between 6 a.m. and noon.

Unstable Angina and Acute Coronary Syndrome. Unstable angina is a much more serious situation and is often an intermediate stage between stable angina and a heart attack, in which an artery leading to the heart (a coronary artery) becomes completely blocked. A patient is usually diagnosed with unstable angina under one or more of the following conditions:

Pain awakens a patient or occurs during rest.
A patient who has never experienced angina has severe or moderate pain during mild exertion (walking two level blocks or climbing one flight of stairs).
Stable angina has progressed in severity and frequency within a 2-month period, and medications are less effective in relieving its pain.

Unstable angina is now usually discussed as part of a condition called acute coronary syndrome (ACS). ACS also includes people with a condition called NSTEMI (non ST-segment elevation myocardial infarction) -- also referred to as non-Q wave heart attack. With NSTEMI, the blood tests suggest a developing heart attack. These conditions are less severe than heart attacks but may develop into full-blown attacks without aggressive treatment. [See In-Depth Report #12: Heart attack and acute coronary syndrome.]

Prinzmetal's Angina. A third type of angina, called variant or Prinzmetal's angina, is caused by a spasm of a coronary artery. It almost always occurs when the patient is at rest. About two-thirds of people with it have severe atherosclerosis in at least one major blood vessel. Irregular heartbeats are common, but the pain is generally relieved immediately with standard treatment.

Click the icon to see an image of a coronary artery spasm.

Silent Ischemia. Some people with severe coronary artery disease do not experience angina pain. This condition is known as silent ischemia, which some experts attribute to abnormal processing of heart pain by the brain. This is a dangerous condition because patients have no warning signs of heart disease. Some studies suggest that people with silent ischemia experience higher complication and mortality rates than those with angina pain. (Angina pain may actually protect the heart by conditioning it before a heart attack.)

Syndrome X. Syndrome X is a condition that occurs when patients have atypical angina chest pain. Their electrocardiograms are abnormal during a stress test, but they have no signs of blocked arteries. It is more likely to occur in women. Although it unclear what causes this condition, imaging tests suggest that Syndrome X may also be caused by ischemia, as is angina.

Prognosis

According to a 2007 report, nearly 16 million Americans have coronary artery disease. In the U.S., coronary artery disease is the leading killer of both men and women. In 2004, nearly 500,000 people died because of CAD. On the positive side, heart attack mortality rates have been declining. Half of men and 63% of women who die of heart disease do not have angina or other warning symptoms prior to their fatal attacks. Although at this time no tests can reliably predict whether a heart attack will occur, experts estimate that up to 30% of fatal attacks and many follow-up surgeries could be avoided with healthy lifestyle changes and by sticking to medical treatments. Two-thirds of patients who have suffered a first heart attack, however, do not take the necessary steps to prevent another.

The following syndromes suggest different degrees of severity among patients with heart disease.

Stable Angina. This condition can usually be managed with lifestyle measures and medications, such as low-dose aspirin. The more severe the angina, however, the greater the chance for progressing to a more serious condition.

Acute Coronary Syndromes (ACS). ACS includes severe and sudden heart conditions that require aggressive treatment but have not developed into a full-blown heart attack. ACS refers to either unstable angina or NSTEMI (non ST-segment elevation myocardial infarction). NSTEMI is also known as non Q-wave myocardial infarction.

Angina is a specific type of pain in the chest caused by inadequate blood flow through the blood vessels (coronary vessels) of the heart muscle (myocardium).

Unstable angina is potentially serious and chest pain is persistent, but blood tests do not show markers for heart attack.
With NSTEMI, the blood tests suggest a developing heart attack, but, most likely, injury in the arteries is less serious than with a full-blown heart attack.

Most discussions of the treatment of unstable angina now refer to acute coronary syndrome. Doctors use the presence of a number of factors to help predict which ACS patients are most at risk for developing a heart attack.

First, patients are categorized by whether they have a history of heart disease or risk factors for heart disease (such as diabetes, high blood pressure, peripheral artery disease) or other complicating conditions (such as lung disease, heart failure). The doctor also evaluates the severity of the angina. Other factors that pose a high risk for ACS include:

Age 65 years or older
Evidence of severe heart tissue injury
Having a lighter weight
Having a history of severe chronic angina
Having abnormal lung sounds called rales (a bubbling or crackling sound) on examination
ST-segment deviation
Having either very slow or very fast heat beats
Having very low blood pressure

Heart Attack. A full-blown heart attack occurs with severe damage to the heart, which blocks oxygen.

ANYONE WHO BELIEVES THEY ARE HAVING A HEART ATTACK SHOULD IMMEDIATELY CALL THE EMERGENCY MEDICAL SYSTEM (911 IN THE UNITED STATES).

People with known heart disease and any unusual chest pain or other symptoms of heart attack that do not clear up with medications should go to the hospital. The degree of pain and the specific symptoms before a heart attack vary greatly among individuals. Symptoms can be abrupt, gradual, or intermittent.

Chest Pain. People with heart disease or risk factors should be concerned about any chest pain, usually precipitated by exercise or stress, that interrupts normal activities and does not clear up after resting or taking angina medications. Chest symptoms might be experienced as follows:

Pain is typically felt as a crushing weight against the chest, accompanied by profuse sweating. The pain may radiate to the left shoulder and arm, the neck or jaw, and even infrequently to the right arm. The arm may be tingling or numb.
Some people may have only a tingling sensation or a sense of fullness, squeezing, or pressure in the chest.
In some patients with a history of heart disease, chest pain is mild. Such patients may have experienced unexplained fatigue, depression, and ill health within a month of a heart attack. Although chest pain is the classic symptom, it occurs in only about half of patients with a heart attack.

Other Common Symptoms.

Nausea, vomiting, and cold sweats
A feeling of indigestion or heartburn
Fainting
A great fear of impending death, a phenomena known as angor animi

Atypical Symptoms. Some studies suggest that nearly half of patients with heart attack do not have chest pain as the primary symptom. Common atypical symptoms of a heart attack include:

Shortness of breath
Cardiac arrest
Dizziness, weakness, and fainting
Abdominal pain

Patients most likely to have atypical symptoms are women and the very elderly (although they can certainly have classic heart attack symptoms as well).

In one study, 52% of elderly people with acute coronary syndrome had atypical symptoms that included shortness of breath, nausea, profuse sweating, pain in the arms, and fainting. Such symptoms were more likely to occur in people with personal or family history of heart disease.
Before a heart attack, women are more likely than men to be nauseous and experience pain high in the abdomen or chest. Their first symptom may be extreme fatigue after physical activity rather than chest pain. Chest pain in women is also more likely to be caused by non-heart problems than in men.

Symptoms That Are Less Likely to Indicate a Heart Attack. The following symptoms are less likely to be due to a heart attack:

Sharp pain brought on by lung movements or coughing
Pain that is mainly or only in the middle or lower abdomen
Pain that can be pinpointed with the top of one finger
Pain that can be reproduced by moving or pressing on the chest wall or arms
Pain that is constant and lasts for hours (although no one should wait hours if they suspect they are having a heart attack)
Pain that is very brief and lasts for a few seconds
Pain that spreads to the legs

However, the presence of these symptoms does not always rule out a serious heart event.

Chest pain is a very common symptom in the emergency room, but heart problems account for only 10 - 33% of all episodes.

The most common causes of chest pain are muscular and bone problems. Problems affecting the ribs and chest muscles include injured muscles, fractures, arthritis, spasms, and infections.

Other causes of chest pain include:

Anxiety attacks
Gastrointestinal disorders (gallstone attacks, peptic ulcer disease, hiatal hernia, heartburn)
Asthma
Spasm in the coronary artery
Abnormalities of the heart muscle
Rupture of the aorta
Collapsed lung
Acute inflammation of the heart
Blood clot in the lung
High thyroid levels (hyperthyroidism)
Anemia
Vasculitis (a group of disorders that cause inflammation of the blood vessels)
Exposure to high altitudes (rare)

Individuals who experience symptoms of a heart attack should take the following actions:

For angina patients, take one nitroglycerin dose either as an under-the-tongue tablet or in spray form at the onset of symptoms. Take another dose every 5 minutes up to three doses or when the pain is relieved, whichever comes first.
Call 911 or the local emergency number. This should be the first action taken if angina patients continue to experience chest pain after taking the full three doses of nitroglycerin. However, only 20% of heart attacks occur in patients with long-standing angina. Therefore, anyone who has heart disease or risk factors for it and experiences heart attack symptoms should contact emergency services.
The patient should chew an aspirin (250 - 500 mg) and be sure that emergency health providers are informed of this so an additional dose is not given.
Patients with chest pain should go immediately to the nearest emergency room, preferably traveling by ambulance. They should not drive themselves.

Click the icon to see an image about heart attack symptoms.

Click the icon to see another image about heart attack symptoms.

Risk Factors

Over 13 million Americans have had angina, a heart attack, or both. Each year, about 1.2 million people will experience a serious heart event. About 25% of all Americans have one or more risk factors for heart disease. Most risk factors for heart disease are related to lifestyle and environmental factors.

Over the past decades, heart disease rates declined in both men and women as they quit smoking and improved dietary habits. This rate, however, has stabilized in recent years, most likely because of the dramatic increase in obesity in the U.S. and other industrialized nations. There have also been minimal changes in other risk factors, including smoking, sedentary behavior, and blood pressure control. Some risk factors cannot be changed, including age, gender, and genetics. Nevertheless, their effects can still be modified with healthy lifestyle changes.

Heart disease may be prevented with a healthy diet and regular exercise, and by quitting smoking if you smoke. Follow your health care provider's recommendations for the treatment and prevention of heart disease.

The American Heart Association guidelines for preventing heart disease recommend:

Improve Cholesterol. People with at least two risk factors and a 10-year risk for heart disease or stroke of more than 20% should aim for LDL levels of less than 100 mg/dl. Statins are now used in more cases.

Keep Blood Pressure Low. People in normal health should have a blood pressure reading of 120/80 mm Hg or less. According to the latest guidelines, blood pressure readings of 120/80 are considered normal, readings of 140/90 or higher indicate hypertension, and readings in between the two are called pre-hypertension. Patients with diabetes or chronic kidney disease should maintain blood pressure readings of 130/80 mm Hg or less, while others should be no higher than 140/90 mm Hg.

Exercise. Everyone in normal health should engage in at least moderate physical activity for a minimum of 30 minutes on most, if not all, days of the week.

Healthy Diet. Everyone should aim for a diet that contains a healthy balance of fruits, vegetables, grains, fish, nuts, legumes, poultry, lean meat, and low-fat dairy items. Avoid saturated fats and trans-fatty acids.

Quit Smoking. Also avoid exposure to secondhand smoke.

Maintain Weight. People should aim for a BMI index of 18.5 - 24.9.

Taking Aspirin. People whose risk for heart disease within 10 years is 10% or more should take a low-dose aspirin every day, unless they have medical reasons to avoid aspirin.

Control Diabetes. People with diabetes should aim for fast blood glucose levels of less than 110 mg/dl and hemoglobin A1C or less than 7%.

Control Atrial Fibrillation. People with atrial fibrillation should use anticoagulants to reduce the risk for blood clots.

Age. About 85% of people who die from heart disease are over the age of 65.

Gender. Coronary artery disease and heart attacks are much more common in middle-aged men. Women have, on average, 10 - 15 more years of heart disease-free life than do men, but as women age, they catch up to men. Women, in fact, are more likely to have angina than men. Younger women with heart disease often do not have the same symptoms as their male counterparts and may be less likely to be diagnosed correctly. They are also more likely than men to die after a heart attack.

In 2007, the American Heart Association issued updated guidelines focusing on prevention of heart disease in women. The new guidelines recommend:

Healthy diet (fresh fruits and vegetables, low-fat dairy products, salt and saturated fat restrictions, alcohol moderation)
Eating oily fish (such as salmon) at least twice a week. Women with existing heart disease should consider taking fish oil supplements of 850 – 1,000 mg eicosapentaenoic acid (EPA) and docosahexaenoic acid (DPA).
Increased physical activity (60 – 90 minutes, preferably 7 days a week)
Quitting smoking
Low-dose aspirin therapy for all women age 65 years and older who can safely take aspirin. High-risk women may require 75 – 325 mg / day; lower-risk women may benefit from 81 mg a day or 100 mg every other day.

Genetic Factors. Genetics are involved in increasing the likelihood of developing important risk factors such as diabetes and high blood pressure. For example, one genetic variant called apolipoprotein E4 (ApoE4) affects cholesterol levels, particularly those associated with heart disease.

Ethnicity. African-American women face the highest risk for death from heart disease, and their rate of heart attacks is increasing. (Mortality rates in men do not differ much by race.) Native American men have a lower risk for heart disease than Caucasian men, and Hispanics have the lowest risk for heart disease of all major American population groups.

African-Americans face a number of biologic and social dangers to their hearts.

They have a higher prevalence of diabetes and hypertension than do Caucasians.
They tend to have poorer diets, higher stress levels, and less access to health care.
All African-Americans risk discrimination in obtaining optimal treatments, but women may be at particular risk for unequal treatment. In one study in which female actors portrayed heart patients, African-American women were 60% less likely to receive aggressive (and expensive) diagnostic tests than African-American men or any Caucasians, even though they presented with similar symptoms.
While African-Americans comprise 13% of the U.S. population, African-Americans have comprised only 2 - 9% of subjects in most major research trials, so knowledge about their specific risks is limited.
Some African-Americans with coronary artery disease appear to have a genetic trait that increases the danger of triglycerides, which may be particularly hazardous for women.

Click the icon to see an image about ethnicity and heart disease risks.

Cholesterol. In spite of its bad press, cholesterol is an essential nutrient necessary for many cellular functions. However, when certain cholesterol levels rise in the blood, they can have dangerous consequences, depending on the type of cholesterol. Low-density lipoprotein (LDL) cholesterol is the "bad" cholesterol responsible for many heart problems. Triglycerides are another type of lipid (fat molecule) that can be bad for the heart. High-density lipoprotein (HDL) cholesterol is the "good" cholesterol that helps protect against heart disease. Doctors test for a "total cholesterol" profile that includes measurements for LDL, HDL, and triglycerides. The ratio of these lipids can affect heart disease risk.

For example, according to one study, men with total cholesterol levels over 240 mg/dl have a risk that is two to four times higher than men whose cholesterol is below 200. A number of studies have demonstrated that reducing LDL and total cholesterol levels and boosting high-density lipoprotein (HDL) levels can improve survival and prevent heart attacks in people with and without heart disease.

It is very difficult to measure LDL levels by themselves, but LDL levels can be reliably calculated by the Friedewald formula: LDL=TC-HDL-TG/5. (LDL=low-density lipoprotein; TC= total cholesterol; HDL=high-density lipoprotein; TG=triglycerides.)

Click the icon to see an image about serum cholesterol.

Cholesterol Goals. In 2004, the National Cholesterol Education Program updated its clinical practice guidelines. The new recommendations set lower treatment goals for LDL levels based on a patient's risk factors for heart disease.

These risk factors include:

Having a first-degree female relative diagnosed with heart disease before age 65 or a first-degree male relative diagnosed before age 55
Being male and over age 45 or female and over age 55
Cigarette smoking
Diabetes
High blood pressure
Metabolic syndrome (risk factors associated with obesity such as low HDL levels and high triglycerides

Having two or more of these risk factors indicates a greater than 20% chance of having a heart attack within 10 years.


Risk Level	Goal (d/L)	Optimal Goal(d/L)
Very High Risk	70	70
High Risk	100	70
Moderate Risk	130	100
Low Risk	160	130

LDL cholesterol, together with other risk factors for heart disease, is the best determinant for whether cholesterol therapy is needed and whether it is working properly. In particular, the new guidelines emphasize lower LDL levels and earlier treatment for people with coronary artery disease, or other forms of atherosclerosis, and diabetes.


Total Cholesterol Goals	LDL Goals	HDL Goals	Triglyceride Goals
Less than 200 mg/dL is desirable. Between 200 and 239 is borderline. Over 240 is high.	70 mg/dL or less is the new goal for very high-risk patients (recent heart attack; current active or unstable cardiovascular or cerebrovascular disease; or two multiple risk factors as defined above.) Below 100 mg/dl is optimal for everyone. It should be the goal for high-risk people including those with existing heart disease, diabetes, or two or more risk factors for heart disease; 70 mg/dL is an optimal goal for these individuals. 130 mg/dl or below for people with two or more risk factors; 100 mg/dL is the optimal goal. 160 mg/dl or less for people at less risk (one or zero risk factors); 130 mg/dL is the optimal goal. Anything over 160 is high with levels over 190 being very high. LDL levels over 190 require medication even with no other cardiac risk factors present.	Levels above 40 mg/dL are desirable; levels above 60 mg/DL are optimal.	Below 150 mg/dL is normal. 150-199 is borderline high. 200-499 is high. Over 500 is very high.
*Risk factors for heart disease include a family history of early heart problems before age 55 for men, before age 65 for women, smoking, high blood pressure, diabetes, being older (over 45 for men and 55 for women), and having HDL levels below 35 mg/dl. People with two or more of these risk factors may have a 10-year risk of heart attack that exceeds 20%, and may therefore need to aim for LDL levels of 100 mg/dL or below.

Other Lipids. Elevated levels of other fatty molecules (lipids) are also now thought to be important indicators of heart disease risk. Studies are finding an elevated risk for angina and first heart attacks in people with elevated levels of lipoprotein(a), or lp(a). This lipoprotein falls somewhere in density between HDL and LDL and may have some properties that increase the risk for blood clots. Some experts suggest, however, that high levels of lp(a) may merely be markers of late-stage atherosclerosis, not a cause.

[See In-Depth Report #23: Cholesterol; and In-Depth Report #43: Heart-healthy diet.]

High blood pressure, or hypertension, has long been a proven cause of coronary artery disease. Blood pressure is categorized as normal, prehypertensive, and hypertensive (which is further divided as Stage 1 or 2 according to severity). High blood pressure is generally considered to be a blood pressure reading greater than or equal to 140 mm Hg (systolic) or greater than or equal to 90 mm Hg (diastolic). Blood pressure readings in the prehypertension category (120 - 139 systolic or 80 - 89 diastolic) indicate an increased risk for developing hypertension. [See Table Blood Pressure Ranges.]

A normal blood pressure reading is 120/80 mm Hg or lower. Most people with high blood pressure should aim for a goal of below 140/90 mm Hg. Patients with certain health problems should aim lower (blood pressure in patients with kidney disease, heart failure, or diabetes should be equal to or lower than 130/80 mm Hg.)

Click the icon to see an image about hypertension.


Blood Pressure Category	Ranges for Most Adults (systolic/diastolic)
Normal Blood Pressure (systolic/diastolic)	Systolic below 120 mm Hg Diastolic below 80 mm Hg
Prehypertension (Formerly Classified as Normal to High-Normal Blood Pressure)	Systolic 120 to 139 mm Hg Diastolic 80 to 89 mm Hg (NOTE: 139/89 or below should be the minimum goal for everyone. People with diabetes or chronic kidney disease should strive for 130/80 or less.)
Mild Hypertension (Stage 1)	Systolic 140 to 159 mm Hg Diastolic 90 to 99 mm Hg
Moderate-to-Severe Hypertension (Stage 2)	Systolic over 160 mm Hg and/or Diastolic over 100 mm Hg
Note: If one of the measurements is in a higher category than the other, the higher measurement is usually used to determine the stage. For example, if systolic pressure is 165 (Stage 2) and diastolic is 92 (Stage 1), the patient would still be diagnosed with Stage 2 hypertension. A high systolic pressure should be a major focus of concern in most adults.

American obesity is at epidemic levels in all age groups. The effect of obesity on cholesterol levels is complex. Although obesity does not appear to be strongly associated with overall cholesterol levels, among obese individuals triglyceride levels are usually high while HDL (beneficial cholesterol) levels tend to be low, both risk factors for heart disease. Obesity has other effects (hypertension, increase in inflammation) that pose major risks to the heart.

Click the icon to see an image of childhood obesity.

Obesity is particularly hazardous when it is one of the components of the metabolic syndrome. This syndrome is diagnosed when three of the following are present: abdominal obesity, low HDL cholesterol, high triglyceride levels, high blood pressure, and insulin resistance. Metabolic syndrome is a pre-diabetic condition that is significantly associated with heart disease and higher mortality rates from all causes. A 2002 study estimated that 24% of the population now has this condition. Obesity is highly linked with type 2 diabetes, and diabetes itself poses a significant risk for high cholesterol levels and heart disease.

Some obese patients with coronary artery disease may consider having bariatric surgery (stomach bypass) to lose excess weight. The weight lost after surgery can help improve blood pressure, cholesterol, blood sugar and other factors associated with CAD. A 2005 study reported that bariatric surgery is safe for patients with CAD who cannot lose weight with diet and exercise, which should always be tried first.

[See In-Depth Report #53: Weight control and diet.]

People who are sedentary are almost twice as likely to suffer heart attacks as are people who exercise regularly. Exercise has a number of effects that benefit the heart and circulation, including:

Improving cholesterol and lipid levels
Reducing inflammation in the arteries
Assisting weight loss programs
Helping to keep blood vessels flexible and open

Studies continue to show that physical activity and avoiding high-fat foods are the two most successful means of reaching and maintaining heart healthy levels of fitness and weight.

Experts have been attempting to define how much exercise is needed to produce heart benefits. In 2002, a well-conducted study on overweight adults confirmed previous research that reported beneficial changes in cholesterol and lipid levels even when people performed low amounts of moderate or high intensity exercise (walking or jogging 12 miles a week). However, more intense exercise is required to significantly change cholesterol levels, notably by increasing HDL (the so-called good cholesterol). Overweight people who have trouble losing pounds can still achieve considerable heart benefits by exercising. Resistance (weight) training has also been associated with heart protection. Exercises that train and strengthen the chest muscles may prove to be very important for patients with angina.

Click the icon to see an image about exercise.

Click the icon to see an image about hypertension and lifestyle changes.

Some studies suggest that for the greatest heart protection, it is not the duration of a single exercise session that counts but the total daily amount of energy expended. Therefore, the best way to exercise may be in multiple short bouts of intense exercise, which can be particularly helpful for older people.

Sudden strenuous exercise (such as snow shoveling and mowing lawns) puts many people at risk for angina and heart attack. Activities that involve raising the arms above the head may also be risky. Patients with angina should never exercise shortly after eating. People with risk factors for heart disease should seek medical clearance and a detailed exercise prescription. And all people, including healthy individuals, should listen carefully to their bodies for signs of distress as they exercise. [See In-Depth Report #29: Exercise.]

Heart disease and stroke are the leading causes of death in people with diabetes. People with diabetes are at risk for the following heart-risk conditions, and the more of these conditions they have, the worse the outlook.

High blood pressure (hypertension). Up to 75% of cardiovascular problems in people with diabetes may be due to hypertension.
Very unhealthy cholesterol and lipid balances (high triglyceride levels and lower HDL).
Blood clotting problems.
Impaired nerve function (neuropathy), which can also damage the heart. Some experts estimate that the mortality rates from neuropathy-related heart conditions range from 15 - 53%.

People with both diabetes and heart disease may have a higher risk for silent ischemia, a condition in which people have blocked arteries but do not experience the angina, the chest pain that signals heart disease. [See In-Depth Report #9: Diabetes - type 1; or In-Depth Report #60: Diabetes - type 2.]

Peripheral artery disease (PAD) occurs when atherosclerosis affects the extremities, particularly the feet and legs. The major risk factors for heart disease and stroke are also the most important risk factors for PAD. (The combination of such conditions with PAD also produces more severe forms of heart or circulatory disease.) Although signs of heart disease are detected in only 20 - 40% of patients with PAD after an initial diagnosis, studies suggest that when intense heart-diagnostics tests are performed, such as angiography or thallium stress tests, co-existing heart disease is detected in up to 90% of all PAD patients. [See In-Depth Report #102: Peripheral artery disease.]

Smokers in their 30s and 40s have a heart-attack rate that is five times higher than their nonsmoking peers. Cigarette smoking may be directly responsible for at least 20% of all deaths from heart disease, or about 120,000 deaths annually. Smoking cigars may increase the risk of early death from heart disease, although evidence is much stronger for cigarette smoking. Although heavy cigarette smokers are at greatest risk, a 2002 study suggested that people who smoke as few as three cigarettes a day are at higher risk for blood vessel abnormalities that endanger the heart. Regular exposure to passive smoke also increases the risk of heart disease in nonsmokers. [See In-Depth Report #41: Smoking.]

Eating habits can be protective or dangerous to the heart. Avoiding saturated fats and trans-fatty acids is particularly important for controlling cholesterol.

Diet plays an important role in the health of the heart. In 2006, the American Heart Association (AHA) issued revised diet and lifestyle recommendations. The current guidelines recommend:

Balance calorie intake and physical activity to achieve or maintain a healthy body weight. (Controlling weight, quitting smoking, and exercising regularly are essential companions of any diet program. Try to get at least 30 minutes, and preferably 60 – 90 minutes, of daily exercise.)
Consume a diet rich in a variety of vegetables and fruits. Vegetables and fruits that are deeply colored (spinach, carrots, peaches, berries) are especially recommended as they have the highest micronutrient content.
Choose whole-grain, high-fiber foods. These include fruits, vegetables, and legumes (beans). Good whole grain choices include whole wheat, oats/oatmeal, rye, barley, brown rice, buckwheat, bulgur, millet, and quinoa.
Consume fish, especially oily fish, at least twice a week (about 8 ounces/week). Oily fish such as salmon, mackerel, and sardines are rich in the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Consumption of these fatty acids is linked to reduced risk of sudden death and death from coronary artery disease.
Limit daily intake of saturated fat (found mostly in animal products) to less than 7% of total calories, trans fat (found in hydrogenated fats, commercially baked products, and many fast foods) to less than 1% of total calories, and cholesterol (found in eggs, dairy products, meat, poultry, fish, shellfish) to less than 300 mg per day. Choose lean meats and vegetable alternatives (such as soy). Select fat-free and low-fat dairy products. Grill, bake, or broil fish, meat, and skinless poultry.
Use little or no salt in your foods. Reducing salt can lower blood pressure and decrease the risk of heart disease and heart failure.
Cut down on beverages and foods that contain added sugars (corn syrups, sucrose, glucose, fructose, maltrose, dextrose, concentrated fruit juice, honey.)
If you consume alcohol, do so in moderation. The AHA recommends limiting alcohol to no more than 2 drinks per day for men and 1 drink per day for women.

[See In-Depth Report #43: Heart-healthy diet.]

Stress. The effects of mental stress on heart disease are controversial. Stress can affect the heart when it activates the sympathetic nervous system (the automatic part of the nervous system that affects many organs, including the heart). Some studies suggest an association between acute stress and a higher risk for serious cardiac events, such as heart rhythm abnormalities and heart attacks, in people with heart disease. However, not all studies report strong evidence that stress has any effect on the heart, particularly in people without any history of heart disease. [See In-Depth Report #31: Stress.]

Depression. Depression increases the severity of heart attack and may even worsen a patient's response to medication for heart disease. Although people with heart disease may become depressed, this does not explain entirely the link between the two problems. Data suggest that depression itself may be a risk factor for heart disease as well as its increased severity.

A number of studies indicate that depression has biologic effects on the heart, including blood clotting and heart rate. One study, for example, reported an association between depression and a greater risk for death from heart problems even in people without a history of heart disease. Even mild depression, which includes feelings of hopelessness experienced over many years, may harm the heart. A 2007 study suggested that depressive symptoms (fatigue, loss of appetite) may be a sign of thickening arteries, the early stage of coronary artery disease. [See In-Depth Report #8: Depression.]

Benefits of Moderate Drinking. Several studies have found heart protection from moderate intake of alcohol (one or two glasses a day). Moderate alcohol consumption can help boost HDL levels. Alcohol may also prevent blood clots and inflammation. Although red wine is most often cited for healthful properties, any type of alcoholic beverage appears to have similar benefit.

Adverse Effects of Heavy Drinking. By contrast, heavy drinking harms the heart. In fact, heart disease is the leading cause of death in alcoholics. Evidence suggests that people who consume more than three drinks a day have abnormal blood clotting factors. Heavy alcohol consumption can raise blood pressure, and binge drinking may increase the risk for hemorrhagic stroke (caused by bleeding in the brain). Large doses of alcohol can trigger irregular heartbeats, which can be dangerous in people with existing heart disease.

Pregnant women and people who can't drink moderately should not drink at all.

Homocysteine and Vitamin B Deficiencies. Deficiencies in the B vitamins folate (known also as folic acid), B6, and B12 have been associated with a higher risk for heart disease in some studies. Such deficiencies produce higher blood levels of homocysteine, an amino acid that has been associated with a higher risk for heart disease, stroke, and heart failure. Researchers have been studying whether vitamin B supplements can reduce homocysteine levels and, consequently, heart disease risks.

Several major 2006 studies indicated that while B vitamin supplements do help lower homocysteine levels, they have no effect on heart disease outcomes. The studies, published in the New England Journal of Medicine, examined patients who had either recently had a heart attack or suffered from diabetes or heart disease. Results showed a similar number of heart attacks and strokes among patients who took B vitamins and those who received placebo. Some experts think that homocysteine may be a marker for heart disease rather than a cause of it.

Click the icon to see the benefits of vitamin B.

Click the icon to see the food sources of vitamin B.

C-Reactive Protein. C-reactive protein is a product of the inflammatory process. Evidence increasingly suggests that high levels may predict future heart disease. It is not known if the protein plays any causal role or whether it is simply a marker for other factors in the disease process.

C. pneumoniae and Other Infectious Organisms. Some microorganisms and viruses have been under suspicion for triggering the inflammation and damage in the arteries that contribute to heart disease. The strongest evidence to date supports a possible role from Chlamydia (C.) pneumoniae (a non-bacterial organism that causes mild pneumonia in young adults). C. pneumoniae has been detected in plaques in the arteries of patients with heart disease. In some studies, evidence of previous infection has been associated with a higher risk for heart events.

Other studies also suggest that cytomegalovirus (CMV), a common virus, may have similar effects. Many people, however, have been infected with these organisms, and no clear association has been found with any of these infections.(H. pylori, the bacteria that causes peptic ulcers, has also been studied for heart effects, but evidence is very weak on any link.)

Erectile Dysfunction. Recent research suggests that erectile dysfunction may be a warning sign of coronary artery disease, even in men who are not considered at risk for the condition. Some studies indicate that men with erectile dysfunction have higher levels of C-reactive protein and more symptoms of atherosclerosis than men without erectile problems.

Periodontal Disease. A number of studies support an association between periodontal disease and cardiovascular disorders. According to a 2003 major analysis, periodontal (gum) disease is associated with a 20% higher risk for ischemic stroke and heart disease. (The added risk may be even higher in adults under 65.) Recent evidence is pointing to the inflammatory response as the common element.

Click the icon to see an image of gum disease.

Anemia. Anemia has adverse effects on the heart and increases the severity of cardiac conditions, including heart failure and heart attacks. A 2002 study suggested that anemia may even be a risk factor for heart disease itself. Blood transfusions after a heart attack improve survival rates in elderly patients who are anemic.

Iron Overload. An inherited disease called hemochromatosis, in which the intestinal tract absorbs too much iron from food, has been associated with atherosclerosis and heart attack. About 10% of Caucasians carry the gene for this condition. There is no strong evidence that excess iron levels in people without hemochromatosis can contribute to heart disease.

Sleep Apnea. Obstructive sleep apnea is a condition in which tissues in the upper throat collapse at intervals during sleep, thereby blocking the passage of air. It has been strongly associated with high blood pressure and obesity, but is also associated with heart disease and heart attacks, regardless of these risk factors. Some evidence suggests that obstructive apneas cause an increase in stiffness and inflammation in the arteries.

Some inborn or natural conditions are not risk factors themselves but have been associated with a higher incidence of heart disease or its consequences:

Factors Before Birth and In Infancy. Low weight at birth and in the womb has been associated with later heart disease in a few studies. Some suggest, however, that this may just reflect poor nutrition in the mother, which appears to affect life-long risk.

Seasonal Differences. More deaths from heart disease occur in December and January, and the fewest in the summertime. Although lower temperatures and snow shoveling may play a role in some cases, more winter deaths have been reported even in warm regions. Holiday stress or fewer daylight hours have been suggested as other reasons for these higher winter rates.

Physical Characteristics. Male pattern baldness, hair in the ear canals, and creased earlobes are associated with a higher risk for heart disease in Caucasian males.

Click the icon to see an image of an ear lobe crease.

Diagnosis

Many tests can diagnose possible heart disease. The choice of which (and how many) tests to perform depends on the patient's risk factors, history of heart problems, and current symptoms. Usually the tests begin with the simplest and may progress to more complicated ones.

Doctors routinely check for high blood pressure and unhealthy cholesterol levels in all older adults. Specific tests are also important in people who may have risk factors or symptoms of diabetes. Doctors may also test for homocysteine, the protein albumin, and blood clotting factors, especially fibrinogen.

An electrocardiogram (ECG) measures and records the electrical activity of the heart. Between 25 - 50% of people who suffer from angina or have silent ischemia, however, have normal ECG readings. The waves measured by the ECG correspond to the contraction and relaxation pattern of the different parts of the heart. Specific waves seen on an ECG are named with letters:

The electrocardiogram (ECG, EKG) is used extensively in the diagnosis of heart disease, from congenital heart disease in infants to myocardial infarction and myocarditis in adults. Several different types of electrocardiogram exist.

P. The P wave is associated with the contractions of the atria (the two chambers in the heart that receive blood from outside).
QRS. The QRS is a series of waves associated with ventricular contractions. (The ventricles are the two major pumping chambers in the heart.)
T and U. These waves follow the ventricular contractions.

The most important wave patterns in diagnosing and determining treatment for heart disease and heart attack are called ST elevations and Q waves.

A depressed or horizontal ST wave suggests some blockage and the presence of a heart disease, even if there is no angina present. (This finding, however, is not very accurate, particularly in women, and can occur without heart problems).
ST elevations and Q waves are the most important wave patterns in diagnosing and determining treatment for a heart attack. They suggest that an artery to the heart is blocked, and that the full thickness of the heart muscle is damaged. ST segment elevations do not always mean the patient has a heart attack. And, some heart attack patients do not have elevated ST segments. Other factors are important in making a diagnosis.

The primary value of exercise stress tests is not to detect coronary artery disease but to help determine the severity and predict the outcome of an existing heart condition. It is considered for the following people:

Patients with possible or probable angina and low or intermediate risk for adverse heart events.
Selected adults who do not have symptoms of heart disease but are at moderate risk to high risk for developing heart disease (a 10 - 20% chance within 10 years). Moreover, heart blockage without angina (silent ischemia) may suggest a more severe condition, at least in men.

Basic Procedure. A stress test (exercise tolerance test) monitors the patient's heart rhythms, blood pressure, and clinical status. It can tell how well the heart handles work and if parts of the heart have decreased blood supply. A typical stress test involves:

The patient walks on a treadmill or rides a stationary bicycle. Exercise continues until the heart is beating at least 85% of its maximum rate, until symptoms of heart trouble occur (changes in blood pressure, heart rhythm abnormalities, angina, fatigue), or the patient simply wants to stop.
For patients who cannot exercise, the doctor may administer dobutamine or arbutamine, which are drugs that simulate the stress of exercise.
An ECG is used to monitor heart rhythms during a stress test. (An echocardiogram or more advanced imaging technique may also be used to visualize the actions of the heart and blood flow.)

More than 25% of patients stop exercising before they reach their own maximum limits because of fear of a heart event. Patients should be reassured that the activities performed in the test under the guidance of a professional are safe.

Interpreting Results. To accurately assess heart problems, experts look at a number of findings derived from the ECG and other tools during exercise. They include:

Exercise capacity. This is a measure of a person's capacity to reach certain metabolic rates.
Heart rate and ST waves. On ECGs, doctors specifically look for abnormalities in part of the wave tracing called an ST segment. A certain type of ST segment depression may suggest the presence of heart disease. However, gender, drugs and other medical conditions can affect the ST segment. Using a measurement that adjusts the ST segment to heart rate improves accuracy.
Dukes Treadmill Score. This important score uses the number of minutes a patient can exercise and other factors that are present in patients with exercise-limiting angina.
Heart rate recovery.
Chronotropic index. This is the percentage of the heart-rate reserve that is used during the exercise. A result of 80% or less suggests a significant risk for serious heart problems in most patients.
Changes in systolic blood pressure.

Using these and other measures, doctors can determine risk fairly accurately, particularly for men of any age with chronic stable angina. The test has limitations, however, and some are significant. For example, a 2002 study indicated that in patients with suspected unstable angina the chances for a future adverse heart event remain high even if the exercise test shows low risk. In addition, for many reasons, the test is less accurate in women, and an echocardiogram may be a more accurate procedure for them. About 10% of patients, particularly younger people, will have false positive test results. In such cases, test results indicate abnormalities when there are no heart problems.

An echocardiogram is a noninvasive test that uses ultrasound images of the heart. This test is more expensive than an ECG, but it can be very valuable, particularly when used with a stress test, to detect the location and extent of heart muscle damage. It appears to be more accurate for women than ECG stress tests, but at this time it is not routinely recommended as a replacement for most women.

Computed tomography (CT) scans used alone or with ECG may be used to detect calcium deposits on the arterial walls, which are strong indicators of current and future coronary artery disease. The presence of calcium does not always signify narrowing of the arteries. But, the absence of calcification in the arteries indicates the patient has no risk for heart disease.

Advanced CT techniques are improving accuracy:

Click the icon to see an image of a CT scan.

Electron Beam Computed Tomography. Electron beam computed tomography (EBCT) is a CT technique that scans the heart so quickly that the motion of the heart appears frozen. This procedure identifies calcification and stratifies cardiac risk accurately.
Multidetector Computed Tomography. Another CT technique called multidetector computed tomography (MDCT) is able to take pictures of the entire heart in 1 millimeter slices in the time it takes for a patient to hold one breath. A 2006 study indicated that MDCT tends to have a high “false-positive” rate (indicating disease when it is not actually there), but for some patients the test may be helpful in ruling out coronary artery disease.

Some expert groups recommend CT scans in selected patients who have an intermediate risk (10 - 20% chance of heart disease within 10 years). For some of these patients, EBCT may be preferred over exercise stress testing, but most experts recommend a stress test as the main diagnostic tool. In general, the use of these expensive imaging tests is probably not very helpful for people at low or high risk. (For people with high risk, the additional information from these tests would not add much value.) More research is needed to determine the benefits of CT scanning in specific individuals.

Radionuclide procedures use imaging techniques and computer analyses to plot and detect the passage of radioactive tracers through the region of the heart. Such tracing elements are typically given intravenously. Radionuclide imaging is useful for diagnosing and determining:

Severity of unstable angina when less expensive diagnostic approaches are unavailable or unreliable
Severity of chronic coronary artery disease
Success of surgeries for coronary artery disease.
Whether a heart attack has occurred

Various imaging techniques may be used with radionuclide procedures, including:

Planar scintigraphy uses a special overhead camera and is the oldest scanning technique.
Single-photon emission computed tomography (SPECT) uses a camera that rotates around the patient and takes pictures of "slices" of the heart. It is more accurate than planar imaging in precisely locating problems in the arteries.
Positron-emission tomographic (PET) scanners employ multiple rings that surround the patients, which detect and record atomic particles (photons) that are emitted by the tracer elements (such as radioactive oxygen, nitrogen, or carbon). It is more expensive and less widely available than SPECT.

Myocardial Perfusion (Blood Flow) Imaging Test (also called the Thallium Stress Test). This radionuclide test is typically used with an exercise stress test to determine blood flow to the heart muscles. It is a reliable measure of severe heart events. It may be useful in determining the need for angiography if CT scans have detected calcification in the arteries. About a minute before the patient is ready to stop exercising, the doctor administers a radioactive tracer into the intravenous line. (Tracers include thallium, technetium, or sestamibi.) Immediately afterwards, the patient lies down for a heart scan, usually with a planar scintigraphy or with SPECT. If the scan detects damage, more images are taken 3 or 4 hours later. Damage due to a prior heart attack will persist when the heart scan is repeated. Injury caused by angina, however, will have resolved by that time.

Radionuclide Angiography. This is a technique for visualizing the chambers and major blood vessels of the heart. It uses an injected radioactive tracer and can be performed during exercise, at rest, or with use of stress-inducing drugs. It is an excellent test for assessing the heart's pumping action and for determining the severity of coronary artery disease. It is an alternative to echocardiograms in certain situations.

Click the icon to see an internal view of the heart.

Magnetic Resonance Angiography (MRA). MRA is a very promising noninvasive imaging technique that can provide three-dimensional images of the major arteries to the heart and identify disease with high accuracy. Experts believe this approach will eventually be a good alternative to angiography.

Click the icon to see an image of a MRI.

Angiography is an invasive test. It is used for patients who show strong evidence for severe obstruction on stress and other tests, and for patients with acute coronary syndrome.

A narrow tube is inserted into an artery, usually in the leg or arm, and then threaded up through the body to the coronary arteries.
A dye is injected into the tube, and an x-ray records the flow of dye through the arteries.
This process provides a map of the coronary circulation, revealing any blocked areas.

Click the icon to see an image of dye in the coronary artery.

Major complications include stroke, heart attacks, and kidney damage. These risks are very low (about 0.1%), however, if the procedure is done in an experienced medical center (one that performs at least 300 of these operations every year). Allergic reactions can also occur. The procedure is expensive, and between 10 - 30% of patients who have this procedure have normal results.

When heart cells become damaged, they release different enzymes and other molecules into the bloodstream. Elevated levels of such markers of heart damage in the blood or urine may help predict a heart attack in patients with severe chest pain and help determine treatment. Some of these factors include:

Troponins. The proteins cardiac troponin T and I are released when the heart muscle is damaged. Both are proving to be among the best diagnostic indications of heart attacks. They help to identify many individuals with ACS who might otherwise be misdiagnosed.
Creatine kinase myocardial band (CK-MB). CK-MB has been a standard marker, but the MB fraction is not as accurate as troponin levels, since elevated levels can appear in people without heart injury.
Myoglobin. Myoglobin is a protein found in heart muscles. It is released early in the injured heart, and it may be useful in combination with CK-MB and the troponins.
Newer biomarkers, including C-reactive protein (CRP), homocysteine, B-type natriuretic peptide (BNP), urinary albumin, and fibrinogen.

Several 2006 studies that evaluated how well biomarkers predict risk of heart events concluded that they do not provide much more useful information than standard risk factors (high blood pressure, unhealthy cholesterol levels, diabetes). At this time, most experts feel that these standard disease risk factors provide the best predictors of the likelihood of developing coronary artery disease, heart attack, or stroke.

Managing Heart Disease

The approach for managing any degree of coronary artery disease involves lifestyle changes. Depending on severity and individual conditions, patients may need one or more medications, surgery, or both.

Healthy diet, regular exercise and quitting smoking if you are a smoker may prevent heart disease. Follow your health care provider's recommendations for treatment and prevention of heart disease.

Experts have come up with a mnemonic device (ABCDE) for remembering 10 factors that are fundamental for management of stable angina and coronary artery disease:

A. Aspirin and anti-angina drugs

B. Blood pressure and beta-blockers

C. Cholesterol-lowering drugs (typically statins) and cigarettes (stopping)

D. Diet and diabetes control

E. Exercise and education

Unstable angina is now usually classified with non-Q myocardial infarction as acute coronary syndrome (ACS) in professional discussions of treatments. ACS usually requires more aggressive treatments, including surgery. [ACS is more fully discussed in In-Depth Report #12: Heart attack and acute coronary syndrome.]

Click the icon to see an image about angina.

Anti-Clotting Medications

Anti-clotting drugs that inhibit or break up blood clots are used at every stage of heart disease. They are generally classified as either antiplatelets or anticoagulants. All anti-clotting therapies carry the risk of bleeding, which can lead to dangerous situations, including stroke.

A thrombus is a blood clot that forms in a vessel and remains there. An embolism is a clot that travels from the site where it formed to another location in the body. Thrombi or emboli can lodge in a blood vessel and block the flow of blood in that location depriving tissues of normal blood flow and oxygen. This can result in damage, destruction (infarction), or even death of the tissues (necrosis) in that area.

Antiplatelet Drugs. These drugs prevent formation of blood platelets. Platelets are very small disc-shaped blood cells that are important for blood clotting.

Aspirin. Aspirin is an antiplatelet. It is the most common anti-clotting drug. Nearly anyone with existing heart disease or at risk for it is advised to take a low-dose aspirin every day.
Thienopyridines. Clopidogrel (Plavix) and ticlopidine (Ticlid) are thienopyridines, another type of anti-platelet drug.
Glycoprotein IIb/IIIa Inhibitors. These powerful blood-thinning drugs include abciximab (ReoPro, Centocor), eptifibatide (Integrilin), tirofiban (Aggrastat), and lamifiban. They are administered intravenously in the hospital and are used after angioplasty surgery and stent placement.

Click the icon to see an image about blood.

Anticoagulants. Anticoagulants help thin blood and include:

Heparin
Warfarin (Coumadin)
Direct thrombin inhibitors

Aspirin. Aspirin is known as a nonsteroidal anti-inflammatory drug (NSAID). It stops blood platelets, which are major clotting factors, from sticking together to form a blood clot. A daily low-dose aspirin (75 - 325 mg) is usually the first choice for preventing heart disease in high-risk individuals. Aspirin can prevent by 25 – 50% the risk of heart attacks and death in people with existing heart disease and a history of heart attack. It also reduces the risk for stroke. According to a 2006 review, aspirin works equally well for both men and women.

Click the icon to see an image about stomach ulcers.

Side effects from prolonged use of aspirin may include stomach ulcers and bleeding. (There may be a slight increased risk for bleeding-related strokes, which are very uncommon, however. Furthermore, this risk may be outweighed by protection against the more common type of stroke, which is caused by artery blockage.)

Clopidogreland Ticlopidine. Clopidogrel (Plavix) and ticlopidine (Ticlide) are anti-platelet drugs known as thienopyridines. When taken with aspirin, these drugs can significantly reduce the risk for heart attack and stroke in patients with acute coronary syndrome (unstable angina or early signs of heart attack). The combination of aspirin and a thienopyridine is essential for patients who have a drug-eluting stent. According to a 2007 American Heart Association advisory, patients who have a drug-eluting stent must take both aspirin and a thienopyridine for at least 1 year after the stent is inserted. Many experts recommend clopidogrel instead of ticlopidine because ticlopidine has been associated with dangerous blood disorders, particularly thrombocytopenia.

Clopidogrel is also recommended for patients who are undergoing angioplasty. For patients having coronary bypass surgery, it should be withheld for at least 5 -7 days prior to surgery because of a significant bleeding risk. Researchers are investigating whether clopidogrel and aspirin together are better than aspirin alone in reducing the risks following coronary bypass surgery. A 2006 study suggested that for some patients with heart disease, clopidogrel plus aspirin does not work better than aspirin alone for preventing a first heart attack or stroke.

Click the icon to see an image of the developmental process of atherosclerosis.

Click the icon to see an image about atherosclerosis.

Anticoagulants are drugs that prevent or delay blood coagulation and the formation of blood clots. Heparin has been the standard anticoagulant, but a number of drugs are now available that are proving to be better choices in many cases.

Standard (Unfractionated) Heparin. The heparin referred to as unfractionated heparin has been the standard for years and is used alone or in combination with aspirin for managing unstable angina. It is no longer the recommended first choice, however, for this patient group. It must be intravenously administered and monitored with frequent blood tests. The major complication is thrombocytopenia (a severe drop in platelets). This condition is extremely serious and can become life-threatening, particularly with bleeding in various body tissues. Alternatives include low-molecular weight heparin and direct thrombin inhibitors.

Low-Molecular Weight Heparin. Enoxaparin (Lovenox), dalteparin (Fragmin), tinzaparin (Innohep) are drugs known as low-molecular weight heparins (LMWHs). Many doctors now recommend these drugs over standard heparin for patients with unstable angina (unless bypass surgery is being planned). They have similar rates of survival, recurring angina, and bleeding as standard heparin. However, they pose lower risks for heart attack, repeat angioplasties, and thrombocytopenia. They require injections but do not require the ongoing monitoring that standard heparin does. Patients may even be able to self-administer LMWHs as people with diabetes do insulin.

Warfarin. Warfarin (Coumadin) is an oral anticoagulant. It prevents clots by inhibiting vitamin K. Warfarin is used with aspirin after a heart attack to prevent another one and to prevent blood clots in patients with atrial fibrillation. Warfarin is also proving to be more effective than aspirin for preventing heart attacks in patients with acute coronary syndromes. Warfarin therapy poses a dangerous risk for bleeding and blood coagulation must be monitored with frequent blood tests.

Direct Thrombin Inhibitors (DTIs). Direct thrombin inhibitors are a more recent group of anti-coagulants. The first DTI was hirudin, a natural substance derived from the saliva of leeches. New forms include argatroban (Novastan), bivalirudin (Angiomax), danaparoid (Orgaran), lepirudin (Refludan), desirudin (Revasc), and ximelagatran (Exanta). Many of these drugs are used along with warfarin and may be good options for patients who develop thrombocytopenia with heparin use. DTIs may prove to be superior to standard heparin for patients with acute coronary syndrome.

Other Medications

Nitrates have been used in the treatment of angina for over 100 years. These drugs release nitric oxide, thereby relaxing the smooth muscles in blood vessels. Many nitrate preparations are available. The most commonly used are nitroglycerin, isosorbide dinitrate, and isosorbide mononitrate. Nitrates can be absorbed from the gastrointestinal tract (oral tablet), skin (ointment or patch), or from under the tongue (sublingual tablet or spray).

Rapid Acting Nitrates. Rapid-acting nitrates are used to treat acute attacks. Nitroglycerin is the most widely used drug for this purpose. It can be administered under the tongue (sublingually or as a spray) or pocketed between the upper lip and gum (buccally) and can relieve angina within minutes. The procedure for taking nitroglycerin during an attack is as follows:

At the onset of an angina attack, the patient administers one sublingual or buccal tablet or one metered dose of the spray.
If the pain is not relieved within 5 minutes the patient takes a second dose; a third can be taken after another 5 minutes if symptoms persist.
If pain continues after a total of three doses in 15 minutes, the patient should go immediately to the nearest emergency room.

Nitroglycerin is very volatile so its potency can be easily lost. Patients should take the following precautions:

Keep no more than 100 tablets on hand, stored in their original container.
When first opened, the cotton filler should be discarded, and the cap screwed on tightly immediately after each use.
A supply should always be kept close at hand in case of an attack, with the rest kept in a cool dry place.

Intermediate to Long-Term Nitrates. Sublingual tablets of isosorbide dinitrate have a somewhat slower onset of action than nitroglycerin and are useful for preventing exercise angina. Ointments, patches, and oral tablets are used for longer-term prevention of angina attacks:

Transdermal patches are applied in the morning to any hair- or injury-free area on the chest, back, stomach, thigh, or upper arm. Hands should be washed after each patch or ointment application, and sites of application should be rotated to avoid skin irritation.
Nitroglycerin ointment is applied by measuring out an even amount on an applicator paper and then placing, not rubbing or massaging, it on the chest, stomach, or thigh. Any ointment that remains from the previous application should be removed.

Long-acting forms may lose their effectiveness over time, so doctors generally schedule nitrate-free breaks to prevent tolerance. Some concern exists that nitrate-free periods might increase the risk for angina and adverse heart events. One large study, however, found no increased danger when patients used a nitroglycerine patch with scheduled breaks. The use of high blood pressure drugs known as ACE inhibitors may help prevent tolerance to nitrates.

Side Effects. Nitrates have many side effects, some of which can be serious.

Common side effects of nitrates include headaches, dizziness, nausea and vomiting, blurred vision, fast heartbeat, sweating, and flushing on the face and neck. Low blood pressure and dizziness can be relieved by lying down with the legs elevated. These effects are significantly worsened by alcohol, beta-blockers, calcium channel blockers, sildenafil (Viagra), and certain antidepressants. The doctor may prescribe medicines to lessen these side effects. Patients should contact their doctor if these side effects are persistent or severe.

Serious side effects requiring immediate medical help include fever, joint or chest pain, sore throat, skin rash (especially on the face), unusual bleeding or bruising, weight gain, and swelling of the ankles.

Withdrawal. Withdrawal from nitrates should be gradual. Abrupt termination may cause angina attacks.

Beta-blockers are useful for preventing angina attacks and reducing high blood pressure. They reduce the heart's oxygen demand by slowing the heart rate and lowering blood pressure. They are recognized for reducing deaths from heart disease and from heart surgeries, including angiography and coronary bypass. Beta-blockers are the drugs of choice for older patients with stable angina and may also be beneficial for people with silent ischemia. They are, however, less useful for the treatment of Prinzmetal’s angina. Beta-blockers are often prescribed along with other drugs such as nitrates, calcium channel blockers, or statins. A 2006 study suggested that beta-blockers and statins may help stabilize coronary artery disease and prevent the development of heart attacks.

Specific Beta-blockers. Beta-blockers include propranolol (Inderal), carvedilol (Coreg), bisoprolol (Zebeta), acebutolol (Sectral), atenolol (Tenormin), labetalol (Normodyne, Trandate), metoprolol (Lopressor, Toprol-XL), and esmolol (Brevibloc). A nasal spray form of propranolol appears to be very helpful in reducing exercise-induced angina attacks.

Side Effects. Beta-blocker side effects include fatigue, lethargy, vivid dreams and nightmares, depression, memory loss, and dizziness. They can lower HDL (“good”) cholesterol. Beta blockers are categorized as non-selective or selective. Non-selective beta blockers such as carvedilol and propranolol can narrow bronchial airways. These beta-blockers should not be used by patients with asthma, emphysema, or chronic bronchitis.

Patients should never abruptly stop taking these drugs. The sudden withdrawal of beta-blockers can rapidly increase heart rate and blood pressure. The doctor may advise a patient to slowly decrease the dose before stopping completely.

Calcium channel blockers reduce heart rate and slightly dilate the blood vessels of the heart, thereby decreasing oxygen demand and increasing oxygen supply. They also reduce blood pressure. CCBs vary chemically, however, and although some are helpful, others may even be dangerous for certain patients with angina.

Click the icon to see an image of the anterior heart arteries.

Long-acting nifedipine (Adalat, Procardia) and nisoldipine (Sular) and newer CCBs, such as amlodipine (Norvasc) and nicardipine (Cardene), may be beneficial for some patients with angina. They can be considered alone for patients who cannot tolerate beta-blockers, but may provide the best results when used in combination with a beta-blocker. Studies suggest that they reduce the need for repeat angioplasties. Their effects on other outcomes, including mortality rates and heart attack, are less clear.
Short-acting CCBs, including short-acting forms of verapamil, diltiazem, nifedipine, and nicardipine, are helpful for many patients with Prinzmetal's angina. However, short-acting forms of certain CCBs, such as nifedipine and nisoldipine, have been associated with severe and even dangerous side effects, including an increase in heart attacks and sudden death in some patients with unstable angina. They also increase the risk for adverse effects in patients with stable angina. Short-acting CCBs are, therefore, not used for stable or unstable angina.

There is no strong evidence that any calcium channel blockers improve survival rates. Overdose can cause dangerously low blood pressure and slow heart beats. Patients with heart failure have a higher risk for death with these drugs and should not take them. No one taking any calcium channel blocker should withdraw abruptly because such action could dangerously increase the risk of high blood pressure. Note: Grapefruit and Seville oranges boost the effects of CCBs, sometimes to toxic levels. (Regular oranges do not appear to pose any hazard.)

Angiotensin converting enzyme (ACE) inhibitors are important heart-protective drugs, particularly for people with diabetes and high blood pressure. They reduce the production of angiotensin, a chemical that causes arteries to narrow, and so are commonly used to lower blood pressure. They may also reduce risk for heart attack, stroke, complications of diabetes, and death in patients at high risk for heart disease.

ACE inhibitors include captopril (Capoten), ramipril (Altace), enalapril (Vasotec), quinapril (Accupril), benazepril (Lotensin), perindopril (Aceon), and lisinopril (Prinivil, Zestril).

Side Effects. Side effects of ACE inhibitors are uncommon but may include an irritating cough, excessive drops in blood pressure, and allergic reactions. In the past, doctors sometimes avoided giving aspirin to patients who were taking ACE inhibitors because the combination was believed to cause kidney problems. But, a 2005 study of patients with both coronary artery disease and heart failure found that taking aspirin and ACE inhibitord together is safe. The researchers also noted that taking aspirin with an ACE inhibitor can significantly reduce the risk of death for older patients with CAD and heart failure. [See In-Depth Report #14: High blood pressure.]

In 2004, the National Cholesterol Education Program issued updated recommendations on how to control cholesterol levels. These guidelines emphasize that patients should lower their LDL (“bad”) cholesterol and recommend that more people take LDL-lowering medication. Lowering LDL cholesterol and raising HDL (“good”) cholesterol can significantly reduce the risks of heart disease. Several different types of drugs (statins, bile-acid binding resins, niacin, and fibrates) are used to treat cholesterol. [See In-Depth Report #23: Cholesterol.]

Statins are the most important of these drugs. Brands include lovastatin (Mevacor), pravastatin (Pravachol), simvastatin (Zocor), fluvastatin (Lescol), atorvastatin (Lipitor), and rosuvastatin (Crestor). A major analysis of over 200 studies found that statins reduced the risk for heart problems by 60% and stroke by 17%. A 2005 review found that the more that statins lower LDL, the more they reduce CAD and other heart disease risks.

An important 2006 study found that aggressive treatment with statins may have the potential to reverse coronary artery disease. In the study, rosuvastatin reduced fatty plaque in the arteries in addition to improving LDL and HDL cholesterol levels. However, a follow-up 2007 study of rosuvastatin indicated that while the drug slowed the rate of atherosclerotic progression, it did not reverse heart disease. Future studies will continue to investigate this issue.

Side effects of statins may include stomach upset, headaches, skin rashes, muscle aches, sexual dysfunction, drowsiness, dizziness, nausea, constipation, and peripheral neuropathy (numbness or tingling in the hands and feet).

The main safety concern with statins is an uncommon condition called myopathy, which can cause muscle and joint pain and possible muscle damage. Doctors will immediately stop statin therapy if myopathy occurs. Patients should talk to their doctor about any unusual muscle discomfort or weakness, or if their urine becomes brown-colored. Statins can also affect the liver, particularly at higher doses, so patients taking these drugs should receive regular liver function tests.

Click the icon to see an image of cholesterol.

Influenza Vaccinations (Flu Shots). Evidence suggests influenza vaccinations help protect against adverse heart events (including after heart surgeries), stroke, and death from all causes in the elderly. Still, studies suggest that only two-thirds of at risk people are vaccinated, mostly because of unwarranted fears of ineffectiveness or adverse effects.

Antibiotics. Researchers have investigated antibiotics for treating patients with heart disease and past infection of the bacteria Chlamydia pneumoniae. Results from several recent large-scale clinical trials suggest that antibiotic treatment provides no benefit in preventing heart attack or other cardiac events in patients with coronary artery disease. In addition, a 2006 study indicated that short-term treatment with the antibiotic clarithromycin may increase the risk for death in patients with coronary artery disease. While it is still possible that C. pneumoniae may play a role in triggering inflammatory responses associated with ACS, antibiotic therapy is no longer considered appropriate for treatment or prevention of heart disease.

Ranolazine (Ranexa) was approved in 2006 for treatment of chronic angina. It is recommended for patients who have not responded to other angina drugs. Ranolazine is taken in combination with amlodipine, beta blockers, or nitrates. The drug appears to work better in men than in women

Gene Therapy and Angiogenesis. Proteins known as growth factors are being investigated for their ability to grow new blood vessels for supplying oxygen to the heart. After promising small trials, two large studies of genetically engineered forms of vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF [GenerX]) failed to detect any benefits. Studies on therapies that actually genetically encode these proteins are underway.

Testosterone Supplements. Some trials using testosterone supplements or patches have reported improved exercise-induced blood flow in the coronary arteries and improvement in angina in some cases. Supplements of this male hormone, however, may increase the risk for prostate cancer. Experts suggest that testosterone be used only in older men with significant deficiencies in testosterone.

Selective Estrogen-Receptor Modulators (SERMs). Selective estrogen-receptor modulators (SERMs), including raloxifene (Evista), have been designed to produce the benefits of estrogen without its risks. They are thought to act like estrogen in some tissues but behave like estrogen blockers (antiestrogens) in others. Raloxifene may have some heart benefits, although it poses a risk for deep vein blood clots, which may have long-term implications for patients with heart problems. A major study is underway to determine its effects on the heart.

Surgery

Surgery is usually recommended for patients who have:

Unstable angina that does not respond promptly to medical treatment
Severe recurrent episodes of angina that last more than 20 minutes
Acute coronary syndrome
Severe coronary artery disease (severe angina, multi-artery involvement, evidence of ischemia), particularly if abnormalities are evident in the left ventricle of the heart, the main pumping chamber

Atherosclerosis is a disease of the arteries in which fatty material is deposited in the vessel wall, resulting in narrowing and eventual impairment of blood flow. Severely restricted blood flow in the arteries to the heart muscle leads to symptoms such as chest pain. Atherosclerosis shows no symptoms until a complication occurs.

Researchers have been investigating whether surgery offers any advantages if used as an early treatment for mild angina. A major analysis in 2003 reported that the use of angioplasty in patients with mild heart blockage did not reduce the risk for heart attack or death over the long term. A landmark 2007 study found that angioplasty was no better than drug therapy for preventing heart attack and stroke in patients with stable coronary artery disease. (For more information, see Angioplasty and Stents.)

Two effective surgical procedures for heart patients are:

Coronary artery bypass grafting (commonly called bypass or CABG)
Percutaneous coronary intervention (commonly called angioplasty or PCI), usually with coronary artery stent placement

Click the icon to see an image about bypass grafting.

Each of these procedures is described below.

Studies have generally reported similar survival rates with either procedure. There are some differences, however, and decision often depends on individual conditions. Patients considering surgery should discuss all options and risks with their doctor. No surgical procedure cures coronary artery disease, and patients must continue to rigorously maintain a healthy lifestyle and any necessary medications. For some patients, lifestyle changes and medications may be able to control the disease without surgery or angioplasty.

Considerations for Choosing Angioplasty with Stent Placement. Angioplasty has the following advantages for most patients. It is:

Less invasive than bypass. (Although a minimally invasive variation of bypass surgery may reduce this distinction.)
Less expensive than bypass. (Although the postoperative need for more medications and the high risk for repeat procedures to reopen the artery may reduce the long-term difference in cost between the two procedures.)
Life-saving emergency procedure for many patients with heart attacks. (The use of bypass after a heart attack has much higher mortality rates than when it is used electively and its use is controversial in heart attack patients.)

It has the following disadvantages:

The blood vessels can close up again (restenosis) so that patients require additional procedures. (New blood thinning drugs, coronary stent coatings, and radiation treatments may help to significantly reduce restenosis rates. However, there is also some indication that stents, especially drug-eluting stents, may increase the risk for blood clots.)
It is not as appropriate as bypass for many patients with angina (people with diabetes, elderly patients, or those with multi-vessel blockage). Increasingly, however, angioplasty is proving to be as safe and as effective as bypass in many high-risk patients. Patients should be sure to discuss with their doctors the relevant risks and benefits of angioplasty and bypass.

Considerations for Choosing Bypass. Bypass is usually the appropriate procedure in patients with high-risk conditions, such as:

Multi-vessel blockage. (In one report comparing surgery to angioplasty in patients with two or three blocked vessels, the mortality rate 1 year after bypass was 0.8% and after angioplasty was 2.5%. About 80% of patients in the study were men.)
Diabetes. (Bypass produces significantly higher survival rates in these patients. Some experts believe angioplasty should rarely, if ever, be used in this population.)
Being elderly.
Certain structural features, such as a left main artery narrowed by 50% or more or a very long diseased portion of the artery.

Considerations for Women. Studies have reported higher mortality rates in women than in men after any heart surgery. Some experts theorize that on average women may be older and sicker when they have a heart operation. A 2002 study, however, suggested that when women with acute coronary syndromes are given the same aggressive and early treatment as men are, their survival rates are equal or even better.

In addition to angioplasty and bypass procedures, a number of other procedures are available or under investigation for coronary artery disease. They include:

Atherectomy
Myocardial Laser Revascularization
Enhanced External Counterpulsation (EECP)

Coronary Artery Bypass Graft Surgery

Coronary artery bypass graft surgery (CABG) is a good alternative to angioplasty for many patients, but it is very invasive. The surgery involves the following processes:

Click the icon to see an animation about CABG.

The chest is opened, and the blood is rerouted through a lung-heart machine.
The heart is stopped during the procedure.
Large blood vessels supply the grafts, which are used to reroute the blood. The blood vessel grafts are transplanted in front of and beyond the blocked arteries, so the blood flows through the new vessels around the blockage.
The standard grafts now use arteries taken from the chest wall. Studies are reporting that with such grafts arteries remain open in 90% of cases after 15 years.
In general, patients with triple bypass procedures stay in the hospital for 5 days. Those with one-vessel bypass may be able to go home in 3 days.

Click the icon to see an illustrated series detailing a heart bypass surgery.

In spite of the invasive nature of this procedure, elective bypass procedures produce better long-term survival rates than angioplasty, particularly in patients with diabetes and multi-vessel blockage. Overall mortality rates after this procedure range from 1% to slightly over 2%. The risk for stroke or heart attack after a bypass operation ranges from 1.3 - 5%. Finding a surgeon who performs at least 100 of the procedures a year helps reduce the risk for complications.

Blood clots may form in the new graft, closing it up or narrowing the treated vessel over time. Therapy with aspirin and other anti-clotting drugs help keep the graft open and working properly. For long-term prevention of closure, as well as for slowing progression of atherosclerosis, aggressive treatment with cholesterol-lowering drugs may be more beneficial than standard anti-clotting drugs.

Bleeding is also a potential complication of CABG. Anti-bleeding (also called hemorrhage-sparing) drugs are sometimes used to limit blood loss in patients who undergo this surgery. In 2006, concerns were raised about one of these drugs, aprotinin (Trasylol). Data suggested that aprotinin seriously increased the risks for kidney failure, heart failure, and stroke.

An important study, published in 2007 in the Journal of the American Medical Association, compared aprotinin with two anti-fibrinolytic drugs, aminocaproic acid (Amicar) and tranexamic acid (Cyklokapron), which are also used to control blood loss. The study of nearly 4,000 patients who had CABG found that over a 5-year period, the death rate for patients who took aprotinin was 21%, and patients had a 48% increased risk of dying. By comparison, the death rate was 16% for aminocaproic acid, 15% for tranexamic acid, and 13% for no anti-bleeding drug. Because aprotinin is more expensive as well as potentially more dangerous than other anti-bleeding drugs, experts are now recommending against its use in CABG.

Minimally invasive bypass (also called buttonhole or keyhole bypass) surgeries are exciting advances in basic bypass surgery. Studies indicate good success of these procedures for patients with disease in single vessels. They are also being investigated for multiple vessels.

One variation of minimally invasive bypass uses a four-inch incision. The surgeon works on the front of the heart while it is beating slowly. To date, there have been no differences in cardiac events or later mental complications between this so-called off-pump procedure and the standard bypass procedure.
In another variation, the heart is stopped, and the patient is put on a machine that reroutes the blood through a device that keeps it oxygenated. Fiberoptic scopes and instruments are passed through a number of finger-sized incisions. The surgeon works on all sides of the heart, guided by a video image from a tiny camera inserted through a 4-inch incision.
Some advanced heart centers now use robotic systems, which allow the surgeon to perform extremely delicate maneuvers on tiny vessels through pencil-size incisions. They are not yet used for the whole bypass process.

Eventually, minimally invasive bypass procedures may prove to be less expensive, require a shorter hospital stay, and have fewer complications than conventional coronary artery bypass surgery -- or even angioplasty. At this time, however, they are experimental procedures, performed in only a few medical centers for select candidates. Long term-success rates are unknown.

Angioplasty and Stents

Percutaneous coronary intervention (PCI), also called angioplasty, involves procedures such as percutaneous transluminal coronary angioplasty (PTCA) that help open the blocked artery.

Click the icon to see an animation about percutaneous transluminal coronary angioplasty.

A typical angioplasty procedure follows these steps:

The cardiologist threads a narrow catheter (a tube) containing a catheter into the blocked vessel.
The doctor opens the blocked vessel using balloon angioplasty, in which the surgeon passes a tiny deflated balloon through the catheter to the vessel.
The balloon is inflated to compress the plaque against the walls of the artery, flattening it out so that blood can once again flow through the blood vessel freely.
In order to keep the artery open afterwards, surgeons use a device called a coronary stent, an expandable metal mesh tube that is implanted during angioplasty at the site of the blockage. (In some cases, a stent may be used as the initial opening device instead of balloon angioplasty.)
Once in place, the stent pushes against the wall of the artery to keep it open.

Click the icon to see an animation about percutaneous transluminal coronary angioplasty.

Complications occur in about 10% of patients (about 80% within the first day). Outcomes are better in hospital settings with experienced teams and backup.

Click the icon to see an illustrated series detailing coronary artery balloon angioplasty surgery.

The most important long-term complication is reclosure (restenosis), which can lead to heart attack if not treated with a repeat procedure. Stenting and other advances have helped significantly in preventing reclosure and reducing heart attack rates. Nevertheless, a repeat procedure is still needed to restore the opening in 10 - 15% of procedures that use stents.

PCI (angioplasty) has been proven to help reduce the frequency of angina attacks. It is commonly recommended for patients who have critically blocked arteries or have already had a recent, acute heart attack. PCI can also help improve survival and prevent heart attacks in patients with acute coronary syndrome (ACS). However, doctors have been uncertain about angioplasty’s benefits for survival and heart attack prevention in lower-risk patients with stable coronary artery disease.

In 2007, a landmark study was published in the New England Journal of Medicine and presented at the 2007 meeting of the American College of Cardiology. The COURAGE study found that PCI works no better than standard heart medication (drugs to control blood pressure, lower cholesterol, and prevent blood clots) in preventing heart attack, stroke, and hospitalization in patients with stable coronary artery disease. Based on this study’s findings, experts are now recommending angioplasty only for patients who have severe heart disease. For patients with stable heart disease, drug therapy may be sufficient enough treatment and allow them to safely defer having surgery.

Angioplasty is less invasive than bypass surgery, requiring only one night in the hospital. Recuperation takes about a week. Chest pain after the procedure is very common and usually due to problems other than ischemia. Mild chest pain is even more common when a stent is used, possibly because the artery is stretched.

Reclosure of the artery during or shortly after angioplasty often occurs. A number of anti-clotting drugs are used to help prevent this.

Aspirin and the anti-platelet drug clopidogrel (Plavix) are often used to prevent reclosure during the procedure.
A high dose of the anticoagulant heparin is typically given before the operation.
Intravenous glycoprotein IIb/IIIa inhibitors, powerful drugs that block platelets, also prevent reclosure after stenting in many high-risk patients, and evidence now strongly suggests that they reduce rates of heart attack and death. Eptifibatide (Integrilin) and tirofiban (Aggrastat) are the standard drugs used during angioplasty. They may be most effective if administered during angioplasty, rather than beforehand.

All of these drugs pose a risk for bleeding complications.

Narrowing or reclosing of the artery (restenosis) can occur within a year of angioplasty or even longer in 15 - 60% of angioplasty patients. Coronary stents, anti-clotting drugs, and other advances have reduced these events significantly, but have not eliminated the problem. Theories for the cause of restenosis include:

The release of oxidants (damaging unstable particles) at the surgical site may cause injury and activate immune factors that produce cellular overgrowth in smooth muscles of the blood vessels.
Other activities, including scarring, may remodel and narrow the blood vessels. (This is most likely the reason for restenosis in patients with stents.)

Symptoms of restenosis include chest pain on exertion. (Heart attacks, however, do not usually occur with such events.) The narrowing of the artery in this case is not due to blood clots, so anti-clotting drugs are not useful. Restenosis usually requires a repeat operation. A number of approaches, mostly investigative, have been developed to prevent restenosis after angioplasty.

Drug-Coated Stents. Stents coated with the drugs sirolimus (Rapamune) or paclitaxel (Taxol) have been increasingly used in the last several years. Drug-eluting stents (as they are also called) can help prevent restenosis. However, because drug-eluting stents reduce arterial tissue growth, they can increase the risks of blood clots. In late 2006, the FDA held several meetings to discuss the increased risks of blood clots associated with drug-eluting stents. The committees found that drug-eluting stents do appear to have a small increased risk of blood clots compared to bare metal stents, but not enough research has been conducted to fully determine their risks for heart attack and death.

Five studies published in the New England Journal of Medicine in March 2007 indicated that drug-eluting stents are safe and effective for patients with coronary artery disease when they are used for FDA-approved indications. Problems have arisen when these stents are used for “off-label” purposes in patients with more complicated health problems. There is still some concern as to whether all stents (both bare metal and drug eluting) are used too frequently for patients who may be better served by drugs or bypass surgery.

In February 2007, the American Heart Association and other professional organization issued an extremely important joint advisory statement. The statement advises that all patients who have drug-eluting stents must continue to take aspirin and clopidogrel (or, rarely, ticlopidine) for at least 1 year after the stent is inserted to reduce the risk of blood clots. Clopidogrel and ticlopidine are thienopyridine drugs that, like aspirin, help prevent blood platelets from clumping together. It is very important that patients who have drug-eluting stents take both aspirin and a thienopyridine drug. If for some reason patients cannot take a thienopyridine drug, they should receive a bare metal stent instead of a drug-eluting stent.

Coronary Artery Brachytherapy. Radiation treatment called coronary artery brachytherapy (Gamma One, Beta-Cath) can slow the cell growth in the arteries that causes restenosis. With this approach, any blockage in the stent is first removed, and a tube with an inflatable balloon is inserted. The surgeon then implants a temporary device that delivers radiation. Brachytherapy has shown excellent results in preventing restenosis and significantly reducing heart events and improving survival. Brachytherapy is also showing promise in preventing restenosis in stented artery grafts that were put in place after bypass surgery and later failed. However, several 2006 studies in the Journal of the American Medical Association indicated that drug-coated stents may work better than brachytherapy in preventing restenosis in failed stents. In these studies, the drug-coated stents were inserted inside the original bare metal stents.

Medications. A number of medications are being studied for prevention of restenosis, although benefits to date have been modest. Other drugs under investigation include statins, various anti-clotting drugs, and B vitamins.

Other Procedures. Other procedures under investigation to keep the arteries open use ultrasound, "soft" x-rays, and cryotherapy (very low temperatures).

Other Treatments

Transmyocardial laser revascularization (TMLR) applies laser energy directly to areas in the heart where blockage has occurred, creating 10 - 50 tiny channels. TMLR is recommended for patients with severe angina who have not responded to surgical bypass or angioplasty procedures. TMLR is not suitable for patients who have severely damaged heart muscles. A variant called percutaneous transmyocardial laser revascularization uses a small laser (a holmium YAG laser), which is smaller than the device used in TMLR and does not require open chest surgery and a general anesthetic.

Patients report improved symptoms and exercise tolerance. Both procedures carry risks for serious complications, however, including some that can be life-threatening. It is not clear if either TMLR procedure improves survival, and, in one study, the quality of life afterwards was less than with standard heart surgeries.

A noninvasive technique called enhanced external counterpulsation (EECP) has been used successfully by over a million people in China. The technique uses an air pump that inflates and deflates pressurized cuffs around the legs, causing blood to be pushed into the heart.

EECP may help patients with angina who have not had pain relief from nitrate drugs and who do not qualify as candidates for bypass or angioplasty. In different studies, it has relieved angina in over 75% of patients who used it and reduced the need for medication. The benefits persist, and there is some evidence that it produces actual cellular changes that benefit the heart. In 2002, the FDA approved EECP for the treatment of heart failure but some insurance companies still consider its use “experimental” and will not pay for it. EECP is not recommended for patients with arrhythmia, serious heart valve problems, or peripheral artery disease.

Atherectomy procedures clear the narrowed arteries by using an approach called debulking. All of these procedures use a catheter (a thin tube) that is inserted into an artery (usually in the groin) and threaded up to the blockage. Devices are inserted through the tube to remove the plaque. They include:

Rotational atherectomy, which uses a tiny cutter spinning at 2,500 rpm
Extractional atherectomy, which "shaves" the plaque
Directional atherectomy, which slices the plaques

Although they are successful in opening arteries, they offer no advantages over standard angioplasty and are used only for special cases.

Resources

www.nhlbi.nih.gov -- National Heart, Lung, and Blood Institute
www.americanheart.org -- American Heart Association
www.acc.org -- American College of Cardiology

References

Boden WE, O'Rourke RA, Teo KK, Hartigan PM, Maron DJ, Kostuk WJ, et al. Optimalmedical therapy with or without PCI for stable coronary disease. N Engl J Med. 2007 Mar 26; [Epub ahead of print]

Crouse JR 3rd, Raichlen JS, Riley WA, Evans GW, Palmer MK, O'Leary DH, et al. Effect of rosuvastatin on progression of carotid intima-media thickness in low-risk individuals with subclinical atherosclerosis: the METEOR Trial. JAMA. 2007 Mar 28;297(12):1344-53. Epub 2007 Mar 25.

Eisenstein EL, Anstrom KJ, Kong DF, Shaw LK, Tuttle RH, Mark DB, et al. Clopidogrel use and long-term clinical outcomes after drug-eluting stent implantation. JAMA. 2007 Jan 10;297(2):159-68. Epub 2006 Dec 5.

Folsom AR, Chambless LE, Ballantyne CM, Coresh J, Heiss G, Wu KK, et al. An assessment of incremental coronary risk prediction using C-reactive protein and other novel risk markers: the atherosclerosis risk in communities study. Arch Intern Med. 2006 Jul 10;166(13):1368-73.

Garcia MJ, Lessick J, Hoffmann MH; CATSCAN Study Investigators. Accuracy of 16-row multidetector computed tomography for the assessment of coronary artery stenosis. JAMA. 2006 Jul 26;296(4):403-11.

Grines CL, Bonow RO, Casey DE Jr, Gardner TJ, Lockhart PB, Moliterno DJ, et al. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians. Circulation. 2007 Feb 13;115(6):813-8. Epub 2007 Jan 15.

Kastrati A, Mehilli J, Pache J, Kaiser C, Valgimigli M, Kelbaek H, et al. Analysis of 14 trials comparing sirolimus-eluting stents with bare-metal stents. N Engl J Med. 2007 Mar 8;356(10):1030-9. Epub 2007 Feb 12.

Lagerqvist B, James SK, Stenestrand U, Lindback J, Nilsson T, Wallentin L; SCAAR Study Group. Long-term outcomes with drug-eluting stents versus bare-metal stents in Sweden. N Engl J Med. 2007 Mar 8;356(10):1009-19. Epub 2007 Feb 12.

Lloyd-Jones DM, Liu K, Tian L, Greenland P. Narrative review: Assessment of C-reactive protein in risk prediction for cardiovascular disease. Ann Intern Med. 2006 Jul 4;145(1):35-42.

Maisel WH. Unanswered questions--drug-eluting stents and the risk of late thrombosis. N Engl J Med. 2007 Mar 8;356(10):981-4. Epub 2007 Feb 12.

Mangano DT, Miao Y, Vuylsteke A, Tudor IC, Juneja R, Filipescu D, et al. Mortality associated with aprotinin during 5 years following coronary artery bypass graft surgery. JAMA. 2007 Feb 7;297(5):471-9.

Mangano DT, Tudor IC, Dietzel C; Multicenter Study of Perioperative Ischemia Research Group; Ischemia Research and Education Foundation. The risk associated with aprotinin in cardiac surgery. N Engl J Med. 2006 Jan 26;354(4):353-65.

Mauri L, Hsieh WH, Massaro JM, Ho KK, D'Agostino R, Cutlip DE. Stent thrombosis in randomized clinical trials of drug-eluting stents. N Engl J Med. 2007 Mar 8;356(10):1020-9. Epub 2007 Feb 12.

Mosca L, Banka CL, Benjamin EJ, Berra K, Bushnell C, Dolor RJ, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation. 2007 Mar 20;115(11):1481-501.

Nicholls SJ, Tuzcu EM, Sipahi I, Grasso AW, Schoenhagen P, Hu T, et al. Statins, high-density lipoprotein cholesterol, and regression of coronary atherosclerosis. JAMA. 2007 Feb 7;297(5):499-508.

Rosamond W, Flegal K, Friday G, Furie K, Go A, Greenlund K, et al. Heart disease and stroke statistics--2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2007 Feb 6;115(5):e69-171. Epub 2006 Dec 28.

Spaulding C, Daemen J, Boersma E, Cutlip DE, Serruys PW. A pooled analysis of data comparing sirolimus-eluting stents with bare-metal stents. N Engl J Med. 2007 Mar 8;356(10):989-97. Epub 2007 Feb 12.

Stewart JC, Janicki DL, Muldoon MF, Sutton-Tyrrell K, Kamarck TW. Negative emotions and 3-year progression of subclinical atherosclerosis. Arch Gen Psychiatry. 2007 Feb;64(2):225-33.

Stone GW, Moses JW, Ellis SG, Schofer J, Dawkins KD, Morice MC, et al. Safety and efficacy of sirolimus- and paclitaxel-eluting coronary stents. N Engl J Med. 2007 Mar 8;356(10):998-1008. Epub 2007 Feb 12.

Wang TJ, Gona P, Larson MG, Tofler GH, Levy D, Newton-Cheh C, et al. Multiple biomarkers for the prediction of first major cardiovascular events and death. N Engl J Med. 2006 Dec 21;355(25):2631-9.

Review Date:
4/16/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Pneumonia

FitSugar — Wed, 08 Oct 2008 17:35:27 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Prognosis
Risk Factors
Diagnosis
Treatment
Medications
Surgery
Prevention
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Diagnosis:

Diagnosing pneumonia may be difficult, since lab tests to grow the bacteria from samples can take many days to process, and chest x-rays cannot always distinguish between pneumonia and other conditions. New tests have the potential to make diagnosis easier and quicker. One is a blood test that identifies a marker of severe inflammation in the body. A new 15-minute urine test shows promise in identifying Legionella pneumophila and Streptococcus pneumoniae in patients on ventilators. Physicians may now sample fluid from the trachea or lungs to identify the pneumonia-causing bacteria.

Treatment:

Treating pneumonia has become increasingly complex as bacteria develop resistance to widely used antibiotics. New antibiotics and combinations of older antibiotics are proving effective against many hardy strains of bacteria. Moreover, guidelines for the appropriate treatment of patients at high risk for pneumonia -- those with heart disease, diabetes, asthma, HIV infection, leukemia, and other lung diseases, for example -- are improving the ability to prevent pneumonia and reduce deaths from the disease.

Drug Warning:

In February 2007, the Food and Drug Administration (FDA) announced that the antibiotic telithromycin (Ketek) would no longer be approved for acute bacterial sinusitis and acute bacterial exacerbations of chronic bronchitis, but it would remain on the market for the treatment of mild-to-moderate pneumonia acquired outside of hospitals or long-term care facilities (community-acquired pneumonia, or CAP). In addition to warnings for liver damage, Ketek will now carry warnings of additional drug-related adverse events, including visual disturbances and loss of consciousness.

Introduction

Pneumonia is an inflammation of the lung that is most often caused by infection with bacteria, viruses, or other organisms. Occasionally, inhaled chemicals that irritate the lungs can cause pneumonia. Healthy people can usually fight off pneumonia infections. However, people who are sick, including those who are recovering from the flu (influenza) or an upper respiratory illness, have weakened immune systems that make it easier for bacteria to grow in their lungs.

When air is inhaled through the nose or mouth, it travels down the trachea to the bronchus, where it first enters the lung. From the bronchus, air goes through the bronchi, into the even smaller bronchioles and lastly into the alveoli.

Pneumonia may be defined according to its location in the lung:

Lobar pneumonia occurs in one part, or lobe, of the lung.
Bronchopneumonia tends to be scattered throughout the lung.

Doctors often classify pneumonia based on where the disease is contracted. This helps predict which organisms are most likely responsible for the illness and, therefore, which treatment is most likely to be effective.

Community-Acquired Pneumonia (CAP). People with this type of pneumonia contracted the infection outside a hospital setting. It is one of the most common infectious diseases. It often follows a viral respiratory infection, such as the flu.

One of the most common causes of bacterial CAP is Streptococcus pneumoniae. Other causes include Haemophilus influenzae, mycoplasma, and Chlamydia.

Hospital-Acquired Pneumonia. Hospital-acquired pneumonia is an infection of the lungs contracted during a hospital stay. This type of pneumonia tends to be more serious, because hospital patients already have weakened defense mechanisms, and the infecting organisms are usually more dangerous than those encountered in the community. Hospital patients are particularly vulnerable to Gram-negative bacteria and staphylococci. Hospital-acquired pneumonia is also called nosocomial pneumonia.

A subgroup of hospital-acquired pneumonia is ventilator-associated pneumonia (VAP), a highly lethal form contracted by patients on ventilators in hospitals and long-term nursing facilities.

Click the icon to see an image of hospital-acquired pneumonia.

Pneumonia-causing agents reach the lungs through different routes:

In most cases, a person breathes in the infectious organism, which then travels through the airways to the lungs.
Sometimes, the normally harmless bacteria in the mouth, or on items placed in the mouth, can enter the lungs. This usually happens if the body's "gag reflex," an extreme throat contraction that keeps substances out of the lungs, is not working properly.
Infections can spread through the bloodstream from other organs to the lungs.

However, in normal situations, the airways protect the lungs from substances that can cause infection.

The nose filters out large particles.
If smaller particles pass through, sensors along the airway prompt a cough or sneeze. This forces many particles back out of the body.
Tiny particles that reach the small tubes in the lungs (bronchioles) are trapped in a thick, sticky substance called mucus. The mucus and particles are pushed up and out of the lungs by tiny hair-like cells called cilia, which beat like a drum. This action is called the "mucociliary escalator."

Click the icon to see an image of respiratory cilia.

If bacteria or other infectious organisms manage to avoid the airway's defenses, the body's immune system attacks them. Large white blood cells called macrophages destroy the foreign particles.

Click the icon to see an image of a macrophage.

The above-mentioned defense systems normally keep the lung healthy. If these defenses are weakened or damaged, however, bacteria, viruses, fungi, and parasites can easily infect the lung, producing pneumonia.

The lungs are two spongy organs in the chest surrounded by a thin, moist membrane called the pleura. Each lung is composed of smooth, shiny lobes; the right lung has three lobes and the left has two. Approximately 90% of the lung is filled with air. Only 10% is solid tissue. There are several parts to each lung.

When a person takes a breath (inhales), air travels from the trachea (windpipe) into the lung through the main bronchus, which branches into tiny flexible tubes called bronchi.

The bronchi divide, like the branches of a tree, into smaller airways called bronchioles.

The bronchioles lead to a group of microscopic sacs called alveoli, which look like clusters of grapes. Each healthy adult lung contains millions of tiny alveoli. (Note: The singular of alveoli is alveolus.)

Click the icon to see an image of the lungs.

Each alveolus has a thin membrane that allows oxygen and carbon dioxide to pass in and out of the capillaries, the smallest of the blood vessels. When you take a deep breath, the membrane unfolds and expands. Fresh oxygen moves into the capillaries, and carbon dioxide passes from the capillaries into the bloodstream, where it is carried out of the body through the lungs.

Blood vessels carry the oxygen-rich blood to the heart, where it is pumped throughout the body.

Causes

Bacteria are the most common cause of pneumonia. However, pneumonia can also be caused by viruses, fungi, and other agents. It is often impossible to identify the specific culprit.

Many bacteria are grouped into one of two large categories by the laboratory procedure used to look at them under a microscope. The procedure is known as Gram staining. Bacteria are stained with special dyes, then washed in a special solution. The color of the bacteria after washing determines whether they are Gram-negative or Gram-positive. Knowing which group the bacteria belong to helps determine the severity of the disease, and how to treat it. Different bacteria are treated with different drugs.

Gram-Positive Bacteria. These bacteria appear blue on the stain and are the most common organisms that cause pneumonia. They include:

Streptococcus (S.) pneumoniae (also called pneumococcus), the most common cause of pneumonia. This Gram-positive bacterium causes 20 - 60% of all community-acquired bacterial pneumonia (CAP) in adults. Studies also suggest it causes 13 - 38% of CAP in children.
Staphylococcus (S.) aureus, the other major Gram-positive bacterium responsible for pneumonia, causes about 2% of CAP and 10 - 15% of hospital-acquired pneumonias. It is the organism most often associated with viral influenza, and can develop about five days after the onset of flu symptoms. Pneumonia from S. aureus most often occurs in people with weakened immune systems, very young children, hospitalized patients, and drug abusers who use needles. It is uncommon in healthy adults.
Streptococcus pyogenes or Group A streptococcus.

Gram-Negative Bacteria. These bacteria stain pink. Gram-negative bacteria commonly cause infections in hospitalized or nursing home patients, children with cystic fibrosis, and people with chronic lung conditions.

Haemophilus (H.) influenzae is the second most common organism causing community acquired pneumonia, accounting for 3 - 10% of all cases. It generally occurs in patients with chronic lung disease, older people, and alcoholics.
Klebsiella (K.) pneumoniae may be responsible for pneumonia in alcoholics and other people who are physically debilitated. It is also associated with recent use of potent antibiotics.
Pseudomonas (P.) aeruginosa is a major cause of hospital-acquired pneumonia (nosocomial pneumonia). It is a common cause of pneumonia in patients with chronic or severe lung disease.
Moraxella (M.) catarrhalis is found in everyone's nose and mouth. Experts have identified this bacterium as an uncommon cause of certain pneumonias, particularly in people with lung problems such as asthma or emphysema.
Neisseria (N.) meningitidis is one of the most common causes of meningitis (central nervous system infection), but the organism has been reported in pneumonia, particularly in epidemics of military recruits.
Other Gram-negative bacteria that cause pneumonia include E. coli, proteus (found in damaged lung tissue), enterobacter and acetinobacter.

Atypical pneumonias produce mild symptoms and a dry cough. Organisms that cause atypical pneumonias include:

Mycoplasma (M.) pneumoniae, the most common atypical pneumonia organism. Mycoplasma is a very small bacterium that lacks a cell wall. Pneumonia caused by M. pneumoniae spreads when someone carrying the infection comes in close contact with others for a long period of time. It is most often found in school-aged children and young adults. The condition, commonly called "walking pneumonia," is usually mild.
Chlamydia (C.) pneumoniae is now thought to cause 10% of all CAP cases. This atypical pneumonia is most common in young adults and children, and is usually mild. It is less common, but usually more severe, in the elderly.
Legionella pneumophila causes Legionnaire disease. It is contracted by breathing in drops of contaminated water. Outbreaks are often been reported in hotels, cruise ships, and office buildings, where people are exposed to contaminated droplets from cooling towers and evaporative condensers. They have also been reported in people who have been near whirlpools and saunas. Legionella pneumophila is not passed from person to person. Some experts believe the organism causes 29 - 47% of all pneumonia cases.

Legionnaire disease was first described in 1976 after an outbreak of fatal pneumonia at an American Legion convention. The newly described organism that caused the disease was named Legionella pneumophila, shown in this picture. (Courtesy of the Centers for Disease Control.)

A number of viruses can cause pneumonia either directly or indirectly. They include:

Influenza (Flu). Pneumonia is a major complication of the flu and can be very serious. It can develop about 5 days after flu symptoms start. The flu weakens the body's defense systems, making it easier for bacteria to grow in the lungs.
Respiratory syncytial virus (RSV). Most infants are infected with RSV at some point, but it is most often mild. However, RSV is a major cause of pneumonia in infants as well as adults with damaged immune systems. Studies indicate that RSV pneumonia may be more common in adults, especially the elderly, than previously thought.
Severe acute respiratory syndrome (SARS). SARS is a respiratory infection caused by a newly-described coronavirus, which appears to have jumped from animals to humans. The disease was first reported in China in 2003.
Human parainfluenza virus. This virus is a leading cause of pneumonia and bronchitis in children, the elderly, and patients with damaged immune systems.
Adenoviruses. Adenoviruses are common and usually are not problematic, although they have been linked to about 10% of childhood pneumonia.
Herpesviruses. In adults, herpes simplex virus and varicella zoster (the cause of chickenpox) can cause pneumonia in people with impaired immune systems.
Avian influenza. Type A influenza subtype H5N1 in birds is spreading around the globe. Fortunately, only a few hundred human cases have been identified. Most have resulted from close contact with infected birds. Person-to-person contact is rare. All patients diagnosed with "bird flu" show signs of pneumonia, although symptoms may be mild. Oseltamivir (Tamiflu) is the most effective treatment for this type of influenza, which can be fatal.

The mouth contains a mixture of bacteria that is normally harmless. However, if this mixture reaches the lungs, it can cause a serious condition called aspiration pneumonia. This may happen after head a injury or general anesthesia, or when a patient takes drugs or alcohol. In such cases, the gag reflex doesn't work as well as it should, so bacteria can enter the airways. Unlike other organisms that are inhaled, bacteria that cause aspiration pneumonia do not need oxygen to live. These bacteria are called anaerobic bacteria.

Impaired immunity leaves patients vulnerable to serious, life-threatening pneumonias known as opportunistic pneumonias. They are caused by organisms that are harmless to people with healthy immune systems. Infecting organisms include:

Pneumocystis carinii, renamed Pneumocystis jiroveci in 2002, is an atypical organism. Originally thought to be protozoa, it is now classified as a fungus. P. jiroveci is very common and generally harmless in people with healthy immune systems. It is the most common cause of pneumonia in AIDS patients.

Click the icon to see an image of pneumocystis carinii.

Fungi, such as Mycobacterium avium
Viruses, such as cytomegalovirus (CMV)

Click the icon to see an image of CMV.

In addition to AIDS, other conditions also put patients at risk for opportunistic pneumonia. They include cancers such as lymphoma and leukemia. Long-term use of corticosteroids and drugs known as immunosuppressants also increase the risk for these pneumonias.

Exposure to chemicals can also cause inflammation and pneumonia. Where you work and live can put you at higher risk for exposure to pneumonia-causing organisms.

Workers exposed to cattle, pigs, sheep, and horses are at risk for pneumonia caused by anthrax, brucella, and Coxiella burnetii, which causes Q fever.

Click the icon to see an image of inhalation anthrax.

Agricultural and construction workers in the Southwest are at risk for coccidoidomycosis (Valley fever). The disease is caused by the spores of the fungus Coccidioides immitis.
Those working in Ohio and the Mississippi Valley are at risk for histoplasmosis, a lung disease caused by the fungus Histoplasma capsulatum.

Click the icon to see an image of coccidoidomycosis.

Workers exposed to pigeons, parrots, parakeets, and turkeys are at risk for psittacosis, a lung disease caused by the bacteria Chlamydia psittaci.
Hantavirus, a rare virus carried by rodents, causes a dangerous form of lung disease. It does not spread from person to person. Cases have occurred in New Mexico, Arizona, California, Washington, and Mexico.

Click the icon to see an image of the hantavirus.

Severe acute respiratory syndrome (SARS) is a contagious respiratory infection that was recognized as a worldwide threat in 2003. It was first identified as a new disease by World Health Organization (WHO) physician Dr. Carlo Urbani. Urbani diagnosed SARS in a 48-year-old American businessman, who had traveled from the Guangdong province of China through Hong Kong to Hanoi, Vietnam. The businessman died from the illness. Dr. Urbani died from SARS just a month later, on March 29, 2003 at the age of 46. SARS spread fast. Within 6 weeks of Urbani's discovery, the disease had infected thousands of people around the world on every continent except Antarctica. Schools closed throughout Hong Kong and Singapore, and national economies were affected. The WHO officially identified SARS as a global health threat, and issued an unprecedented travel advisory. It wasn't clear at the time whether SARS would become a global pandemic or settle into a less aggressive pattern. The latter seems to have happened. As of a May 2005, there was no known SARS transmission anywhere in the world, according to the U.S. Centers for Disease Control and Prevention (CDC). The SARS outbreak is a dramatic example of how quickly world travel can spread a disease. According to reports from the CDC and WHO, more than 8,000 people became sick with SARS during the outbreak. Of that group, 774 died. The outbreak is also an example of how quickly a networked health monitoring system can respond to an emerging threat

Causes And Risk Factors. SARS is a serious form of atypical pneumonia that causes acute respiratory distress and sometimes death. It is caused by a new member of the coronavirus family, the family that includes the virus that causes the common cold). The discovery of the SARS-related virus represents one of the fastest identifications of a new organism in history.

SARS is spread by droplet contact. When someone with SARS coughs or sneezes, infected droplets are sprayed into the air. Like other coronaviruses, the SARS virus may live on hands, tissues, and other surfaces for up to 6 hours in these droplets and up to 3 hours after the droplets have dried. While droplet transmission through close contact has been responsible for most cases of SARS, there is evidence that SARS might also spread by infected droplets carried on hands and other objects the droplets had touched. Airborne transmission was a real possibility in some cases. Live virus had even been found in the stool of people with SARS, where it has been shown to survive for up to 4 days. And the virus may be able to live for months or years when the temperature is below freezing.

With other coronaviruses, re-infection (contracting the same disease after recovery or during initial illness) is common. Preliminary reports suggest that this may also be the case with SARS.

The estimated incubation period is 2 - 10 days, although there have been documented cases where the onset of illness was considerably faster or slower. People with active symptoms of illness are clearly contagious. It is not known, however, how early contagion begins before symptoms appear, or how long contagion might linger after the symptoms have disappeared.

Prevention. The best way to prevent SARS is to avoid direct contact with people who have SARS until 10 days after their fever and other symptoms are gone. Reduce travel to locations where there is an uncontrolled SARS outbreak. The CDC has identified hand hygiene as the cornerstone of SARS prevention. Wash your hands often with soap and water, or use an alcohol-based instant hand sanitizer. Cover your mouth and nose when sneezing or coughing. Consider respiratory secretions infectious. Clean commonly touched surfaces with an EPA-approved disinfectant. In some situations, masks, and goggles may be useful for preventing the spread of airborne or droplet infection. Gloves should be used in handling potentially infectious secretions.

Vaccine. In December 2004, the U.S. National Institutes of Health began a small clinical trial to test a preventive SARS vaccine. Interim results showed the vaccine to be safe and well tolerated. Chinese researchers began testing a SARS vaccine in May 2004.

Symptoms. The hallmark symptoms of SARS are fever of 100.4° F (38.0° C) or higher and a dry cough, with difficulty breathing or other respiratory symptoms. The following symptoms, listed in order of how often they appeared, were found in more than half of the first SARS patients:

Fever
Chills and shaking
Muscle aches
Cough
Headache

Less common symptoms (also in order) include:

Dizziness
Cough that produces mucus (sputum)
Sore throat
Runny nose
Nausea and vomiting
Diarrhea

Signs and Tests. Listening to the chest with a stethoscope (auscultation ) may reveal abnormal lung sounds. In most people with SARS, progressive chest x-ray changes or chest CT changes reveal the presence of pneumonia.

Much attention was given early in the outbreak to the development of a quick, sensitive test for SARS. Specific tests for the SARS virus include the PCR for SARS virus, antibody tests to SARS (such as ELISA or IFA), and direct SARS virus isolation. All current tests have some limitations. General tests used in the diagnosis of SARS might include:

Chest x-ray or chest CT is abnormal.
CBC. People with SARS tend to have a low white blood cell count (leukopenia), a low lymphocyte count (lymphopenia), or a low platelet count (thrombocytopenia).
Clotting profiles. SARS patients often have prolonged blood clotting times.
Metabolic blood tests. Lactate dehydrogenase (LDH) and alanine transaminase (ALT) levels are often high. ALT and LDH are most often measured to evaluate the presence of tissue damage.
CPK blood test. Creatine phosphokinase (CPK) is an enzyme found predominantly in the heart, brain, and skeletal muscle. Levels of the CPK enzyme are sometimes elevated in patients with SARS.
Sodium and potassium blood tests are sometimes below normal levels.

Treatment. People suspected of having SARS should be evaluated immediately by a physician. Antibiotics are sometimes given in an attempt to treat bacterial causes of atypical pneumonia. Antiviral medications have also been used. High doses of steroids have been employed to reduce lung inflammation. In some serious cases, serum from people who have already gotten well from SARS (convalescent serum) has been given. Evidence of general benefit of these treatments has been inconclusive.

Other supportive care such as supplemental oxygen, chest physiotherapy, or mechanical ventilation is sometimes needed.

Prognosis. The overall worldwide death rate due to SARS at the end of the outbreaks was 14 - 15%, although it was up to 50% in infected people over age 65. Many more were sick enough to require breathing assistance from a machine (mechanical ventilation). Many others required ICU care.

Today, intensive public health policies are proving to be effective in controlling outbreaks. Many nations have stopped the epidemic within their own countries. All nations must be vigilant, however, to keep this disease under control.

Complications.

Respiratory failure
Liver failure
Heart failure
Myelodysplastic syndromes (bone marrow abnormalities leading to anemia, low platelet counts, and low white blood cell counts)

Call Health Care Provider. Call your health care provider if you suspect you or someone you have had close contact with has SARS.

Symptoms

General Symptoms. The symptoms of bacterial pneumonia develop very quickly and typically include:

A single episode of shaking chills followed by fever
Chest pain on the side of the infected lung. Severe abdominal pain sometimes occurs in people with pneumonia in the lower lobes of the lung.
Shortness of breath
Rapid breathing and heart beat
Cough, which may be initially dry, but eventually produces sputum
Nausea, vomiting, and muscle aches

Emergency Symptoms. Symptoms of pneumonia indicating a medical emergency include the following:

High fever
Rapid heart rate
Bluish-toned (cyanotic) skin
Labored and heavy breathing.
Mental confusion
Coughing up mucus (sputum) containing pus or blood

Symptoms in the Elderly. It is important to note that older people may have fewer or different symptoms than younger people. Symptoms may come on much more slowly. An elderly person who experiences even a minor cough and weakness for more than a day should seek medical help. Some elderly people may exhibit confusion, lethargy, and general deterioration.

Pneumonia caused by anaerobic bacteria such as prevotella (formerly called bacteroides) can produce dangerous abscesses in the lungs. People with such pneumonias may have prolonged fever and a productive cough. There is frequently blood in the mucus that is coughed up. Blood may indicate dead lung tissue. About a third of these patients experience weight loss.

General Symptoms for Atypical Pneumonias. Atypical pneumonia is most commonly caused by mycoplasma and usually appears in children and young adults.

The disease progresses gradually.

General flu-like symptoms often occur first. They may include fatigue, fever, weakness, headache, nasal discharge, sore throat, earache, and stomach and intestinal distress.
Vague pain under and around the breastbone may occur, but the severe chest pain associated with typical bacterial pneumonia is uncommon.
Patients may have a severe hacking cough, but it usually does not produce sputum.

Symptoms of Legionnaire Disease. Symptoms of Legionnaire disease usually occur more rapidly and include high fever, a dry cough, and shortness of breath. These symptoms are often accompanied by headache, muscle pains, fatigue, gastrointestinal problems, and mental confusion.

Prognosis

More than a million people are hospitalized each year for pneumonia, making it the third most frequent cause of hospitalizations (births are first, and heart disease is second). Although the majority of pneumonias respond well to treatment, the infection kills 40,000 - 70,000 people each year.

Hospitalized Patients. For patients who require hospitalization for pneumonia, the death rate is 10 - 25%. If pneumonia develops in patients already hospitalized for other conditions, death rates range from 50 - 70%, and are higher in women than in men.

Older Adults. Community-acquired pneumonia is responsible for 350,000 - 620,000 hospitalizations in the elderly every year. Older adults have lower survival rates than younger people. Even when older individuals recover from CAP, they have higher-than-normal death rates over the next several years. Elderly people who live in nursing homes or who are already sick are at particular risk.

Very Young Children. About 20% of deaths in stillborn and very young infants are due to pneumonia. Small children who develop pneumonia and survive are at risk for developing lung problems in adulthood.

Pregnant Women. Pneumonia poses a special hazard for pregnant women, possibly due to changes in a pregnant woman's immune system. This complication can lead to premature labor and increases the risk of death during pregnancy.

Patients With Impaired Immune Systems. Pneumonia is particularly serious in people with impaired immune systems. This is particularly true for AIDS patients, in whom pneumonia causes about half of all deaths.

Patients With Serious Medical Conditions. Pneumonia is also very dangerous in people with diabetes, cirrhosis, sickle cell disease, cancer, and in those whose spleens have been removed.

Specific organisms vary in their effects. Mild pneumonia is usually associated with the atypical organisms mycoplasma and chlamydia. Severe pneumonia is most often associated with a wide range of organisms. Some are very virulent (potent) but are extremely curable, while others are difficult to treat.

Mycoplasma and chlamydia are the most common causes of mild pneumonias and are most likely to occur in children and young adults. They rarely require hospitalization when they are appropriately treated, although recovery may still be prolonged. Severe and life-threatening cases are more likely to occur in elderly people with other medical conditions.
Streptococcus pneumoniae is the most common cause of pneumonia and, in fact, all bacterial upper respiratory infections. It can produce severe pneumonia, with mortality rates of 10%. Nevertheless, pneumococcal pneumonia is very responsive to many antibiotics.
Staphylococcus aureus is a Gram-positive bacterium that often causes severe pneumonia in hospitalized and high-risk patients and following influenza A and B. People who get this form of pneumonia may develop pockets of infection in their lungs (abscesses) that are difficult to treat and can cause the death of lung tissue (necrosis). Mortality rates are 30 - 40%, in part because the patients who develop this infection are generally very ill or vulnerable.
Pseudomonas aeruginosa and Klebsiella pneumoniae are Gram-negative bacteria that pose a risk for abscesses and severe lung tissue damage.
Legionella pneumophila is very virulent and can cause widespread damage. Treatments have improved dramatically since it was first identified. However, a 2002 study suggested that many patients experience long-term problems, including coughing, shortness of breath, fatigue, and neurological and muscular complications.
Viral pneumonia is usually very mild, but there are exceptions. Respiratory syncytial virus (RSV) pneumonia rarely poses a danger for healthy young adults, but it can be life-threatening in infants and serious in the elderly.

Abscess. An abscess in the lung is a thick-walled, pus-filled cavity that forms when infection has destroyed lung tissue. It typically occurs as a result of aspiration pneumonia, when a mixture of organisms is carried into the lung. Untreated abscesses can cause hemorrhage (bleeding) in the lung, but targeted antibiotic therapy significantly reduces their danger. Abscesses are more common with Staphylococcus aureus, Pseudomonas aeruginosa, or Klebsiella pneumoniae, and uncommon with Streptococcus pneumoniae.

Respiratory Failure. Respiratory failure is one of the top causes of death in patients with pneumococcal pneumonia. Acute respiratory distress syndrome (ARDS) is the specific condition that occurs when the lungs are unable to function and oxygen is so severely reduced that the patient's life is at risk. Failure can occur if pneumonia leads to mechanical changes in the lungs (ventilatory failure) or oxygen loss in the arteries (hypoxemic respiratory failure).

Bacteremia. Bacteremia, bacteria in the blood, is the most common complication of pneumococcus infection, although it rarely spreads to others sites. Bacteremia is a frequent complication of infection from Gram-negative organisms, including Haemophilus influenzae.

Pleural Effusions and Empyema. The pleura are two thin membranes that line the chest and lungs:

The visceral pleura cover the lungs.
The parietal pleura cover the chest wall.

In some cases of pneumonia the pleura become inflamed, which can result in breathlessness and acute chest pain when breathing.

In about 20% of pneumonia cases fluid builds up between the pleural membranes, a condition known as pleural effusion. Ordinarily, the narrow zone between the two membranes contains only a tiny amount of fluid, which lubricates the lungs.

In most cases, particularly in Streptococcus pneumoniae, the fluid remains sterile (no bacteria are present), but occasionally it can become infected and even filled with pus, a condition called empyema. Empyema is more likely to occur with specific organisms such as Staphylococcus aureus or Klebsiella pneumoniae infections. The condition can cause permanent scarring.

Collapsed Lung. In some cases, air may fill up the area between the pleural membranes, causing the lungs to collapse. This is called pneumothorax. It may be a complication of pneumonia (particularly Streptococcus pneumoniae ) or of the invasive procedures used to treat pleural effusion.

Pneumothorax occurs when air leaks from inside of the lung to the space between the lung and the chest wall. The lung then collapses. The dark side of the chest (right side of the picture) fills with air from outside of the lung tissue.

Other Complications of Pneumonia. In rare cases, infection may spread from the lungs to the heart and possibly throughout the body. This can cause abscesses in the brain and other organs. Severe hemoptysis (coughing up blood) is another potentially serious complication of pneumonia, particularly in patients with lung problems such as cystic fibrosis.

Kidney complications and electrolyte imbalances are common in patients admitted to the hospital with pneumonia. If not treated, these problems cause more severe illness and increase the risk of death. Treatment with intravenous saline can usually resolve the problem.

The pneumonias cased by the atypical organisms mycoplasma and chlamydia are usually mild. Some research suggests, however, that chlamydia may have powerful inflammatory effects in the blood vessels. This effect may have certain adverse long-term consequences even in healthy younger individuals.

Heart Disease and Stroke. Research has suggested that chlamydia may trigger the immune system to react, causing inflammation in the coronary arteries. Over time, this can cause hardening of the arteries (atherosclerosis). Atherosclerosis can lead to heart attacks and strokes. Studies on a causal relationship between chlamydia and heart disease have been mixed.

Click the icon to see an image of arterial plaque.

Chylamydia pneumoniae has been associated with a thickening in the carotid arteries that lead to the brain -- a risk factor for stroke. It is not clear whether the organism poses any significant risk for stroke.

Click the icon to see an image of atherosclerosis of the internal carotid artery.

Asthma. Chlamydia pneumoniae, Mycoplasma pneumoniae, and RSV are becoming suspects in many cases of severe adult asthma. One small Australian study found evidence of previous chlamydia infection in 64% of the asthmatic patients tested.

Risk Factors

Risk factors for pneumonia often depend on the specific type of disease.

CAP is the most common type of pneumonia. It develops outside of the hospital. Each year 2 - 4 million people in the US develop CAP, and 600,000 are hospitalized. The elderly, infants, and young children are at greatest risk for the disease.

Pneumonia that is contracted in the hospital is called hospital-acquired or nosocomial pneumonia. It affects an estimated 5 -10 of every 1,000 hospitalized patients every year. More than half these cases may be due to strains of bacteria that have developed resistance to antibiotics. In fact, methicillin-resistant Staphyllococcus aureus and multidrug-resistant Pseudomonas aeruginosa are leading causes of death from hospital-acquired pneumonia. The elderly, the very young, and those with chronic or severe medical conditions, are at highest risk.

In addition, the following conditions within the hospital put patients at higher risk:

Surgery, particularly in people over the age of 80. Among the surgical procedures that pose a particular risk are splenectomy (removal of the spleen), abdominal aortic aneurysm repair, or operations that impair coughing.
Being in the intensive care unit (ICU). This is particularly true for newborns or patients on breathing machines (mechanical ventilators). In one study, 10% of ICU patients on a breathing machine developed pneumonia. Such patients who lie flat on their backs are at particular risk for aspiration pneumonia. Raising the patient up may reduce this risk.
Sedation. Hospital patients who receive sedatives also have a higher risk of developing nosocomial pneumonia.
Previous use of antibiotics, particularly within 6 months.

Hospitalized patients are particularly vulnerable to Gram-negative bacteria and staphylococci, which can be especially dangerous in people who are already ill.

Chronic Lung Disease. Chronic obstructive lung diseases (COPD), which include chronic bronchitis and emphysema, affect 15 million people in the U.S. This condition is a major risk factor for pneumonia. In patients with COPD, vaccination with the pneumococcal vaccine can substantially reduce the risk of developing pneumonia or decrease its severity.

Bronchitis is the inflammation of the bronchi, the main air passages to the lungs. It generally follows a viral respiratory infection. Symptoms include coughing, shortness of breath, wheezing, and fatigue.

Click the icon to see an image of emphysema.

People With Compromised Immune Systems. People with impaired immune systems are extremely susceptible to pneumonia. It is a common problem in people with HIV and AIDS. In one study, the primary bacteria were found to be Legionella pneumophilia and Streptococcus pneumoniae. Smoking and chemotherapy for cancer were more common in those with legionella pneumonia. The patients tended to have a higher CD4 count, undetectable viral load, and more frequent need for antiretroviral therapy. Their pneumonia was more severe than in HIV patients diagnosed with pneumococcal pneumonia. Those with legionell were more likely to have respiratory failure, need ventilation, have pneumonia in both lungs, and were more likely to die. However, AIDS was more common in the patients with pneumococcal pneumonia.

In addition to AIDS, other conditions that compromise the immune system include organ transplantation, chemotherapy, and adult and pediatric cancers, especially leukemia and Hodgkin's lymphoma. Patients who are on corticosteroids or other medications that suppress the immune system are also prone to infection.

Gastroesophageal Reflux Disease. Gastroesophageal reflux disease (GERD) is a condition in which acids from the stomach move up into the esophagus. This is called reflux. Current studies indicate an association between GERD and various problems that occur in the sinuses, ears, nasal passages, and airways of the lung. People with GERD appear to have an above-average risk for chronic bronchitis, chronic sinusitis, emphysema, pulmonary fibrosis (lung scarring), and recurrent pneumonia. If a person inhales fluid (aspirates) from the esophagus into the lungs, serious pneumonia can occur. GERD may contribute to these conditions by triggering inflammation in these upper passages.

However, GERD drugs may increase one's risk. Patients at high risk for pneumonia should take gastric acid-suppressing drugs only when necessary and at the lowest possible dose. A 2004 study found that the use of gastric acid-suppressing drugs raises the risk of developing CAP. The highest risks were associated with proton pump inhibitors (PPIs) such as Prilosec and Nexium, but H2-receptor antagonists such as Tagamet and Pepcid also elevated risk. The researchers theorize that reducing levels of germ-killing stomach acid allow germs to spread in the upper gastrointestinal tract and move into the respiratory tract. The risk posed by these medications is highest in the elderly, children, and patients with asthma, COPD, and compromised immune systems.

Acute stroke. Acute stroke is a risk factor for developing pneumonia. In one German study, the incidence of stroke-associated pneumonia (SAP) was 22% in patients admitted to the intensive care following a stroke. Dysphagia, non-lacunal basal-ganglia infarction, or any infection present on admission, and National Institutes of Health Stroke Scale score greater than or equal to 10 were found to be independent risk factors for the development of SAP. Other risk factors included combined brainstem and cerebellar infarction, infarction affecting more than 66% of the middle cerebral arterial territory, hemispheric infarction exceeding middle cerebral artery territory, impaired vigilance, mechanical ventilation, age of 73 or greater, and cardioembolic stroke. Patients with lacunal strokes were found to be at less risk of SAP.

Click the icon to see an image of gastric reflux.

Dormitory or Barrack Conditions. Recruits on military bases and college students living in dormitories are at higher than average risk for Mycoplasma pneumonia. These groups are at lower risk, however, for more serious types of pneumonia.

Smoke and Environmental Pollutants. The risk for pneumonia in people who smoke more than a pack a day is three times that of nonsmokers. Those who are chronically exposed to secondhand cigarette smoke, which can injure airways and damage the cilia, are also at risk. Quitting smoking reduces the risk of dying from pneumonia to normal, but the full benefit takes 10 years to be realized. Toxic fumes, industrial smoke, and other air pollutants may also damage cilia function, which is a defense against bacteria in the lungs.

Drugs and Alcohol. Alcohol or drug abuse is strongly associated with pneumonia. These substances act as sedatives and can diminish the reflexes that trigger coughing and sneezing. Alcohol also interferes with the actions of macrophages, the white blood cells that destroy bacteria and other microbes. Intravenous drug abusers are at risk for pneumonia from infections that originate at the injection site and spread through the bloodstream to the lungs.

Fatty Diet: A diet high in fatty acids such as palm oils appears to increase the risk of CAP in young and middle-aged women by as much as 54%. Higher intake of monosaturated fats appears to decrease the risk of pneumonia.

Certain children have a higher-than-normal risk for pneumonia and recurrence. Conditions that predispose infants and small children to pneumonia include:

Impaired immune system
Leukemia
Infection with the respiratory syncytial virus (RSV)
Gastroesophageal reflux disorder
Inborn lung or heart defects
Abnormalities in muscle coordination of the mouth and throat
Asthma
Certain genetic disorders such as sickle-cell disease, cystic fibrosis, and Kartagener's syndrome, which result in poorly functioning cilia, the hair-like cells lining the airways

Diagnosis

Diagnostic Difficulties in Community-Acquired Pneumonia (CAP). It is important to determine whether the cause of CAP is a bacterium, atypical bacterium, or virus, since they require different treatments. In children, for example, S. pneumonia is the most common cause of pneumonia, but respiratory syncytial virus may also cause the disease. Although symptoms may differ, they often overlap, which can make it difficult to identify the organism by symptoms alone.

Nevertheless, in many cases of mild-to-moderate CAP, the physician is able to diagnose and treat pneumonia based solely on a history and physical examination.

Diagnostic Difficulties with Hospital-Acquired (Nosocomial) Pneumonia. Diagnosing pneumonia is particularly difficult in hospitalized patients for a number of reasons:

Many hospitalized patients have similar symptoms, including fever or signs of lung infiltration on x-rays.
In hospitalized patients, sputum or blood tests often indicate the presence of bacteria or other organisms, but such agents do not necessarily indicate pneumonia.

Doctors making a diagnosis of pneumonia should rule out other conditions, using a chest x-ray, two sets of blood cultures, a urine analysis for legionella, and a lung fluid sample, among other tests.

The patient's history is an important part of making a pneumonia diagnosis. Patients should be sure to report any of the following:

Recent or chronic respiratory infection
Exposure to people with pneumonia or other respiratory illnesses (such as tuberculosis)
History of smoking
Alcohol or drug abuse
Recent travel
Occupational risks

Use of the Stethoscope. The most important diagnostic tool for pneumonia is the stethoscope. Sounds in the chest that may indicate pneumonia include:

Rales, a bubbling or crackling sound. Rales on one side of the chest or heard while the patient is lying down are strongly suggestive of pneumonia.
Rhonchi, abnormal rumblings indicating the presence of thick fluid.
A dull thud obtained by percussion. The physician will also use a test called percussion, in which the chest is tapped lightly. A dull thud, instead of a hollow drum-like sound, indicates certain conditions suggestive of pneumonia. These conditions include including consolidation (a condition in which the lung becomes firm and inelastic), and pleural effusion (fluid build-up in the space between the lungs and the lining around it).

Although current antibiotics can destroy a wide spectrum of organisms, it is best to use an antibiotic that targets the specific one making a person sick. Unfortunately, people carry many bacteria, and sputum and blood tests are not always effective in distinguishing between harmless and harmful kinds.

In severe cases, a doctor needs to use invasive diagnostic measures to identify cause of the infection. Standard lab tests used to help diagnose pneumonia include:

Sputum Tests. The color of the mucus (sputum) sample coughed up from the lungs can reveal the severity of the disease. Only a sputum sample will reveal the infecting organism.

The patient coughs as deeply as possible to bring up mucus from the lungs, since a shallow cough produces a sample that usually only contains normal mouth bacteria. Some people may need to inhale a saline spray to produce an adequate sample. In some cases, a tube will be inserted through the nose into the lower respiratory tract to induce a deeper cough.

The physician will check the sputum for:

Blood, which means an infection is present
Color and consistency: If it is yellow, green, or brown, an infection is likely.

The sputum sample is sent to the laboratory, where it is analyzed for the presence of bacteria and to determine whether the bacteria are gram-negative or Gram-positive.

Blood Tests. The following blood tests may be performed:

White blood cell count (WBC). High levels indicate infection.
Blood cultures. Cultures are done to determine the specific organism causing the pneumonia, but they usually can not distinguish between harmless and dangerous organisms. They are accurate in only 10 - 30% of cases. Their use is generally limited to severe cases.
Detection of antibodies to S. pneumoniae. Antibodies are immune factors that target specific foreign invaders. One type of immunohistochemical test for S. pneumoniae is showing tremendous promise.
Polymerase Chain Reaction (PCR). In some difficult cases, PCR may be performed. A test makes multiple copies of the genetic material (RNA) of a virus or bacteria to make it detectable.
Procalcitonin test. This marker of systemic inflammatory response to infection is increasingly recognized as a valuable method of determining which patients need antibiotics, and when antibiotic therapy can be safely stopped. Such information is critical to preventing the development of antibiotic-resistant bacteria.

Urine Tests. Urinary antigen tests for Legionella pneumophila and Streptococcus pneumoniae may be performed in patients with severe CAP. The S. pneumoniae test takes only 15 minutes and may identify up to 77% of pneumonia cases and rule out S. pneumoniae infection in 98% of patients. It may not be useful in children.

Invasive Tests. In critically-ill patients with ventilator-associated pneumonia, physicians have tried sampling fluid taken from the lungs or trachea. The techniques enabled the physicians to identify the pneumonia-causing bacteria and start the appropriate antibiotics. However, this made no difference in the length of stay in the ICU or hospital, and there was no significant difference in outcome.

Laboratory Tests for Less Common Organisms

If uncommon organisms -- such as legionella, mycoplasma, and chlamydia -- are strongly suspected, more advanced laboratory tests may be used:

Specialized techniques can detect antibodies to the organisms in blood samples, but these antibodies, such as those responding to mycoplasma or chlamydia, are not present early enough in the course of pneumonia to permit prompt diagnosis and treatment.
PCR is useful for identifying certain atypical strains, including mycoplasma and Chlamydiapneumoniae and, possibly, Haemophilus influenzae type b, but it is expensive.
A urine test can be used to diagnose some cases of Legionnaire disease.
Specialized tests called DNA probes are being developed to detect these organisms in respiratory secretions.

X-Rays. A chest x-ray is nearly always taken to confirm a diagnosis of pneumonia.

X-rays are a form of electromagnetic radiation (like light). They are of higher energy, however, and can penetrate the body to form an image on film. Structures that are dense (such as bone) will appear white, air will be black, and other structures will be shades of gray depending on density. X-rays can provide information about obstructions, tumors, and other diseases, especially when coupled with the use of barium and air contrast within the bowel.

A chest x-ray may reveal the following:

White areas in the lung called infiltrates, which indicate infection
Complications of pneumonia, including pleural effusions and abscesses

Other Imaging Tests. Computed tomography (CT) scans or magnetic resonance imaging (MRI) scans may be useful in some circumstances, especially when:

X-ray results are unclear
Patients do not respond to antibiotics
Complications occur
Patients have other serious health problems

Click the icon to see an image of a CT scan.

CT and MRI can help detect the presence of tissue damage, abscesses, and enlarged lymph nodes. They can also detect some tumors that block bronchial tubes. No imaging technique can determine the actual organism causing the infection. However, features on CT scan of patients with certain forms of pneumonia -- for example, that caused by Legionella pneumophila -- are usually different from features produced by other bacteria in the lungs.

Invasive diagnostic procedures may be required when:

Patients have life-threatening complications
Standard treatments have failed for no known reason
AIDS or other immune problems are present

Invasive procedures include:

Thoracentesis. If a doctor detects pleural effusion during the physical exam or on an imaging study, and suspects that empyema (pus) is present, a thoracentesis is performed.

Fluid in the pleura is withdrawn using a long thin needle inserted between the ribs.
The fluid is then sent to the lab for multiple tests.

Complications of this procedure are rare, but can include collapsed lung, bleeding, and introduction of infection.

Bronchoscopy. A bronchoscopy is done in the following way:

The patient is given a local anesthetic, supplementary oxygen, and sedatives.
The physician inserts a fiber optic tube into the lower respiratory tract through the nose or mouth.
The tube acts like a telescope into the body, allowing the physician to view the windpipe and major airways and look for pus, abnormal mucus, or other problems.
The doctor removes specimens for analysis and can also treat the patient by removing any foreign bodies or infected tissue encountered during the process.

Click the icon to see an image of bronchoscopy.

Bronchoalveolar lavage (BAL) may be done at the same time as bronchoscopy. This involves injecting high amounts of saline through the bronchoscope into the lung and then immediately sucking the fluid out. The fluid is then analyzed in the laboratory. Studies find BAL to be an effective method for detecting specific infection-causing organisms.

The procedure is usually very safe, but complications can occur. They include allergic reactions to the sedatives or anesthetics, asthma attacks in susceptible patients, and bleeding. Fever may follow the procedure.

Lung Biopsy. In very severe cases of pneumonia or when the diagnosis is unclear, particularly in patients with damaged immune systems, a lung biopsy may be required. A lung biopsy involves taking some tissue from the lungs and examining it under a microscope.

Lung Tap. This procedure typically uses a needle inserted between the ribs to draw fluid out of the lung for analysis. It is known by a number of names including lung aspiration, lung puncture, thoracic puncture, transthoracic needle aspiration, percutaneous needle aspiration, and needle aspiration. It is a very old procedure that is not done often any more, since it is invasive and poses a slight risk for collapsed lung. Some experts argue, however, that a lung tap is more accurate than other methods for identifying bacteria, and the risk it poses is slight. Given the increase in resistant bacteria, they believe its use should be reconsidered in young people.

Common Causes of Persistent Coughing. Over 30 million people seek medical help each year for persistent coughing, which is nearly always temporary and harmless when other symptoms, such as fever, are not present. The four most common causes of persistent coughing are asthma, postnasal drip, gastroesophageal reflux disease (GERD), and chronic bronchitis. Other obvious common causes of chronic cough include heavy smoking or the use of heart drugs known as ACE inhibitors.

Acute Bronchitis. Acute bronchitis is an infection in the passages that carry air from the throat to the lung. The infection causes a cough that produces phlegm. Acute bronchitis is almost always caused by a virus and usually clears up on its own within a few days. In some cases, acute bronchitis caused by a cold can last for several weeks.

Chronic Bronchitis. Chronic bronchitis causes shortness of breath and is often accompanied by infection, mucus production, and coughing, but it is a long-term and irreversible condition. The same microbes that cause pneumonia can cause chronic bronchitis, and symptoms of the two disorders are often similar. They include fatigue, coughing, fever, and production of sputum. There are significant differences between chronic bronchitis and pneumonia:

Patients with bronchitis are less likely to have wheezing, shortness of breath, chills, very high fevers, and other signs of severe illness.
Those with pneumonia usually cough up heavy sputum, which is also more likely to contain blood.
X-rays of patients with bronchitis do not show fluid or consolidation in the lung.

Asthma. In asthma, the cough is accompanied by wheezing and occurs mostly at night or during activity. Fever is rarely present (unless the patient also has an infection). Asthmatic symptoms from occupational causes can cause persistent coughing, which is usually worse during the work week. Tests -- the methacholine inhalation challenge and pulmonary function studies -- may be effective in diagnosing asthma.

Anthrax. Because of current terrorist concerns, it is important to differentiate between anthrax and community-acquired pneumonia. According to one study, people with inhalation anthrax are more likely to have rapid heart rate and less likely to have headache, nasal symptoms, and muscle aches than those with pneumonia. Blood tests with anthrax also show high hematocrit and low albumin and sodium levels. Certain chest x-ray findings also raise the likelihood of anthrax.

Other Disorders that Affect the Lung. Many conditions mimic pneumonia, particularly in hospitalized patients. They include:

Tuberculosis
Bronchial asthma
Bronchiectasis, an irreversible widening of the airways usually associated with birth defects, chronic sinus or bronchial infection, or blockage
Atelectasis, a collapse of lung tissue
Heart failure. If it affects the left side of the heart, fluid build-up can occur in the lungs and cause persistent cough, shortness of breath, and wheezing.
Severe allergic reactions, such as reactions to drugs
Acute respiratory distress syndrome (ARDS)
Lung cancer
Interstitial pulmonary fibrosis, a non-infectious inflammation of the lung marked by progressive damage and scarring

Ruling Out Causes in Children. Important causes of coughing in children at different ages include:

Asthma
Physical abnormalities in infants under 18 months
Sinusitis in children 18 months to 6 years
Psychologic causes in older children and adolescents

Acute bronchitis is an infection in the passages that carry air from the throat to the lung. In such cases, the airway tubes become inflamed and collect mucus, causing a cough that produces phlegm. In 95% of cases, acute bronchitis is caused by a virus and is spread from person to person through coughing. In some cases, mycoplasma or chlamydia may be responsible.

Symptoms. The cough in acute bronchitis usually lasts for 7 - 10 days. In about half of patients, coughing can last for up to 3 weeks, and 25% of patients continue to cough for more than one month.

Complications. Acute bronchitis is usually temporary. It can last for weeks to months if the airways are not healing properly. Pneumonia should be suspected if coughing is continuous and hacking, if blood appears in the sputum, and if the patient has a high fever and signs of severe illness. These signs include shortness of breath or extreme weakness and fatigue. [See In-Depth Report #94: Colds and the flu. ]

Of particular interest and some concern are the roles of mycoplasma and chlamydia, two of the infectious organisms that cause acute bronchitis. These agents are being investigated for their roles as possible causes of asthma. Chlamydia is also being investigated as a trigger for coronary artery disease.

Treatments.

Bronchodilators. For some patients with acute bronchitis, inhaled medications called bronchodilators may be effective. These drugs relax and open the airways and may relieve symptoms and reduce the duration of the coughing. The most common bronchodilator used for acute bronchitis is albuterol (Proventil, Ventolin). It is called salbutamol outside the US. The drug is a short-acting beta-2 agonist.
Antibiotics. Acute bronchitis almost never warrants antibiotics. (Coughing caused by pneumonia, however, does require antibiotics.) A 5-year study of more than 800 patients found that those with uncomplicated acute bronchitis all recovered within the same time period, regardless of whether or not they received antibiotics. For most patients, coughing lasted an average of 12 days. For a quarter of the patients, coughing lasted 17 days.

Treatment

Patients with pneumonia are generally treated with:

Antibiotics
Respiratory support with oxygen, if needed

Up to 10% of all adult hospitalizations in the U.S. are due to pneumonia. Studies indicate that many patients are hospitalized unnecessarily for pneumonia, and those patients could be released sooner. A number of strategies are being devised to determine when and which patients can be safely discharged. Studies have shown that low-risk patients with mild-to-moderate pneumonia do just as well when treated as outpatients and return to work and normal activities faster than those treated in the hospital.

One approach for determining whether a patient should be hospitalized categorizes patients into 5 classes depending on risk factors for severity, with class 1 being the least severe (having less than a 0.5% risk for death) and class 5 being the most severe (having at least a 10% risk of death).

Ruling out the Least Severe Cases. The procedure for determining the need for hospitalization starts by selecting patients in the lowest risk groups (classes 1 and 2) who can be discharged with outpatient care only. This can often be done with a simple physical examination, which can rule out a severe condition. Patients in low-risk categories have the following characteristics:

Under age 50 and not a patient in a nursing home
No other major illnesses
No serious symptoms such as altered mental state, breathing problems, bluish skin, very low blood pressure, or very high fever

Even these criteria, however, are flexible. Physicians must use their own judgment and take all factors into consideration. As examples, the following young people with signs of pneumonia should be hospitalized, even if they otherwise fit low-risk (class 1) categories:

Any infant under the age of one month
Young adults with alcoholism or severe psychiatric condition
Young adults or children with abnormal heart rhythm
Young adults or children who are vomiting heavily
Children who are dehydrated

Determining The Next Levels of Severity. If a patient is not in a class 1 category or does not appear to need hospitalization, the next step is to determine which of the other 4 higher classes the patient fits into. This step involves assigning points to other findings, including:

Laboratory test results
X-ray findings
Demographics (Is the patient male or female? Does the patient live in a nursing home?)

The points are added and the patients are scored:

Patients who score the lowest are assigned class 2 and 3. They can usually be treated at home or need only to be hospitalized for 24 hours for observation.
Patients with higher scores are placed in classes 4 and 5, and are hospitalized.

Home care may be possible even in severe cases when there is good support and available home nursing services. Often, caregivers can even be trained to administer intravenous antibiotics and chest therapy to patients at home.

Joint guidelines issued in 2007 by the Infectious Disease Society of America and the American Thoracic Society (ITSA/ATS) recommend that mild CAP in otherwise healthy patients be treated with oral macrolide antibiotics (azithromycin, clarithromycin, or erythromycin).

Many patients with heart disease, kidney disease, diabetes, or other comorbid conditions may still be treated as outpatients. However, they should be given a fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin) or a beta-lactam (preferably high-dose amoxicillin or amoxicillin-clavulanate), plus a macrolide, unless they live in an area with high S. pneumoniae resistance to macrolides.

The following tips are also suggested:

Drink plenty of liquids.
Do not suppress a cough. Coughing is an important reflex for clearing the lungs. Some doctors advise taking expectorants, such as guaifenesin (Breonesin, Glycotuss, Glytuss, Hytuss, Naldecon Senior EX, Robitussin) to loosen mucus. However, there is no proof that any of these products make much difference in outcome.
Mild pain can be treated with aspirin (in adults only), acetaminophen (Tylenol), or ibuprofen (Advil, Motrin).
For severe pain, codeine or other stronger pain reliever may be prescribed. It should be noted, however, that codeine and other narcotics suppress coughing, so they should be used with care in pneumonia. Such pain relievers often require monitoring.
A laboratory study reported that aromatic oils containing oregano, thyme, and rosewood destroyed S. pneumoniae. It is not known whether they have any effect on pneumonia in people.
Patients should practice chest therapy.

Treatment. If the pneumonia is severe enough for hospitalization, the standard treatment is intravenous administration of antibiotics for 5 - 8 days. In cases of uncomplicated pneumonia, many patients may require only 2 or 3 days of intravenous antibiotics followed by oral therapy. Antibiotics taken by mouth are prescribed when the patient has improved substantially or leaves the hospital.

ITSA/ATS guidelines recommend patients admitted to the hospital (but not the ICU) be treated with fluoroquinolones or a beta-lactam plus a macrolide (preferably cefotaxime or ceftriaxone and ampicillin).

Duration of Stay. Patients should remain in hospital until all their vital signs are stable. Most patients become stabilized in 3 days. Many experts use 7 variables to measure stability and to determine whether the patient can go home:

Temperature. (Some experts believe that patients can go home when their temperature drops to 101° F. Stricter criteria require that it be at or close to 98.6° F.)
Respiration rate. (Goal is a normal breathing rate, although expert opinion differs on the degree of normality required to be discharged.)
Heart rate. (Goal is 100 beats per minute or less.)
Blood pressure. (Goal is systolic blood pressure of 90 mmHg or greater.)
Oxygenation. (Goal is determined by the physician.)
The ability to eat. (Goal is regular appetite.)
Mental function. (Goal is normal.)

Patients or their families should discuss these criteria with their doctor. In a 2002 study, 42% of patients who had 2 or more signs of instability when they left the hospital were either readmitted or died within 30 days, compared with 10.5% of completely stabilized patients.

Chest therapy using incentive spirometry, rhythmic inhalation and coughing, and chest tapping are all important techniques to loosen the mucus and move it out of the lungs. It should be used both in the hospital and during recovery at home.

Incentive Spirometry. The patient uses an incentive spirometer at regular intervals to improve breathing and loosen sputum. The spirometer is a hand-held clear plastic device that includes a breathing tube and a container with a movable gauge. The patient exhales and then inhales forcefully through the tube, using the pressure of the inhalation to raise the gauge to the highest level possible.

Rhythmic Breathing and Coughing. During recovery, the patient performs rhythmic breathing and coughing every 4 hours:

Before starting the breathing exercise, the patient should tap lightly on the chest to loosen mucus within the lung. If available, a caregiver should also tap on the patient's back.
The patient inhales rhythmically and deeply 3 or 4 times.
The patient then coughs as deeply as possible with the goal of producing sputum.

Medications

Dozens of antibiotics are available for treating pneumonia, but selecting the best drug is sometimes difficult. Patients with pneumonia need an antibiotic that is effective against the organism causing the disease. When the organism is unknown, "empiric therapy" is given, meaning the doctor guesses which antibiotic is likely to work based on factors such as the patients' age, health, and severity of the illness.

In determining the appropriate antibiotic, the physician must first answer a number of questions:

How severe is the pneumonia? Mild-to-moderate cases can be treated at home with oral antibiotics, while severe pneumonia usually requires intravenous antibiotics administered in the hospital.
If the organism causing the pneumonia is not known, was the disorder community- or hospital-acquired? Different organisms are usually involved in each setting, and the physician can use this information to guess the most likely organism causing the pneumonia.
If the organism is known, is it typical or atypical? Community-acquired pneumonias, for example, are usually caused by the typical bacteria Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis, which have traditionally been treated with penicillin or other standard antibiotics. These antibiotics do not affect atypical organisms, such as legionella, mycoplasma, or chlamydia. These organisms are generally treated with a macrolide or possibly a newer quinolone.
Does the patient have an impaired immune system? Antibiotics used to treat such patients may differ from those used in patients with healthy immune systems.

Once an antibiotic has been chosen, there are still difficulties:

Individuals respond differently to the same antibiotic, depending on age, health, size, and other factors.
Patients can be allergic to certain antibiotics, thus requiring alternatives.
Patients may harbor strains of bacteria that are resistant to certain antibiotics.

For a more detailed discussion of the different types of antibiotics, see the "Antibiotic Classes" section below.

Many cases of community-acquired pneumonia are caused by S. pneumoniae, Gram-positive bacteria that usually respond to antibiotics known as beta-lactams (which include penicillin,) and to macrolides. However, resistant strains of S. pneumoniae are increasingly common. Most resistant strains respond to fluoroquinolines such as levofloxacin (Levaquin), gemifloxacin (Factive) or moxifloxacin (Avelox), or to ketolides (telithromycin).

In addition, other important causes of CAP, particularly in younger people, are atypical bacteria, which respond to macrolides (erythromycin, clarithromycin, or azithromycin), to ketolides, or to newer fluoroquinolones.

Antibiotic treatment for CAP is determined by a number of factors, including the patient's history of antibiotic therapy, co-existing diseases (such as COPD, diabetes, and heart failure), and whether the patient is well enough to be treated at home or requires hospitalization or nursing home care. Treatment options can include a single drug, such as levofloxacin or doxycycline, or combination treatment, such as a macrolide administered with a beta-lactam.

Antibiotics taken by mouth are generally sufficient for patients whose CAP is mild enough to be treated at home. Intravenous antibiotics are required for hospitalized patients with CAP. Antibiotic therapy should be given for a minimum of 5 days -- longer if the patient still has a fever and more than one sign of clinical instability.

Gram-Positive Pneumonia. S. aureus is a common cause of hospital-acquired pneumonia and is a potentially life-threatening infection. Resistance to penicillin is the rule in these cases, but certain specialized penicillins such as nafcillin may be effective. The alternatives to penicillins are first- or second generation cephalosporins. Unfortunately, resistance to these agents is increasing as well. Vancomycin is used for highly resistant bacteria.

Gram-Negative Pneumonia. Patients with hospital-acquired pneumonia are at high risk for infection from Gram-negative organisms such as Pseudomonas aeruginosa and Klebsiella pneumonia, which require aggressive therapy. Powerful antibiotics used against these organisms include the fourth-generation cephalosporins, carbapenems, or ciprofloxacin alone or in combination with an aminoglycoside (entamicin or tobramycin). A pilot study of inhaled (aerosol) tobramycin showed the novel form of this aminoglycoside to be as effective against P. aeruginosa as its intravenous formulation. Multidrug therapy may be necessary, particularly for patients on mechanical ventilators, who are at very high risk for multiple dangerous organisms. A 2006 study of high-dose ampicillin-sulbactam for multidrug-resistant (MDR) Acinetobacter baumannii pneumonia showed the combination to be 66.7 - 77.8% successful in curing critically ill, ventilator-dependent patients of the bacterial infection.

Trimethoprim-sulfamethoxazole is the first choice for both preventing and treating P. Jiroveci (formerly called P. carinii) pneumonia in HIV-positive patients. Clindamycin-primaquine may be used in patients who do not respond to standard therapies.

A study of children with leukemia found atovaquone to be an excellent alternative for preventing P. jiroveci pneumonia in children who cannot tolerate trimethoprim-sulfamethoxazole, the current standard preventing therapy.

Most antibiotics have the following side effects (although specific antibiotics may have other side effects or fewer of the standard ones).

The most common side effect for nearly all antibiotics is stomach problems.
Antibiotics raise the risk of vaginal infections. Taking acidophilus supplements or eating yogurt with active acidophilius cultures may help restore healthy bacteria that offset the risk for such infections.
Overuse of antibiotics can cause infection with Clostridium difficile, a pathogen responsible for causing severe diarrhea, colitis, and abdominal pain. It can be fatal.
Allergic reactions can occur with all antibiotics, but are most common with medications derived from penicillin or sulfa. These reactions can range from mild skin rashes to rare but severe -- even life-threatening -- anaphylactic shock.
Certain drugs, including some over-the-counter (OTC) medications, interact with antibiotics. Patients should inform the physician of all medications and OTC preparations they are taking and of any drug allergies they might have.

Beta-Lactams

Beta-lactam antibiotics share common chemical features. They include penicillins, cephalosporins, and some newer similar agents. They interfere with bacterial cell walls.

Penicillins. Penicillin was the first antibiotic. There are many forms to this still-important agent:

Natural penicillins include penicillin G (for intravenous use) and V (for oral use).
Penicillin derivatives called aminopenicillins, particularly amoxicillin (Amoxil, Polymox, Trimox, Wymox, or any generic formulation), are now the most common penicillins used. Amoxicillin is inexpensive and, at one time, was highly effective against S. pneumoniae. Unfortunately, bacterial resistance to amoxicillin has increased significantly, both among S. pneumoniae and H. influenzae. Ampicillin is similar and is an alternative to amoxicillin, but requires more doses and has more severe gastrointestinal side effects.
Amoxicillin-clavulanate (Augmentin) is an augmented penicillin that works against a wide spectrum of bacteria. An extended release form has been approved for treating adults with community-acquired pneumonia caused by bacterial strains that have become resistant to penicillin.
Antistaphylococcal penicillins were developed to treat Staphylococcus aureus. The standard drug was methicillin, but it is no longer used routinely due to very high rates of resistance in hospital-acquired pneumonias. Resistance in community-acquired Staphylococcus aureus is also increasing. Alternatives include vancomycin and linezolid.
Certain penicillins used against Pseudomonas aeruginosa include ticarcillin and piperacillin. Piperacillin is more effective that ticarcillin.

Many people have a history of an allergic reaction to penicillin, but research suggests that the allergy may not recur in a significant number of adults. Skin tests are available to help determine if those with a history of penicillin allergies could use these important antibiotics.

Cephalosporins. Most of these agents are not very effective against bacteria that have developed resistance to penicillin. They are classed according to their generation:

First generation includes cephalexin (Keflex), cefadroxil (Duricef, Ultracef), and cephradine (Velosef).
Second generation includes cefaclor (Ceclor), cefuroxime (Ceftin), cefprozil (Cefzil), and loracarbef (Lorabid),
Third generation includes cefpodoxime (Vantin), cefdinir (Omnicef) cefditoren (Sprectracef), cefixime (Suprax), and ceftibuten (Cedex). Ceftriaxone (Rocephin) is an injected cephalosporin. These are effective against a wide range of Gram-negative bacteria. Cefditoren has also been shown to be 85% effective against Haemophilus influenzae and 90% effective against penicillin-resistant strains of S. pneumoniae.

Other Beta-Lactam Agents. Carbapenems include meropenem (Merrem), biapenem, faropenem, ertapenem (Invanz) and combinations (imipenem/cilastatin [Primaxin]). These agents cover a wide spectrum of bacteria. They are now used for serious hospital-acquired infection and for bacteria that have become resistant to other beta-lactams. Imipenem has serious side effects when used alone, so it is given in combination with cilastatin to offset these adverse effects. The newer agents are less toxic, although they may not be as potent.

Sanfetrinem, a novel beta-lactam antibiotic known as a trinem is proving to be effective against S. pneumoniae,H. influenzae, and M. catarrhalis.

Ceftobiprole is an investigational beta-lactam in phase III clinical trials for methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant streptococci, and other Gram-negative pathogens. Other anti-MRSA beta-lactams in clinical development include CS-023/RO-4908463, a carbapenem, and ceftaroline, a cephalosporin (PPI-0903).

Fluoroquinolones

Fluoroquinolones (quinolones) interfere with the bacteria's genetic material to prevent reproduction.

Ciprofloxacin (Cipro), a second-generation quinolone, remains the most potent quinolone against Pseudomonas aeruginosa. It is not very effective for Gram-positive bacteria such as Streptococcus pneumoniae.
"Respiratory" quinolones are currently the most effective drugs available for a wide range of bacteria. Such drugs include levofloxacin (Levaquin), sparfloxacin (Zagam), and gemifloxacin (Factive). Some of the newer fluoroquinolones only need to be taken once a day.
The fourth generation quinolones Moxifloxacin (Avelox) and clinafloxacin, which is still under development, are proving to be effective against anaerobic bacteria.

S. pneumoniae -- strains resistant to the "respiratory" quinolones are uncommon in the U.S., but resistance is dramatically increasing.

Many quinolones cause side effects, including sensitivity to light and neurologic, psychiatric, and heart problems. Pregnant women should not take these agents. The drugs also enhance the potency of oral anti-clotting agents.

Macrolides, Azalides, and Ketolides

Macrolides and azalides also affect the genetics of bacteria. They include:

Erythromycin
Azithromycin (Zithromax, Zmax)
Clarithromycin (Biaxin)
Roxithromycin (Rulid)

These antibiotics are effective against atypical bacteria such as mycoplasma and chlamydia. They are also used in some cases for S. pneumoniae and M. catarrhalis, but there is increasing bacterial resistance to these agents. All but erythromycin are effective against H. influenzae. Macrolide-resistance rates doubled between 1995 and 1999 as more and more children were being treated with these antibiotics. Some research suggests these agents may reduce the risk of a first heart attack in some patients by reducing inflammation in the blood vessels.

Extended-release (ER) azithromycin (Zmax) is the first anti-pneumonia antibiotic that can be given in a single dose. It is effective against Gram-positive, Gram-negative, and atypical pathogens. Studies have shown the results to be equal (noninferior) to that acheived with 7 days of levofloxacin or clarithromycin ER in patients wtih CAP. A single-dose antibiotic decreases the likelihood that a patient will discontinue taking the antibiotic early, which rapidly contributes to the development of drug-resistant bacteria.

Ketolides. Ketolides are a new class of antibiotic drugs. They are derived from erythromycin and were developed to combat organisms that have become resistant to macrolides. Telithromycin (Ketek), the first antibiotic in the ketolide class, was approved by the FDA in 2004 for treatment of community-acquired pneumonia (CAP).

In February 2007, the FDA withdrew approval of Ketek for treatment of acute bacterial sinusitis. The agency decided that the serious risks of telithromycin outweigh its benefits for sinusitis treatment. The decision followed several 2006 reports of patient deaths due to severe liver damage. Telithromycin is approved for treatment only of CAP. The drug carries a black box warning noting the potentially serious side effects, including liver failure, vision problems, loss of consciousness, and neuromuscular problems.

Tetracyclines

Tetracyclines inhibit bacterial growth. They include doxycycline, tetracycline, and minocycline. They can be effective against S. pneumoniae and M. catarrhalis, but bacteria that are resistant to penicillin are also often resistant to doxycycline. The side effects of tetracyclines include skin reactions to sunlight, burning in the throat, and tooth discoloration.

Aminoglycosides

Aminoglycosides (gentamicin, kanamycin, tobramycin, amikacin) are given by injection for very serious bacterial infections. They can be given only in combination with other antibiotics. Some are available in inhaled forms or by applying a solution directly to mucous membranes, skin, or body cavities. They can have very serious side effects, including hearing damage, balance problems, and kidney damage.

Lincosamide

Lincosamides prevent bacteria from reproducing. The most common lincosamide is clindamycin (Cleocin). This antibiotic is useful against S. pneumoniae and S. aureus, but not against H. influenzae.

Glycopeptides

Glycopeptides (vancomycin, teicoplanin) are used for Staphylococcus aureus infections that have become resistant to standard antibiotics. The drug can be taken by mouth or given intravenously. The latest generation of glycopeptides, a derivative of vancomycin, is called telavancin. Currently in phase III studies of hospital-acquired pneumonia, it looks positive for the treatment of Gram-positive pneumonia.

Trimethoprim-Sulfamethoxazole

Trimethoprim-sulfamethoxazole (Bactrim, Cotrim, Septra) is less expensive than amoxicillin. It is particularly useful for adults with mild bacterial upper respiratory infections who are allergic to penicillin. The drug is no longer effective against certain streptococcal strains. It should not be used in patients whose infections occur after dental work, or in people allergic to sulfa drugs. Allergic reactions can be very serious.

Oxazolidinone

Linezolid (Zyvox) is the first antibacterial drug in a new class of synthetic antibiotics called oxazolidinones. It has been shown to work against certain aerobic Gram-positive bacteria.

Other Agents

Inhaled polymyxin, a drug used in cystic fibrosis patients, is showing efficacy against pneumonia caused by multidrug-resistant Gram-negative bacteria, including pseudomonas and klebsiella.

Prevention of RSV. Two agents have been approved for protecting high-risk infants against RSV pneumonia:

Palivizumab (Synagis) is known as a monoclonal antibody, a genetically engineered antibody that targets the RSV virus. It is given by an injection into the muscle. Early studies of motavizumab, another monoclonal antibody in development, also show potent protection against RSV.
RSV immune globulin (RespiGam) is made up of antibodies to RSV that are obtained from the blood of healthy infants. RespiGam is given as a shot.

Treatment of RSV. Ribavirin is the first treatment approved for RSV pneumonia, although it has only modest benefits. The American Academy of Pediatrics recommends it for children at high risk for serious complications of RSV. In one study, a combination of ribavirin with RSV immune globulin was more effective than either drug used alone.

Drugs called bronchodilators, which open up the airways, are sometimes used to treat RSV infection. However, evidence is conflicting. One study involving albuterol, a common bronchodilator, found that epinephrine may be more effective.

Surgery

Although most patients with pneumonia do not require invasive therapy, it may be necessary in patients with abscesses, empyema, or certain other complications.

Thoracotomy is the standard surgery for pneumonia. It requires general anesthesia and an incision to open the chest and view the lungs. This procedure allows the surgeon to remove dead or damaged lung tissue. In severe cases, the entire lobe of the lung is removed. This is calledalobectomy. Remaining healthy lung tissue re-expands after surgery to make up for tissue that has been removed.

Chest tubes are used to drain infected pleural fluid. Tubes are not typically required for pneumonia or abscesses. The tubes are inserted after the patient is given a local anesthetic. They remain in place for 2 - 4 days, and are removed in one quick movement. This can be very distressing, although some patients experience no discomfort. Complications of chest tubes include infection, accidental injury of the lung, perforation of the diaphragm, and fluid build-up within the lung if the pleural fluid is removed too rapidly. Removing the chest tubes may cause the lung to collapse, requiring the reintroduction of a chest tube to inflate the lung.

Click the icon to see an illustrated series detailing chest tube insertion.

Prevention

The best way to prevent serious respiratory infections such as pneumonia is to avoid those who are sick (if possible), and to practice good hygiene. [See In-Depth Report #94: Colds and influenza.]

Colds and flu are spread primarily from infected persons who cough or sneeze. A very common method for transmitting a cold is by shaking hands. Hands should always be washed before eating and after going outside. Using ordinary soap is sufficient. Alcohol-based gels are also effective for every day use, and may even kill cold viruses. If extreme hygiene is required, alcohol-based rinses are needed.

Antibacterial soaps add little protection, particularly against viruses. In fact, one study suggests that common liquid dish washing soaps are up to 100 times more effective than antibacterial soaps in killing respiratory syncytial virus (RSV). Wiping surfaces with a solution that contains one part bleach to 10 parts water is very effective in killing viruses.

Bacteria abound in hospitals and long-term care facilities, and are particularly virulent in areas with the sickest patients, such as intensive care units. Health care facilities are revising many of their practices and educating physicians, nurses, and therapists how to reduce the likelihood of transmitting bacteria.

A Swiss study found that coating endotracheal tubes with a solution of silver chloride and silver salts inhibited the growth of bacteria and reduced the transmission of Pseudomonas aeruginosa.
Another more widely adopted method involves the daily use of oral antibiotics to clean the mouths of patients on ventilators. This practice has been shown to lower the incidence of ventilator-associated pneumonia.

Foods Containing Lactobacilli (Good Bacteria). Friendly bacteria inside the intestines may help keep you healthy. Researchers are studying the possible protective value of certain strains of lactobacilli bacteria found in the intestines. One such strain is acidophilus, which is used to make yogurt. According to a Finnish study, children attending day care who drank milk containing the strain lactobacilli GG reduced their risk of respiratory infections by 10 - 20%. More research is needed. (The strain used in the Finnish study was not the kind found in most commercial yogurt products.)

Vitamins. Studies are mixed when it comes to whether or not vitamin supplements protect against upper respiratory infections. Large doses of vitamin C, for example, may help reduce the duration of a cold, but they do not appear to protect against one in the first place. Two studies in 2002 on multivitamins reported opposite results, with one finding fewer infections and one finding no difference. It is possible that vitamin C or multivitamin supplements may be helpful in specific people, such those who are vitamin deficient or have medical problems that impair their immune systems.

A review of more than 134,000 Swiss patients found that use of cholesterol-lowering statin drugs was associated with a significantly lower risk of fatal pneumonia and a somewhat lower risk of less-severe pneumonia.

Breast-feeding. Some evidence suggests that women who breast-feed reduce the risk of respiratory infections in their children.

Low Stress and Active Social Life. Several studies have reported that socially active people with low stress have fewer colds than people who have high stress levels or those who have low stress and few social connections.

Zinc appears to have certain important effects on the immune system, and it may have a direct effect on viruses. Zinc preparations in lozenge or nasal gel form are now available as cold treatments. However, research findings regarding the benefits of zinc have varied. (The differing results may be due to different zinc preparations.)

A nasal gel containomg zinc gluconate has shown some success, possibly because the gel sticks to the nasal passages long enough for the zinc to interact with the virus. In a 2003 study, patients who took the nasal gel within 14 - 48 hours of getting sick had less severe symptoms and felt better faster than those who took a placebo. The finding supports earlier studies reporting that Zicam shortened the duration of a cold by about two days.
Zinc lozenges are showing mixed results. One 2000 study suggested that the use of zinc acetate lozenges (e.g., Fast-Dry, Galzin) may be more effective and have a better taste than other formulations, such as zinc gluconate (Cold-Eeze, Orazinc). On the other hand, a 2002 study reported that zinc gluconate reduced the duration of colds significantly. To further confuse matters, the two zinc lozenge preparations were directly compared in a 2000 study, and neither was effective. The reasons for these conflicting results are not clear.
A small 2001 study on a nasal spray preparation found no benefits. The spray preparation had less zinc than the nasal gel.

In any case, no one with an adequate diet and a healthy immune system should take zinc for prolonged periods for preventing colds.

Side Effects of Zinc. Side effects include:

Dry mouth
Constipation
Nausea
Bad taste (possibly only with zinc gluconate lozenges)
Overdose may cause severe vomiting, dehydration, and restlessness. Call a physician if any of these symptoms occur.
In rare cases, an allergic response may occur.

Food and Drug Interactions. Zinc may also interact with drugs or other elements.

It may reduce absorption of certain antibiotics.
Foods high in calcium or phosphorus may reduce zinc absorption.
Used in high doses for long periods of time, zinc can cause copper deficiencies.

Herbal remedies and dietary supplements are not regulated by the FDA. This means that manufacturers and distributors do not need FDA approval to sell their products. In addition, any substance that affects the body's chemistry can, like any drug, produce side effects that may be harmful. There have been a number of reported cases of serious and even deadly side effects from herbal products.

The following are special concerns for people taking natural remedies for colds:

Echinacea. The herbal remedy echinacea is commonly taken to prevent onset and ease symptoms of cold or flu. Studies have been mixed on its effectiveness. It is difficult to test, however, since it is available in different species (notably, E. purpurea and E. augustifolia ), and preparations vary from using extracts to dried forms of the root, the herb, or the whole plant. If echinacea is helpful at all, it may be more effective taken before symptoms develop than during the cold or flu. However, evidence suggests that it is not helpful at all. In addition, allergic reactions have been reported. People with autoimmune diseases or who have plant allergies should avoid taking it. There have also been some reports of a reaction called erythema nodosum associated with echinacea. This involves a rash, sometimes accompanied by fever, headache, muscle and joint aches, and sore throat.
Grapeseed extract is sometimes touted as a natural antihistamine. A 2002 study, however, reported no benefits from it.
Chinese herbal cold and allergy medications may contain trace amounts of aristolochic acid, a chemical that is toxic to the kidneys and considered a carcinogen. Products containing aristolochic acid have been associated with several reports of kidney failure in Europe. Of specific concern are studies suggesting that up to 30% of herbal patent remedies imported from China having been laced with potent pharmaceuticals such as phenacetin and steroids. Most reported problems occur in herbal remedies imported from Asia, with one study reporting a significant percentage of such remedies containing toxic metals.

Brands and Benefits. Zanamivir (Relenza) and oseltamivir (Tamiflu) are called neuraminidase inhibitors. They are newer agents that have been designed to block a key viral enzyme called neuraminidase, which helps viruses spread (replicate).

Both zanamivir and oseltamivir have the following benefits:

Neuraminidase inhibitors are effective for treating both A and B strains of influenza. M2 inhibitors, which prevent the virus from reproducing, are only effective against type A.
They shorten the duration of the flu by 1 - 3 days.
They may help reduce transmission of the virus, although evidence is needed to confirm these findings.
They may have a lower risk than M2 inhibitors for emerging viral strains that are resistant to their effects. In January 2006, the Centers for Disease Control and Prevention (CDC) released a Heath Alert (the highest level of importance) regarding the use of M2 inhibitors (amantadine and rimantadine) for the prevention or treatment of flu. Due to significant increase in influenza A resistance to this class of antiviral medication, the CDC recommended against its use for the remainder of the 2005 - 2006 flu season.
Oseltamivir has been shown to prevent influenza from progressing to pneumonia in 50% of children who were given the drug within 1 day of being diagnosed with the flu.
They have fewer serious side effects than the M2 inhibitors.
Both have some benefits for preventing influenza. Only oseltamivir has been approved for this purpose, however, and only in people over age 13.

Limitations and Side Effects. Although they have many advantages compared to the M2 inhibitors, they are much more expensive. They also need to be taken within 2 days of symptoms to be effective. There are also some differences between the two agents that could be significant for some individuals:

Zanamivir (Relenza) is administered as a nasal spray or inhaler. People with asthma or other lung disorders may experience airway spasms and should use this drug with caution. Side effects are minor in most patients. Of concern, however, was a 2001 British study, which found that a majority of elderly patients were not able to properly use the zanamivir (Relenza) inhaler device, rendering the medicine virtually ineffective. The study was small, however, and other reports suggest that zanamivir is sill effective in this older group.
Oseltamivir comes in capsule and liquid form. Side effects are also minor, but about 10 - 15% of patients experience nausea and vomiting. Patients with kidney dysfunction should take lower doses.

To date both M2 inhibitors and oseltamivir have been approved for prevention of influenza.

M2 inhibitors. Amantadine and rimantadine protect against the influenza A infection itself in about half of individuals. Rimantadine is preferred for prevention during outbreaks of influenza A because it has fewer adverse side effects. Unfortunately, a majority of influenza A strains are now resistant to both M2 inhibitors.
Neuraminidase Inhibitors. Both zanamivir (Relenza) and oseltamivir (Tamiflu) help prevent both influenza A and B. Only oseltamivir has been approved for this purpose, however, and only in people over 13. Both appear to be very effective in preventing influenza in people who have been exposed to family members with the flu.

Antiviral drugs are not a substitute for vaccines, but they are extremely important add-on therapy for people in certain high-risk groups. They may also be used:

In combination with the flu vaccine during seasons where there is a poor match between the virus and vaccine.
In high-risk individuals who are vaccinated after the flu season has started. In such cases, it takes about 2 weeks (or longer in children) for the vaccine to take effect. The anti-viral drugs offer protection during that period.
As supplementary protection for vaccinated people in high-risk groups, such as the elderly or people with compromised immune systems.
In people who cannot have vaccinations for whatever reason.
For people who provide care for high-risk individuals.
For high-risk individuals who cannot or will not be vaccinated.

Viral Influenza Vaccines (Flu Shot)

Description of Vaccines. Vaccines against the flu (or a "flu shot") use inactivated (not live) viruses. They are designed to provoke the immune system to attack antigens contained on the surface of the virus. Antigens are foreign molecules that the immune system specifically recognizes and targets for attack.

Antigens are large molecules (usually proteins) on the surface of cells, viruses, fungi, bacteria, and some non-living substances such as toxins, chemicals, drugs, and foreign particles. The immune system recognizes antigens and produces antibodies that destroy them.

Unfortunately, the antigens in these influenza viruses undergo genetic alterations (called antigenic drift) over time, so they are likely to become resistant to a vaccine that worked in the previous year. Vaccines must be redesigned annually to match the current strain.

Influenza A. The influenza A virus is further categorized by primary molecular antigens (hemagglutinin and neuraminidase), which serve as the targets for the vaccines. Influenza A is a particular problem because it can infect other species, such as pigs or chickens, and undergo major genetic changes.
Influenza B viruses tend to be more stable than influenza A viruses, but they too vary. Although influenza B has been far less common than A, a vaccine for type B is important because experts are concerned that small children who have not developed immunity to the virus will experience severe flu if they are exposed to type B.

A live but weakened intranasal vaccine (FluMist) for healthy people aged 5 - 49 years is approved by the FDA. It is known as a live, attenuated, trivalent, intranasal influenza vaccine (LAIV). The vaccine is engineered to grow only in the cooler temperatures of the nasal passages, not in the warmer lungs and lower airways. It boosts the specific immune factors in the mucous membranes of the nose that fight off the actual viral infections. FluMist is a nasal spray. In one study it protected up to 93% of children against the flu.

Timing and Effectiveness of the Vaccine. Ideally, people should get a flu shot every October or November. However, it may take longer for a full supply of the vaccine to reach certain locations. In such cases, the high-risk groups should be served first.

Antibodies to the influenza virus usually develop within 2 weeks of vaccination. Immunity peaks within 4 - 6 weeks, then gradually wears off. That is why most people should get a flu shot every year.

In healthy adults, the flu shot reduces the chance of illness by 70 - 90%. The current flu vaccines may be slightly less effective in the elderly and those with certain chronic diseases. Even in people with weak immune systems, however, the vaccine usually protects against serious flu complications, particularly pneumonia. In fact, among the elderly, interesting studies are now suggesting that influenza vaccination may help protect against stroke, adverse heart events, and death from all causes.

Children Who Should Be Vaccinated.The American Academy of Pediatrics (AAP) and the CDC recommend flu shots for all healthy children 6 - 23 months of age. The flu shot is not approved for children less than 6 months of age.

In addition, any child over the age of 2 years who has a condition that requires regular medical care or who has been hospitalized for a serious illness (particularly lung or kidney disease, diabetes, sickle cell anemia, or immune deficiencies) should also receive a flu shot. Children who are receiving long-term aspirin therapy should also be immunized against the flu, because they are at higher risk for Reye syndrome, a life-threatening disease, if they get the flu.

Children with Asthma. Recent and major studies have found that the flu shot is safe for children with asthma. It is very important for these patients to reduce their risk for respiratory diseases. Unfortunately, 90% of asthma patients remain unvaccinated.

Older Children and Adults Who Should Be Vaccinated. The following, in order of priority, are the population groups who should be vaccinated each year. The first two groups have the highest need for influenza vaccinations and are given top priority:

All adults age 65 and older. Older adults who receive a flu shot have lower hospitalization rates than those who don't. Evidence now suggests that vaccination may help protect against adverse heart events (including after heart surgeries), stroke, and death from all causes in the elderly. Still, studies suggest that only two-thirds of this group are vaccinated, mostly because of unwarranted fears of ineffectiveness or adverse effects.
People of any age at high risk for serious complications from influenza. Such people include those with heart disease, lung problems, immune deficiencies, diabetes, kidney disease, or chronic blood disease. While there have been concerns about the safety of the vaccinations in certain high-risk patients, such as those with HIV or asthma, studies now suggest that the vaccine is generally safe in these patient groups. Furthermore, their risk for serious complications from influenza outweighs any potential adverse effects from the vaccines.
Adults ages 50 - 64 with chronic medical conditions. The US Advisory Committee on Immunization Practices (ACIP) suggests that all adults over age 50 be vaccinated, although this is not recommendation of the CDC.

Other adults who should consider influenza vaccinations include:

People at risk for flu complications who are traveling to the tropics at any time or to the Southern Hemisphere between April and September.
Pregnant women who are at risk for flu complications who will be in their second or third trimester during flu season. (Vaccinations should usually be given after the first trimester.)
Health care providers with direct patient contact, child care providers, and residents of long-term care facilities should also be vaccinated.

Side Effects. Possible side effects include:

Allergic Reaction. Newer vaccines contain very little egg protein, but an allergic reaction still may occur in people with strong allergies to eggs.
Soreness at the Injection Site. Up to two-thirds of people who receive the influenza vaccine develop redness or soreness at the injection site for 1 - 2 days afterward.
Flu-like Symptoms. Some people actually experience flu-like symptoms, called oculo-respiratory syndrome, which include cough, wheezing, tightness in the chest, and sore throat. Such symptoms tend to occur 2 - 24 hours after the vaccination and generally last up to 2 days. These symptoms are not the flu itself, but are an immune response to the virus proteins in the vaccine. (Anyone with a fever at the time the vaccination is scheduled, however, should wait to be immunized until the ailment has subsided.)
Guillain-Barre Syndrome. Isolated cases of Guillain-Barre syndrome occurred in about one of every 100,000 people vaccinated with the swine-flu vaccine in 1976, but it has not been a problem with subsequent vaccines. Guillain-Barre disease can cause paralysis.

The pneumococcal vaccine protects against S. pneumoniae bacteria, the most common cause of respiratory infections. There are two effective vaccines available: One called a 23-valent polysaccharide vaccine (Pneumovax, Pnu-Immune) for adults, and another called 7-valent conjugate vaccine (Prevnar or PCV7) for infants and young children. Experts are now recommending that more people, including healthy elderly people, be given the pneumococcal vaccine, particularly in light of the increase in antibiotic-resistant bacteria.

Click the icon to see an image of pneumococcal pneumonia.

Pneumococcal Vaccine in Young Children. The pneumococcal vaccine (Prevnar or PCV7) is very effective in children. Evidence suggests that this vaccination, plus the vaccination against Haemophilus influenzae (an important cause of meningitis), has led to 25,000 fewer cases of serious bacterial infections each year.

The pneumococcal vaccine is now recommended by many experts for the following groups:

All children up to age 2. The pneumococcal vaccine (Prevnar or PCV7) has now been added to the Recommended Childhood Immunization Schedule. The pneumococcal vaccine (Prevnar or PCV7) is very effective in children. Studies are suggesting that it prevents common ear infections as well as serious infections such as pneumonia. In one study, a similar vaccine under investigation protected not only children in day care from serious respiratory infections, but their younger unvaccinated siblings had fewer infections as well.
Children up to age 5 who are at risk for pneumonia or complications of influenza, such as those with sickle-cell disease, immune deficiencies, or chronic medical conditions.
Other children aged 2 - 5 who are higher risk for serious pneumococcal infections should be considered for vaccinations. They include African-Americans, Native Americans, children in group child care, socially or economically disadvantaged children, or those who have had frequent or complicated acute middle ear infections within the past year. (In one study, the vaccine reduced the number of ear infections episodes by 6%.)

The recommended schedule of immunization for Prevnar (PCV7) is four doses, given at 2, 4, 6, and 12 - 15 months of age. Infants starting immunization between 7 and 11 months should have three doses. Children starting their vaccinations between 12 and 23 months only need 2 doses. Those who are over 2 years old need only 1 dose.

Pneumococcal Vaccine in Older Children and Adults. The vaccine is proving to help reduce the rate of pneumonia in young adults, although not to the degree that it protects young children. Its benefits for the elderly, other than protection against bloodstream infection, are unclear. Still, pneumonia is declining among adults, which may be due to fewer infections transmitted from vaccinated young children. Many experts now recommend the vaccine for the following older children or adults:

All people over age 65. (Anyone vaccinated more than 5 years previously should be revaccinated.) The vaccination is protective against pneumococcal bacteremia (blood infection) in this group, but it does not appear to protect against community-acquired pneumonia itself.
Adults with any chronic condition that increases the risk for pneumonia. This includes patients with heart disease, chronic lung disease (COPD or emphysema, but not asthma), or diabetes.
Individuals with immune deficiencies, such as HIV, or those undergoing treatments to suppress the immune system.
Patients with autoimmune diseases, such as rheumatoid arthritis and lupus. Unfortunately, studies suggest the vaccine may not be as effective in these patients as it is in those with healthy immune systems. Nevertheless they are at high risk for serious respiratory infections and should be vaccinated.
Patients with kidney disease or kidney transplants. Older people who have had transplant operations or those with kidney disease may require a revaccination after 6 years.
Patients with problems in the spleen.
Alcoholics (especially those with cirrhosis).
People living in long-term care facilities.
Alaska Natives or Native Americans who may be at increased risk for pneumonia.

Because the vaccine is inactive, it is safe for pregnant women and people with immune deficiencies. In fact, when the vaccine is administered to pregnant women, it may actually protect their infants against certain respiratory infections.

Protection lasts for more than 6 years in most people, although it may wear off faster in elderly people than in younger adults. Anyone at risk for serious pneumonia should be revaccinated 6 years after the first dose, including those who were vaccinated before age 65. Subsequent booster doses, however, are not recommended.

Side Effects. Pain and redness at the injection site, fever, and joint aches are possible with the pneumococcal vaccine. Children are more likely to have fever side effects within 48 hours if they receive other vaccines at the same time. They are also likely to have fewer side effects after the second dose. In rare cases, such local reactions can be severe. Even if a person is mistakenly re-vaccinated before the effects of the first vaccination have worn off, the risk for severe side effects is very low. Allergic reactions are very rare.

Resources

www.lungusa.org -- American Lung Association
www3.niaid.nih.gov -- National Institute of Allergy and Infectious Diseases
www.cdc.gov -- Centers for Disease Control and Prevention

References

Alperovich M, Neuman MI, Willett WC, Curhan GC. Fatty acid intake and the risk of community-acquired pneumonia in U.S. women. Nutrition. 2007;23(3):196-202.

Barr CE, Schulman K, Iacuzio D, Bradley JS. Effect of oseltamivir on the risk of pneumonia and use of health care services in chidlren with clinically diagnosed influenza. Curr Med Res Opin. 2007;23(3):523-531.

Bast DJ, Dresser L, Duncan CL, et al. Short-course therapy of gemifloxacin effective against against pneumococcal pneumonia in mice. Chemother. 2006;18(6):634-640.

Betrosian AP, Franzeskaki AF, Xanthaki A, Georgiadis G. High-dose ampicillin-sulbactam as an alternative treatment of late-onset VAP from multi-drug resistant Acetinobacter baumannii. Scand J Infect Dis. 2007;39:38043.

Bush K, Heep M, Macielag MJ, Noel GJ. Anti-MRSA beta-lactams in development, with a focus on ceftobiprole: the first anti-MRSA beta-lactam to demontrate clinical efficacy. Expert Opin Investig Drugs. 2007;16(4):419-429.

Canadian Critical Care Trials Group. A randomized trial of diagnostic techniques for ventilator-associated pneumonia. N Engl J Med.2006;355(25):2619-2630.

Chan EY, Ruest A, Meade MO, Cook DJ. Oral decontamination for prevention of pneumonia in mechanically ventilated adults: systematic review and meta-analysis. BMJ. 2007. Mar 26; [Epub ahead of print].

Christ-Crain M, Soltz D, Bingisser R, et al. Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia. Am J Respir Crit Care Med. 2006;174:84-93.

Digiandomenico A, Rao J, Harcher K, et al. Intranasal immunization with heterologously expressed polysaccharide protects against multiple Pseudomonas aeruginosa infections. Proc Nat Acad SciUSA. 2007;104(11):4624-4629.

Gastmeier P, Sohr D, Geffers C, Behnke M, Ruden H. Risk factors for death due to nosocomial infection in intensive care unit patients: findings from the krankenhaus infektions surveillance system. Infect Control Hosp Epidemiol. 2007;28(4):466-472.

Granizo JJ, Gimenez MJ, Barbarean J, Coronel P, Gimeno M, Aguilar L. The efficacy of cediftoren pivoxil in the treatment of lower respiratory tract infections, with a focus on the per-pathogen bacteriologic response in infections caused by Streptococcus pneumoniae and Haemophilus influenzae: a pooled analysis of seven clinical trials. Clin Ther. 2006;28(12):2061-2069.

Guarner J, Packard MM, Nolte KB, et al. Usefulness of immunohistochemical diagnosis of Streptococcus pneumoniae in formalin-fixed, paraffin-embedded specimens compared with culture and Gram stain techniques. Am J Clin Pathol. 2007;127(4):612-618.

Hallal A, Cohn SM, Namias N, et al. Aerosol tobramycin in the treatment of ventilator-associated pneumonia: a pilot study. Surg Infect (Larchmt ). 2007;8(1):73-82.

Labarere J, Stone RA, Obrosky DS, et al. Comparisons of outcomes for low-risk outpatients and inpatients with pneumonia: a propensity-adjusted analysis. Chest. 2007;131(2):480-488.

Laohavaleeson S, Kuti JL, Nicolau DP. Telavancin, a novel lipoglycopeptide for serious Gram-positive infections. Expert Opin Investig Drugs. 2007;16(3):347-357.

Lawrence SJ, Puzniak LA, Shadel BN, Gillespie KN, Kollef MH, Mundy LM. Clostridium difficile in the intensive care unit: epidemiology, costs, and colonization pressure. Infect Control Hosp Epidemiol. 2007;28(2):123-130.

Lee TA, Weaver FM, Weiss KB. Impact of pneumococcal vaccination on pneumonia rates in patients with COPD and asthma. J Gen Intern Med. 2007;22(1):62-67.

Lodise TP Jr, Pypstra R, Kahn JB. Probability of target attainment for ceftobiprole as derived from a population pharmacokinetic analysis of 150 subjects. Antimicrob Agents Chemother. 2007. Mar 26; [Epub ahead of print].

Madden RM, Pui CH, Hughes WT, Flynn PM, Leung W. Prophylaxis of Pneumocystis carinii pneumonia with atovaquone in children with leukemia. Cancer. 2007. Mar 7; [Epub ahead of print].

Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44:S27-S72.

Mesaros N, Nordmann P, Plesiat P, et al. Pseudomonas aeruginosa: resistance and therapeutic options at the turn of the new millennium. Clin Microbiol Infect. 2007. Jan 31; [Epub ahead of print].

Muller B, Harbath S, Stolz D, et al. Diagnostic and prognostic accuracy of clinical and laboratory parameters in community-acquired pneumonia. BMC Infect Dis. 2007;7:10.

Nair V, Niederman MS, Masani N, Fishbane S. Hyponatremia in community-acquired pneumonia. Am J Nephrol. 2007;29(2):184-190.

Nisar N, Guleria R, Kuman S, Chand Chawla T, Ranjan Biswas N. Mycoplasma pneumoniae and its role in asthma. Postgrad Med J. 2007;83:100-104.

Oosterhuis-Kafeja F, Beutels P, Van Damme P. Immunogenicity, efficacy, safety and effectiveness of penumococcal conjugate vaccines (1998-2006). Vaccine. 2007;25(12):2194-2212.

Pedro-Botet ML, Sopena N, Garcia-Cruz A, et al. Streptococcus pneumoniae and Legionella pneumophila pneumonia in HIV-infected patients. Scand J Infect Dis. 2007;39(2):122-128.

Pereira GH, Muller PR, Levin AS. Salvage treatment of pneumonia and initial treatment of tracheobronchitis caused by multidrug-resistant Gram-negative bacilli with inhaled polymyxin B. Diagn Microbiol Infect Dis. 2007. Mar 8; [Epub ahead of print].

Ramstedt M, Houriet R, Mossialos D, Haas D, Mathieu HJ. Wet chemical silver treatment of endotracheal tubes to produce antibacterial surfaces. J Biomed Mater Res B Appl Biomater. 2007. Mar 23; [Epub ahead of print].

Sakai F, Tokuda H, Goto H, et al. Computed tomographic features of Legionella pneumophila pneumonia in 28 cases. Comput Assist Tomogr. 2007;31(1):125-131.

Schlienger RG, Fedson DS, Jick SS, Jick H, Meier CR. Statins and the risk of pneumonia: a population-based, nested case-control study. Pharmacotherapy. 2007;27(3):325-332.

Spaude KA, Abrutyn E, Kirchner C, Kim A, Daley J, Fisman DN. Influenza vaccination and risk of mortality among adults hospitalized with community-acquired pneumonia. Arch Intern Med 2007;167(1):53-59.

Swainston HT, Keam SJ. Azithromycin extended-release: a review of its use in acute bacterial sinusitis and community-acquired pneumonia in the U.S. Drugs. 2007;65(5):773-792.

Thorpe C, Edwards L, Snelgrove R, et al. Discovery of a vaccine antigen that protects mice from Chlamydia pneumoniae infection. Vaccine. 2007;25(1):2252-2260.

Tolentino-Delos Reyes AF, Ruppert SD, Shiao SY. Evidence-based practice: use of the ventilator bundle to prevent ventilator-associated pneumonia. Am J Crit Care. 2007;16(1):20-27.

Verhamme KM, DeCoster W, DeRoo L, et al. Pathogens in early-onset and late-onset intensive care unit-acquired pneumonia. Infect Control Hosp Epidemiol. 2007;28(4):389-397.

Viejo Banuelos JL. Respiratory manifestations of avian influenza. Arch Bronchoneumol. 2006;42(Suppl 2):12-18.

Walter U, Knoblich R, Steinhagen C, Donat M, Benecke R, Kloth A. Predictors of pneumonia in acute stroke patients admitted to a neurological intensive care unit. J Neurol. 2007. Mar 14; [Epub ahead of print].

Wu H, Pfarr DS, Johnson S, et al. Development of motavizumab, an ultra-potent antibody for the prevention of respiratory syncytial virus infection in the upper and lower respiratory tract. J Mol Biol. 2007. Feb 20; [Epub ahead of print].

Review Date:
4/3/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Review provided by VeriMed Health Network.

A.D.A.M. Copyright

adam.com

Non-small cell lung cancer

FitSugar — Wed, 08 Oct 2008 17:35:06 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Risk Factors
Lifestyle Changes
Diagnostic Tests
Staging Systems
Surgical Procedures
Radiation Treatments
Treatment Options by Stages...
Chemotherapy Treatments
Investigative Agents
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Research News:

About 3,000 nonsmokers die each year of lung cancer resulting from exposure to secondhand smoke, according to a 2006 Surgeon General report.
Advexin, a genetic therapy that contains the p53 tumor-suppressor gene, is showing promise. A 2006 study in Japan found that out of 13 patients with advanced NSCLC receiving Advexin, 10 had stabilized. Advexin is in Phase II clinical trials for NSCLC.
Studies are finding that NSCLC tumors in people who never smoked have a much higher rate of epithelial growth-factor receptor (EGFR) mutations. EGFR helps new blood vessels grow to feed tumors. This discovery may help tailor future treatments to specific patient populations. It also helps explain why some newer treatments seem effective mostly in patients who never smoked.

Treatment News:

Video-assisted thoracic surgery (VATS) is a new, less-invasive surgical technique that uses a thin tube containing a miniature camera and surgical instruments. Though the procedure is not appropriate in all cases, it offers significant advantages, especially in older or frail patients, in the treatment of early stage non-small cell lung cancer (NSCLC).
Bevacizumab, a monoclonal antibody, was approved in October 2006 as a first-line treatment (in combination with carboplatin and paclitaxel) for inoperable, locally advanced, metastatic, or recurrent non-squamous, non-small cell lung cancer.
Gefitinib (Iressa), a drug that targets EGFR, proved disappointing in final clinical trials. However, erlotinib (Tarceva), a drug that targets a different part of the EGFR molecule, has shown benefits. Erlotinib is now approved as a second-line chemotherapy to treat patients with locally advanced or metastatic NSCLC after a previous course of chemotherapy failed.

Introduction

Although lung cancer accounts for only 13% of all cancers, it is among the most lethal, accounting for over 28% of all cancer deaths. It is more deadly than colon, breast, and prostate cancers combined. An estimated 160,390 people will die from lung cancer in 2007. Death rates have been declining in men over the past decade, and they have now stabilized in women.

The lungs are two spongy organs surrounded by a thin moist membrane called the pleura. Each lung is composed of smooth, shiny lobes: the right lung has three lobes, and the left has two. About 90% of the lung is filled with air; only 10% is solid tissue.

Air is carried from the trachea (the windpipe) into the lung through flexible airways called bronchi.
Like the branches of a tree, the bronchi in turn divide into over a million smaller airways called bronchioles.
The bronchioles lead to grape-like clusters of microscopic sacs called alveoli.
In each adult lung, there are about 300 million of these tiny alveoli. A thin membrane makes up the alveoli sacs. Oxygen and carbon dioxide pass through this membrane to and from capillaries.
Capillaries, the smallest of our blood vessels, carry blood throughout the body.

The major features of the lungs include the bronchi, the bronchioles, and the alveoli. The alveoli are the microscopic blood vessel-lined sacks in which oxygen and carbon dioxide gas are exchanged.

Lung cancer develops when genetic mutations (changes) occur in a normal cell within the lung. As a result, the cell becomes abnormal in shape and behavior, and reproduces endlessly. The abnormal cells form a tumor that, if not surgically removed, invades neighboring blood vessels and lymph nodes and spreads to nearby sites. Eventually, the cancer can spread (metastasize) to locations throughout the body.

The two major categories of lung cancer are small cell lung cancer and non-small cell lung cancer. Most lung cancers are non-small cell cancer, the subject of this report. Less common cancers of the lung are known as carcinoids, cylindromas, and certain sarcomas (cancer in soft tissues).

Some experts believe all primary lung cancers come from a single common malignant (cancerous) stem cell that, as it copies itself, can develop into any one of these cancer types in different individuals.

In addition, cancers in the lung may have spread from other primary sites, such as the breast, thyroid, or colon. In these cases, doctors name the cancer after its original location; for example, "breast cancer with lung metastases."

Non-small cell lung cancers are categorized into three types: squamous cell carcinoma (also called epidermoid carcinoma), adenocarcinoma, and large cell carcinoma. These separate types are grouped together because, in early stages before the cancers have spread, they all can be treated surgically.

Squamous Cell Carcinoma. Squamous cells are formed from reserve cells, which are round cells that replace injured or damaged cells in the lining (the epithelium) of the bronchi, the major airways. Tumors formed from squamous cells are usually found in the center of the lung, either in a major lobe or in one of the main airway branches. They may grow to large sizes and form cavities in the lungs.

Click the icon to see an image of squamous cell carcinoma.

When squamous cell cancer metastasizes, it may travel to the bone, adrenal glands, liver, small intestine, and brain.

Squamous cell carcinoma is nearly always caused by smoking and used to be the most common cancer. It still makes up 25 - 40% of all lung cancers.

Adenocarcinoma. Adenocarcinomas usually arise from the mucus-producing cells in the lung. About two-thirds of adenocarcinomas develop in the outer regions of the lung, while one-third develop in the center of the lung. In 1965, 12% of lung cancers were adenocarcinomas. They are now estimated to account for 30 - 50% of all lung cancers and are the most common lung cancers in many countries. They are also the most common lung cancers in women. In fact, a 2000 European study showed that nearly 34% of the women with lung cancer under investigation had adenocarcinoma, compared to 26.4% who had squamous cell carcinoma, and 22.3% with small cell lung cancer. Adenocarcinoma is also increasing dramatically in men. Until recently, adenocarcinoma was only weakly linked to smoking. Experts now suggest, however, that the dramatic increase in recent decades in this lung cancer type may be due to low-tar, filtered cigarettes. People who smoke them draw tiny particles deeper into the lungs, thereby possibly increasing the risk for adenocarcinoma.

The course of this cancer varies widely. Most often, it develops slowly and causes few or no symptoms until it is far advanced. In some cases, however, it can be extremely aggressive and rapidly fatal. In 50% of cases in which this cancer spreads, it spreads only to the brain. Other common locations it spreads to include the other lung, the liver, the adrenal glands, and bone.

Click the icon to see an image of adenocarcinoma.

Bronchoalveolar Lung Cancer. Bronchoalveolar lung cancer is actually a subtype of adenocarcinoma. It develops as a layer of column-like cells on the lung and spreads through the airways, causing great volumes of sputum. This cancer also is increasing in incidence.

Large Cell Carcinoma. Large cell carcinoma, which makes up about 10 - 20% of lung cancers, includes cancers that cannot be identified under the microscope as squamous cell cancers or adenocarcinomas.

Click the icon to see an image of large cell carcinoma.

Small cell lung cancer may, like squamous cells, be derived from reserve cells or other cells in the epithelium. It causes 15 - 25% of all lung cancers; without chemotherapy, it is very aggressive and usually rapidly fatal. It requires a different treatment approach from non-small cell lung cancer, so it is not discussed in this report.

Click the icon to see an image of small cell carcinoma.

Causes

Cigarette Smoke. Smoking causes 87% of lung cancer deaths, accounting for 30% of all cancer deaths. Cigarettes, nicotine, or both may contribute to lung cancer in one or more of the following ways:

In general, chronic exposure to nicotine may cause an acceleration of coronary artery disease, peptic ulcer disease, reproductive disturbances, esophageal reflux, hypertension, fetal illnesses and death, and delayed wound healing.

The smoke is the most dangerous component of the cigarette. Chemicals formed during smoking trigger genetic mutations that lead to cancer. When people inhale cigarette smoke, they bring into their lungs tar that includes over 4,000 chemicals, some of which are carcinogenic (cancer-causing). Other inhaled chemicals in cigarette smoke that may increase the risk for cancer include cyanide, benzene, formaldehyde, methanol (wood alcohol), acetylene (the fuel used in torches), and ammonia. Smoke also contains nitrogen oxide and carbon monoxide, both of which are harmful gases.
Nicotine itself may be a hazard. A 2000 laboratory study suggested that the human body might be converting inhaled nicotine into a chemical called aminoketone, which has been linked to the formation of tobacco-related lung cancer. A 2001 study reported that nicotine triggered new blood vessel growth, which could, in theory, promote growth of any existing tumors. A study published in 2005 found that nicotine was responsible for disabling a gene that induces the death of cancer cells in lung tumors. Whether or not these studies apply to long-term use of nicotine replacement products (such as patches), or to cigarette smoking, is still unclear. The studies should certainly not discourage people from using nicotine replacement methods for quitting. However, these studies may indicate that people should not use these devices on a long-term basis.

Radon. Radon is a gas produced naturally by the breakdown of uranium. It is often present in the soil and in water and can seep into any dwelling. Radon may be responsible for between 10% and 14% of lung cancer deaths, making it, after smoking, the second leading cause of this cancer.

Other Contributors. Toxic particles leading to precancerous changes in the lung are also found in marijuana. In one study, 53.8% of cigarette smokers, 66.7% of marijuana smokers, and all of those subjects who smoked both substances showed evidence of precancerous changes in the lungs.

There is considerable debate over the lung cancer risk posed by depleted uranium used in military weapons (such as in the Gulf and Balkan conflicts). A 2001 study estimated that it would cause an additional 8 deaths from lung cancer out of every 10,000 people or soldiers who were highly exposed to this substance. The study was based on a mathematical model, however, and the issue is not settled.

Other lung carcinogens include asbestos, arsenic, certain petrochemicals (materials made from crude oil or natural gas), and other airborne (carried through the air) byproducts of various mining and manufacturing processes.

Click the icon to see an image of the tobacco plant.

Genetic mutations that cause cancer generally occur in two types of genes:

Tumor-suppressor genes, which prevent cells from endlessly copying themselves
Proto-oncogenes, which encourage cells to keep making copies of themselves [when a proto-oncogene changes (becomes mutated), it is then called an oncogene]

Damage to either type of gene can cause a mutation that results in an uncontrolled division of cells. This uncontrolled division forms tumors.

It is unlikely that a single specific abnormality causes all lung cancer. It probably takes a variety of mutations to start the devastating chain of events leading to cancer. The following mutations are among those under investigation:

BPDE-caused mutations: The chemical BPDE, a byproduct of tobacco smoke, is involved with a number of genetic mutations, including those to an oncogene called K-ras and to three tumor-suppressor genes known as p53, PPP2R1B, and p16. When normal, the tumor-suppressor genes are involved in cell repair and healthy copying of the cell. When they are damaged or blocked, out of control cell production can occur, leading to cancer. About 10% of the population may carry a gene that protects against lung cancer, by reducing levels of BPDE.
Chemotherapy resistance genes: Tumors that contain the p53 mutation may also be more resistant to chemotherapy.
Rb Mutations: Another important contributor to lung cancer is a genetically defective protein called retinoblastoma (Rb), which is associated with very aggressive tumors. Low levels of the normal Rb gene may sometimes predict aggressive cancer, especially in patients with small cell lung cancer.
Mutations to the FHIT gene: Another potentially important mutation may be an abnormality in the FHIT gene. This mutation causes the cells lining the lung to become more vulnerable to the effects of tobacco smoke and other carcinogens.

Symptoms

Lung cancer is unlikely to produce symptoms until the disease is advanced. When symptoms develop, they may result from the lung tumor itself, from its effects on tissues outside the lung, or from the spread of malignant cells to other organs.

Early symptoms may include the following:

Frequent bouts of pneumonia, or pneumonia that does not clear up in a normal period of time
Coughing (particularly coughing up blood)
Weight loss
Fever
Shortness of breath
Chest pain

Later-stage symptoms include the following:

Shortness of breath: This common symptom is the result of cancer that has spread in the lung and the pleura, the membrane covering the lung.
Superior vena cava syndrome: In some cases, tumor growth or spreading of the cancer presses against the superior vena cava, a large vein that returns blood from the upper part of the body to the heart. When this happens, a condition called superior vena cava syndrome may occur, leading to obvious swelling in the arms and face.
Trouble swallowing: The esophagus is the pipe that takes food from the mouth to the stomach. The cancer may spread to or press against the esophagus, interfering with swallowing and nutrition.
Hoarseness: Cancer can damage the nerves that control the voice box, causing hoarseness.
Pancoast syndrome: Damage to the brachial plexus, a group of nerves branching from the neck, can cause pain, weakness, or numbness in the arm or hand (Pancoast syndrome).
Bronchoalveolar lung cancer may produce very large amounts of mucus.
Hypercalcemia: Some lung cancers produce substances that remove calcium from bone and release it into the bloodstream, causing a condition called hypercalcemia. Patients with this disorder can experience nausea, vomiting, constipation, weakness, and fatigue.

Other lung cancers (usually small cell cancer) cause the body to retain water, lowering the blood's sodium levels. This condition, called hyponatremia, can produce confusion, weakness, and even seizures.

Risk Factors

Before cigarettes became popular in the beginning of the 20th century, lung cancer was rare. In 2007, lung cancer is expected to strike up to 213,380 Americans, and about 160,390 are expected to die from it.The disease usually occurs in people over 50 years old. Men have a significantly greater incidence of lung cancer compared to women. On the encouraging side, the rate of lung cancer in men has been declining significantly over the past decade. While lung cancer rates have been increasing dramatically in women (by 600% from 1950 to 2000), they now appear to be stabilizing.

Smoking appears to be the primary risk factor in 85 - 90% of lung cancers. About 15% of all people who smoke develop lung cancer. The risk depends on the duration of the addiction and the number of pack years. (One pack year equals the number of packs of cigarettes smoked per day, multiplied by the number of years that the person has smoked.) Genetic damage in the lung occurs in nearly all chronic smokers, even if cancer has not developed.

An elevated risk for lung cancer can persist for more than 20 years after quitting smoking, although the risk drops significantly even in the first year after quitting. And, there are benefits to quitting smoking even for people who are well into middle age.


Quitting Age	Percentage
30	2%
40	3%
50	6%
60	10%

Second-Hand Smoke. The Environmental Protection Agency has classified second-hand smoke as a carcinogen (cancer-causing chemical). Exposure to second-hand tobacco smoke increases the risk of lung cancer in the nonsmoker by about 20 - 30%. A 2006 Surgeon General report found that about 3,000 nonsmokers die each year of lung cancer resulting from exposure to secondhand smoke.

There may be some ethnic differences in lung cancer risk. For example, African-Americans face a risk that is two to four times higher than that in Caucasians, regardless of smoking status. It is not clear what factors are responsible for this higher risk. Some African-Americans appear to have a genetic vulnerability to the harmful chemicals in cigarette smoke.

In China, an estimated one third of all young male smokers will eventually die because of tobacco-related illnesses. Their risk for lung cancer, however, is much less than it is for chronic lung disease, the opposite of the Western trend. A 2001 study reported that the lower rate of lung cancer among Chinese people might be due to a slow rate of clearing nicotine, which results in smoking fewer cigarettes.

People with High Exposure to Radon. Studies have shown that radon raises the risk of lung cancer in underground miners by 40%. It is unclear whether the results of these studies would apply to people exposed to radon in their homes One study suggests that people with intense or prolonged exposure to radon in their homes do indeed face the same risk as miners exposed to similar levels of radon. A cumulative long-term exposure to radon and smoking also increases the danger. Most people move an average of 10 or 11 times over their lifetime, so the risk of developing lung cancer through radon exposure is very low in most individuals, even for those who lived for awhile in areas with high radon levels. People with homes that have high radon levels and those who sleep or spend many hours to days in basements with detectable but moderate levels should consider taking protective measures.

Workers Highly Exposed to Carcinogens. An estimated 9,000 - 10,000 men and 900 - 1,900 women develop lung cancer each year because of occupational exposure to carcinogens. More than half of these cases are attributable to past exposure to asbestos, which has long been known to be a risk factor for mesothelioma (cancer of the pleura, the lining around the lung) and can increase the risk of lung cancer in smokers. With better protective measures, these rates are expected to fall in the future.

Other chemicals that put workers at risk for lung cancer include:

Arsenic (insecticide and herbicide sprayers, tanners, oil refinery workers)
Chloromethyl methyl ether (workers exposed to certain polymers, water repellents, or products using chloride and formaldehyde)
Chromium compounds (workers using certain alloys, paints, pigments, and preservatives)
Depleted uranium (soldiers exposed to weapons during battlefield conditions)
Crystalline silica

By contrast, agricultural workers seem to have a lower lung cancer rate, despite their possible occupational exposures to risky chemicals. While this rate has traditionally been attributed to good health habits, including low tobacco use, a 2000 study suggests that agricultural workers' exposure to endotoxin may be responsible. Endotoxin is a component of common bacteria found in soil and animals and may have cancer-preventing effects on the immune system.

Exposure to Smoke from Grills. Grilling and high-heat frying emit chemicals called heterocyclic amines, which are known to be carcinogenic. A 2000 study of Chinese women found that smokers who stir-fried meat daily and inhaled cooking fumes had a higher risk of lung cancer than did those who stir-fried meat less frequently. No higher risk was found among nonsmokers.

Air Pollution. Although any risk from air pollution is very small, it nevertheless may be a contributor to those lung cancers not obviously related to smoking. Some studies, including a major analysis of vital statistics in 2002, have found an association between increased risk for lung cancer and long-term exposure to very small particulates, especially sulfates, present in polluted air. The risk, if any, is very small.

A family history of lung cancer may play a role in increasing susceptibility to this disease. In one study, people who had parents or siblings with respiratory tract cancers had a 30% higher risk for lung cancer, compared to people without a family history. Women with mothers or sisters with lung cancer had triple the risk. A higher risk occurred in both smokers and nonsmokers. There was no association between a history of other cancers and lung cancer. Both genetic factors and secondhand smoke appeared to contribute to the danger in these individuals.

Smokers with emphysema or chronic inflammatory lung diseases, such as asthma, are at increased risk for lung cancer. Both smokers and nonsmokers whose lungs are scarred from recurrent lung diseases, such as pneumonia or tuberculosis, are also at increased risk, particularly for bronchoalveolar lung cancer.

Lifestyle Changes

Quitting improves lung function almost immediately. Some evidence suggests that the benefits for the lungs are even more significant for women who quit than for men. It should be noted, however, that it can take 20 years or longer, particularly in heavy smokers, for the lungs to be restored to a fully healthy condition in which the risk for lung cancer is as low as for nonsmokers. Quitting is extremely difficult. No one should be discouraged if they relapse. Everyone should keep trying to quit. With continued efforts, many people succeed.

The many methods of quitting smoking include counseling and support groups, nicotine patches, gums and sprays, and incremental reduction.

At this time perhaps the most effective method for quitting is a combination of the following:

Nicotine replacement products that reduce withdrawal symptoms and cravings.
The antidepressants bupropion (Zyban) or nortriptyline (Pamelor, Aventyl), which reduce emotional effects and cravings associated with withdrawal, and improve abstinence rates.
Professional counseling or support organizations that may be effective, in addition to the medication, in helping people maintain abstinence.

[See In-Depth Report #41: Smoking.]

While people are in the process of quitting (and afterwards), they should maintain as healthy a lifestyle as possible.

Phytochemicals. Some data suggest that diets rich in fresh fruits and vegetables may be protective against lung cancer in both smokers and non-smokers. Some studies have reported protection from specific plant chemicals (phytochemicals), such as the following:

Isothiocyanates. These chemicals are found in cruciferous vegetables (broccoli, cauliflower, and Brussels sprouts). They may help block the effects of carcinogens in smoke, suppress tumor growth, and inhibit growth-promoting steroid hormones.
Flavonoids. Major sources are apples, grapefruit, onions, red wine, and tea. In one study on flavonoids, apple eaters had the lowest cancer risk, 68% less than those who ate fruit infrequently. In another, those who ate relatively more onions, apples, and white grapefruit had less than half the lung cancer risk as people who ate relatively small amounts of these foods. Flavonoids are also found in soybeans, berries, broccoli, carrots, citrus fruits, eggplant, peppers, squash, and tomatoes. Specific flavonoids in dark chocolate may be protective against lung cancer (but not other cancers).
Lycopene. Lycopene is found in tomatoes, which have been associated with a lower risk for lung cancer. Cooking the tomatoes appears to increase the potency of lycopene.
Cryptoxanthin. Some studies suggest that eating foods rich in cryptoxanthin, a yellow-orange pigment, reduces the risk for lung cancer. Foods with high amounts of cryptoxanthin include pumpkin, corn, papaya, red bell peppers, tangerines, oranges, and peaches. More research is needed in this area, however.
Isoflavones. Isoflavones, found in soy beans and flax seed, behave like estrogen in some ways and not in others. Some evidence suggests the genistein (a type of isoflavone) in soy may have properties that are protective against lung cancer.

Click the icon to see an image of phytochemicals.

Note: Studies on these chemicals are not consistent. It is unlikely that individual phytochemicals offer protection, but rather that the benefits come from a collection of vitamins and plant chemicals contained in fruits and vegetables. Fruit, especially, appears to be protective.

Fats and Oils. Some studies have indicated that diets high in animal fats increase the risk for lung cancer. Others have suggested some protection from cod liver oil, which contains omega-3 fatty acids (found in fatty fish), omega-6 fatty acids (found in flax and in soybean and canola oils), and monounsaturated oils (found in olive and canola oils). Of interest was a 2002 study reporting that women who had a high intake of cheese had a lower risk of lung cancer. Despite these intriguing pieces of information, the ability of these substances to protect against lung cancer remains controversial, and discontinuation of smoking remains the best advice.

Click the icon to see an image of fats and oils.

Vitamin Supplements. Even with a healthful diet, smoking reduces the levels of a number of vitamins, importantly vitamin C. There is no evidence, however, to support any protection from antioxidant supplements, including vitamins E, A, or beta carotene.

In fact, evidence is now suggesting that high doses of vitamin C, vitamin E, and beta carotene supplements may have harmful effects. A 2000 study, for example, reported a higher risk for cancer in male smokers who took multivitamins plus A, C, or E. The strongest studies to date on negative effects of antioxidant supplements have reported an increase in lung cancer and overall mortality rates among smokers who took beta carotene supplements. In determining reasons for this disturbing effect, one animal study suggested that beta carotene increased enzymes in the lungs that actually promote cancerous changes. In other words, antioxidants may actually be harmful in people who already harbor cancer cells. This is particularly important information for smokers, who may carry precancerous or cancerous cells for years prior to developing the disease. The best way of achieving healthy levels of important nutrients is from healthy foods.

Click the icon to see the benefits of vitamin A.

Click the icon to see dietary sources of vitamin A.

Trace Element Supplements. Trace elements may be important in cancer risk and prevention.

Selenium appears to inhibit cell production and may have other anti-cancer properties. A few studies have reported some protection with selenium. However, a major 2002 analysis supports previous work, indicating that taking selenium helps only people who are deficient to begin with.

Click the icon to see the benefits of selenium.

Zinc may prove to be more important than selenium. Some research suggests that zinc may help protect smokers by blocking cadmium. Smokers have higher levels of cadmium in their body, and there may be a link between cadmium and a higher risk for lung cancer. Some laboratory studies have indicated that zinc might help protect against tumor progression. There is no evidence that taking zinc supplements will reduce the risk for lung cancer, however.

A 2003 study reported a lower risk in lung cancer in men and women who were physically active. Both moderate and intensive exercises were associated with protection.

People concerned about radon in their home or area can purchase a test approved by the Environmental Protection Agency. Methods for removing radon include installing a soil suction system. It should be noted, however, that home prevention measures rarely reduce radon levels to zero. Simply sleeping by an open window reduces the risk.

Nonsteroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors (coxibs) both block cyclooxygenase (COX) enzymes. NSAIDs block COX-1 and 2, and coxibs selectively block COX-2. Evidence now strongly suggests that the COX-2 enzyme plays a role in blood vessel growth (angiogenesis) that can feed lung cancers.

NSAIDs. NSAIDs include aspirin, ibuprofen (Advil), and naproxen (Aleve, Naprosyn, Naprelan, Anaprox). These agents inhibit COX-2, but they also target another COX enzyme. Studies are now reporting an association between regular use of aspirin or other NSAIDs and a reduced risk for non-small cell lung cancer.

COX-2 Inhibitors. The COX-2 inhibitors are more recent forms of NSAIDs. Currently, only celecoxib (Celebrex) is still on the market. Rofecoxib (Vioxx) and valdecoxib (Bextra) were withdrawn from the market due to their high risk of causing strokes and heart attacks. Because they target the COX-2 enzyme specifically, researchers are focusing on these drugs for a possible role in treating lung cancer and preventing recurrence.

Diagnostic Tests

Chest X-Rays. In a small percentage of cases, a routine chest x-ray reveals the first signs of lung cancer. Usually, however, symptoms of existing lung cancer, such as coughing, chest pain, and blood in the sputum, will lead to a chest x-ray. If non-small cell lung cancer is present, chest x-rays may show lesions (damaged or abnormal tissue) in the center of the lung, cavities formed by squamous cell carcinoma, or lace-like pattern of cells spreading through the lungs. By the time lung cancer is diagnosed by chest x-rays, however, it has often spread so far that it cannot be surgically cured. Four major studies found no survival benefits in early detection from chest x-rays and sputum screening. Regular screening for lung cancer using x-rays is therefore not currently recommended.

Computed Tomography. Computed tomography (CT), particularly the specific technique called low-dose spiral (or helical) CT, is more effective than x-rays for detecting cancer in patients with suspected lung cancer. It is the standard imaging procedure for determining if and where the cancer has spread (metastasized). Surgeons also use CT scans to evaluate patients before lung surgery.

CT stands for computerized tomography. In this procedure, a thin x-ray beam is rotated around the area of the body to be visualized. Using very complicated mathematical processes called algorithms, the computer is able to generate a 3-D image of a section through the body. CT scans are very detailed.

The use of helical CT for early screening is still controversial. Studies of CT scans in smokers suggest that early screening will detect about 2% of lung cancers, most of these in early stages. In the studies, 62 - 82% of the patients with stage 1A cancer (when the tumor has not spread yet) were still alive at 5 years. Neither study, however, was controlled (compared with other groups, such as non-smokers). The survival figures were likely to be higher than in actual practice.

Click the icon to see an image of a CT scan of the chest.

Evidence regarding the survival benefits of early detection is not clear. Many experts are highly opposed to widespread screening for lung cancer. Some evidence, for example, suggests that lung cancer cells in non-small cell lung cancer are often very aggressive at microscopic levels (before a tumor is formed). If this were true, the cancer would be highly likely to have already spread, long before it was visible with CT scans. Moreover, some studies have found no association between tumor size at the time of diagnosis and survival times. On the other hand, some suspicious areas detected by CT scans may actually be innocent, and these patients might be more likely to die from aggressive treatments than from the disorder itself.

It should also be noted that about 98% of suspicious areas seen on CT scans turn out to be benign. Even after rescreening, many scans will show suspicious areas that turn out to be harmless but will require invasive and expensive biopsies. Additional experience with CT scans, however, may allow experts to better determine which abnormalities are likely to be benign.

High-risk individuals who are still interested in early screening with CT scans should ask their doctor about available clinical trials.

Computed tomography is the standard imaging procedure for determining if and where the cancer has spread (metastasized). Other imaging tests, however, may be useful for staging and tracking lung cancers (staging means finding out how advanced the cancer is).

Positron Emission Tomography. Positron emission tomography (PET), specifically a technique known as FDG/PET, is the most accurate noninvasive test for detecting early lung cancer. It is also the best imaging technique for staging lung cancers, not only those located in the lungs, but also those that have spread, particularly into the space between the two lungs (the mediastinum). With this imaging test, the patient is first injected with a specially formulated liquid sugar (called FDG), and then viewed with a machine that records energy given off by tumor cells.

PET is expensive and not widely available. However, its supporters suggest that it may prevent many unnecessary surgeries by identifying patients whose cancer has advanced past the stage at which surgery is helpful. There is some evidence that FDG/PET scan can detect a metabolic (processing) response to treatments that may help predict the outlook for the patient.

Scintigraphy. Scintigraphy is an imaging procedure in which patients are administered low-level radioactive agents that bind to cancer cells, which then can be tracked by special cameras to reveal the cancer cells' location and intensity. Agents selected are those that can best bind successfully with specific tumor types. For example, a 2001 study of the binding agent 111In-DOTA-LAN demonstrated excellent results in identifying non-small cell lung tumors. This study further suggests the possibility of using such highly-targeted binding agents as lung cancer treatments.

Magnetic Resonance Imaging. Magnetic resonance imaging (MRI), an imaging procedure that uses radio wave energy, is frequently used instead of CT scanning to locate brain and bone metastases that can be associated with lung cancer.

Biopsies of lung tissue are needed to confirm lung cancer. This requires invasive procedures that may vary from simple needle aspiration to chest surgery.

Needle Aspiration. Sometimes, a biopsy specimen is obtained by inserting a needle between the ribs, and then guiding it with the use of computed tomography scans, ultrasound, or fluoroscopy (a device allowing an x-ray view). Specific techniques include transbronchial or transthoracic needle aspiration (TBNA or TTNA) or endoscopic ultrasound-guided needle aspiration (EUS-NA). Their use depends on how much of the area can be observed with less invasive imaging methods. There is a 5 -10% risk for bleeding or collapsed lung with needle aspiration.

Thoracoscopy. Thoracoscopy is usually very effective for diagnosing cancer in the outer areas of the lungs, or those involving the pleura (membrane surrounding the lungs). This is a surgical procedure that uses a fiber-optic tube to view the area:

The procedure requires general anesthesia.
The surgeon passes surgical instruments and a fiber-optic tube through a small incision in the chest. The tube has a camera in it, which allows the surgeon to look at the lungs on a video screen.

Bronchoscopy. To locate cancer that develops in the central areas and major airways of the lung (usually squamous or small cell cancer), bronchoscopy is typically performed. The procedure is done as follows:

The patient is given a local anesthetic, supplementary oxygen, and sedatives.
The doctor inserts a bronchoscope, a hollow flexible tube often containing a fiber-optic light source, into the lower respiratory tract through the nose or mouth.
The tube acts like a telescope into the body, allowing the doctor to see the windpipe and major airways. In a procedure called fluorescence bronchoscopy, the doctor injects the patient with a drug that makes cancer tissue appear red when exposed to laser light from the bronchoscope.
The surgeon removes specimens for biopsy, ideally combining techniques to include cutting tissue, brushings, and a washing process called bronchoalveolar lavage (BAL). BAL involves injecting saline through the bronchoscope into the lung and then immediately suctioning the fluid back through the hollow tube of the bronchoscope; the fluid is then analyzed in the laboratory. Both brushing and washing procedures may be very valuable additions.

Advances in this procedure, such as laser-induced fluorescence endoscopic bronchoscopy, may improve early detection of cancer.

Bronchoscopy is usually very safe, but complications can occur; they include allergic reactions to the sedatives or anesthetics, asthma attacks in susceptible patients, and bleeding. Fever may follow the procedure.

Click the icon to see an image of bronchoscopy procedure.

Click the icon to see an image of a bronchoscope.

Mediastinoscopy. Mediastinoscopy uses a tube inserted between the lungs to locate the appropriate areas for biopsy. It is performed if the physician suspects that cancer has spread to nearby lymph nodes but has not yet metastasized.

Sputum Analysis for Presence of Cancer Cells. Some experts are now recommending an analysis of coughed-up sputum as a useful and cost-effective measure for identifying cancer cells, particularly those located in central areas of the lung. However, although sputum analysis appears to be as accurate as any other screening test currently conducted, it may miss cancers such as adenocarcinoma, which form in mucus-producing cells typically in the outer portion of the lungs. If a sputum analysis does not show cancer cells, but other signs of lung cancer are present, including blood in the sputum and suspicious areas on x-rays, other tests are performed.

Biomarkers. Biologic markers, called biomarkers, are high levels of substances that are released by tumors and indicate the presence of specific cancers. Biomarkers can be found in sputum, blood, and tissue samples. They can include enzymes, hormones, amino-acid compounds, antigens (identified by antibodies that specifically target them), growth factors, and other chemicals. Some biomarkers may prove to reveal the presence of cancer cells before they are evident on CT scans or other imaging tests. For example, genetic mutations, notably K-ras and p53, can now be detected in cells found in sputum, or cells taken during bronchoscopy. Such mutations occur only with cancerous changes and may enable early detection. Other markers that prove to be important for predicting aggressive cancers are high levels of matrix metalloproteinase (MMP9) and vascular endothelial growth factor (VEGF), which are compounds involved with angiogenesis (the process in which blood vessels serving the tumor develop).

As part of the doctor's initial examination, patients may have a pulmonary function test to evaluate lung health and capacity. In addition, since the heart and lungs are often involved in complications following lung cancer surgery, the doctor may be especially interested in taking a complete history of those systems in patients who might need surgery.

Staging Systems

Tests to Determine Cancer Stage. After diagnosing non-small cell lung cancer, the doctor makes treatment choices by determining the cancer's stage (how large the tumor is and how far the cancer has spread). To stage the cancer and determine other aspects of the disease, a number of tests are conducted:

The cancer cells are examined microscopically for size, shape, and other configurations.
Computer tomography (CT), magnetic resonance imaging (MRI), or both, are used to scan the lung and perhaps other locations, such as the liver, upper abdomen, and brain, to determine the extent of the disease.

Physical Examination. A detailed physical examination of the whole body is very important to identify or rule out the spread of cancer to other areas, and to determine the general condition of the patient. For example, questions about dizziness or headaches can help the doctor determine if the cancer has spread to the brain, while bone or joint pain might suggest that the cancer has spread to the bone. The doctor will also look for head and neck symptoms that might reveal the presence of other tumors. Also, according to a 2000 review, the patient's weight loss and ability to function are two very important factors for predicting survival following treatment. Patients who are mobile and have lost less than 10% of their pre-treatment weight tend to have better survival rates.

In lung cancer, the stage of the disease at the time of diagnosis is a major factor in determining how to treat the cancer, and how long the patient can expect to live. In general, survival is longest for patients with very early-stage disease and shortest for patients with very advanced disease that has spread to several regions of the body. Staging is based on the results of physical and surgical examinations, and laboratory and imaging tests, including biopsies.

To determine the stage, medical professionals first categorize each tumor by size and by how far it has extended. This identification method is called the TNM system.

The TNM categories then determine the stage (numbered 0 to IV), indicating how advanced the cancer is.

TNM stands for Tumor, regional lymph Nodes, and Metastasis (cancer spread beyond the original tumor).

T refers to the size and extension of the tumor itself. In TX and T0, the tumor is indicated by cancer cells in sputum or lung samples but cannot be seen. Tis: Carcinoma in situ. The cells are cancerous, but the tumor does not show evidence of spreading. In T1, the tumor is 3 cm or less in size, is still contained in the lung or the membrane covering the lung, and has not reached the main airway.

In T2, the tumor has one or more of the following features:

It is greater than 3 cm
It involves the main airway
It is 2 cm or more away from the ridge (the carina) at the lowest part of the windpipe
It has invaded the pleura
It is associated with collapsed lung tissue (atelectasis) or swelling that blocks part (but not all) of the lung

In T3, a tumor of any size has directly invaded any of the following:

Chest wall
Diaphragm
The membrane covering organs and structures in the chest
The outer wall of the membrane around the heart (pericardium)

In addition, one or more of the following conditions are present:

The tumor is in the main airway, less than 2 cm away from the carina, but is not in the trachea (windpipe).
The tumor is associated with a collapsed lung or swelling that blocks the entire lung.

In T4, the tumor has invaded any of the following:

The area between the lungs (mediastinum)
The heart
The great vessels (the blood vessels that carry blood from the heart)
Carina, trachea, or esophagus
Main portion of the spine

In addition, one or both of the following occurs: separate tumors are present in the same lobe; the tumor is accompanied by an increased amount of fluid between the pleural membrane and the lung.

N followed by a number from 0 to 3 refers to whether the cancer has reached regional (in the area of tumor) lymph nodes. In stage N0, the regional lymph nodes are still cancer-free.

In N1, the cancer has spread to the nearest lymph nodes around the airways, to the hilum (a central zone in the lung where blood and lymph vessels enter), or both. The tumor has extended directly into lymph nodes within the lung. In N2, the cancer has spread to lymph nodes in the middle of the chest that are still next to the affected lung, to the nodes below the carina, or to both regions.

In N3 the cancer has spread to lymph nodes in the middle of the chest that are next to the opposite lung, to the hilum in the opposite lung, to lymph nodes in nearby or opposite muscle tissue, or to lymph nodes above the collar bone.

M Stages refer to metastasis. In M0, metastasis has not occurred.

In M1 distant metastasis has occurred. This includes the presence of a separate tumor in a different lobe.

Staging factors are used to help determine treatment and outlook. The following suggest a more aggressive disease:

The presence of respiratory symptoms
A tumor larger than 3 cm
High numbers of blood vessels in the tumor

Researchers are always looking for more accurate ways to determine a treatment and outlook for lung cancer. For example, some research involves specific biomarkers and related blood vessel development within tumors. These markers might eventually help determine how aggressive a cancer is likely to be, and what the best treatment approach is.

If the cancer is still localized, surgery can produce 5-year survival rates of up to 75% in stage I patients and up to 50% in stage II patients. Unfortunately, very few patients are diagnosed at such early stages. In locally advanced stages, the standard treatment is concurrent radiation and chemotherapy. However, even with this approach average survival times are less than 2 years. Even if an initial tumor has been surgically removed or irradiated, cancer recurrence rates are very high. The risk for recurrence is lower in smokers who quit after treatment.

On an encouraging note, advances in therapies for later stage lung cancer are now offering some hope for improving survival. Still at this time, the mortality rate for lung cancer is still extremely high, and reports of improved response or survival rates using drugs or combinations of therapies do not mean cures. Ultimately, the patient must weigh a diminished quality of life using aggressive treatments against a chance for a modestly prolonged life.

Surgical Procedures

Surgery is performed in the following circumstances:

The surgical removal of an entire lobe or parts of a lung is the primary treatment for eligible patients in early stages of cancer. Recurrence is high after surgery, although the new tumor is often operable.
Some patients with stage IIIA cancer may also benefit from surgery. The intent at this stage is to extend survival time, rather than cure the disease.
Surgery is not out of the question in rare cases of metastasis when the cancer appears in a single operable location, such as the brain.

Unfortunately, lung surgery may be too risky for patients with other lung diseases or serious medical conditions, and because lung cancers tend to occur in smokers over 50, such health problems are likely to be present. Long-term survival rates appear to be better in patients treated at hospitals that perform large numbers of lung cancer surgeries, and when surgeries are performed by thoracic surgeons, who specialize in chest procedures.

The type of surgery depends on the amount of lung or other tissue that needs to be removed.

Wedge Resection or Segmentectomy. Wedge resection and segmentectomy remove only a small part of the lung; consequently, they preserve almost normal breathing function after the operation.

Lobectomy. Removal of one of the lobes of the lung is called lobectomy. The patient's lung function must be adequate before undergoing this procedure. The operation carries an overall mortality rate of 3 - 5%, with older patients having the highest risk.

Click the icon to see an illustrated series detailing surgery to remove diseased lobes of the lung.

Pneumonectomy. Pneumonectomy removes the entire lung. The procedure itself carries a mortality rate of 5 - 8%, with the oldest patients having the greatest risk. In such patients, recurrence almost always occurs.

Surgical advances are allowing a wider range of options, including minimal surgeries for early cancers and surgeries that relieve cancer symptoms in late stages of the disease.

Thoracoscopy. Thoracoscopy, also known as video-assisted thoracic surgery (VATS), is a less-invasive technique that employs a thin tube containing a miniature camera and surgical instruments. It requires much smaller incisions than open surgery and speeds recovery to the point that patients are up within hours. Though the procedure is not appropriate in all cases, it offers significant advantages, especially in older or frail patients. The death and complication rates following VATS are lower than those following conventional surgeries. Pain is reduced, and patients are released from the hospital quicker. Several studies found that the 5-year survival and recurrence rates in patients with stage I NSCLC treated with VATS were comparable to those in patients treated with traditional open chest surgeries.

Laser Surgery. Laser surgeries allow removal of minimal amounts of lung tissue and are proving useful for improving symptoms in stage II and IIIA patients. They may also be beneficial in treating cancers that have spread to the throat, obstructing it.

Photodynamic Therapy. Photodynamic therapy uses bronchoscopy and special laser light beams combined with a light-sensitive drug, called porfimer sodium (Photofrin), to kill cancer cells. The most common side effect is sun sensitivity. Serious side effects include bleeding in the lungs. Photodynamic therapy may be considered for patients in early-stage disease who are not candidates for other surgical procedures. It may also be used to reduce symptoms in late-stage disease.

Cryosurgery. Cryosurgery uses a probe chilled to below freezing to destroy the tumor cells on contact and is being investigated in combination with radiation therapy. It may also be an alternative in early stage cancer for patients who cannot have surgery.

Electric Cauterization. Electric cauterization, the use of electricity to produce heat that destroys tissue, is also under investigation as a treatment for early-stage disease.

Back Surgery. Spinal cord compression is a common cause of pain in patients with advanced lung cancer. Because such patients can live for a year or longer, some research indicates that back surgery followed by radiation therapy can significantly improve the quality of life for many of these patients.

Radiation Treatments

In addition to surgery, radiation is the other primary treatment for early-stage lung cancer. Doctors are also studying the benefits of radiation treatment in advanced lung cancer.

Radical Radiation in Early-Stage Cancer. Radical radiation is used as the sole procedure in stage I and some stage II patients who have adequate lung function but, for medical or other reasons, cannot be treated with surgery. In these cases, the 5-year survival rate is about 20%, and the cancer is likely to recur. Survival rates may be higher or lower, depending on the tumor size. In general, treatment with radiation therapy alone shows less benefit with larger tumors. A 2002 analysis suggested that the use of radiotherapy after surgery in patients whose tumors had been completely removed might be associated with reduced survival rates. Nevertheless, a recent study confirmed earlier results that show that radiation therapy by itself is as effective as surgery in patients who are unable or unwilling to have surgery for early stage non-small cell lung cancer.

Combined Treatments for Improving Survival in Advanced Cancer. Radiation is also being investigated in various combinations with chemotherapy, surgery, or both. At this time, concurrent radiation treatment plus platinum-based chemotherapy may extend survival times in advanced lung cancer. Other combinations are showing promise.

Palliative Radiation. Doctors use palliative radiation to shrink tumors and reduce pain and symptoms. Palliative radiation is appropriate for patients with advanced disease and poor lung functions, or in those with metastasized cancer. In up to 85% of patients with advanced disease, palliative radiation therapy helps relieve pain, shortness of breath, the superior vena cava syndrome, coughing up blood, and symptoms caused by brain metastases. Radiation, in these cases, is not generally used with the intention of reducing mortality rates, although it may increase survival in some patients, such as those with excellent lung function whose tumors are small.

Delaying radiation therapy until symptoms develop does not appear to reduce survival times or impair quality of life compared to starting it right away, in patients with minimal or no symptoms.

Radiation Therapy in Metastasis to the Brain. Radiation is the primary treatment when cancer has spread to the brain unless the cancer is small enough to be treated surgically. When radiation is used, a technique called stereotactic radiosurgery may be used to deliver powerful, highly targeted radiation to specific areas in the brain. Some trials are investigating using radiation to the head to prevent metastasis to the brain.

The goal of radiation treatment is to administer doses as high as possible to kill as many cancer cells as possible, without destroying surrounding healthy tissues or causing a dangerous reaction. Doctors may try different procedures for the same patient. The exact radiation procedure depends on the site of the cancer or how far it has spread:

External-Beam Radiation. External-beam radiation therapy focuses a beam of radiation directly on the tumor. It is generally used for metastasized cancer.
Brachytherapy. Brachytherapy involved the implantation of radioactive seeds through thin tubes directly into the cancer sites. Brachytherapy may be used for lung cancers that have spread to the throat and caused obstruction. High-dose-rate brachytherapy may also have some value for patients with inoperable tumors in the central region of the lung.

Hyperfractionated radiotherapy gives smaller than standard doses a number of times a day (usually two or three). This allows doctors to use a higher cumulative dose over the whole course of treatment. It is not as useful as therapy by itself, but should be combined with chemotherapy to have any survival benefits.

Hyperfractionated Accelerated Radiotherapy. Continuous hyperfractionated accelerated radiotherapy (CHART) administers multiple doses per day but uses standard doses. This allows the total dose of radiation to be administered over a shorter time period than the standard 6 weeks. CHART is proving to extend survival rates of patients with localized cancer over that of standard radiotherapy or non-accelerated hyperfractionated radiation. It can cause severe swallowing problems. A modification in which treatment is suspended for 2 days out of 7 may help reduce this effect.

Three-dimensional (3-D) conformal radiotherapy delivers external-beam radiation designed to closely match the specific targeted organs or tissues. This allows significantly higher doses to attack the cancer while reducing the risk to healthy cells. In a 2003 report, 3-year survival rates in stage IIIA patients were nearly 60%, and nearly half the patients experienced no side effects.

Stereotactic body radiotherapy, an advance on conformal radiation, uses a body frame and an abdominal press to immobilize the patient's body and limit breath movement. This allows a more accurate delivery of high-energy radiation. The technique is still investigational.

Radiation can have significant side effects when used as part of intensive treatments, such as hyperfractionated radiotherapy or radiotherapy in combination with chemotherapy. Among the most serious problems is severe inflammation in the esophagus (esophagitis) or the lungs (pneumonitis). Infection is also a danger.

The use of targeted approaches, such as conformal radiotherapy, may help reduce these complications. Investigators are also studying drugs, notably amifostine, which appear to help reduce throat and lung inflammation caused by radiation, without reducing its cancer-fighting effects.

Treatment Options by Stages

In the occult stage (TX, N0, M0), cancer cells are found in a sample of a patient's coughed-up sputum, but no cancer cells have yet been detected in the lung.

Treatment Options. Surgical removal of the tumor, if one can be located, allows identification of its stage and often results in cure.

Stage 0 or carcinoma in situ (Tis, N0, M0) are noninvasive cancers and only a few layers of cancer cells are detected within one local area. The cancer has not grown through to the top lining in the lung and can be surgically removed. There is a high risk for development of a second tumor, however.

Treatment Options:

Surgery, often a limited procedure, where only part of a lobe is removed from the lung.
In patients who cannot be treated surgically, consider photodynamic therapy, cryotherapy, or brachytherapy.

In stage I, the cancer has reached higher layers of the lung but has not spread into the lymph nodes or beyond the lung.

General Treatment Options. The primary treatment is surgery, such as lobectomy (removal of a whole lobe), if possible. Patients with poor lung function should undergo partial lobectomy, if possible. Radiation treatments may be appropriate and beneficial for patients who cannot have surgery. It is not clear if early-stage lung cancer patients, who have radiation or chemotherapy in addition to surgery, have higher survival rates. A 2002 analysis suggested that the use of radiotherapy after surgery in patients whose tumors had been completely removed might be associated with reduced survival rates. An analysis of studies using chemotherapy in addition to surgery or radiotherapy, however, indicated benefits in survival. The overall 5-year survival rates for early stage-cancer are in the range of 30 - 50%. Patients should consider clinical trials for prevention of recurring (returning) cancer after the initial treatment. The risk for recurrence is highest in patients who continue to smoke.

Stage IA (T1, N0, M0). The 5-year survival rates for stage IA patients after successful treatment can be as high as 80%. Treatment options are:
- Lobectomy or sometimes pneumonectomy (removal of one lung)
- Wedge or segment removal, particularly in patients with poor lung function who cannot withstand lobectomy
- Radiation in selected patients whose condition is inoperable (for example, frail patients with T1 tumors); 5-year survival rates can be equal to those with surgery, between 32 - 60%
- Clinical trials of adjuvant chemotherapy following surgery

Stage 1B (T2, N0, M0). Stage IB survival rates after treatment can be better than 60%. Treatment options are:
- Lobectomy or sometimes pneumonectomy; wedge or segment removal, particularly patients with poor lung function
- Clinical trials of chemotherapy following surgery
- Clinical trials of chemotherapy before surgery (induction therapy; studies are promising)
- Clinical trials for radiation treatments in selected patients whose condition is inoperable
- Clinical trials of chemotherapy before, after, or during radiation treatments

In stage II the cancer cells have spread to nearby lymph nodes.

General Treatment Options. Surgery, usually removal of a lobe (lobectomy) or one lung (pneumonectomy), is the treatment of choice. Five-year survival rates associated with stage II surgery can vary. A 2000 review of existing research places the numbers as high as 40 - 50%, but notes that they can drop to 25% and below if the cancer has spread beyond the immediate lymph nodes.

Patients whose cancer is inoperable may consider radiation treatments. In patients who can complete treatment, 5-year survival rates average 20 - 30%, with higher rates for stage IIA. Patients should consider clinical trials for prevention of recurring cancer after primary treatment. To date, however, supplementing surgical treatment with radiation or chemotherapy does not appear to prolong survival rates.

Stage IIA (T1, N1, M0). Survival rates can be as high as 60%. Treatment options are:
- Surgery
- Radiation
- Clinical trials of chemotherapy following surgery
- Clinical trials of chemotherapy before, after, or during radiation treatments
- Clinical trials of chemotherapy to reduce tumor size before surgery (induction therapy)
Stage IIB (T2, N1, M0) or (T3, N0, M0). Survival rates can be over 40%. Treatment options are:
- Surgery
- Radiation
- Clinical trials of chemotherapy following surgery
- Clinical trials of chemotherapy before surgery (induction therapy)
- Clinical trials of chemotherapy before, after, or given at the same time as radiation treatments

In stage III, the cancer cells have spread beyond the lung to the chest wall, diaphragm, or further lymph nodes, such as those in the neck.

General Treatment Options. Generally, the treatment of choice for stage III tumors is radiation and sometimes surgery, chemotherapy, or combinations of all three.

Combination approaches may be significantly more effective than single treatments. For example, of particular interest is a treatment approach that starts with chemotherapy and radiation, given at the same time, followed by surgery. In one study, 5-year survival in stage III patients treated this way was nearly 50%.

Stage IIIA (T1, N2, M0) or (T2, N2, M0) or (T3, N1, M0) or (T3, N2, M0).
- Surgery, if the tumor and affected lymph nodes can be completely removed. Consider platinum-based chemotherapy or radiation therapy after surgery.
- Radiation treatment plus platinum-based chemotherapy, given at the same time, is an option for those in otherwise good health. This regimen should be followed by surgery, if possible.
- Consider clinical trials using advanced radiation techniques, including continuous hyperfractionated accelerated radiation, or 3-D conformal radiation.
- Consider other clinical trials, including those of various combination treatments, preventive radiation therapy to the brain, and new second-line drugs.
Stage IIIB (Any T, N3, M0) or (T4, Any N, M0). Some patients may consider surgery if there is no lymph node involvement (T4, N0), and tumor can be removed. Surgery is not an option for other patients with stage IIIB cancer. Treatment options are:
- Radiation alone, usually for symptom control; it may improve survival in certain patients, such as those with lymph node involvement above the collar bone
- Chemotherapy alone
- Concurrent (given at the same time) cisplatin-based chemotherapy plus radiation, sometimes followed by surgery if possible
- Clinical trials using induction chemotherapy alone to shrink tumors, which may then be treated with surgery or radiation
- Clinical trials using advanced radiation techniques, including continuous hyperfractionated accelerated radiation, or 3-D conformal radiation
- Other clinical trials, including those of various combination treatments, preventive radiation therapy to the brain, and new second-line drugs

In stage IV (any T, any N, M1), the cancer has spread (metastasized) to other parts of the body.

Treatment Options are:

Combination of two- or three-drug chemotherapies that include platinum-based drugs and newer agents; the best patient candidates are those in otherwise good health, who have a limited number of distant metastasized sites. Chemotherapy is not recommended for patients who are too ill
External-beam radiation for symptom relief
Paclitaxel or gemcitabine as a single medication
Other clinical trials
If metastasized cancer involves only one or two areas in the brain, it may respond to surgery followed by radiation to the brain

Recurring or additional new tumors occur, usually in the lung again, in half of treated patients. Research shows that a single tumor in the lung is more often a new tumor that, in many cases, may be operable.

Treatment Options are:

Radiation for symptom control
Chemotherapy with or without bevacisumab (Avastin)
If the cancer spread to only one site in the brain, it may respond to surgery, followed by whole-brain radiation. Extended disease-free survival is possible. If the brain tumor is not operable, it is treated with radiation. Even if cancer returns in the brain (in 50% of cases), treating it again is possible in many patients, if the disease has not spread elsewhere
Laser therapy or interstitial radiation for tumors inside the airways
Stereotactic radiosurgery (in a few selected patients)

Chemotherapy Treatments

Chemotherapy is the use of drugs given by mouth or by injection to destroy cancer cells that may have spread beyond the tumor. Until recently, there has been some doubt about the effectiveness of chemotherapy for lung cancer. A major 2002 analysis of 52 trials supported its use, particularly with platinum-based regimens, and with the use of supportive care.

Chemotherapy in early stages: Chemotherapy is proving to be beneficial in many patients as an additional (adjuvant) treatment with surgery or radiation.
Chemotherapy in advanced disease: Chemotherapy may be used as first-line treatment in patients with inoperable or metastasized lung cancer. It is typically used in late stages to reduce symptoms and, in some cases, extend survival. Since 2006, the combination of bevacizumab (Avastin, a monoclonal antibody) and platinum-based chemotherapy is also a first line treatment choice for such patients, if the cancer is the non-squamous type

Powerful platinum compounds, either cisplatin (Platinol) or carboplatin (Paraplatin), are the basis for most chemotherapy regimens. Two-drug combinations, with one drug being a platinum-based agent, are currently the preferred regimens. Reasonable combinations include paclitaxel (Taxol) and carboplatin or cisplatin. This regimen can also include gemcitabine, docetaxel, or vinblastine or its derivative (vindesine or vinorelbine). There does not seem to be any significant differences in effectiveness among them. Gemcitabine and vinorelbine combination might be a good option for patients who cannot tolerate platinum compounds. Chemotherapy for lung cancer may have reached its peak. Still, investigative chemotherapeutic drugs may yet improve response. Many experts are pinning their hope on agents called biologic response modifiers, such as gefitinib (Iressa) or LY900003 (Affinitak). To date, however, they have not achieved better results than standard platinum-based chemotherapies. Gefitinib (Iressa), a second-line therapy for non-small cell lung cancer (NSCLC), is now available only for a limited group of patients. These patients have benefited from gefitinib in the past, or they are enrolled in a clinical study with the drug. While this medicine initially showed great promise in clinical trials, results from a newer study failed to show that it prolonged survival in advanced lung cancer patients who failed other treatments.

If you are currently taking gefitinib, do not stop taking it without talking to your doctor.

Erlotinib (Tarceva) is in the same medication class as gefitinib. It is approved for patients with locally advanced or metastatic NSCLC, who have failed one type of chemotherapy treatment in the past (it is a second-line treatment). Unlike gefitinib, erlotinib shows survival and progression-free benefits compared to placebo. However, it should not be combined with platinum-based chemotherapy.

Chemotherapy treatments are usually performed in an outpatient setting and in regular cycles for several months. How many chemotherapy cycles to administer in late-stage cancers, the timing of those cycles, and the sequences of the drugs are still matters of investigation. For instance, research suggests that a three- or four-course cycle may achieve the same survival times and better quality of life than the standard of six or more course cycles. Changing even one day in a drug sequence can sometimes significantly affect outcome. Such fine-tuning of chemotherapy regimens is likely to have the most effect on patients with advanced-stage disease, which requires more tailored treatment than early-stage disease.

Treatment for lung cancer depends on the type of cancer and the stage of the disease. Chemotherapy is a form of treatment for lung cancer that may cure, shrink, or keep the cancer from spreading.

Side effects of chemotherapy treatments are common, and they are more severe with higher doses. Side effects increase over the course of treatment. Some trials suggest that they can be reduced by giving the drugs for shorter durations, without loss of cancer-killing effects. Common side effects include the following:

Diarrhea
Temporary hair loss
Weight loss
Fatigue
Depression
Nausea and vomiting: Drugs known as serotonin antagonists, especially ondansetron (Zofran), can relieve these two side effects. Serotonin antagonists work well in nearly all patients given moderate drugs, and in most patients who take drugs that are more powerful. In one study, a combination of dexamethasone (a steroid) with ondansetron, taken within 24 hours of chemotherapy, achieved either a major or complete reduction in nausea and vomiting.
Anemia: Anemia, an abnormally low number of red blood cells, is common in lung cancer. Treatments include transfusions or injections of erythropoietin, an agent that causes more red blood cell production. Erythropoietin is available as epoetin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp), which requires fewer injections. These agents improve well-being and quality of life. Trials are in progress to determine if they may have survival benefits as well.

These side effects are nearly always temporary. Most patients are able to continue with normal activities for all but perhaps 1 or 2 days per month.

Serious complications of chemotherapy can also occur and may vary depending on the specific drugs. They include the following:

Increased chance for infection from suppression of the immune system.
Severe drops in white blood cells (neutropenia): Certain chemotherapy drugs, such as taxanes, pose a higher risk for this complication than other drugs. White blood cell count can improve with the addition of a type of drug called granulocyte colony-stimulating factor (filgrastim and lenograstim).
Liver and kidney damage: Amifostine (Ethyol) reduces the risk for kidney damage in patients taking repeated regimens of cisplatin-based therapy. It is also a radioprotector; that is, it helps prevent severe effects in the esophagus from radiotherapy, with or without chemotherapy.
Abnormal blood clotting (thrombocytopenia).
Allergic reaction, particularly to platinum-based agents: A simple skin test is under investigation that may identify people with a potential allergic response.

Second-line chemotherapy is used for patients whose cancers have recurred after first-line chemotherapy. Some experts believe that the longer survival rates for advanced lung cancer seen for the past 5 years may be due to these drugs. Because platinum-based agents are most often used first, they are not beneficial for second-line therapy. The following are commonly used second-line agents.

Docetaxel (Taxotere). Docetaxel is the drug of choice at this time for cancers that do not respond to initial chemotherapy. Studies have reported that it achieves longer survival times than supportive care alone. It is usually given every 21 days. This regimen causes more side effects than pemetrexed, the newer major second-line drug. Weekly doses of docetaxel are effective and less toxic than the 3-week schedule. It is not clear if survival rates are comparable to those of pemetrexed with that schedule, however.

Pemetrexed (Alimta). Pemetrexed, known as an anti-folate, is another promising new agent for second-line therapy and possibly for first-line treatment as well. The drug targets a number of enzymes that play a role in how cancer cells increase. Some research suggests that it is as effective as docetaxel. Pemetrexed does have some serious toxic effects, but they can be significantly reduced with folic acid and vitamin B12 supplements. It is then less toxic than docetaxel, when docetaxel is given every 21 days, but not when it is given weekly.

Gefitinib (Iressa) and Other Tyrosine Kinase Inhibitors. Much research is focusing on drugs that block small molecules involved with the growth of blood vessels that feed the tumor (a process called angiogenesis). Compounds called growth factors, which may be important in cancer cell production, control the growth of these new blood vessels. Researchers, then, are interested in medications that literally turn off these growth factors or their receptors, such as epidermal growth factor receptor (EGFR). In so doing, the agents may be able to cut off cancer's lifeblood. Gefitinib and erlotinib are angiogenesis inhibitors that target receptors of an epidermal growth factor called tyrosine kinase. Interestingly, studies are finding that NSCLC tumors in people who have never smoked have a much higher rate of EGFR mutations. This helps to explain why gefitinib and erlotinib are more effective in treating NSCLC in people who have never smoked.

Gefitinib (Iressa) was approved in 2003 as a second-line therapy for non-small cell lung cancer. Many patients report significant improvement in symptoms and quality of life, and the drug initially showed great promise. In one study, gefitinib reduced tumor size by 50% in about 10% of the patients. However, recent large-scale clinical trial results have failed to confirm any survival advantage for most patients. At this time, gefitinib is available only for patients who have benefited from it in the past.
Erlotinib (Tarceva) was approved as a single agent second-line therapy in November 2004. Study results show that the drug prolonged survival by several more months than placebo (6.7 versus 4.7 months). Erlotinib is administered orally and has very low toxicity (rash and diarrhea are common).

Chemotherapy Following Surgery (Adjuvant Chemotherapy). Chemotherapy is being evaluated in combination with surgery, radiation therapy, or both. Fairly strong evidence is now supporting the use of platinum-based chemotherapy as adjuvant treatment after surgery in patients with lung cancers in stages Ib-IIIa, with some research indicating a 5% improvement in five-year survival rates. Not all studies confirm survival benefits, however, and trials are ongoing.

Chemotherapy before Surgery (Induction Chemotherapy). Some researchers are testing induction chemotherapy, which is used to shrink potentially operable tumors before surgery. Studies have been mixed in reporting any survival benefits in patients with advanced lung cancer.

Combined and Multi-Modal Therapy. In stage III cancers, investigators are researching very intensive treatments that use two or more combinations of chemotherapy, radiation, and surgery.

For example, radiation plus chemotherapy may be helpful in patients whose tumors are surgically removable.

In inoperable lung cancer, combining radiation with chemotherapy is proving to extend the time to recurrence, the overall duration of survival, or both, compared to radiation alone. Evidence also suggests that giving radiation treatments at the same time as chemotherapy (instead of in separate cycles) improves 5-year survival rates, compared to a sequential approach (separate cycles following each other). Chemotherapy and radiation treatments given at the same time are more toxic, however.

Other approaches use even more intensive multi-modal therapy. For example, some trials use radiation therapy with chemotherapy, followed by surgery. Patients are then sometimes given additional chemotherapy or radiation. In other promising regimens, patents are given concurrent radiation and chemotherapy followed by chemotherapy alone. Such approaches are very toxic but appear to improve survival in selected patients.

Severe inflammation in the esophagus is the most common severe side effect of the radiation and chemotherapy combination. There is also a very high risk of serious infections, including pneumonia, herpes zoster, and cytomegalovirus. Long-term antibiotic therapy may be needed.

Although patients over 70 may suffer more from toxic effects than younger patients, studies now suggest that they can achieve survival rates with combined treatments that are equal to those in younger patients.

There are many painkilling medications available. Research shows that aggressive pain relief can help patients manage cancer treatment symptoms (in addition to pain) better. For example, a 2001 study suggested that reducing pain in elderly cancer patients markedly lowered their fatigue levels, and improved other symptoms as well.

Opioids are the most potent painkillers. The correct use of these strong medications is very important for reaching acceptable pain relief, and preventing a toxic response. For example, the long-lasting version of oxycodone (OxyContin) must be swallowed whole; chewing, inhaling, or injecting it can create a deadly overdose.

Investigative Agents

According to a 2001 article, of the nearly 500 cancer drugs currently in development, 58 of them (about 13%) are aimed at fighting lung cancer. Only the number of breast cancer drugs exceeded that percentage. Unfortunately, none to date have shown any real benefit in terms of patient survival. However, some drugs are showing promise, and at this time, these agents are the best hope for improving lung cancer survival rates.

Monoclonal antibodies (MAbs) are genetically designed immune factors. MAbs mark foreign compounds called antigens for attack by the immune system. Trastuzumab (Herceptin) and cetuximab (Erbitux) are MAbs under investigation for lung cancer. Bevacizumab (Avastin) was approved in October 2006 as a first-line treatment (in combination with carboplatin and paclitaxel) for inoperable, locally advanced, metastatic, or recurrent non-squamous, non-small cell lung cancer.

All three of these MAbs block epidermal growth factor. These agents are of particular interest for patients who have cancers that produce too much of the protein called HER2. These agents show great promise in combination with chemotherapies and newer drugs, such as the tyrosine kinase inhibitors. For example, the disease-free survival time in patients with advanced NSCLC is longer when adding bevacizumab to platinum-based chemotherapy.

Antisense oligonucleotides are drugs being used to block molecules that result in too many cells that cause cancers. LY900003 (Affinitak), for example, targets an enzyme called PKC-alpha, which promotes tumor growth. Early studies with Affinitak showed some promising results. However, a 2003 study found no difference in survival when patients received Affinitak in combination with platinum-based chemotherapy, compared to patients receiving chemotherapy alone.

Genasense (G3139, oblimersen) blocks Bcl-2. Bcl-2 is a protein that is expressed in abnormally high amounts in some cancers. This antisense drug is also under investigation.

Advexin, a genetic therapy that contains the p53 tumor-suppressor gene, is showing promise. In one early study, 60% of patients experienced partial or total tumor shrinkage when the agent was used in combination with radiation therapy. A 2006 study in Japan found that out of 13 patients with advanced NSCLC receiving Advexin, 10 had stabilized. Three of the stabilized patients remained stable for over 9 months. One patient had a partial response to Advexin. The only side effect of the multiple doses given was a passing fever that disappeared within 24 hours. Advexin is in Phase II clinical trials for NSCLC.

Vaccines use inactivated genetic materials from cancer cells, such as defective p53 or ras genes, to cause a highly targeted immune response to attack the cancer.

Retinoids are vitamin A-like antioxidant chemicals that help repair cell damage and appear to support growth of lung cells. A number of retinoid-like agents (retinal palmitate, TAC-101, 23-cis-retinoic acid, N-acetyl-cysteine) are being studied for the treatment or prevention of lung cancer.

Resources

www.cancer.gov -- National Cancer Institute
www.cancer.org -- American Cancer Society
www.cancercare.org -- Cancer Care
www.lungusa.org -- The American Lung Association
www.asco.org -- American Society of Clinical Oncology
www.alcase.org -- Alliance for Lung Cancer
www.lungcancer.org -- Joint project of Cancer Care and the Oncology Nursing Society
www.nccn.org -- National Comprehensive Cancer Network
www.lungcanceronline.org -- Lung cancer information
www.epa.gov/iaq/radon -- National radon information
www.clinicaltrials.gov -- Find clinical trials
www.cancer.gov/clinicaltrials -- Find clinical trials

References

Abeloff MD, Armitage JO, Niederhuber JE, Kastan MB, McKena WG. Clinical Oncology. 3rd ed. Orlando, Fl: Churchill Livingstone; 2004:1690-1701.

American Cancer Society. Cancer Facts and Figures 2006. Atlanta, Ga: American Cancer Society; 2006.

American Cancer Society. Cancer Facts and Figures 2007. Atlanta, Ga.: American Cancer Society; 2007:34.

Janne PA. Non-small Cell Lung Cancer in Never-smokers: A Biologically and Clinically Distinct Type of Lung Cancer. In: ASCO 2007 Educational Book. Meeting of the American Society of Clinical Oncology, Chicago, Ill.: June 1-5, 2007.

Kagawa S, Fujiwara T, Saijo Y, et al. A multicenter phase I study of adenoviral p53 (ADVEXIN) in Japanese patients with advanced non-small cell lung cancer. Journal of Clinical Oncology. 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 2564.

Mehra R, Moore BA, Crothers K, Tetrault J, Fiellin DA. The association between marijuana smoking and lung cancer: a systematic review. Arch Intern Med. 2006 Jul 10;166(13):1359-67.

National Cancer Institute. Lung Cancer Home Page. Bethesda, Md.: U.S. National Institutes of Health. Available online.

National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer. Version 1.2007. Available online.

Tarceva [Package Insert]. Melville, NY: OSI Pharmaceuticals; 2005.

U.S. Department of Health and Human Services. The Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon General. Atlanta, Georgia: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Coordinating Center for Health Promotion, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2006.

U.S. Food and Drug Administration, Center for Drug Evaluation and Research. List of Approved Oncology Drugs with Approved Indications. In: Oncology Tools. Available online.

U.S. Preventive Services Task Force. Lung cancer screening. Ann Int Med. 2004;140:738-739.

Xin M, Deng X. Nicotine Inactivation of the Proapoptotic Function of Bax through Phosphorylation. J Biol Chem. 2005 Mar 18;280(11):10781-9.

Review Date:
8/3/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Heart failure

FitSugar — Wed, 08 Oct 2008 17:35:10 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Risk Factors
Complications
Diagnosis
Treatment
Medications
Surgery and Devices
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Permanent Implantable Heart Approved

In 2006, the FDA approved the first permanent artificial heart. The AbiCor is intended for patients who are not eligible for heart transplants and who are only expected to survive about a month without medical treatment. Patients who received the AbiCor have survived, on average, about 5 months.

Statin Drug Approved for Heart Failure

In 2006, the FDA approved the cholesterol drug atorvastatin (Lipitor) to reduce the risks of hospitalization for heart failure in patients with heart disease.

Drug Research

The investigational drug tolvaptan improved symptoms in patients hospitalized with severe heart failure and fluid build-up in the lungs, according to several 2007 Journal of the American Medical Association (JAMA) studies. However, the drug did not reduce the risks of re-hospitalization and death.

Preserved Versus Reduced Ejection Fraction

Heart failure with preserved left-ventricular ejection fraction (LVEF) is becoming more common, suggests several 2006 studies published in JAMA and the New England Journal of Medicine. Unfortunately, this type of heart failure is less well studied than reduced LVEF. Experts are urging that more studies be conducted to determine better treatment options for preserved LVEF. Both types of heart failure have high mortality rates.

Systolic Blood Pressure Predictor of Mortality

Patients who are admitted to the hospital with heart failure and low systolic blood pressure have a poorer chance of survival than patients admitted with high blood pressure, indicates a 2006 JAMA study.

Diet and Lifestyle Factors

Daily consumption of whole-grain breakfast cereals may reduce the risk for heart failure, suggests research presented at a 2007 American Heart Association conference on heart disease prevention.
A drink or two a day is associated with lower risk of heart failure, indicates a 2006 Journal of the American College of Cardiology study. However, heavy alcohol consumption can increase the risk for heart failure.

Introduction

To understand what occurs in heart failure, it is useful to be familiar with the anatomy of the heart and how it works. The heart is composed of two independent pumping systems, one on the right side, and the other on the left. Each has two chambers, an atrium and a ventricle. The ventricles are the major pumps in the heart.

The Right Side of the Heart. The right system receives blood from the veins of the whole body. This is "used" blood, which is poor in oxygen and rich in carbon dioxide.

The right atrium is the first chamber that receives blood.
The chamber expands as its muscles relax to fill with blood that has returned from the body.
The blood enters a second muscular chamber called the right ventricle.
The right ventricle is one of the heart's two major pumps. Its function is to pump the blood into the lungs.
The lungs restore oxygen to the blood and exchange it with carbon dioxide, which is exhaled.

The Left Side of the Heart. The left system receives blood from the lungs. This blood is now oxygen rich.

The oxygen-rich blood returns through veins coming from the lungs (pulmonary veins) to the heart.
It is received from the lungs in the left atrium, the first chamber on the left side.
Here, it moves to the left ventricle, a powerful muscular chamber that pumps the blood back out to the body.
The left ventricle is the strongest of the heart's pumps. Its thicker muscles need to perform contractions powerful enough to force the blood to all parts of the body.
This strong contraction produces systolic blood pressure (the first and higher number in blood pressure measurement). The lower number ( diastolic blood pressure) is measured when the left ventricle relaxes to refill with blood between beats.
Blood leaves the heart through the ascending aorta, the major artery that feeds blood to the entire body.

The Valves. Valves are muscular flaps that open and close so blood will flow in the right direction. There are four valves in the heart:

The tricuspid regulates blood flow between the right atrium and the right ventricle.
The pulmonary valve opens to allow blood to flow from the right ventricle to the lungs.
The mitral valve regulates blood flow between the left atrium and the left ventricle.
The aortic valve allows blood to flow from the left ventricle to the ascending aorta.

Click the icon to see an image of the internal structures of the heart.

The Heart's Electrical System. The heartbeats are triggered and regulated by the conducting system, a network of specialized muscle cells that form an independent electrical system in the heart muscles. These cells are connected by channels that pass chemically caused electrical impulses.

Click the icon to see an image of the conduction system of the heart.

Heart failure is not a disease. It is a condition or process in which the heart is unable to pump enough blood to meet the needs of the body's tissues. The heart doesn't "fail" in the sense of ceasing to beat (as occurs during a heart attack). Rather, it weakens, usually over the course of months or years, so that it is unable to pump out all the blood that enters its chambers. As a result, fluids tend to build up in the lungs and tissues, causing congestion. This condition used to be called "congestive heart failure," but the name was officially changed to heart failure in 2005.

Ways the Heart Can Fail. Heart failure can occur in several ways:

The muscles of the heart pumps (ventricles) become thin and weakened. They stretch (dilate) to the extent that they cannot pump the blood with enough force to reach all the body's tissues.
The heart muscles stiffen or thicken. Here, they lose elasticity and cannot relax. Insufficient blood enters the chamber, so not enough blood is pumped out into the body to serve its needs.
Sometimes the valves of the heart are abnormal. (Valves open or close to control the flow of blood entering or leaving the heart). They may narrow, such as in aortic stenosis, causing a back up of blood, or they may close improperly so that blood leaks back into the heart. The mitral valve (which regulates blood flow between the two chambers on the left side of the heart) often becomes leaky in severe heart failure -- a condition called mitral regurgitation.

Click the icon to see an image of the valves of the heart.

The very mechanisms that the body uses to compensate for inefficient heart pumping can, over time, change the architecture of the heart (called remodeling) and finally lead to irreversible problems.

The specific effects of heart failure on the body depend on whether it occurs on the left or right side. Over time, however, in either form of heart failure, the organs in the body do not receive enough oxygen and nutrients, and the body's wastes are removed slowly. Eventually, vital systems break down.

Failure on the Left Side (Left-Ventricular Heart Failure). Failure on the left side of the heart is more common than failure on the right side. The failure can be a result of abnormal systolic (contraction) or diastolic (relaxation) action:

Systolic. Systolic heart failure is a pumping problem. In systolic failure, the heart muscles weaken and cannot pump enough blood throughout the body. The left ventricle is usually stretched (dilated). Fluid backs up and accumulates in the lungs (pulmonary edema). Systolic heart failure typically occurs in men between the ages of 50 - 70 years who have had a heart attack.
Diastolic. Diastolic heart failure is a filling problem. When the left ventricle muscle becomes stiff and cannot relax properly between heartbeats, the heart cannot fill fully with blood. When this happens, fluid entering the heart backs up. This causes the veins in the body and tissues surrounding the heart to swell and become congested. Patients with diastolic failure are typically women, overweight, and elderly, and have high blood pressure and diabetes.

Failure on the Right Side (Right-Ventricular Heart Failure). Failure on the right side of the heart is most often a result of failure on the left. Because the right ventricle receives blood from the veins, failure here causes the blood to back up. As a result, the veins in the body and tissues surrounding the heart to swell. This causes swelling in the feet, ankles, legs, and abdomen.

Ejection Fraction. To help determine the severity of left-sided heart failure, doctors use an ejection fraction (EF) calculation, also called a left-ventricular ejection fraction (LVEF). This is the percentage of the blood pumped out from the left ventricle during each heartbeat. An ejection fraction of 50 - 75% is considered normal. Patients with left-ventricular heart failure are classified as either having a preserved ejection fraction (greater than 50%) or a reduced ejection fraction (less than 50%).

In general, systolic heart failure has been thought to be associated with a reduced ejection fraction, whereas diastolic heart failure was associated with a preserved (normal) ejection fraction. However, several 2006 studies indicated that diastolic heart failure can occur regardless of the ejection fraction, although it is more common in patients with a preserved ejection fraction. Mortality rates among patients with reduced LVEF and preserved LVEF are similar.

Although reduced LVEF heart failure is better studied, and its treatment goals more clearly defined, several important 2006 studies suggest that preserved LVEF heart failure is becoming increasingly common. The studies, published in the Journal of the American Medical Association and the New England Journal of Medicine, indicated that patients with preserved LVEF heart failure are more likely to be female and older, and have a history of high blood pressure and atrial fibrillation (a disturbance in heart rhythm). Experts are now urging that more studies focus on patients with preserved LVEF so that better treatment options can be established.

Causes

Heart failure has many causes and can evolve in different ways.

It can be a direct, last-stage result of heart damage from one or more of several heart or circulation diseases.
It can occur over time as the heart tries to compensate for abnormalities caused by these conditions, a condition called remodeling.

In all cases, the weaker pumping action of the heart means that less blood is sent to the kidneys. The kidneys respond by retaining water and salt. This in turn increases edema (fluid buildup) in the body, which causes widespread damage.

Uncontrolled high blood pressure (hypertension) is also a major cause of heart failure even in the absence of a heart attack. In fact, about 75% of cases of heart failure start with hypertension. It generally develops as follows:

The heart muscles thicken to make up for increased blood pressure.
The force of the heart muscle contractions weaken over time, and the muscles have difficulty relaxing. This prevents the normal filling of the heart with blood.

[See In-Depth Report #14:High blood pressure.]

Hypertension is a disorder characterized by consistently high blood pressure. Generally, high blood pressure consists of systolic blood pressure (the "top" number, which represents the pressure generated when the heart beats) higher than 140, or diastolic blood pressure (the "bottom" number, which represents the pressure in the vessels when the heart is at rest) over 90.

Coronary artery disease is the end result of a complex process called atherosclerosis (commonly called "hardening of the arteries"). It is the most common cause of heart attack and involves the build-up of unhealthy cholesterol in the arteries, with inflammation and injury in the cells of the blood vessels. The arteries narrow and become brittle. Heart failure in such cases most often results from a pumping defect in the left side of the heart. [See In-Depth Report #3: Coronary artery disease and angina ; and In-Depth Report #23: Cholesterol.]

Click the icon to see an image of atherosclerosis.

People now often survive heart attacks, but eventually many develop heart failure from the physical damage done to the heart muscles by the attack. Ironically, heart attack recovery is probably one of the major factors in the dramatic increase in heart failure cases over the past decade. On an encouraging note, however, new therapies that are reducing the severity of heart attacks may help stabilize heart failure rates. [See In-Depth Report #12: Heart attack.]

The valves of the heart control the flow of blood leaving and entering the heart. Abnormalities can cause blood to back up or leak back into the heart.

Click the icon to see an image of the heart valves.

In the past, rheumatic fever, which scars the heart valves and prevents them from closing, was a major cause of death from heart failure. Fortunately, antibiotics have relegated this disease to a minor cause of heart failure. Birth defects may also cause abnormal valvular development. Although more children born with heart defects are now living to adulthood, they still face a higher than average risk for heart failure as they age.

Cardiomyopathy is disease that damages the heart muscles and leads to heart failure. There are several different types. Injury to the heart muscles may cause the heart muscles to thin out (dilate) or become too thick (become hypertrophic). In either case, the heart doesn't pump correctly.

Dilated Cardiomyopathy. Dilated cardiomyopathy involves an enlarged heart ventricle. The muscles thin out, reducing the pumping action, usually on the left side. Although this condition is associated with genetic factors, the direct cause often is not known. (This is called idiopathic dilated cardiomyopathy.) Research strongly indicates that viruses, such as Coxsackie virus, or other infections may be at the base of this condition. Experts think that an autoimmune response occurs in which infection-fighting antibodies attack a person's own proteins in the heart, mistaking them for foreign substances.

Click the icon to see an image of dilated cardiomyopathy.

Hypertrophic Cardiomyopathy. In hypertrophic cardiomyopathy, the heart muscles become thick and contract with difficulty. Some research indicates that this occurs because of a genetic defect that causes a loss of power in heart muscle cells and, subsequently, lower pumping strength. To compensate for this power loss, the heart muscle cells grow. This condition, rare in the general population, is often the cause of sudden death in young athletes.

Click the icon to see an image of hypertrophic cardiomyopathy.

High blood pressure, heart attacks, or other initial processes that impair the pumping actions of the heart trigger a number of hormonal and neurochemical mechanisms to correct imbalances in pressure and blood flow. Unfortunately, while these corrective responses help in the short term, they increase the work of the heart. The mechanisms are now viewed as major contributors to the end stages of heart failure. Some are described briefly in the following sections.

Remodeling. The heart responds to high blood pressure and overload by enlarging in order to increase blood input. This leads to structural damage called remodeling:

In order to accommodate the increased blood input, the heart muscle cells elongate. The muscular walls of the heart that they form become thinner and inefficient.
The muscle cells undergo other changes that result in calcium loss. Calcium is a mineral that is crucial for healthy heart contractions.
The thinner heart muscles and the impaired heart contractions further weaken the heart's pump.
Mitral valve regurgitation is a possible outcome of remodeling. The mitral valve regulates blood flow between the two chambers on the left side of the heart. In response to remodeling, the structural changes in the heart may distort the mitral valve so that the blood leaks backward into the left atrium of the heart instead of flowing out into the body's circulation.
These changes are generally irreversible, although heart pacemakers and certain drugs, including beta-blockers and ACE inhibitors, may reverse some of the remodeling in some patients.

Activation of the Sympathetic Nervous System. The sympathetic nervous system consists of the nerve cells that automatically govern and regulate the beating heart.

This nervous system responds to the failing heart pump by signaling the release of stress hormones, in particular a powerful one called norepinephrine.
These hormones flood the heart, causing it to beat even faster.
These rapid heart beats, although intended to accommodate the weakened pumping actions, only accelerate the damage.

The Renin-Angiotensin-Aldosterone System (RAAS). The renin-angiotensin-aldosterone system (RAAS) is a group of hormones that are responsible for the opening and narrowing of blood vessels and retention of fluids. They also affect cell development in the heart.

The RAAS hormones are called into action by the failing heart.
They respond to the lower blood volume of the weakened heart by constricting the blood vessels and retaining fluids and sodium.
The heart then works harder to pump blood through these narrowed vessels. Blood pressure, then, is forced to increase, which creates a vicious cycle.

Immune System Response. The immune system may also compound the damage. In response to injury in the heart muscle cells or in other parts of the body that occurs as the heart fails, the immune system releases factors intended to protect these areas.

In excess, however, they can cause inflammation and damage.

The most important of these factors are called cytokines. Active cytokines include tumor necrosis factor (TNF) and possibly interleukins 1 and 6.
High levels of these cytokines have been observed in patients with the most severe classes of heart failure.
They may play an important role in the process leading to remodeling. High levels of these cytokines may actually trigger muscle cell growth and enlargement of the heart.

Other Players. Other molecules or compounds have been identified that might play a positive or negative role in the process of the failing heart.

Natriuretic peptides are a family of compounds released to counterbalance the effects of RAAS. Atrial natriuretic peptide (ANP) is a specific member of this family that opens blood vessels and counteracts the sodium-retaining properties of aldosterone (one of the RAAS hormones). It is of particular interest to researchers looking for new treatments.
Endothelin is a powerful protein involved in blood vessel constriction, cell proliferation and build-up, and other negative effects on the heart.
Nitric oxide is important for blood vessel dilation and elasticity.

Symptoms

Many symptoms of heart failure result from the congestion that develops as fluid backs up into the lungs and leaks into the tissues. Other symptoms result from inadequate delivery of oxygen-rich blood to the body's tissues. Since heart failure can progress rapidly, it is essential to consult a doctor immediately if any of the following symptoms are detected.

Fatigue and shortness of breath (dyspnea) are the first symptoms. They are caused by fluid in the lungs. Patients typically report that they feel out of breath after mild exertion. It is unlike the breathlessness of angina, which feels like a heavy weight pressing on the chest.

Fluid retention. Patients may complain of leg or abdominal swelling.
Wheezing or cough. Patients may have asthma-like wheezing or a dry hacking cough that occurs a few hours after lying down, but then stops after the patient sits up.
Central sleep apnea. This disorder results when the brain fails to signal the muscles to breathe during sleep. It occurs in up to half of people with heart failure. Sleep apnea causes disordered breathing at night. If heart failure progresses, the apnea may be so acute that a person, unable to breathe, may awaken from sleep in panic.
Loss of muscle mass. Over time, patients may lose muscle weight due to low cardiac output.

Ultimately, fluid in the lungs may build up. This is called pulmonary edema. When this happens, symptoms become more severe.

In addition to shortness of breath, patients sometimes have a cough that produces a pinkish froth.
Patients may experience a bubbling sensation in the lungs and feel as if they are drowning.
Typically, the skin is clammy and pale, sometimes nearly blue. This is a life-threatening situation, and the patient must go immediately to an emergency room.

Fatigue. As with left-side heart failure, an early symptom of right-side (right-ventricular) failure is extreme tiredness.
Fluid accumulation. This first occurs in the feet, then the ankles and legs, and finally in the abdomen. The liver may also be enlarged.
Weight gain. Although appetites are often depressed, patients with heart failure gain weight because they retain salt and water.
Loss of muscle mass.

Risk Factors

Nearly 5 million Americans currently suffer from heart failure. About 550,000 new cases of heart failure are now diagnosed each year. In 1970 there were only 250,000 new cases, so the annual numbers have risen dramatically. Such numbers represent an increasingly older population. Although there has been a dramatic increase over the last several decades in the number of people who suffer from heart failure, survival rates have been improving greatly.

Coronary artery disease and high blood pressure are the main causes of heart failure. Other diseases that damage or weaken the heart muscle or heart valves can also cause heart failure. Heart failure is most common in people over age 65, African-Americans, and women.

Heart failure is the most common reason for hospitalization in the elderly, and as the population ages, the incidence of heart failure is rising dramatically. According to one report, it occurs at a rate of about 10 in 1,000 people after age 65. The positive implication is, however, that people are living longer with heart failure.

Men are at higher risk for heart failure than women, although the difference narrows with age. Women also have a better survival rate than men do when heart failure is caused by valvular heart disease, high blood pressure, or alcohol abuse. (Some studies indicate that this is because men may be more susceptible to the process of heart muscle-cell remodeling, a damaging effect of hypertension.)

The survival rates of women and men are more similar, however, when heart failure evolves from coronary artery disease or heart attack. Women are much more likely to develop heart failure after a heart attack than men. In such cases, some evidence suggests that the reasons for this may include less aggressive approach to treatment for the initial heart conditions.

African-Americans are at higher risk for heart failure than Caucasians, and studies have reported that they tend to do much worse. In a 2003 study, however, in which Caucasians and African-Americans had comparable treatment, African-Americans actually had lower 1-year mortality rates (with slightly higher rates of rehospitalizations). Some evidence suggests that African-Americans are more often likely than Caucasians to develop diastolic heart failure (a failure of the heart muscle to relax normally), which is often a precursor to systolic heart failure (impaired ability to pump blood). Caucasians tend to develop systolic heart failure first.

According to a 2006 New England Journal of Medicine study, people whose parents had heart failure have a greatly increased risk of developing heart failure, particularly left-ventricular systolic heart failure. Earlier studies have suggested that a family history of early heart failure caused by cardiomyopathies (diseases that damage the heart muscle) may also predispose people to the disease. Researchers are looking for changes in specific genes that might regulate systems involved in heart failure and so increase susceptibility in certain populations.

Chronic alcohol abuse can damage the heart muscles, can cause hypertension, and may prove to be one cause of idiopathic dilated cardiomyopathy. Moderate alcohol consumption, on the other hand (generally defined as 2 drinks a day for men and 1 drink for women), may protect against heart failure. Non-drinkers, though, are not advised to begin drinking.

Coronary artery disease. More than 60% of heart failure cases may be due to coronary artery disease and its risk factors (smoking, sedentary living, obesity).
Heart attack. The injured heart after an attack is at high risk for failure. The improved survival rates from heart attack over the past decades have actually been responsible for the dramatic increase in heart failure rates.
High blood pressure. Hypertension is a significant risk factor and is present in 75% of patients with heart failure.
Diabetes. People with diabetes are at high risk for heart failure, particularly if they also have coronary artery disease. Even blood sugar abnormalities that precede diabetes increase the risk.
Obesity. Obesity is associated with both hypertension and type 2 diabetes, conditions that place people at risk for heart failure. Evidence strongly suggests that obesity itself is a major risk factor for heart failure, particularly in women. In a major 2002 study, about 14% of heart failure cases in women and 11% in men could be attributed to obesity. Both overweight and obese women had a significantly higher than normal risk for heart failure. Only obesity led to a significant risk in men.
Valvular heart disease. Specific valvular conditions that are common in patients with heart failure include aortic stenosis and mitral regurgitation.
Severe emphysema. Chronic obstructive pulmonary disease is a major risk factor for right-side heart failure.

Emphysema is a lung disease involving damage to the air sacs (alveoli).There is progressive destruction of alveoli and the surrounding tissue that supports them. As the disease gets worse, large air cysts take the place of normal lung tissue. Air is trapped in the lungs.

Cardiomyopathies due to various causes, including birth defects, HIV infection, and other infections.
In rare cases, heart failure can occur in women around the time of childbirth, a condition called peripartum cardiomyopathy.

Click the icon to see an image of peripartum cardiomyopathy.

An overactive thyroid (hyperthyroidism) or underactive thyroid (hypothyroidism) can have severe effects on the heart and increase the risk for heart failure.
Amyloidosis. A starchy protein (amyloid) that builds up in tissues and organs can lead to heart failure.
Surviving childhood cancers. Survivors face a risk for developing heart failure in later years, particularly those treated with chemotherapies such as doxorubicin. Newer cancer advances may reduce this risk.
Acute myocarditis. This rare viral infection involves the heart muscle and can produce temporary but potentially life-threatening heart failure.

Long-term use of anabolic steroids (male hormones used to build muscle mass) increases the risk for heart failure. The drug itraconazole (Sporanox), used to treat skin, nail, or other fungal infections, has been linked to heart failure. In 2006, the FDA warned that the cancer drug imatinib (Gleevec) has been associated with heart failure cases. Most patients who took imatinib and developed heart failure had a history of diabetes, high blood pressure, or heart disease.

Complications

At least 20% of hospitalizations in older adults are due to heart failure. For people over age 65, it is the number one cause of death, with nearly 290,000 people dying from this disease each year. Nevertheless, although heart failure produces very high mortality rates, treatment advances in hypertension, heart surgeries, and heart pacemakers are improving survival rates.

The most serious and life-threatening complications of heart failure are:

Arrhythmias (irregular beatings of the heart)
Acute pulmonary edema (fluid in the lungs)

Left-side heart failure tends to be more severe than right-side heart failure, particularly when it is associated with the following conditions:

Coronary artery disease
HIV infection
Amyloidosis (a metabolic disorder than can lead to organ failure)
Chemotherapy that uses the drug doxorubicin

The outlook is better in patients with left-side heart failure associated with:

Idiopathic cardiomyopathy (the cause is unknown)
Heart failure due to childbirth

Weight Issues. If patients with heart failure are overweight to begin with, their condition tends to be more severe. Once heart failure develops, however, an important indicator of a worsening condition is the occurrence of cardiac cachexia, which is unintentional rapid weight loss (a loss of at least 7.5% of normal weight within 6 months).

Impaired Kidney Function. Heart failure weakens the heart’s ability to pump blood. This can affect other parts of the body including the kidneys (which in turn can lead to fluid build-up). Decreased kidney function is common in patients with heart failure, both as a complication of heart failure and as a complication of other diseases associated with heart failure (such as diabetes). Studies suggest that in patients with heart failure, impaired kidney function increases the risks for heart complications including hospitalization and death.

Congestion (Fluid Buildup). In left-sided heart failure, fluid builds up first in the lungs. Later, as right-sided heart failure develops, fluid builds up in the legs, feet, and abdomen. According to one study, patients with severe symptoms who had congestion (fluid buildup) had poorer survival rates than those without fluid build up. Two-year survival rates were 87% in those who were congestion-free compared to 41 - 67% in patients with various signs of congestion (such as swelling, difficulty breathing when lying down, and weight gain from fluid buildup). Fluid buildup is treated with lifestyle measures, such as reducing salt in the diet, as well as drugs, such as diuretics. Sometimes, for hospitalized patients, an ultrafiltration device is used to remove excess water and salt from the body (see Surgery and Devices).

Atrial Fibrillation. This abnormal rhythm is a rapid quivering beat in the upper chambers of the heart. It is a major cause of stroke and very dangerous in people with heart failure.

Left Bundle Branch Block. Left bundle-branch block is an abnormality in electrical conduction in the heart. It develops in about 30% of patients with heart failure and is a major risk factor for serious adverse heart events.

Systolic Blood Pressure. An important 2006 study indicated that patients who arrive at the hospital with heart failure and low systolic blood pressure have a poorer prognosis than those who arrive with high systolic blood pressure. Researchers think that high systolic blood pressure may be a signal for unique clinical characteristics.

Sleep Apnea. With this disorder, a person stops breathing during the night, perhaps hundreds of times, usually for periods of 10 seconds or longer. It is a very strong risk factor for heart failure, and patients with apnea have a higher mortality rate than those who do not.

Depression. The presence of depression indicates a poorer outlook for the heart. Studies indicate that depression may have adverse biologic effects on the immune and nervous systems, blood clotting, blood pressure, blood vessels, and heart rhythms.

Seasonal and Daily Patterns. Studies have shown that more emergency room visits and higher mortality rates occur during winter months and on Mondays in patients with heart failure. One factor in this higher risk may be sudden and strenuous exertion, particularly snow-shoveling, which is associated with a risk for heart attack in people with heart problems.

Diagnosis

Doctors can often make a preliminary diagnosis of heart failure by medical history and careful physical examination.

The medical history risks for heart failure include:

High blood pressure
Diabetes
Poor cholesterol levels
Heart or peripheral vascular disease
Sleep apnea
Thyroid problems
Obesity
Lifestyle factors (smoking, alcohol use)

The following physical signs, along with medical history, strongly suggest heart failure:

Enlarged heart
Irregular heart sounds
Abnormal sounds in the lungs
Swelling or tenderness of the liver
Fluid retention in legs and abdomen
Elevation of pressure in the veins of the neck

Both blood and urine tests are used to check for problems with the liver and kidneys and to detect signs of diabetes. Lab tests can measure:

Cholesterol and lipid levels
Blood sugar (glucose)
Red blood cell count (to rule out anemia)
Blood sugar levels
Thyroid function

Urine tests can be used to assess the presence of a protein called albumin. Albumin in the urine is usually a sign of kidney disease, but even tiny amounts (microalbumin) signal an increased risk for heart failure in people with and without diabetes.

The exercise stress test measures heart rate, blood pressure, and oxygen consumption while a patient is performing physically, usually walking on a treadmill. It is an important diagnostic component in determining heart failure symptoms. Doctors also use exercise tests to gauge long-term outlook and the effects of particular treatments.

An electrocardiogram (ECG) cannot diagnose heart failure, but it can indicate underlying heart problems. It is sometimes called an EKG. The test is simple and painless to perform. It may be used to diagnose:

Enlargement of the heart muscle, which may help to determine long-term outlook
The presence of coronary artery disease
Abnormal cardiac rhythms. A rhythm pattern called a prolonged QT interval, for example, might predict people with heart failure who are at risk for severe complications and would need more aggressive therapies.

The major benefit of an ECG is that it can help determine which patients do not need an echocardiogram, a more accurate (but more expensive) diagnostic test.

The electrocardiogram (ECG, EKG) is used extensively to diagnose heart disease, from congenital heart disease in infants to myocardial infarction and myocarditis in adults. There are several different types of electrocardiograms.

The best diagnostic test for heart failure is echocardiography. Echocardiography is a noninvasive, entirely safe test that uses ultrasound to image the heart as it is beating. Cardiac ultrasounds provide the following information:

Accurate indications of valve function
The amount of blood flow through the heart's chambers
The location of the failure and where it has occurred

Doctors use information from the echocardiogram for calculating the ejection fraction (how much blood is pumped out during each heartbeat), which is important for determining the severity of heart failure.

Radionuclide Ventriculography. Radionuclide ventriculography is an imaging technique that uses a tiny amount of radioactive material (called a trace element). The substance is injected into a patient. As it passes through the bloodstream it is picked up on x-rays. This is a very important imaging technique for patients with heart failure. It is very sensitive in revealing heart enlargement or evidence of fluid accumulation around the heart and lungs. It is typically used in concert with angiography.

Magnetic Resonance Imaging. Magnetic resonance imaging (MRI) scans that use contrast dyes to improve resolution are proving helpful for identifying patients with irreversible heart damage. Damage appears as very bright areas on the scan.

Doctors may recommend angiography if they suspect that blockage of the arteries is contributing to heart failure. This procedure is invasive.

A thin tube called a catheter is inserted into one of the large arteries in the arm or leg.
It is gently guided through the artery until it reaches the heart.
The catheter measures internal blood pressure at various locations, giving the doctor a comprehensive picture of the extent and nature of the heart failure.
Dye is then injected through the tube into the heart.
X-rays called angiograms are taken as the dye moves through the heart and arteries.
These images help locate problems in the heart's pumping action or blockage in the arteries.

Major complications of angiography are rare (about 0.1%) but can occur. They include stroke, heart attacks, and kidney damage. The more experienced the medical center in this procedure, the lower the risk.

Click the icon to see an image of cardiac catheterization.

Researchers are looking for biologic factors (called biomarkers) that will confirm a diagnosis or suggest a better or worse prognosis. Many are under investigation.

Tumor Necrosis Factor. Elevated levels of tumor necrosis factor (TNF) may be a very strong and accurate predictor of a poor outlook. This immune substance is known to be a potent substance in the inflammatory process.

Natriuretic Peptides. Natriuretic peptides are substances that help regulate salt and water balance in the body. Levels of these peptides increase as heart failure symptoms worsen. Blood tests for brain natriuretic peptide (BNP) are now used to help diagnose heart failure. There are two types of BNP tests: The enzyme-linked immunosorbent assay (ELISA) and the radioimmunosorbent assay (RIA). Research from 2006 suggested that the ELISA test may be more accurate, but it is also more expensive.

BNP testing can be very helpful in correctly diagnosing heart failure in patients who come to the emergency room complaining of shortness of breath (dyspnea). A 2006 study indicated that this test can also help predict which patients with dyspnea are at greatest risk of dying within a year from heart failure.

Brain Metabolites. High levels of a compound called N-acetylaspartate, generated as a byproduct of chemical processes in the brain, may indicate a poor outlook.

Treatment

Guidelines for evaluating the severity of heart failure and determining treatments use a staging system that is similar to the one used for major cancers:

Stage A: Patients are at high risk for heart failure, but there is no evidence of structural damage to the heart. Risk factors include high blood pressure, heart diseases, diabetes, obesity, metabolic syndrome, and previous use of medications that damage the heart (such as some chemotherapy).
Stage B: Patients have a structural heart abnormality but no symptoms of heart failure. Abnormalities include left ventricular hypertrophy and low ejection fraction, asymptomatic valvular heart disease, and a previous heart attack.
Stage C: Patients have a structural abnormality and current or previous symptoms of heart failure, including shortness of breath, fatigue, and difficulty exercising.
Stage D: Patients have end-stage symptoms that do not respond to standard treatments.

According to expert guidelines, the first step in managing heart failure is to treat the primary conditions causing or complicating heart failure. These include:

Coronary artery disease. Treatment includes a healthy diet, exercise, smoking cessation, medications, and, possibly, bypass or angioplasty. [See In-Depth Report #3: Coronary artery disease and angina.]
Cholesterol and lipid problems. Treatments include lifestyle management and medications, especially statins. [See In-Depth Report #23: Cholesterol.]
High blood pressure. A normal systolic blood pressure is considered below 120 mm Hg, and a normal diastolic blood pressure is below 80 mm Hg. Patients with diabetes or chronic kidney disease should maintain blood pressure readings of 130/80 or less, while other patients with high blood pressure should aim for readings no higher than 140/90. Effective reduction of blood pressure reduces the risk of heart failure by 30 - 50%. [See In-Depth Report #14: High blood pressure.]
Diabetes. Treating diabetes is extremely important for reducing the risk for heart disease. ACE inhibitors are especially beneficial, particularly for people with diabetes. Recent research suggests that metformin, a drug used to treat diabetes, may also help prevent heart failure. [See In-Depth Report #60: Diabetes - type 2; and In-Depth Report #9: Diabetes - type 1.]
Valvular abnormalities such as aortic stenosis and mitral regurgitation. Surgery may be required.
Abnormal health rhythms (arrhythmias). Ventricular assisted devices, notably biventricular pacers (BVPs), are proving to be important in preventing hospitalizations for patients with these conditions.
Anemia. Giving erythropoietin (EPO) and iron injections to patients with heart failure and underlying anemia not only reverses the anemia, but may markedly improve heart symptoms as well. [See In-Depth Report #57: Anemia.]
Thyroid function. Various medications are used to treat overactive thyroid (hyperthyroidism) or underactive thyroid (hypothyroidism). [See In-Depth Report #38: Hypothyroidism.]
Sleep apnea. Continuous positive airway pressure (CPAP) is an effective treatment for sleep apnea. CPAP may help reduce systolic blood pressure and improve left ventricular systolic function. [See In-Depth Report#65:Sleep apnea.]

Click the icon to see an image of CPAP treatment.

Treatments for patients with Stage B risk for heart failure include all of the treatments recommended in Stage A. In addition, the following types of drugs and devices may be recommended for some patients. These include:

Angiotensin-converting enzyme (ACE) inhibitors for patients with a recent or past history of heart attack. Also for patients who have not had a heart attack if they have a low left ventricular ejection fraction (LVEF) and no heart failure symptoms. A reduced LVEF indicates that the heart’s left ventricle is not pumping blood efficiently.
Beta blockers for patients with a recent or past history of heart attack. Also for patients who have not had a heart attack but who do have reduced LVEF without heart failure symptoms.
Angiotensin-receptor blockers (ARBs) for patients who have had a heart attack or have low LVEF, but who cannot take ACE inhibitors.
Implantable defibrillators for patients who have weakened heart pumps (ischemic cardiomyopathy), who had a heart attack more than 40 days prior, and who have low LVEF.

Treat conditions as recommended in Stage A plus:

Restrict dietary salt. Lowering salt in the diet can help diuretics work better.
ACE inhibitors, beta blockers, and diuretics are recommended for most patients.
ARBs are recommended for patients who cannot tolerate ACE inhibitors.
Aldosterone inhibitors or digitalis may be used for some patients.
A hydralazine and nitrate combination (BiDil) may be used for African-American patients who are taking an ACE inhibitor and beta blocker and who still have heart failure symptoms.
Avoid drugs that can worsen heart failure symptoms. These include nonsteroidal anti-inflammatory drugs (NSAIDs), most calcium channel blockers, and most drugs used to treat irregular heart rhythms (arrhythmia).
Exercise training for appropriate patients.
Biventricular pacemakers and implantable defibrillators for some patients.

Treatment includes appropriate measures used for Stages A, B, and C plus:

Heart transplantation referral for appropriate patients.
Left-ventricular assist devices (LVADs) as permanent therapy for patients who are not candidates for heart transplants. LVADs are surgically implanted to help pump blood through the body.
Hospice and end-of-life care information for patients and families.

Medications

Many different medications are used in the treatment of heart failure. They include:

Angiotensin-converting enzyme (ACE) inhibitors
Angiotensin-receptor blockers (ARBs)
Beta blockers
Diuretics
Aldosterone blockers
Digitalis
Hydralazine and nitrates
Statins
Nesiritide (Natrecor)
Aspirin

Angiotensin-converting enzyme (ACE) inhibitors are among the most important drugs for treating patients with heart failure. ACE inhibitors open blood vessels and decrease the workload of the heart. They are used to treat high blood pressure but can also help improve heart and lung muscle function. Major studies suggest that ACE inhibitors may reduce the risk of death, heart attack, and hospital admissions by 28% in patients with existing heart failure.

ACE inhibitors are particularly important for patients with diabetes. A large study reported that patients with diabetes who took these drugs had fewer heart attacks and lower overall mortality rates than patients who took other types of high blood pressure medications. ACE inhibitors may also help slow progression of kidney disease, in addition to controlling blood pressure.

Doctors sometimes avoid giving aspirin to patients who are taking ACE inhibitors due to concerns that this drug combination can cause kidney problems. A 2005 study of patients with both coronary artery disease and heart failure indicated that an aspirin and ACE inhibitor combination is not harmful, and that aspirin can significantly reduce mortality risk for these patients.

Choosing an ACE inhibitor. ACE inhibitors treat Stage A high-risk conditions such as high blood pressure, heart disease, and diabetic nerve disorders (neuropathy). They also treat Stage B patients who have had a heart attack or who have left ventricular systolic disorder, and Stage C patients with heart failure. Specific brands and stages include:

Benazepril (Lotrel) -- (Stage A)
Captopril (Capoten) -- (Stages A, B, C)
Enalapril (Vasotec) -- (Stages A, B, C)
Fosinopril (Monopril) -- (Stages A, C)
Lisinopril (Prinivil, Zestril) -- (Stages A, B, C)
Moexipril (Univasc) -- (Stage A)
Perindopril (Aceon) -- (Stage A)
Quinapril (Accupril) -- (Stages A, C)
Ramipril (Altace) -- (Stages A, B, C)
Trandolapril (Mavik) -- (Stages A, B, C)

Side Effects of ACE Inhibitors:

Low blood pressure is the main side effect of ACE inhibitors. This can be severe in some patients, especially at the start of therapy.
Irritating cough is a common side effect, which some people find intolerable. Although all ACE inhibitors can have this side effect, sometimes switching to another brand will reduce this symptom.
Although ACE inhibitors can protect against kidney disease, they also increase potassium retention in the kidneys. This increases the risk for cardiac arrest if potassium levels become too high. Because of this action, they are not generally given with potassium-sparing diuretics or potassium supplements.
A rare but severe side effect is granulocytopenia, which is an extreme reduction in infection-fighting white blood cells.
In very rare cases, patients suffer a sudden and severe allergic reaction called angioedema that causes swelling in the eyes and mouth and may close off the throat.

Patients who have difficulty tolerating ACE inhibitor side effects are usually switched to an angiotensin-receptor blocker (ARB).

ARBs, also known as angiotensin II receptor antagonists, are similar to ACE inhibitors in their ability to open blood vessels and lower blood pressure. They may have fewer or less-severe side effects than ACE inhibitors, especially coughing, and are sometimes prescribed as an alternative to ACE inhibitors. Some patients with heart failure take an ACE inhibitor along with an ARB.

Brands and Indications. ARBs are used to treat Stage A high-risk conditions such as high blood pressure and diabetic nerve disorders (neuropathy). They are also used to treat Stage B patients who have had a heart attack or who have left ventricular systolic disorder, and Stage C patients with heart failure. Specific brands, and the stage of heart failure they are used for, are listed below.

Candesartan (Atacand) -- (Stages A, C)
Eprosartan (Teveten) -- (Stage A)
Irbesartan (Avapro) -- (Stage A)
Losartan (Cozaar) -- (Stages A, B)
Olmesartan (Benicar) -- (Stage A)
Telmisartan (Micardis) -- (Stage A)
Valsartan (Diovan) -- (Stages A, B, C)

Common Side Effects

Low blood pressure
Dizziness and lightheadedness
Raised potassium levels
Drowsiness

Beta blockers are almost always used in combination with other drugs, such as ACE inhibitors and diuretics. They help slow heart rate and lower blood pressure. Research presented at the 2006 American College of Cardiology meeting indicated that beta-blockers are an important treatment for most patients with left ventricular heart failure. Data from the study found that the beta blocker carvedilol (Coreg) significantly lowered the risk of death or rehospitalization within 3 - 6 months after hospital discharge.

Beta blockers can help patients with heart failure by:

Treating high blood pressure, angina, arrhythmias, and preventing heart attack in high-risk patients.
Preventing left ventricular remodeling in patients with enlarged heart chambers and weakened heart muscles (dilated cardiomyopathy), and in those who have suffered a first heart attack.
Blocking inflammatory immune factors called cytokines, including tumor necrosis factor (TNF). TNF may play a key role in the process leading to heart failure.
Preventing norepinephrine (adrenaline) from binding to heart cells. Elevated levels of norepinephrine, a stress hormone, can overstimulate the failing heart and are associated with severe heart failure.

Brands and Indications. Beta blockers treat Stage A high blood pressure. They are also treat Stage B patients (both those who have had a heart attack and those who have not had a heart attack but who have heart damage). Recent guidelines identify three drugs best for treating Stage C patients with heart failure. Specific brands and stages include:

Acebutolol (Sectral) -- (Stage A)
Atenolol (Tenormin) -- (Stages A, B)
Betaxolol (Kerlone) -- (Stage A)
Bisoprolol (Zebeta) -- (Stages A, C)
Cartelol (Cartrol) -- (Stage A)
Carvedilol (Coreg) -- (Stages A, B, C)
Labetalol (Trandate) -- (Stage A)
Metoprolol succinate (Toprol XL) -- (Stages A, C)
Metoprolol tartrate (Lopressor) -- (Stages A, B)
Nadolol (Corgard) -- (Stage A)
Penbutolol (Levatol) -- (Stage A)
Pindolol (Visken) -- (Stage A)
Propranolol (Inderal) -- (Stages A, B)
Timolol (Blocadren, Timolide) -- (Stages A, B)

Beta Blocker Concerns

Do not abruptly stop taking these drugs. The sudden withdrawal of beta blockers can rapidly increase heart rate and blood pressure. Your doctor may want you to slowly decrease the dose before stopping completely.
Beta blockers are categorized as non-selective or selective. Non-selective beta blockers such as carvedilol and propranolol can narrow bronchial airways. Patients with asthma, emphysema, or chronic bronchitis should not use these beta blockers.
Beta blockers can lower HDL (“good”) cholesterol.
These drugs can hide warning signs of low blood sugar (hypoglycemia) in patients with diabetes.
Beta blockers are usually used in combination with ACE inhibitors, but the two drugs are not started at the same time. Research presented at the 2005 European Society of Cardiology meeting indicates that either a beta blocker or an ACE inhibitor can be prescribed at first, and the other drug added on later.

Common Side Effects

Fatigue and lethargy
Vivid dreams and nightmares
Depression
Memory loss
Dizziness and lightheadedness
Reduced ability to exercise
Coldness in extremities (legs, toes, arms, hands)

Check with your doctor about any side effects. Do not stop taking these drugs on your own.

Diuretics cause the kidneys to rid the body of excess salt and water. Fluid retention is a major symptom of heart failure. Aggressive use of diuretics can help eliminate excess body fluids, while reducing hospitalizations and improving exercise capacity. These drugs are also important to help prevent heart failure in patients with high blood pressure. In addition, certain diuretics, notably spironolactone (Aldactone), block aldosterone, a hormone involved in heart failure. This drug class is beneficial for patients in late stages of heart failure (Stages C and D).

Diuretic Types and Brands. Diuretics come in many brands and are generally inexpensive. Some need to be taken once a day, some twice a day. Treatment is usually started at a low dose and gradually increased. Diuretics are virtually always used in combination with other drugs, especially ACE inhibitors and beta blockers. There are three main types of diuretics:

Potassium-sparing diuretics. These include amiloride (Midamor), spironolactone (Aldactone), and triamterene (Dyrenium).
Thiazide diuretics. These include chlorothiazide (Diuril), chlorthalidone (Hygroton), indapamide (Lozol), hydrochlorothiazide (Esidrix, HydroDiuril), and metolazone (Mykrox, Zaroxolyn).
Loop diuretics. Because loop diuretics act faster than other diuretics it is important to avoid dehydration and potassium loss. Loop diuretics include bumentanide (Bumex), furosemide (Lasix), and torsemide (Demadex).

Problems with Diuretics. Loop and thiazide diuretics deplete the body's supply of potassium, which, if left untreated, increases the risk for arrhythmias. Arrhythmias are heart rhythm disturbances that can, in rare instances, lead to cardiac arrest. In such cases, doctors will prescribe lower doses of the current diuretic, recommend potassium supplements, or use potassium-sparing diuretics either alone or in combination with a thiazide. Potassium-sparing drugs have their own risks, which include dangerously high levels of potassium in people with existing elevated levels of potassium or in those with damaged kidneys. However, all diuretics are generally more beneficial than harmful.

Common Side Effects

Fatigue
Depression and irritability
Urinary incontinence
Reduced sexual drive

Aldosterone is a hormone that is critical in controlling the body's balance of salt and water. Excessive levels may play important roles in hypertension and heart failure. Drugs that block aldosterone are prescribed for some patients with Stage C heart failure.

Spironolactone (Aldactone, Spirinol) is both a potassium-sparing diuretic and an aldosterone blocker. A major study of patients with heart failure found that spironolactone reduced death rate by 30%. Like all medications for heart failure, it must be used with care; elevated potassium levels are a potential risk of therapy.
Eplerenone (Inspra), a newer aldosterone blocker, has been specifically approved for treatment of heart failure. It is prescribed for patients who have heart failure following a heart attack. Its actions are similar to potassium-sparing diuretics and, like these drugs, it poses some risk for high potassium levels.

Digitalis is derived from the foxglove plant. It has been used to treat heart disease since the 1700s. Digoxin (Lanoxin) is the most commonly prescribed digitalis preparation. Digoxin decreases heart size and reduces certain heart rhythm disturbances (arrhythmias).

Unfortunately, digitalis does not reduce mortality rates, although it does reduce hospitalizations and worsening of heart failure. Controversy has been ongoing for more than 100 years over whether the benefits of digitalis outweigh its risks and adverse effects.

Digitalis may be useful for patients with left-ventricular systolic dysfunction who do not respond to other drugs (diuretics, ACE inhibitors). It is also used for patients who have atrial fibrillation.

Digitalis does not appear to help patients with left-ventricular diastolic heart failure. It may be harmful in patients with right-ventricular heart failure and those who stop taking digoxin after using it in combination with ACE inhibitors.

Side Effects and Problems. While digitalis is generally a safe drug, it can have toxic side effects due to overdose or other accompanying conditions. The most serious side effects are arrhythmias (abnormal heart rhythms that can be life-threatening). Early signs of toxicity may be irregular heartbeat, nausea and vomiting, stomach pain, fatigue, visual disturbances (such as yellow vision, seeing halos around lights, flickering or flashing of lights), and emotional and mental disturbances.

Many factors increase the chance for side effects.

Advanced age
Low blood potassium levels (which may be caused by diuretics)
Hypothyroidism
Anemia
Valvular heart disease
Impaired kidney function

Digitalis also interacts with many other drugs, including quinidine, amiodarone, verapamil, flecainide, amiloride, and propafenone.

A blood test that monitors drug levels in patients taking the drug can limit the rate of toxicity to about 2%. For most patients with mild-to-moderate heart failure, low-dose digoxin may be as effective as higher doses. If side effects are mild, patients should still consider continuing with digitalis if they experience other benefits.

Hydralazine and nitrates are two older drugs that help relax arteries and veins, thereby reducing the heart's workload and allowing more blood to reach the tissues. In 2005, the FDA approved BiDil, a drug that combines isosorbide dinitrate and hydralazine. BiDil is approved to specifically treat heart failure in African-Americans. African-Americans have a particularly high risk for heart failure. BiDil is the first drug approved for a specific racial group. The Food and Drug Administration (FDA) based its approval on a landmark 2004 study published in the New England Journal of Medicine, which showed that African-Americans who took the drug were 43% more likely to survive heart failure than patients who took placebo. Some experts suggest that BiDil could also benefit other racial groups.

Statins are important drugs used to lower cholesterol and to prevent heart disease leading to heart failure. These drugs include lovastatin (Mevacor), pravastatin (Pravachol), simvastatin (Zocor), fluvastatin (Lescol), atorvastatin (Lipitor), and rosuvastatin (Crestor). In 2007, the FDA approved atorvastatin to reduce the risks for hospitalization for heart failure in patients with heart disease.

In a 2006 Journal of the American Medical Association study, patients with heart failure who began taking a statin drug had a 24% lower relative risk of death and a 21% lower relative risk of hospitalization for heart failure than patient who did not take a statin. Statins appeared to help these patients regardless of whether or not they had co-existing coronary heart disease.

Aspirin is a type of non-steroid anti-inflammatory (NSAID). A 2005 study in the Journal of the American College of Cardiology indicated that aspirin is important for preventing heart failure death in patients with heart disease, and can safely be used with ACE inhibitors. However, some research has suggested that NSAIDs may increase the risk of heart failure for patients with a history of heart disease, especially when used in combination with ACE inhibitors or diuretics. Patients with heart disease should ask their doctor which NSAIDs are right for them.

Nesiritide treats patients who have arrived at a hospital with decompensated heart failure. Decompensated heart failure is a life-threatening condition in which the heart fails over the course of minutes or a few days, often as the result of a heart attack or sudden and severe heart valve problems. However, nesiritide may cause serious kidney damage.

In 2005, the FDA released recommendations from an expert panel concerning the appropriate and inappropriate use of nesiritide. The panel emphasized that nesiritide should be used to treat only patients with decompensated heart failure who have shortness of breath (dyspnea) and trouble breathing. The drug should not be a replacement for diuretics.

Despite these warnings, some doctors have prescribed nesiritide “off-label” to treat patients with severe heart failure outside of a hospital setting. Research presented at the 2007 American College of Cardiology annual conference criticized this practice by demonstrating that nesiritide plus standard treatment does not reduce the risk of heart- or kidney-related death or hospitalization. In addition, the research suggested some concerns about nesiritide’s overall safety.

Tolvaptan. Tolvaptan is an investigational drug that is being studied in combination with standard therapy for treatment of heart failure. It is especially being investigated for acute decompensated heart failure, a type of heart failure categorized by fluid build-up in the lungs (pulmonary edema) for which there are few available treatments. In patients hospitalized with heart failure, tolvaptan plus standard drugs improved breathing problems (dyspnea) and reduced fluid accumulation (edema) and body weight, according to two studies published in 2007 in the Journal of the American Medical Association. However, the drug did not appear to reduce the risk of re-hospitalization or death.

Levosimendan. Levosimendan is an experimental inotropic drug that is being investigated as a treatment for severely ill patients with heart failure. It belongs to a new class of drugs called calcium sensitizers that may help improve heart contractions and blood flow. Clinical trials suggest that levosimendan may improve survival in patients hospitalized for heart failure. The drug also appears to reduce levels of BNP (brain natriuretic peptide), a chemical marker for heart failure severity.

Prograf. Tacrolimus (Prograf) was approved in 2006 to help prevent organ rejection in patients who have received a heart transplant. The drug suppresses the immune system. Patients who receive this drug are at increased risk of developing lymphoma (a cancer of the immune system).

Surgery and Devices

Revascularization surgery helps to restore blood flow to the heart. It can treat blocked arteries in patients with coronary artery disease and may help selected patients with heart failure. Surgery types include coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI). CABG is a traditional type of open heart surgery. PCI, also called angioplasty, uses a catheter to inflate a balloon inside the artery. A metal stent may also be inserted during a PCI procedure. [See In-Depth Report#03:Coronary artery disease.]

A 2006 study suggested that early treatment with revascularization surgery may be particularly important for patients with systolic heart failure, a condition that occurs when the heart does not pump out enough blood. This condition has a very high death rate. Researchers found that CABG or PCI surgery halved the risk of dying compared to standard drug therapy. Patients in the study first underwent a positron emission tomography (PET) test to determine if they would be good candidates for surgery.

Click the icon to see an illustrated series detailing coronary artery balloon angioplasty.

Click the icon to see an illustrated series detailing heart bypass surgery.

In appropriate patients, mitral valve surgery may significantly reduce the severity of heart failure. In a study of 92 patients with late-stage heart failure and faulty valves, reconstruction of the heart's mitral valve drastically improved heart function.

An experimental mesh "heart sock" is being investigated as an adjunct to mitral valve repair surgery. Research presented at the 2004 American Heart Association Scientific Sessions suggested that the device reduced the progression of heart failure and halved the need for transplant surgery. The "sock" helps realign the shape of the heart and improve heart function. To date, it has been tested in patients with dilated cardiomyopathy.

Ventricular Remodeling. Ventricular remodeling (also called partial left ventriculectomy or the Batista procedure, after its inventor) may allow some patients with dilated cardiomyopathy to avoid a heart transplant.

The procedure involves the following:

The surgeon first performs ventriculectomy, which is the removal of a section of healthy heart muscle weighing about 3 ounces.
The surgeon then reshapes the heart to a more normal size and form.
Any faulty heart valves are repaired.

Ventricular remodeling is still relatively new, and mortality rates are very high. Studies on long-term improvement are mixed. More research is needed to target the patients who would most benefit.

Patients who suffer from severe heart failure and whose symptoms do not improve with drug therapy or mechanical assistance may be candidates for heart transplantation. Some 3,600 people are awaiting a transplant, although only about 2,000 operations are performed each year.

The most important factor for heart transplant eligibility is overall health. Chronological age is less important. Most heart transplant candidates are between the ages of 50 – 64 years. About 72% of transplant patients are male, and 70% are white.

While the risks of this procedure are high, the 1-year survival rate is about 86% for men and 84% for women. The 3-year survival rate is 78% for men and 75% for women. Five years after a heart transplant, about 71% of men and 67% of women remain alive. In general, the highest risk factors for death 3 or more years after a transplant operation are coronary artery disease and the adverse effects (infection and certain cancers) of immunosuppressive drugs used in the procedure. The rejection rates in older people appear to be similar to those of younger patients.

In 2004, the FDA approved a temporary artificial heart (Syncardia) intended to keep patients alive in the hospital while they waited for a heart transplant. In 2006, the FDA approved the first permanent implantable artificial heart (AbiCor). The AbiCor is available only for patients who are not eligible for a heart transplant and who are not expected to live more than a month without medical treatment. The device requires a large chest cavity, which means that most women will not be eligible for it. Of the 14 men who have received the AbiCor, the average survival was less than 5 months after surgery. Only one patient was discharged from the hospital. The device’s manufacturer is working on a new model that it hopes will extend survival by as long as 5 years.

A growing array of heart devices and machines are changing the face of heart failure treatment. They have gained widespread acceptance for use as a bridge to transplant in patients who are on medications but still have severe symptoms and are awaiting a donor heart. Increasingly, though, doctors are exploring the possibility that such devices may be satisfactory treatments themselves, forestalling the need for a transplant altogether in some patients.

Ventricular Assist Devices (VADs). Ventricular assist devices are machines that help improve pumping actions. Several models with slightly different features are in use or under investigation. Some include the following:

Left ventricular assist device (LVAD) are used for patients whose heartbeat has slowed dangerously (a condition called bradycardia) to help take over the pumping action of the failing heart. Studies suggest that in some people the use of an LVAD may allow some of the damaged heart muscle to heal, perhaps even helping some patients avoid heart transplants. These devices are also being studied in combination with drug therapy to help recover heart function and improve patients’ chances for survival. Until recently, these machines required remaining in the hospital. Smaller battery-powered LVAD units, however, are allowing many patients to leave the hospital and are proving to be effective bridges to heart transplants in adults. The HeartMate, for example, a portable LVAD about the size of a portable CD player (2 in. by 4 in.), is implanted in the upper abdomen. The implanted device plugs into an external power base, which is used when the patient is at rest to recharge the battery and provide continuous power.
Fully implanted miniature artificial pumps that assist the heart (not replace it) are also being tested. The DeBakey ventricular assist device (VAD) for example, is a tiny heart pump that weighs less than 4 ounces. It has been approved in Europe and is being tested in the United States. The Jarvik 2000 heart pump is also showing promise.
The intra-aortic balloon pump (IABP) is helpful for maintaining heart function in people with left-side failure waiting for transplants and in those who develop a sudden and severe deterioration of heart function. The IABP is an implanted thin balloon that is usually inserted into the artery in the leg and threaded up to the aorta leading from the heart. Its pumping action is generated by inflating and deflating the balloon at certain rates. Usually, it is used only for short periods, but some studies indicate that patients may be able to use it safely for somewhat longer periods (an average duration of 23 days in one study).

There are risks involved with many of these devices, including bleeding, blood clots, and right-side heart failure. Infections are a particular hazard.

Pacers (Pacemakers). Pacers, or pacemakers, help regulate the heart’s beating action, especially when the heart beats too slowly. Biventricular pacers (BVPs) are a special type of pacemaker used for patients with heart failure. Because BVPs help the heart’s left and right chambers beat together, this treatment is called cardiac resynchronization therapy (CST). BVPs may particularly help heart failure patients who have left bundle branch block, a condition in which the electrical impulses in the heart do not follow their normal pattern. In general, BVPs are recommended for patients with moderate-to-severe heart failure. A small 2006 study suggested that a defibrillator may be better suited for patients with moderate heart failure, while indicating a BVP might be best for patients with severe heart failure.

Implantable Cardioverter-Defibrillators. Devices called implantable cardioverter-defibrillators (ICDs), which are sometimes combined with pacemakers, work well for preventing arrhythmias (abnormal heart rhythms) in heart failure patients. Studies have also found them effective in preventing sudden death from severe rhythm disturbances in patients with weakened hearts from previous arrhythmias and in patients with genetic hypertrophic cardiomyopathy. Patients who have an ICD should avoid taking fish oil supplements. A 2005 Journal of the American Medical Association study found that omega-3 fatty acid supplements may increase the risk of rapid heart beat (ventricular tachycardia) or irregular heart rhythm (ventricular fibrillation) in some of these patients.

ICDs have many benefits, and recent expert guidelines recommend that they be used in more patients with heart failure. However, in June 2005, certain ICD models and biventricular pacemaker-defibrillators were recalled by the manufacturer because of a circuitry flaw that prevents the devices from delivering therapeutic electrical shocks when needed. The problem may result in patient death. Although the FDA did not make any specific recommendations, the agency encourages patients who may have such a device to ask their doctor if they should have it removed or replaced.

In April 2006, two studies published in the Journal of the American Medical Association evaluated data concerning the safety and reliability of implantable pacemakers and defibrillators. The studies found that from 1990 – 2002, pacemakers became increasingly reliable. From 1998 – 2002, ICDs had a significantly higher rate of malfunction than pacemakers, although the reliability of ICDs appeared to improve from 2003 – 2004.

In October 2006, the U.S. Heart Rhythm Society issued recommendations for doctors, manufacturers, and the FDA to help improve communication concerning performance and recalls of ICDs and pacemakers. Experts stress that the chance of an ICD or pacemaker saving a person’s life far outweigh the possible risks of these devices failing.

Ultrafiltration devices are used in hospitals to pump excess water and salt from the body. Catheters are inserted into several of the patient’s veins. The catheters are connected to a blood filter device. Blood is withdrawn through one of the catheters and filtered in the device to remove excess fluid. The filtered blood is then returned to the patient through another catheter. A 2006 study reported that ultrafiltration devices may work better than diuretic drugs for patients with acute decompensated heart failure (ADHF). ADHF is heart failure that has rapidly deteriorated so that patients require immediate hospitalization.

Lifestyle Changes

Between 30 - 47% of patients who require hospitalization for heart failure are back in the hospital within 6 months. Many people return because of lifestyle factors such as poor diet, failure to comply with medications, and social isolation.

In one study, elderly people who had no emotional support at home had triple the risk of a heart attack after hospitalization for heart failure than those who did have such support. (Women had eight times the risk.) In another study, the greatest risk factor for death and readmission to the hospital after a first hospitalization was being single, regardless of the health of the patient at discharge. A third study confirmed that a strong marriage predicted long-term survival. Evidence continues to mount that programs that offer intensive follow-up to ensure that the patient complies with lifestyle changes and medication regimens at home are reducing rehospitalization rates and improving survival. Patients without available rehabilitation programs should seek support from local and national heart associations and groups.

Patients should weigh themselves each morning and keep a record. Any changes are important:

A sudden increase in weight of more than 2 - 3 pounds may indicate fluid accumulation and should prompt an immediate call to the doctor.
Rapid wasting weight loss over a few months is a very serious sign and may indicate the need for surgical intervention.

Whole Grains. Evidence suggests that daily consumption of whole grain foods may help prevent heart failure. In research presented at a 2007 American Heart Association conference, people who ate whole-grain breakfast cereals seven or more times a week had a 28% lower risk of developing heart failure than those who never ate these cereals.

Mediterranean Diet. Evidence suggests that the Mediterranean diet helps protect the heart and may even reduce the risk for heart failure after a first heart attack. The diet emphasizes whole grains, fish, olive oil, garlic, and moderate daily intake of wine. There are several variations to the Mediterranean diet but general recommendations include:

Limit red meats.
Limit dairy products.
Eat moderate amounts of fish and poultry. Fish is the diet’s main protein source. Some studies suggest that fish is the primary heart-protective ingredient in this diet. However, patients who have an implantable defibrillator should not take fish oil supplements. A 2005 study suggested that these supplements may worsen heart rhythm problems in some patients.
Eat plenty of fresh fruits and vegetables, nuts, legumes, beans, and whole grains.
Daily glass or two of wine. Light-to-moderate alcohol use may reduce the risk for heart failure, (but heavy alcohol consumption is a risk factor).
Plenty of fresh fruits and vegetables, as well as nuts, legumes, beans, and whole grains.

DASH Diet. The Dietary Approaches to Stop Hypertension (DASH) diet is an important lifestyle step in managing blood pressure. It may also be useful for many patients with heart failure. This diet is not only rich in important nutrients and fiber but also includes foods that contain two and a half times the amounts of electrolytes, potassium, calcium, and magnesium found in the average American diet.

Potassium-rich foods, which are important for patients with heart failure, include bananas, oranges, prunes, cantaloupes, carrots, spinach, celery, alfalfa, mushrooms, lima beans, potatoes, avocados, and broccoli. However, patients who take potassium-sparing diuretics or ACE inhibitors, and those with kidney dysfunction, may have to restrict their potassium intake.

The DASH diet is rich in whole grains and fresh fruits and vegetables. It stresses avoiding saturated fats, as any healthy diet does, although it includes calcium-rich dairy products that are non- or low-fat. When choosing fats, the diet recommends monounsaturated oils such as olive or canola oil.

Salt Restriction. People with high blood pressure are generally urged to restrict salt, although certain people may be more susceptible to its effects. For example, a high intake of salt may be an independent risk factor for the development of heart failure in people who are overweight. All patients with heart failure should limit their salt intake, and in severe cases, very stringent salt restriction may be necessary. Patients should not add salt to their cooking and their meals. They should also avoid foods high in sodium. These salty foods include ham, bacon, hot dogs, lunch meats, prepared snack foods, dry cereal, cheese, canned soups, soy sauce, and condiments. Some patients may need to reduce their water intake as well. People with high cholesterol levels or diabetes require additional dietary precautions. [See In-Depth Report #43: Heart-healthy diet. ]

People with heart failure used to be discouraged from exercising. Now, experts think that exercise, when performed under medical supervision, is extremely important for many patients with stable conditions. Studies have reported that patients with stable conditions who engage in regular moderate exercise (three times a week) experience a better quality of life and lower mortality rates than those who do not exercise.

The following guidelines are critical:

Experts warn that exercise is not appropriate for all patients with heart failure. If you have heart failure, always consult your doctor before starting an exercise program.
People who are approved for, but not used to, exercise should start with 5 - 15 minutes of easy exercise with frequent breaks. Although the goal is to build up to 30 - 45 minutes of walking, swimming, or low-impact aerobic exercises three to five times every week, even shorter times spent exercising are useful.

Studies report benefits from specific exercises:

Progressive strength training may be particularly useful for patients with heart failure since it strengthens muscles, which commonly deteriorate in this disorder. Strength training typically uses light weights, weight machines, or even the body's weight (leg raises or sit-ups, for example). Even performing daily handgrip exercises can improve blood flow through the arteries.
Patients who exercise regularly using supervised treadmill and stationary-bicycle exercises can increase their exercise capacity by 14 - 36%. In one study, patients as old as 91 years increased their oxygen consumption significantly after 6 months of supervised treadmill and stationary bicycle exercises. Exercising the legs may help correct problems in heart muscles. In one study, patients who did leg extension exercises for 8 weeks had higher levels of an enzyme involved in forming new blood vessels. Exercise has also been associated with reduced inflammation in blood vessels.
Dancing may be a fun and beneficial alternative to standard aerobic exercise, according to research presented at the 2006 annual meeting of the American Heart Association. In a study of patients with stable chronic heart failure, dancing helped improve cardiopulmonary fitness, arterial elasticity, and quality of life. Patients in the study danced fast and slow waltzes for 21 minutes, three times a week.

Bed rest may be required in cases of severe heart failure. To reduce congestion in the lungs, the patient's upper body should be elevated. For most patients, resting in an armchair is better than lying in bed. Relaxing and contracting leg muscles is important to prevent clots. As the patient improves, a doctor will progressively recommend more activity.

Experts have traditionally recommended that people with heart failure avoid warm baths, which can increase the heart rate. Some studies now report that carefully controlled bathing for short periods may not be harmful and may actually be beneficial, reducing irregular heart beats and increasing cardiac output and ejection fraction. Warm water may behave like a vasodilating drug, opening up the vessels gently and improving circulation. In clinical trials, patients sat in warm water or a dry sauna for 10 minutes, with their bodies tilted at a 45 degree angle.

Warning Note: Prolonged periods in hot or even warm conditions can be dangerous. Any patient with heart failure should consult their doctor first, not bathe unaccompanied, and be sure that the temperature does not go above 106° Fahrenheit for water bathing or 140° Fahrenheit for dry saunas.

Stress reduction techniques, such as meditation and relaxation response methods, may have direct physical benefits for lowering stress hormones. These hormones include cortisol, which suppresses the immune system, and norepinephrine (also known as adrenaline), the chemical messenger associated with heart dysfunction.

Patients with heart failure may resort to alternative remedies. Such remedies are often ineffective and may have severe or toxic effects. Of particular note for patients with heart failure is an interaction between St. John's wort (an herbal medicine used for depression) and digoxin (a heart drug). St. John's wort can significantly interfere with this drug.

Arginine. Some evidence suggests that arginine (also called L-arginine) may have some benefit. This amino acid appears to reduce endothelin, a protein that causes blood vessel constriction and is found in high amounts in patients with heart failure. It can have adverse effects, however, including gastrointestinal problems. It can also lower blood pressure and change levels of certain chemicals and electrolytes in the body. It may increase the risk for bleeding. Some people have an allergic reaction to it, which in same cases may be severe. It may worsen asthma.

Coenzyme Q10 and Vitamin E. Small studies have suggested that coenzyme Q10 (CoQ10) may help patients with heart failure, particularly when combined with vitamin E. CoQ10 is a vitamin-like substance found in organ meats and soybean oil. More recent studies, however, have found that CoQ10 and vitamin E do not help the heart or prevent heart disease. According to a 2005 Journal of the American Medical Association study, vitamin E supplements can actually increase the risk of heart failure, especially for patients with diabetes or vascular diseases.

Crataegus Extract. An herbal remedy, Crataegus Extract WS1442, which is made from the leaves of the Crataegus tree, may have antioxidant properties that can help patients with heart failure. In a study presented at the 2007 American College of Cardiology annual meeting, over 2,000 patients with severe heart failure were randomized to receive either Crataegus Extract or placebo (plus standard drug treatment) for 2 years. The researchers noted a 20% reduction in heart-related deaths among patients who received the extract, and suggested that the herb extended patients’ lives by 4 months during the first 18 months of the study.

Other Vitamins and Supplements. A wide variety of other vitamins (thiamin, B6, and C), minerals (calcium, magnesium, zinc, manganese, copper, selenium), nutritional supplements (carnitine, creatine), and herbal remedies (hawthorn) have been proposed as treatments for heart failure. None have been adequately tested. There is no evidence that a particular vitamin or supplement can cure heart failure. In any case, vitamins are best consumed through the food sources contained in a healthy diet.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been several reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

Resources

www.nhlbi.nih.gov -- National Heart, Lung, and Blood Institute
www.americanheart.org -- American Heart Association
www.acc.org -- American College of Cardiology
www.hfsa.org -- Heart Failure Society of America
www.heartfailure.org -- Heart Failure Online
www.unos.org -- United Network for Organ Sharing
www.organdonor.org -- National Transplant Society
www.organdonor.gov -- US government organ donor site

References

Ahmed A, Rich MW, Fleg JL, Zile MR, Young JB, Kitzman DW, et al. Effects of digoxin on morbidity and mortality in diastolic heart failure: the ancillary digitalis investigation group trial. Circulation. 2006 Aug 1;114(5):397-403.

Battaglia M, Pewsner D, Juni P, Egger M, Bucher HC, Bachmann LM. Accuracy of B-type natriuretic peptide tests to exclude congestive heart failure: systematic review of test accuracy studies. Arch Intern Med. 2006 May 22;166(10):1073-80.

Bhatia RS, Tu JV, Lee DS, Austin PC, Fang J, Haouzi A, et al. Outcome of heart failure with preserved ejection fraction in a population-based study. N Engl J Med. 2006 Jul 20;355(3):260-9.

Birks EJ, Tansley PD, Hardy J, George RS, Bowles CT, Burke M, et al. Left ventricular assist device and drug therapy for the reversal of heart failure. N Engl J Med. 2006 Nov 2;355(18):1873-84.

Bryson CL, Mukamal KJ, Mittleman MA, Fried LP, Hirsch CH, Kitzman DW, et al. The association of alcohol consumption and incident heart failure: the Cardiovascular Health Study. J Am Coll Cardiol. 2006 Jul 18;48(2):305-11.

Bursi F, Weston SA, Redfield MM, Jacobsen SJ, Pakhomov S, Nkomo VT, et al. Systolic and diastolic heart failure in the community. JAMA. 2006 Nov 8;296(18):2209-16.

Carlson MD, Wilkoff BL, Maisel WH, Carlson MD, Ellenbogen KA, Saxon LA, et al. Recommendations from the Heart Rhythm Society Task Force on Device Performance Policies and Guidelines Endorsed by the American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) and the International Coalition of Pacing and Electrophysiology Organizations (COPE). Heart Rhythm. 2006 Oct;3(10):1250-73.

Davis BR, Piller LB, Cutler JA, Furberg C, Dunn K, Franklin S, et al. Role of diuretics in the prevention of heart failure: the Antihypertensive andLipid-Lowering Treatment to Prevent Heart Attack Trial. Circulation. 2006 May 9;113(18):2201-10. Epub 2006 May 1.

Gheorghiade M, Abraham WT, Albert NM, Greenberg BH, O'Connor CM, She L, et al. Systolic blood pressure at admission, clinical characteristics, and outcomes inpatients hospitalized with acute heart failure. JAMA. 2006 Nov 8;296(18):2217-26.

Gheorghiade M, Konstam MA, Burnett JC Jr, Grinfeld L, Maggioni AP, Swedberg K, et al. Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heartfFailure: the EVEREST clinical status trials. JAMA. 2007 Mar 25; [Epub ahead of print]

Go AS, Lee WY, Yang J, Lo JC, Gurwitz JH. Statin therapy and risks for death and hospitalization in chronic heart failure. JAMA. 2006 Nov 1;296(17):2105-11.

Hildebrandt P. Systolic and nonsystolic heart failure: equally serious threats. JAMA. 2006 Nov 8;296(18):2259-60.

Konstam MA, Gheorghiade M, Burnett JC Jr, Grinfeld L, Maggioni AP, Swedberg K, et al. Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial. JAMA. 2007 Mar 25; [Epub ahead of print]

Lee DS, Pencina MJ, Benjamin EJ, Wang TJ, Levy D, O'Donnell CJ, et al. Association of parental heart failure with risk of heart failure in offspring. N Engl J Med. 2006 Jul 13;355(2):138-47.Maisel WH. Pacemaker and ICD generator reliability: meta-analysis of device registries. JAMA. 2006 Apr 26;295(16):1929-34.

Maisel WH, Moynahan M, Zuckerman BD, Gross TP, Tovar OH, Tillman DB, et al. Pacemaker and ICD generator malfunctions: analysis of Food and Drug Administration annual reports. JAMA. 2006 Apr 26;295(16):1901-6.

Mueller C, Laule-Kilian K, Schindler C, Klima T, Frana B, Rodriguez D, et al. Cost-effectiveness of B-type natriuretic peptide testing in patients with acute dyspnea. Arch Intern Med. 2006 May 22;166(10):1081-7.

Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006 Jul 20;355(3):251-9.

Review Date:
4/11/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Foot pain

FitSugar — Wed, 08 Oct 2008 17:35:02 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Treatment: Corns and Callus...
Treatment: Bunions
Treatment: Hammertoes
Treatment: Ingrown Toenails...
Treatment: Forefoot Pain...
Treatment: Heel Pain
Treatment: Flat Feet
Treatment: Abnormally High ...
Treatment: Tarsal Tunnel Sy...
Treatment: Foot Injury
Prevention
Shoes
Insoles and Orthotics
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Treatment for Ingrown Toenail:

Orthonyxia, a surgical technique that implants a small metal brace into the top of the nail, was as effective as traditional surgical techniques for preventing ingrown toenail from recurring, according to one study.
A nonsurgical method for treating ingrown toenail with chemicals uses either sodium hydroxide or phenol, but one study shows that sodium hydroxide procedures have a better outcome and faster recovery than phenol procedures.

Treatment for Forefoot Pain:

Ultrasound-guided injection of alcohol might provide relief from Morton's neuroma, according to one study. Symptoms improved in 94% of patients who had the treatment, a success rate comparable to that of surgery.

Treatment for Heel Pain:

NSAIDs reduce pain and disability in people with plantar fasciitis when used with other techniques, such as night splints and stretching.
Studies show that extracorporeal shockwave therapy provides a very small reduction in heel pain without side effects. It may be a good option for patients who haven't responded well to conservative treatment.

Work-related Foot Problems:

An estimated 120,000 job-related foot injuries occur every year, about a third of them involving the toes. A number of foot problems -- including arthritis of the foot and ankle, toe deformities, pinched nerves between the toes, plantar fasciitis, adult-acquired flat foot, and tarsal tunnel syndrome -- have been attributed to repetitive use at work.

Introduction

Foot pain is very common. About 75% of people in the United States have foot pain at some time in their lives. Most foot pain is caused by shoes that do not fit properly or that force the feet into unnatural shapes (such as pointed-toe, high-heeled shoes).

The foot is a complex structure of 26 bones and 33 joints, layered with an intertwining web of more than 120 muscles, ligaments, and nerves. It serves the following functions:

Supports weight
Acts as a shock absorber
Serves as a lever to propel the leg forward
Helps maintain balance by adjusting the body to uneven surfaces

Because the feet are very small compared with the rest of the body, the impact of each step exerts tremendous force upon them. This force is about 50% greater than the person's body weight. During a typical day, people spend about 4 hours on their feet and take 8,000 - 10,000 steps. This means that the feet support a combined force equivalent to several hundred tons every day.

Foot pain generally starts in one of three places: the toes, the forefoot, and the hindfoot.

The Toes. Toe problems most often occur because of the pressure imposed by ill-fitting shoes.

The Forefoot. The forefoot is the front of the foot. Pain originating here usually involves one of the following bone groups:

The metatarsal bones (five long bones that extend from the front of the arch to the bones in the toe)
The sesamoid bones (two small bones embedded at the top of the first metatarsal bone, which connects to the big toe)

The Hindfoot. The hindfoot is the back of the foot. Pain originating here can extend from the heel, across the sole (known as the plantar surface), to the ball of the foot (the metatarsophalangeal joint).

Condition	Location	Symptoms	Recommended Footwear
Toe Pain
Corns and calluses	Around toes, usually little toe, bottom of feet or areas exposed to friction.	Hard, dead, yellowish skin.	Wide (box-toed) shoes; soft cushions under heel or ball of foot, or customized or gel insoles for calluses. Doughnut-shaped pads for corns.
Ingrown toenails	Toenails.	Nail curling into skin causes pain, swelling, and, in extreme cases, infection.	Sandals, open-toed shoes.
Bunions and bunionettes (tailor's bunion)	Big toe (bunions) or little toe (bunionettes).	The following can occur alone or in combination: Metatarsus primus varus. The first (big toe) metatarsal bone shifts away from the second, and the big toe points inward. Medial exostosis. This is a bony bump at the base of the big toe, which protrudes outward. Area next to bony bump is red, tender, and occasionally filled with fluid. Toe joint may be inflamed. Hallux valgus. This is a deformity in which the bone and joint of the big toe shift and grow inward, so that the second toe crosses over the big toe.	Soft, wide-toed shoes or sandals. Bunion shields or splints. Thick doughnut-shaped moleskin pads, custom-made orthotics or foot slings, if necessary. Avoid shoes with stitching along the side of the "bump."
Morton's neuroma (also called interdigital neuroma)	Inflammation of the nerve, usually between the third and fourth toes and bottom of the foot near these toes.	Cramping and burning pain, or electric-shock sensation. The condition may produce a thick protective sheath around the nerve that feels like a ball. This may be detected by pressing top to bottom on the top of the foot using one hand and moving the other hand from side to side. Morton's neuroma is aggravated by prolonged standing and relieved by removal of the shoes and forefoot massage.	Wide (box-toed) shoes. Orthotic or insole with pad that reduces stress on the painful area.
Hammertoe or claw toe	Usually second toe, but may develop in any or all of the three middle toes.	Toes form hammer or claw shape. In hammertoe, the first knuckle of the toe is mainly affected. In claw toe the entire toe is deformed. No pain at first, but pain increases as tendon becomes tighter and toes stiffen.	Wide (box-toed) shoes. Toe pads or specially designed shields, splints, caps, or slings. (Splints or slings are not for people with diabetes.)
Front-of-the-Foot Pain
Metatarsalgia	Ball of the foot.	Acute, recurrent, or chronic pain without a known cause.	Wide (box-toed) shoes. Orthotic with pad that reduces metatarsal pressure. Gel cushions. Metatarsal bandage.
Stress fracture	Most often in the area beneath the second or third toe.	Sudden pain (which persists) when injury occurs.	Low-heeled shoes with stiff soles.
Sesamoiditis	Ball of foot beneath big toe.	Pain and swelling.	Low-heeled shoe with stiff sole and soft padding inside.
Heel and Back-of-the-Foot Pain
Plantar fasciitis or heel spurs	Back of the arch right in front of heel.	At onset, some people report a tearing or popping sound. Pain is most severe with first steps after getting out of bed. Pain decreases after stretching, returns after inactivity.	Over-the-counter foot insole (cut quarter-size hole surrounding painful area). Possible night splints. Orthotics if necessary.
Bursitis of the heel	Center of the heel.	Pain, with warmth and swelling. Increases during the day.	Heel cup.
Haglund's deformity (pump bump)	Fleshy area on the back of the heel.	Tender swelling aggravated by shoes with stiff backs.	Soft shoes. Heel pads. Possible orthotic to support heel.
Achilles tendinitis	Achilles tendon: area along the back between calf muscles and heel.	Pain worsens during physical activities (particularly running), after which the tendon usually swells and stiffens. If it ruptures, popping sound may occur followed by acute pain similar to a blow at the back of the leg.	Insoles, tendon strap, heel cups.
Arch and Bottom-of-the Foot Pain
Tarsal tunnel syndrome	Anywhere along the bottom of the foot.	Numbness, tingling, or burning sensations, pain, most commonly felt at night.	Specially designed orthotics to relieve pressure.
Flat feet or posterior tibial tendon dysfunction (PTTD)	The arch.	No arch. Often no pain or discomfort. Three stages in PTTD: Pain and weakness in the tendon. The arch flattens but is still flexible. The foot becomes rigid and possibly painful at the ankle. Sometimes people report fatigue, pain, or stiffness in the feet, legs, and lower back.	For children, possible custom-made insoles.
High arches (hollow feet)	The arch.	High arches. Lower back pain, possible tendency to lower limb injuries.

Causes

Nearly all causes of foot pain can be grouped under one of the following:

Ill-fitting shoes. Poorly fitting shoes are a frequent cause of foot pain. High-heeled shoes concentrate pressure on the toes and can aggravate, if not cause, problems with the toes.
Certain medical conditions. Any medical condition that causes a disturbance in the way a person walks can contribute to foot pain. This may include diseases or conditions that lead to pain or numbness in the feet (such as diabetes), leg and foot deformities, spinal problems, and neurological disorders such as Parkinson's disease or cerebral palsy.
High-impact exercise. High-impact exercising, such as jogging or strenuous aerobics, can injure the feet. Common injuries include corns, calluses, blisters, muscle cramps, acute knee and ankle injuries, plantar fasciitis, and metatarsalgia.

Arthritic Conditions. Arthritic conditions, particularly osteoarthritis and gout, can cause foot pain. Although rheumatoid arthritis almost always develops in the hand, the ball of the foot can also be affected.

Diabetes. Diabetes is an important cause of serious foot disorders. [For more information, see In-Depth Report #9: Diabetes - type 1 and In-Depth Report #60: Diabetes - type 2.]

Obesity. Obesity can cause foot and ankle pain.

Pregnancy. Pregnancy can cause fluid buildup and swollen feet. The increased weight and imbalance of pregnancy contributes to foot stress.

Medications. Some medications, such as calcitonin and drugs used for high blood pressure, can cause foot swelling.

Click the icon to see an image of foot inspection.

Risk Factors

A risk factor is anything that increases your chances of getting a disease or condition. The following are factors that increase your risk for foot pain:

Elderly people are at very high risk for foot problems. As you age, your feet widen and flatten, and the fat padding on the sole of the foot wears down. The skin on the feet also becomes dryer. Foot pain in older adults may be the first sign of age-related conditions, such as arthritis, diabetes, and circulatory disease. Foot problems can also impair balance and function in this age group.

Taking fashion to extreme limits, some people have turned to cosmetic surgery as a drastic way to fit into high-heeled shoes. Procedures include surgical shortening of the toes, narrowing of feet, or injecting silicone into the pads of the feet. Such methods may increase your risk for future foot pain. The American Orthopaedic Foot and Ankle Society (AOFAS) and other foot-related medical associations have expressed concern over this trend. The AOFAS strongly advises against cosmetic foot surgery and urges consumers to carefully consider the relative risks and benefits of undergoing unnecessary surgical procedures.

Women are at higher risk than men for severe foot pain, probably because of high-heeled shoes. Severe foot pain appears to be a major cause of general disability in older women.

An estimated 120,000 job-related foot injuries occur every year, about a third of them involving the toes. A number of foot problems -- including arthritis of the foot and ankle, toe deformities, pinched nerves between the toes, plantar fasciitis, adult-acquired flat foot, and tarsal tunnel syndrome -- have been attributed to repetitive use at work.

For example, in a study of New York police officers who walked an average of 3 miles a day, 20% experienced foot pain at the end of their workday. (Insoles can relieve much of this pain.) No studies, however, have scientifically distinguished between injuries due to work versus those due to regular use. This is an important issue because of its potential impact on disability claims.

Pregnant women have an increased risk of foot problems due to weight gain, swelling in their feet and ankles, and the release of certain hormones that cause ligaments to relax. These hormones help when bearing the child, but they can weaken the feet.

People who engage in regular high-impact aerobic exercise are at risk for plantar fasciitis, heel spurs, sesamoiditis, shin splints, Achilles tendon, and stress fractures. Women are at higher risk for stress fractures than are men.

Gaining weight puts added stress on the feet and can lead to foot or ankle injuries. The added pressure on the soft tissues and joints of the foot in overweight people increases the likelihood of developing tendinitis and plantar fasciitis.

Treatment: Corns and Calluses

A corn is a protective layer of dead skin cells that forms due to repeated friction. It is cone-shaped and has a knobby core that points inward. This core can put pressure on a nerve and cause sharp pain. Corns can develop on the top of, or between, toes. If a corn develops between the toes, it may be kept pliable by the moisture from perspiration and is therefore called a soft corn.

Corns develop as a result of friction from the toes rubbing together or against the shoe. They often occur from the following:

Shoes, socks, or stockings that fit too tightly around the toes
Pressure on the toes from high-heeled shoes
Shoes that are too loose, due to the friction of the foot sliding within the shoe
Deformed and crooked toes

Calluses are composed of the same material as corns. Calluses, however, develop on the ball or heel of the foot. The skin on the sole of the foot is ordinarily about 40 times thicker than the skin anywhere else on the body, but a callus can even be twice as thick. A protective callus layer naturally develops to guard against excessive pressure and chafing as people get older and the padding of fat on the bottom of the foot thins out. If calluses get too big or too hard, they may pull and tear the underlying skin.

Risk factors for calluses include the following:

Poorly fitting shoes
Walking regularly on hard surfaces
Flat feet

Of note, in people with diabetes, the presence of calluses is a strong predictor of ulceration, particularly in those who have a history of foot ulcers.

Preventing Corns and Calluses and Relieving Discomfort. To prevent corns and calluses and relieve discomfort if they develop:

Do not wear shoes that are too tight or too loose. Wear well-padded shoes with open toes or a deep toe box (the part of the shoe that surrounds the toes). If necessary, have a cobbler stretch the shoes in the area where the corn or callus is located.
Wear thick socks to absorb pressure, but do not wear tight socks or stockings.
Apply petroleum jelly or lanolin hand cream to corns or calluses to soften them.
Use doughnut-shaped pads that fit over a corn and decrease pressure and friction. They are available at most drug stores.
Place cotton, lamb's wool, or mole skin between the toes to cushion any corns in these areas.

Removing Corns and Calluses. To remove a corn or callus, soak it in very warm water for 5 minutes or more to soften the hardened tissue, then gently sand it with a pumice stone. Several treatments may be necessary. Do not trim corns or calluses with a razor blade or other sharp tool. Unsterile cutting tools can cause infection, and it is easy to slip and cut too deep, causing excessive bleeding or injury to the toe or foot.

Medicated Solutions and Pads. There are numerous over-the-counter pads, plasters, and medications for removing corns and calluses. These treatments commonly contain salicylic acid, which may cause irritation, burns, or infections that are more serious than the corn or callus. Use caution with these medications. The following people should not use them:

Patients with diabetes
Patients with reduced feeling in the feet due to circulation problems or neurological damage
Patients who do not have the flexibility or eyesight to use them properly

Treatment: Bunions

A bunion is a deformity that usually occurs at the head of one of the five long bones (the metatarsal bones) that extend from the arch of the foot and connect to the toes. A bunion typically develops in the following way:

Most often it occurs in the first metatarsal bone (the one that attaches to the big toe). A bunion may also develop in the bone that joins the little toe to the foot (the fifth metatarsal bone), in which case it is known as either a bunionette or a tailor's bunion.
A bunion begins to form when the big or little toe is forced in toward the rest of the toes, causing the head of the metatarsal bone to jut out and rub against the side of the shoe.
The underlying tissue becomes inflamed, and a painful bump forms.
As this bony growth develops, the bunion is formed as the big toe is forced to grow at an increasing angle toward the rest of the toes. One important bunion deformity, hallux valgus, causes the bone and joint of the big toe to shift and grow inward, so that the second toe crosses over it.

Several conditions can cause bunions:

Narrow high-heeled shoes with pointed toes can put enormous pressure on the front of the foot.
Injury in the joint may cause a bunion to develop over time.
Genetics play a role in 10 - 15% of all bunions.

Flat feet, gout, arthritis, and occupations (such as ballet) that place undue stress on the feet can also increase the risk for bunions.

Shoes and Protective Pads. Pressure and pain from bunions and bunionettes can be relieved by wearing appropriate shoes, such as the following:

Soft, wide, low-heeled leather shoes that lace up
Athletic shoes with soft toe boxes
Open shoes or sandals with straps that don't touch the irritated area

A thick doughnut-shaped, moleskin pad can protect the protrusion. In some cases, an orthotic can help redistribute weight and take pressure off the bunion. Nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroid injections may offer some pain relief.

Surgery. If discomfort persists, surgery may be necessary, particularly for more serious conditions, such as hallux valgus. There are more than 100 surgical variations, ranging from removing the bump to realigning the toes.

The most common surgery, an office procedure known as bunionectomy, involves shaving down the bone of the big toe joint. In one procedure the surgeon uses a very small incision, through which the bone-shaving drill is inserted. The physician shaves off the bone, guided by feel or x-ray. This technique is not a cure, but patient satisfaction is high and results are long-lasting.

Click the icon to see an illustrated series detailing bunion removal.

More extensive surgeries may be required to realign the toe joint. Although there are variations of each, they generally involve one or more of the following:

Osteotomy (cutting and realigning the joint). Long-term studies on osteotomies report that 90% of patients are satisfied with the procedure.
Exostetectomy (removal of the large bony growth). This technique is only useful when there is no shift in the toe bone itself.
Arthrodesis (removal of damaged portion of the joint, followed by implantation of screws, wires, or plates to hold the bones together until they heal). This is the gold standard procedure for very severe cases or when previous procedures have failed. Most patients report good results.
Arthroplasty (removal of damaged portion of the joint with the goal of achieving a flexible scar). This technique offers symptom relief and faster rehabilitation than arthrodesis, but it can cause deformity and some foot weakness. Arthroplasty tends to be used in older patients. Biologic or synthetic implants for supporting the toes are showing promise as part of this procedure.
Tendon and Ligament Repair. If tendons and ligaments have become too loose, the surgeon may tighten them.

In severe cases, surgeons are testing bone grafts to restore bone length in patients who have had previous bunion surgeries or damage from osteoarthritis.

Complications, though uncommon in even the most complex procedures, can include:

Continued pain
Infection
Possible numbness
Irritation from implants used to support the bone
An excessively shortened metatarsal bone

Recovery from more invasive procedures, such as arthrodesis or osteotomy, may take 6 - 8 weeks, and it can be that long before a patient can put full weight on the foot. In such cases, the patient will need to wear a cast or use crutches. Elderly patients may need wheelchairs.

Treatment: Hammertoes

A hammertoe is a permanent deformity of the toe joint, in which the toe bends up slightly and then curls downward, resting on its tip. When forced into this position long enough, the tendons of the toe shrink, and the toe stiffens into a hammer- or claw-like shape.

Hammertoe is most common in the second toe, but it can develop in any or all of the three middle toes if they are pushed forward and do not have enough room to lie flat in the shoe. The risk is increased when the toes are already crowded by the pressure of a bunion. Risks include:

Lying down for long periods
Diabetes
Diseases that affect the nerves and muscles

Click the icon to see an image of a hammertoe.

Treatment for Hammertoe. At first, a hammertoe is flexible, and any pain it causes can usually be relieved by putting a toe pad, sold in drug stores, into the shoe. To help prevent and ease existing discomfort from hammertoes, shoes should have a deep, wide toe area. As the tendon becomes tighter and the toe stiffens, other treatments, including exercises, splints, and custom-made shoe inserts (orthotics) may help redistribute weight and ease the position of the toe.

Surgery. Patients with severe cases of hammertome may need surgery. If the toe is still flexible, only a simple procedure that releases the tendon may be involved. Such procedures sometimes require only a single stitch and a Band-Aid. If the toe has become rigid, surgery on the bone is necessary, but it can still be performed in the doctor's office. A procedure called PIP arthroplasty involves releasing the ligaments at the joint and removing a small piece of toe bone, which restores the toe to its normal position. The toe is held in this position with a pin for about 3 weeks, and then the pin is removed. One study reported that 92% of patients who had arthroscopy were still pain free after 5 years.

Treatment: Ingrown Toenails

Ingrown toenails can occur on any toe but are most common on the big toes. They usually develop when tight-fitting or narrow shoes put too much pressure on the toenail and force the nail to grow into the flesh of the toe. Incorrect toenail trimming can also contribute to the risk of developing an ingrown toenail. Other causes are:

Fungal infections
Injuries
Abnormalities in the structure of the foot
Repeated impact on the toenail from high-impact aerobic exercise

An ingrown toenail is a condition in which the edge of the toenail grows into the skin of the toe. The big toe is most commonly affected. Symptoms include pain, redness, and swelling around the toenail.

Caring for Toenails. Trim toenails straight across and keep them long enough so that the nail corner is not visible. If the nail is cut too short, it may grow inward. If the nail does grow inward, do not cut the nail corner at an angle. This only trains the nail to continue growing inward. When filing the nails, file straight across the nail in a single movement, lifting the file before the next stroke. Do not saw back and forth. A cuticle stick can be used to clean under the nail.

Treatments. To relieve pain from ingrown toenails, try wearing sandals or open-toed shoes. Soaking the toe for 5 minutes twice a day in a warm water solution of Domeboro or Betadine can help. People who are at increased risk for infections, such as those with diabetes, should have professional treatment.

Antibiotic ointments can treat ingrown toenails that are infected. Apply the ointment by working a wisp of cotton under the nail, especially the corners, to lift the nail up and drain the infection. The cotton will also help force the toenail to grow out correctly. Change the cotton daily, and use the antibiotic consistently.

In severe cases, more intensive treatments are needed. Surgery involves simply cutting away the sharp portion of ingrown nail, removing the nail bed, or removing a wedge of the affected tissue. One study found that orthonyxia, a newer surgical technique that implants a small metal brace into the top of the nail, is as effective as traditional surgical techniques for preventing ingrown toenails from recurring.

Nonsurgical methods can also treat ingrown toenails. One technique uses chemicals to remove the skin. Both sodium hydroxide and phenol may be used, but research shows that sodium hydroxide produces a better outcome and faster recovery than phenol. Other nonsurgical methods include using cauterization (heating), or lasers, to remove the skin.

Treatment: Forefoot Pain

Forefoot pain refers to pain and discomfort felt toward the top of the foot. The rate of forefoot pain and deformity increases with age. When a cause cannot be determined, any pain on the ball of the foot is generally referred to as metatarsalgia.

Forefoot pain may be due to:

Morton's neuroma
Sesamoiditis
Stress fractures

A neuroma usually means a benign tumor of a nerve. However, Morton’s neuroma, also called interdigital neuroma, is not actually a tumor. It is a thickening of the tissue surrounding the nerves leading to the toes. Morton’s neuroma usually develops when the bones in the third and fourth toes pinch together, compressing a nerve. It can also occur in other locations. The nerve becomes enlarged and inflamed. The inflammation causes a burning or tingling sensation and cramping in the front of the foot. Other causes of this condition include:

Tight, poorly-fitting shoes
Injury
Arthritis
Abnormal bone structure

Treatment for Neuromas. Pain from Morton's neuroma can be reduced by massaging the affected area. Roomier shoes (box-toed shoes), pads of various sorts, and cortisone injections in the painful area are also helpful. A combination of cortisone injections and shoe modifications provides better immediate relief than changes in footwear alone. Ultrasound-guided injection of alcohol might also provide relief from Morton's neuroma, research finds.

If these treatments are not effective, the enlarged area may need to be surgically removed. In one long-term study of one surgeon's experience, 85% of patients reported good to excellent satisfaction nearly 6 years after surgery. About 65% were pain free. Some numbness is common afterward, but it rarely bothers patients. Occasionally, the nerve tissue may re-grow and form another neuroma.

Sesamoiditis is an inflammation of the tendons around the small, round bones that are embedded in the head of the first metatarsal bone, which leads to the big toe. Sesamoid bones bear much stress under ordinary circumstances; excessive stress can strain the surrounding tendons. Often there is no clear-cut cause, but sesamoid injuries are common among people who participate in jarring, high-impact activities, such as ballet, jogging, and aerobic exercise.

Treatment for Sesamoiditis. Rest and reducing stress on the ball of the foot are the first lines of treatment for sesamoiditis. A low-heeled shoe with a stiff sole and soft padding inside is all that is usually required. In severe cases, surgery may be necessary.

A stress fracture in the foot, also called fatigue or march fracture, usually results from a break or rupture in any of the five metatarsal bones (mostly the second or third). These fractures are caused by overuse during strenuous exercise, particularly jogging and high-impact aerobics. Women are at higher risk for stress fracture than men.

A fracture in the first metatarsal bone, which leads to the big toe, is uncommon because of the thickness of this bone. If it occurs, however, it is more serious than a fracture in any of the other metatarsal bones because it dramatically changes the pattern of normal walking and weight bearing.

Treatment for Stress Fractures. Patients should seek treatment if pain persists for 3 weeks. In a study of young athletes, treatment after that time reduced the chance that they could return to their sport. Surgery may be needed if conservative measures fail. In most cases, however, stress fractures heal by themselves if you avoid rigorous activities. Some health care providers recommend moderate exercise, particularly swimming and walking. It is best to wear low-heeled shoes with stiff soles. Occasionally, a health care provider may recommend wearing a special wooden shoe and a compressive wrap to make walking more comfortable.

Treatment: Heel Pain

The heel is the largest bone in the foot. Heel pain is the most common foot problem and affects 2 million Americans every year. It can occur in the front, back, or bottom of the heel. Types of heel pain include:

Achilles tendinitis
Bursitis of the heel
Excess pronation
Haglund's deformity
Heel spur syndrome
Plantar fasciitis

Each type of heal pain is described in more detail below. General treatment guidelines are as follows:

The American Orthopaedic Foot and Ankle Society (AOFAS) suggests shoe inserts, medications, and stretching as a first line of therapy for heel pain. One study found that 95% of women who used an insert and did simple stretching exercises for the Achilles tendon and plantar fascia experienced improvement after 8 weeks.
If these treatments fail, the patient may need prescription heel orthotics and extended physical therapy. Surgery may be an option if other methods have failed.

Achilles tendinitis is an inflammation of the tendon that connects the calf muscles to the heel bone. It is caused by small tears in the tendon from overuse or injury. This condition is most common in people who engage in high-impact exercise, particularly jogging, racquetball, and tennis.

People at highest risk for this disorder from these activities are those with a shortened Achilles tendon. Such people tend to roll their feet too far inward when walking, and may bounce when they walk. A shortened tendon can be due to an inborn structural abnormality, or it can develop from regularly wearing high heels.

An inflamed or torn Achilles tendon causes intense pain and affects mobility.

Evidence is uncertain about the best way to treat either acute or chronic Achilles tendinitis. Some approaches include:

Treatments to Relieve Pain and Reduce Inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin or ibuprofen (Advil), may help ease pain and reduce inflammation. It is also helpful to apply ice for 20 - 30 minutes, four or five times a day. (Note: Corticosteroid injections are sometimes used, although evidence suggests they don't help very much, and they can pose a risk for rupture of the tendon.)

Gentle Stretching. Gentle calf muscle stretches may also help reduce pain and spasms. If the calf is swollen, elevate the leg. Exercise is safe when the heel is no longer swollen or tender, even if pain is still present. If pain increases with exercise, stop immediately.

Laser Therapy. Low-level laser therapy that emits energy directed at pain trigger points has helped some patients. No strong evidence supports its use to date, however.

Surgery vs. Nonsurgical Treatment. Chronic inflammation may lead to rupture of the Achilles tendon. If pain continues, the ruptured tendon will require a cast and perhaps surgery, called tendon transfer. Although some experts believe a cast without surgery is a sufficient treatment for such rupture, there is a chance the tendon may rupture again in the future, even after it heals. Some experts suggest surgery for active people and nonsurgical treatment for older people.

Surgery requires a long incision with a postoperative period of immobilization that can average 6 weeks. Complications can include a significant surgical scar, infection, and muscle atrophy, although surgery reduces pain and preserves foot function in the long term. Less invasive techniques are being tested. In one study, selected patients with ruptured tendons were hospitalized for about 5 days and fitted with special footgear (Variostabil, which continuously raised the back of the foot). The footgear was effective for most patients, and the tendon ruptured again in only 5% of cases.

Bursitis of the heel is an inflammation of the bursa, a small sack of fluid beneath the heel bone. Nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin or ibuprofen (Advil), and steroid injections will help relieve pain from bursitis. Applying ice and massaging the heel are also beneficial. A heel cup or soft padding in the heel of the shoe reduces direct impact when walking.

Pronation is the normal motion that allows the foot to adapt to uneven walking surfaces and to absorb shock. Excessive pronation occurs when the foot has a tendency to turn inward and stretch and pull the fascia. It can cause not only heel pain, but also hip, knee, and lower back problems.

Haglund's deformity, known medically as posterior calcaneal exostosis, is a bony growth surrounded by tender tissue on the back of the heel bone. It develops when the back of the shoe repeatedly rubs against the back of the heel, aggravating the tissue and the underlying bone. It is commonly called pump bump because it frequently occurs with high heels. (It can also develop in runners, however.)

Treatment for Haglund's Deformity. Applying ice followed by moist heat will help ease discomfort from a pump bump. Nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin or ibuprofen (Advil), will also reduce pain. Your doctor may recommend an orthotic device to control heel motion. Corticosteroid injections are not recommended because they can weaken the Achilles tendon.

In severe cases, surgery may be necessary to remove or reduce the bony growth. According to one study, however, surgery was not effective for more than 30% of patients and, in fact, the condition worsened in 14% of patients who had surgery. A more recent study reported that surgery cured 90% of cases, but patients took 6 months to 2 years to fully recover. Experts advise patients to try all conservative measures before choosing surgery.

Plantar fasciitis is a common foot problem that accounts for 1 million office visits per year. Plantar fasciitis occurs from small tears and inflammation in the wide band of tendons and ligaments that stretches from the heel to the ball of the foot. This band, much like the tensed string in a bow, forms the arch of the foot and helps serve as a shock absorber for the body.

The term plantar means the sole of the foot, and fascia refers to any fibrous connective tissue in the body. Most people with plantar fasciitis experience pain in the heel with their first steps in the morning. The pain also often spreads to the arch of the foot. The condition can be temporary, or it may become chronic if ignored. Resting can provide relief, but only temporarily.

Heel spurs are calcium deposits that can develop under the heel bone as a result of the inflammation that occurs with plantar fasciitis. Heel spurs and plantar fasciitis are sometimes blamed interchangeably for pain, but plantar fasciitis can occur without heel spurs, and spurs commonly develop without causing any symptoms at all.

Causes of Plantar Fasciitis. The cause of plantar fasciitis is often unknown. It is usually associated with overuse during high-impact exercise and sports. Plantar fasciitis accounts for up to 9% of all running injuries. Because the condition often occurs in only one foot, however, factors other than overuse are likely to be responsible in many cases. Other causes of this injury include poorly-fitting shoes, lack of calf flexibility, or an uneven stride that causes an abnormal and stressful impact on the foot.

Treatment Goals. The three major treatment goals for plantar fasciitis are:

Reducing inflammation and pain
Reducing pressure on the heel
Restoring strength and flexibility

Embarking on an exercise program as soon as possible and using NSAIDs, splints, or heel pads as needed can help relieve the problem. Pain that does not subside with NSAIDs may require more intensive treatments, including leg supports and even surgery.

Exercises to Restore Strength and Flexibility. Stretching the plantar fascia is the mainstay therapy for restoring strength and flexibility. One exercise involves the following:

Put the hands on a wall and lean against them.
Place the uninjured foot on the floor in front of the injured foot.
Raise the heel of the injured foot.
Gently stretch the injured leg and foot.

With stretching treatments, the plantar fascia nearly always heals by itself but it may take as long as a year, with pain occurring intermittently. A moderate amount of low-impact exercise (such as walking, swimming, or cycling) also seems to be beneficial.

Treatment. Inflammation and pain is most commonly treated with ice and over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin or ibuprofen. NSAIDs reduce pain and disability in people with plantar fasciitis when used with other techniques, such as night splints and stretching.

Corticosteroids are powerful anti-inflammatory agents. An injection of a steroid plus a local anesthetic (such as xylocaine) may provide relief in severe cases of plantar fasciitis. (Steroid injections are not used for pain that is only due to heel spurs). For athletes or performers who need immediate relief, an effective method is to administer the steroid dexamethasone using a procedure called iontophoresis, which introduces the drug into the foot's tissue using an electrical current.

Several non-drug approaches can relieve pressure on the heel, including:

Sturdy Shoes and Insoles. It is important to wear comfortable but sturdy shoes that have thick soles, rubber heels, and a sole insole to relieve pressure. (An insole with an arch support might also be helpful.) Cutting a round hole about the size of a quarter in the sole cushion under the painful area may help support the rest of the heel while relieving pressure on the painful spot. Heel cups are not very useful. When combined with exercises that stretch the arch and heel cord, over-the-counter insoles may offer the same relief as prescribed orthotics.
Night Splints. Some evidence suggests that splints worn at night may be helpful for some people. One device, for example, uses an Ace bandage and an L-shaped fiberglass splint to keep the foot stretched while the patient is sleeping. This allows the muscle to heal. One study reported that nearly any splint, regardless of cost, is equally effective in about three-quarters of patients. Although patient compliance may be better with custom-made prescribed orthotics than with tension night splints, one study found they are equally effective in improving pain.
Elevated Heels. Some people report relief from mild symptoms with the use of shoes or cowboy boots that have elevated heels. This approach, however, may not work in some people and is not recommended for anyone with a moderate-to-severe condition. (Heel cups have not been proven to be very useful.)
Orthotics. For severe conditions, such as fallen arches or structural problems that cause imbalance, insoles, called orthotics, molded from a plaster cast of the patient's foot may be needed. (See "Insoles and Orthotics" section).
Extracorporeal Shock Wave Therapy (ESWT). ESWT may be used as an alternative to surgery for patients who have not responded to other treatments. The therapy uses low-dose sound waves to injure the surrounding tissues in the heel, which is believed to trigger healing of the tissues that are causing the pain. Studies show that the treatment provides a very small reduction in heel pain without side effects. It can be considered as an option for patients who haven't responded well to extensive conservative treatment.
Surgery. Surgery may be needed for some patients, typically those who have disabling heel pain that does not respond to other treatments for at least a year. A typical surgery is called instep plantar fasciotomy. It relieves pressure on the nerves that are causing pain by removing and therefore releasing part of the plantar fascia. A less invasive method uses a procedure called endoscopy, which requires smaller incisions. Wearing a below-the-knee walking cast after surgery for 2 weeks may reduce the need for pain relief and speed recovery time compared to the use of crutches.
Botox. Small studies show that injections of botulinum toxin (Botox), a protein used to temporarily paralyze certain muscles, reduces pain and improves patients' future ability to walk. More research is needed on this treatment.

Treatment: Flat Feet

Flat foot, or pes planus, is a defect of the foot that eliminates the arch. The condition is most often inherited. Arches, however, can also fall in adulthood, in which case the condition is sometimes referred to as posterior tibial tendon dysfunction (PTTD). This occurs most often in women over age 50, but it can occur in anyone. The following are risk factors for PTTD:

Wearing high heels for long periods of time is a particular risk for flat feet. Over the years, the Achilles tendon in the back of the calf shortens and tightens, so the ankle does not bend properly. The tendons and ligaments running through the arch then try to compensate. Sometimes they break down, and the arch falls.
Some studies have indicated that the earlier a person starts wearing shoes, particularly for long periods of the day, the higher the risk for flat feet later on.
Other conditions that can lead to PTTD include obesity, diabetes, surgery, injury, rheumatoid arthritis, or the use of corticosteroids.

Some research suggests that flat feet in adults can, over time, actually exert abnormal pressure on the ankle joint that can cause damage. One indirect complication of flat arches may be urinary incontinence or leakage during exercise. The less flexible the arch, the more force reaches the pelvic floor, jarring the muscles that affect urinary continence. Nevertheless, whether flat feet pose any significant problems in adults is unknown. For example, one study on athletes with flat feet indicated that they had no higher risk for leg or foot injuries than did athletes with normal arches.

Treatment for Flat Feet in Children. Doctors usually can't diagnose flat feet until a child is 6 years old. Children with flat feet typically don't have symptoms, and often outgrow the condition. Children who are experiencing symptoms might need to change shoes or wear arch supports. In rare cases, minimally invasive joint insert surgery may be an option.

Treatment for Flat Feet in Adults. In general, conservative treatment for flat feet acquired in adulthood (posterior tibial tendon dysfunction) involves pain relief and insoles or custom-made orthotics to support the foot and prevent progression.

In severe cases, surgery may be required to correct the foot posture, usually with procedures called osteotomies or arthrodesis that typically lengthen the Achilles tendon and adjust tendons in the foot. One procedure uses an implant to support the arch. These procedures have potential complications. Conservative methods should be tried first.

Treatment: Abnormally High Arches

An overly-high arch (hollow foot) can cause problems. Army studies have found that recruits with the highest arches have the most lower-limb injuries and that flat-footed recruits have the least. Contrary to the general impression, the hollow foot is much more common than the flat foot.

Clawfoot, or pes cavus, is a deformity of the foot marked by very high arches and very long toes. Clawfoot is a hereditary condition, but can also occur when muscles in the foot contract or become unbalanced due to nerve or muscle disorders.

Claw toe is a deformity of the foot in which the toes are pointed down and the arch is high, making the foot appear claw-like. Claw toe can be a condition from birth or develop as a consequence of other disorders.

Treatment: Tarsal Tunnel Syndrome

Tarsal tunnel syndrome results from compression of a nerve that runs through a narrow passage behind the inner ankle bone down to the heel. It can cause pain anywhere along the bottom of the foot. It can occur with:

Diabetes
Back pain
Arthritis
Injury to the ankle
Abnormal blood vessels
Scar tissue that press against the nerve

Magnetic resonance imaging (MRI) and the dorsiflexion-eversion test can diagnose this syndrome.

Treatment for Tarsal Tunnel Syndrome. Specially designed shoe inserts called orthotics can relieve pain from tarsal tunnel syndrome, because they help redistribute weight and take pressure off the nerve. Corticosteroid injections may also help. Surgery is sometimes performed, particularly if symptoms persist for more than a year, although its benefits are a matter of debate. Tarsal tunnel syndrome caused by known conditions, such as tumors or cysts, may respond better to surgery than tarsal tunnel syndrome of unknown cause. It can take months after this surgery for a person to recover and resume normal activities. Only experienced surgeons should perform tarsal tunnel syndrome surgery.

Treatment: Foot Injury

If you suspect that you have broken or fractured bones in a toe or foot, call a doctor, who will probably order x-rays. Even if you can walk, you still might have a fracture. People are often able to walk even if a foot bone has been fractured, particularly if it is a chipped bone or a toe fracture.

Over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat mild pain caused by muscle inflammation. Aspirin is the most common NSAID. Others include ibuprofen (Motrin, Advil, Nuprin, Rufen), ketoprofen (Actron, Orudis KT), naproxen (Aleve, Naprelan), and tolmetin (Tolectin). A gel containing ibuprofen can be applied to sore joints. Acetaminophen (Tylenol) is not an NSAID, and although it is a mild pain reliever, it will not reduce inflammation. It is important to note that high doses or long-term use of any NSAID can cause gastrointestinal disturbances with sometimes serious consequences, including dangerous bleeding. No one should take NSAIDs for prolonged periods of time without consulting a doctor.

The acronym RICE stands for rest, ice, compression, and elevation -- the four basic elements of immediate treatment for an injured foot.

Rest. Patients should get off injured foot as soon as possible.
Ice. This is particularly important to reduce swelling and promote recovery during the first 48 hours. Wrap a bag or towel containing ice around the injured area on a repetitive cycle of 20 minutes on, 40 minutes off.
Compression. Lightly wrap an Ace bandage around the area.
Elevation. Elevate the foot on several pillows.

Minor injuries like sprains may be treated at home if broken bones are not suspected. The acronym RICE is helpful for remembering how to treat minor injuries: "R" stands for rest, "I" is for ice, "C" is for compression, and "E" is for elevation. Pain and swelling should decrease within 48 hours, and gentle movement may be beneficial, but don't put pressure on a sprained joint until the pain is completely gone (one to several weeks).

Prevention

The American Podiatric Medical Association offers the following tips for preventing foot pain:

Don't ignore foot pain -- it's not normal. If the pain persists, see a doctor who specializes in podiatry.
Inspect feet regularly. Pay attention to changes in color and temperature. Look for thick or discolored nails (a sign of developing fungus), and check for cracks or cuts in the skin. Peeling or scaling on the soles of feet could indicate athlete's foot. Any growth on the foot is not considered normal.
Wash feet regularly, especially between the toes, and dry them completely.
Trim toenails straight across, but not too short. (Cutting nails in corners or on the sides increases the risk for ingrown toenails.)
Make sure shoes fit properly. Purchase new shoes later in the day when feet tend to be at their largest, and replace worn out shoes as soon as possible.
Select and wear the right shoe for specific activities (such as running shoes for running).
Alternate shoes. Don't wear the same pair of shoes every day.
Avoid walking barefoot, which increases the risk for injury and infection. At the beach or when wearing sandals, always use sunblock on your feet, as you would on the rest of your body.
Be cautious when using home remedies for foot ailments. Self-treatment can often turn a minor problem into a major one.
It is critical that people with diabetes see a podiatric physician at least once a year for a checkup. People with diabetes, poor circulation, or heart problems should not treat their own feet, including toenails, because they are more prone to infection.

Skin creams can help maintain skin softness and pliability. A pumice stone or loofah sponge can help get rid of dead skin.

Taking a warm footbath for 10 minutes two or three times a week will keep the feet relaxed and help prevent mild foot pain caused by fatigue. Adding 1/2 cup of Epsom salts increases circulation and adds other benefits. Taking footbaths only when the feet are painful is not as helpful.

In addition to wearing proper shoes and socks, walking often -- and properly -- can prevent foot injury and pain. The head should be erect, the back straight, and the arms relaxed and swinging freely at the side. Step out on the heel, move forward with the weight on the outside of the foot, and complete the step by pushing off the big toe.

Exercises specifically for the toe and feet are easy to perform and help strengthen them and keep them flexible. Helpful exercises include the following:

Raise and curl the toes 10 times, holding each position for a count of five.
Put a rubber band around both big toes and pull the feet away from each other. Count to five. Repeat 10 times.
Pick up a towel with the toes. Repeat five times.
Pump the foot up and down to stretch the calf and shin muscles. Perform for 2 or 3 minutes.

Early Development. The first year of life is important for foot development. Parents should cover their babies' feet loosely, allowing plenty of opportunity for kicking and exercise. Change the child's position frequently. Children generally start to walk at 10 - 18 months. They should not be forced to start walking early. Wearing just socks or going barefoot indoors helps the foot develop normally and strongly and allows the toes to grasp. Going barefoot outside, however, increases the risk for injury and other conditions, such as plantar warts.

Shoes. Children should wear shoes that are light and flexible, and since their feet tend to perspire, their shoes should be made of materials that breathe. Replace footwear every few months as the child's feet grow. Footwear should never be handed down. Protect children's feet if they participate in high-impact sports.

Shoes

In general, the best shoes are well cushioned and have a leather upper, stiff heel counter, and flexible area at the ball of the foot. The heel area should be strong and supportive, but not too stiff, and the front of the shoe should be flexible. New shoes should feel comfortable right away, without a breaking-in period.

Well-fitted shoes with a firm sole and soft upper are the best way to prevent many problems with the feet. They should be purchased in the afternoon or after a long walk, when the feet have swelled. There should be 1/2 inch of space between the longest toe and the tip of the shoe (remember, the longest toe is not always the big toe), and the toes should be able to wiggle upward.

Stand when being measured, and have both feet sized, buying shoes that fit whichever foot is largest. Wear the same socks as you would regularly wear with the new shoes. Women who are accustomed to wearing pointed-toe shoes may prefer the feel of tight-fitting shoes, but with wear their tastes may adjust to shoes that are less confining and properly fitted.

Ideally, the shoe should have a removable insole. Thin, hard soles may be the best choice for older people. Elderly people wearing shoes with thick inflexible soles may be unable to sense the position of their feet relative to the ground, significantly increasing the risk for falling.

High heels are the major cause of foot problems in women. Although people believe that foot binding is a problem limited to Chinese women of the past, many fashionable high heels are designed to constrict the foot by up to an inch. Women who insist on wearing high-heeled shoes should at least look for shoes with wide toe room, reinforced heels that are relatively wide, and cushioned insoles. They should also keep the amount of time they spend wearing high heels to a minimum.

The way shoes are laced can be important for preventing specific problems. Laces should always be loosened before putting shoes on. People with narrow feet should buy shoes with eyelets farther away from the tongue than people with wider feet. This makes for a tighter fit for narrower feet and a looser fit for wider feet. If, after tying the shoe, less than an inch of tongue shows, the shoes are probably too wide. Adjust tightness both at the top and bottom of the shoe. When shoes with high arches cause pain, skip eyelets when lacing them to relieve pressure.

If shoes need breaking in, place moleskin pads next to areas on the skin where friction is likely to occur. Once a blister occurs, moleskin is not effective. Change shoes during the day, and rotate between different pairs of shoes. As soon as the heels show noticeable wear, replace the shoes or their heels.

Avoid extreme variations between exercise, street, and dress shoes.

Exercise and Sports. Shoes purchased for exercise should be specifically designed for a person's preferred sport. For instance, a running shoe should especially cushion the forefoot, while tennis shoes should emphasize ankle support. Athletic socks are almost as important as shoes. Experts often recommend padded acrylic socks.

Occupational Footwear. Because a number of occupations put the feet in danger, workers in high-risk jobs should be sure their footwear is protective. For example, non-electric workers at risk for falling or rolling objects or punctures should wear shoes with steel toes and possibly other metal foot guards. Electric workers should wear footgear with no metal parts (or insulated steel toes) and rubber soles and heels. Chemical workers should wear shoes made of synthetics or rubber, not leather.


Aerobic Dancing	Sufficient cushioning to absorb shock and pressure, which should be many times greater than shock from walking. Arches that maintain side-to-side stability. Thick upper leather support. Box toe. Orthotics may be required for people with ankles that over-turn inward or outward. Soles should allow for twisting and turning.
Cycling	Rigid support across the arch to prevent collapse during pedaling. Heel lift. Cross-training or combo hiking/cycling shoes may be sufficient for the casual biker. Toe clips or specially designed shoe cleats for serious cyclers. In some cases, orthotics may be needed to control arch and heel and balance the forefoot.
Running	Sufficient cushioning to absorb shock and pressure. Fully bendable at the ball of the foot. Enough traction on the sole to prevent slipping. Consider insole or orthotic with arch support for problem feet.
Tennis	Allows side-to-side sliding. Low-traction sole. Snug fitting heel with cushioning. Padded toe box with adequate depth. Soft-support arch.
Walking	Lightweight. Breathable upper material (leather or mesh). Wide enough to accommodate ball of the foot. Firm padded heel counter that does not bite into heel or touch anklebone. Low heel close to ground for stability. Good arch support. Front provides support and flexibility.

Insoles and Orthotics

Insoles are flat cushioned inserts that are placed inside the shoe. They are designed to reduce shock, provide support for heels and arches, and absorb moisture and odor. In general, they can be very helpful for many people.

People respond very differently to specific insoles. What may work for one person may not for another. Consider the thickness of socks when purchasing insoles to be sure they do not squeeze the toes up against the shoes. Insoles can be purchased in athletic and drug stores. Shoe stores that specialize in foot problems often sell customized, but more expensive, insoles. In general, over-the-counter insoles offer enough support for most people's foot problems. Most well-known brands of athletic shoes have built-in insoles.

Brands and Materials. There are many types of insoles available. They are composed of various materials, such as cork, leather, plastic foam, and rubber. Very effective insoles are now made from viscoelastic polymers (such as Sorbothane, Airplus, Spenco, Dr. Scholl's Massaging Gel, and others), which are gel-like materials that act both as liquids and solids.

Heel Cushions for Shortened Achilles Tendons. People who have developed short, tightened Achilles tendons (usually women who have worn high-heeled shoes for prolonged periods) should consider using heel cushions. Like insoles, heel cushions are inserted inside the shoes. They should be at least 1/8 inch thick, but not more than 1/4 inch thick.

For severe conditions, such as fallen arches or structural problems that cause imbalance, podiatrists or physicians may need to fit and prescribe orthotics, or orthoses, which are insoles molded from a plaster cast of the patient's foot. Orthotics are usually categorized as rigid, soft, or semi-rigid.

Before seeking prescription orthotics, people with less severe problems should consider testing the lower-priced, over-the-counter insoles.

Types of orthotics include:

Rigid Orthotics. Rigid orthotics are used to control motion in two major foot joints that lie directly below the ankle. They are often used to prevent excessive pronation (the turning in of the foot) and are useful for people who are very overweight or have uneven leg lengths. Some experts warn that rigid orthotics may cause sesamoiditis or benign tumors from pinched nerves.
Soft Orthotics. Soft orthotics are designed to absorb shock, improve balance, and remove pressure from painful areas. They are made from a lightweight material and are often beneficial for people with diabetes or arthritis. Soft orthotics need to be replaced periodically, and because they are bulkier than rigid orthotics, they may require larger shoes.
Semi-Rigid Orthotics. Semi-rigid orthotics are designed to provide balance, often for a specific sport. They are typically made of layers of leather and cork reinforced by silastic.

Resources

www.apma.org -- American Podiatric Medical Association
www.aofas.org -- American Orthopaedic Foot and Ankle Society
www.acfas.org -- American College of Foot and Ankle Surgeons
www.aapsm.org -- American Academy of Podiatric Sports Medicine
www.apta.org -- American Physical Therapy Association
www.diabetes.org -- American Diabetes Association
http://ndep.nih.gov/campaigns/Feet/Feet_overview.htm -- National Diabetes Education Program
www.arthritis.org -- Arthritis Foundation
www.podiatrynetwork.com -- Podiatry Network

References

Bostanci S, Kocyigit P, Gurgey E. Comparison of phenol and sodium hydroxide chemical matricectomies for the treatment of ingrowing toenails. Dermatol Surg. 2007;33:680-685.

Donley BG, Moore T, Sferra J, Gozdanovic J, Smith R. The efficacy of oral nonsteroidal anti-inflammatory medication (NSAID) in the treatment of plantar fasciitis: a randomized, prospective, placebo-controlled study. Foot Ankle Int. 2007;28:20-23.

Frey C, Zamora J. The effects of obesity on orthopaedic foot and ankle pathology. Foot Ankle Int. 2007;28:996-999.

Gollwitzer H, Diehl P, von Korff A, Rahlfs VW, Gerdesmeyer L. Extracorporeal shock wave therapy for chronic painful heel syndrome: a prospective, double blind, randomized trial assessing the efficacy of a new electromagnetic shock wave device. J Foot Ankle Surg. 2007;46:348-357.

Hughes RJ, Ali K, Jones H, Kendall S, Connell DA. Treatment of Morton's neuroma with alcohol injection under sonographic guidance: follow-up of 101 cases. Am J Roentgenol. 2007;188:1535-1539.

Kruijff S, van Det RJ, van der Meer GT, van den Berg IC, van der Palen J, Geelkerken RH. Partial matrix excision or orthonyxia for ingrowing toenails. J Am Coll Surg. 2008;206:148-153.

Malay DS, Pressman MM, Assili A, Kline JT, York S, Buren B, Heyman ER, Borowsky P, LeMay C. Extracorporeal shockwave therapy versus placebo for the treatment of chronic proximal plantar fasciitis: results of a randomized, placebo-controlled, double-blinded, multicenter intervention trial. J Foot Ankle Surg. 2006;45:196-210.

Review Date:
12/14/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M. Copyright

adam.com

Urinary tract infection

FitSugar — Wed, 08 Oct 2008 17:35:27 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Risk Factors
Complications
Diagnosis
Treatment
Medications
Other Treatments
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Urinary Tract Infections (UTIs) in the United States

According to Urologic Diseases in America, a report published in 2007 by the U.S. National Institutes of Health:

UTIs are the most expensive of all urologic diseases, accounting for about $3.5 billion a year in medical costs, including $96.4 million in prescriptions.
Over 60% of women will experience a UTI at least once in their lifetime. At least a third of women experience a UTI by the time they are 24 years old.
Only 20% of UTIs occur in men. However, men are far more likely than women to be hospitalized for an infection.
Childhood risk for UTIs is 2% for boys and 8% for girls. Vesicouretereal reflux, a condition in which urine backs up into the kidneys, affects about 10% of all children.

Circumcision Prevents UTIs

Baby boys who are uncircumcised are 10 - 12 times more likely than circumcised boys to develop UTIs during their first year of life, indicates the Urologic Diseases in America report.

High Doses of Zinc Increase UTI Risk

People who take very high daily doses of zinc supplements may face an increased risk for UTIs and other urologic problems, suggests a 2007 study in the Journal of Urology. Patients in the study who took 80 mg/day of zinc were more likely to be hospitalized for urinary complications than those who did not take zinc.
In general, the upper limit for zinc supplements should not exceed 40 mg/day. Eight mg/day for women and 11 mg/day for men are the recommended average doses. However, very high doses of zinc are sometimes prescribed for certain medical conditions, such as age-related macular degeneration.

Introduction

A urinary tract infection (UTI) is a condition where one or more structures in the urinary tract become infected after bacteria overcome its strong natural defenses. In spite of these defenses, UTIs are the most common of all infections and can occur at any time in the life of an individual. Almost 95% of cases of UTIs are caused by bacteria that typically multiply at the opening of the urethra and travel up to the bladder (known as the ascending route). Much less often, bacteria spread to the kidney from the bloodstream.

The male and female urinary tracts are relatively the same except for the length of the urethra.

Different classifications have been devised to help doctors choose treatments and determine the causes of UTIs.

Primary or Recurrent UTIs. UTIs are classified as primary or recurrent, depending on whether they are the first infection or whether they are repeat events.

Community- or Hospital-Acquired. UTIs are also sometimes grouped according to where they are acquired:

Community-Acquired Infections. Most UTIs are thought to develop in the community at large. It is unclear how primary community-acquired infections occur or how they are spread. Although most cases have been thought to arise sporadically, a rare outbreak in 1996 - 2000 caused by drug-resistant bacteria suggests epidemic spread of community-acquired infections could be more common than previously thought and may be spread via contaminated food. Most community-acquired infections are not serious and probably develop when the intestines become colonized with bacteria that are also predisposed to infecting the urinary tract.
Hospital-Acquired Infections. UTIs are also commonly acquired in the hospital, often due to contaminated urinary catheters. Hospital-acquired infections (known as nosocomial infections) tend to be more serious because the bacteria that cause them are often resistant to drug treatment and patients are often in poor general health.

Uncomplicated and Complicated. UTIs are also sometimes further defined as either being uncomplicated or complicated depending on the factors that trigger the infections.

Uncomplicated infections are only associated with bacterial infection, most often Escherichia coli (E. coli). They affect women much more often than men.
Complicated infections, which occur nearly as often in men as women, are also caused by bacteria but they occur as a result of some anatomical or structural abnormality. Often they are associated with catheter use in the hospital setting, bladder and kidney dysfunction, or kidney transplant (especially in the first three months after transplant). Recurrences occur in up to 50 - 60% of patients with complicated UTI if the underlying structural or anatomical abnormalities are not corrected.

Classifications Based on Symptoms and Levels of Infection. UTIs can also occur without symptoms and with symptoms but very low bacterial levels.

When bacteria are present and there are no symptoms it is called asymptomatic UTI or also bacteriuria.
Some patients can also have symptoms of infection with very low bacterial counts. In such cases, the condition is called acute urethral syndrome.

Cystitis. Cystitis is the most common urinary tract infection and is sometimes referred to as acute uncomplicated UTI. It occurs in the lower urinary tract (the bladder and urethra) and nearly always in women. In most cases, the infection is brief and acute and only the surface of the bladder is infected. Deeper layers of the bladder may be harmed if the infection becomes persistent, or chronic, or if the urinary tract is structurally abnormal.

Pyelonephritis (Kidney Infection). When infection spreads to the upper tract (the ureters and kidneys) it is called pyelonephritis, or more commonly, kidney infection. As many as half of all women with cystitis may have infections of the upper urinary tract at the same time as cystitis.

Click the icon to see an image of the kidney.

Urethritis. When infection is limited only to the urethra, the infection is known as urethritis. This is a common sexually transmitted disease in men.

Complicated UTIs may develop because of any one of a number of physical problems and affect any gender and age group. The common feature in most complicated UTIs is the inability of the urinary tract to clear out bacteria because of a physical condition that causes obstruction to the flow of urine or problems that hinder treatment success.

Most women who have had an uncomplicated UTI have occasional recurrences. About 25 - 50% of these women can expect another infection within a year of the previous one. Between 3 - 5% of women have ongoing, recurrent urinary tract infections, which follow the resolution of a previous treated or untreated episode.

Recurrence is often categorized as either reinfection or relapse:

Reinfection. About 80% of recurring UTIs are reinfections. A reinfection occurs several weeks after antibiotic treatment has cleared up the initial episode and can be caused by the same bacterial strain that caused the original episode or a different one. The infecting organism is usually introduced through the rectal region from fecal matter and moves up through the urinary tract.
Relapse. Relapse is the less common form of recurrent urinary tract infection. It is diagnosed when a UTI recurs within 2 weeks of treatment of the first episode and is due to treatment failure. Relapse usually occurs in kidney infection (pyelonephritis) or is associated with obstructions such as kidney stones, structural abnormalities or, in men, chronic prostatitis.

When a person has no symptoms of infection but significant numbers of bacteria have colonized the urinary tract, the condition is called asymptomatic UTI (also called asymptomatic bacteriuria). (In general, there must be at least 100,000 bacteria per milliliter of urine.) The condition is harmless in most people and rarely persists, although it does increase the risk for developing symptomatic UTIs.

Screening for asymptomatic bacteriuria is not necessary during most routine medical examinations, with the following exceptions:

Pregnant women. Pregnant women with asymptomatic bacteriuria have a 30% risk for acute pyelonephritis in their second or third trimester. Therefore, they need screening and treatment for this condition.
People undergoing urologic surgery (such as prostate surgery in men). The presence of an infection during surgery can lead to serious consequences.

Some groups recommend screening women with diabetes for asymptomatic bacteriuria. However, a 2003 study suggested that treating women who test positive for this condition does not reduce their risk of complications from UTIs. Asymptomatic bacteriuria may be an indicator for serious health problems in the elderly, but screening for the condition is not warranted in this group.

Some people have symptoms of cystitis but have a bacterial count lower than that ordinarily found in UTI. Such patients are sometimes diagnosed with acute urethral syndrome. This condition is usually caused by E. coli or other bacteria that cause cystitis, but in lower numbers, or by a sexually transmitted disease such as Chlamydia or gonorrhea.

Interstitial cystitis (IC) is an inflammation of the bladder wall that occurs almost exclusively in women. The average age of patients with IC is 40 years, but 25% of cases occur in women under age 30. Symptoms are very similar to cystitis, but no bacteria are present. These women often complain of experiencing pain during sex. Pelvic pain, depression, and stress may intensify symptoms. Women with IC also frequently suffer from other conditions, including allergies, urinary incontinence, sinusitis, and irritable bowel syndrome (IBS). Some doctors think that IC may be related to autoimmune diseases such as fibromyalgia and lupus.

IC is difficult to diagnose and treat. Pentosan (Elmiron) is the most frequent drug treatment, but doctors prescribe other medications as well (see Medications section). Some evidence suggests that diet can worsen IC symptoms. For instance, patients should avoid coffee (both caffeinated and decaf), alcohol, cola, vinegar, citrus fruits, tomatoes, chili, strawberries, pineapple, onions, pizza, chocolate, and apples, according to research presented at the 2006 American Urological Association scientific meeting.

The Urinary System. The urinary system helps maintain proper water and salt balance throughout the body and also expels urine from the body. It is made up of the following organs and structures:

The two kidneys, located on each side below the ribs and toward the middle-back, play the major role in this process. They filter waste products, water, and salts from the blood to form urine.
Urine passes from each kidney to the bladder through thin tubes called ureters.
Ureters empty into the bladder, which rests on top of the pelvic floor. This is a muscular structure similar to a sling running between the pubic bone in front to the base of the spine.
The bladder stores the urine, which is then eliminated from the body via another tube called the urethra, which is the lowest part of the urinary tract. (In men it is enclosed in the penis. In women it leads directly out.)

Defense Systems Against Bacteria. Infection does not always occur when bacteria are introduced into the bladder. A number of defense systems protect the urinary tract against infection-causing bacteria:

Urine itself functions as an antiseptic, washing potentially harmful bacteria out of the body during normal urination. (Urine is normally sterile, that is, free of bacteria, viruses, and fungi.)
The ureters are structurally designed to prevent urine from backing up into the kidney.
The prostate gland in men secretes infection-fighting substances.
The immune system in both sexes continuously fights bacteria and other harmful micro-invaders. In addition, immune system defenses and antibacterial substances in the mucous lining of the bladder eliminate many organisms.
In normal fertile women, the vagina is colonized by lactobacilli, beneficial microorganisms that maintain a highly acidic environment (low pH). Acid is hostile to other bacteria. Lactobacilli also produce hydrogen peroxide, which helps eliminate bacteria and reduces the ability of E. coli to adhere to vaginal cells. (E. coli is the major bacterial culprit in urinary tract infections.)
Some interesting research suggests that when bacteria infect the bladder, the cells that line the bladder literally sacrifice themselves and self-destruct (a process called apoptosis). In so doing, they fall away from the lining, carrying the bacteria with them. This eliminates about 90% of the E. coli.
Some researchers have identified a possible natural antibiotic called human beta-defensin-1 (HBD-1), which fights E. coli within the female urinary and reproductive tracts.

Click the icon to see an image of the prostate gland.

Causes

The bacterial strains that cause UTIs include:

Escherichia (E.) coli is responsible for 75 - 90% of uncomplicated cystitis cases in younger women and in more than half the cases in older women (over age 50). In most cases of UTI, E. coli, which originates as a harmless microorganism in the intestines, spreads to the vaginal passage, where it invades and colonizes the urinary tract. Some bacteria may be able to invade into deeper tissue in the bladder, where they survive to reinfect the patient after resolution of the previous infection.
Staphylococcus saprophyticus accounts for 5 - 15% of UTIs, mostly in younger women. Infections caused by this bacterium tend to have a seasonal variation, with a higher incidence in the summer and fall than in the winter and spring.
Klebsiella, Enterococci bacteria, and Proteus mirabilis account for most of remaining bacterial organisms that cause UTIs. They are generally found in UTIs in older women.
Rare bacterial causes of UTIs include ureaplasma urealyticum and Mycoplasma hominis, which are generally harmless organisms.

The bacteria that cause kidney infections (pyelonephritis) are generally the same bacteria that cause cystitis. There is some evidence, however, the E. coli strains in pyelonephritis are more virulent (able to spread and cause illness).
Complicated UTIs that are related to physical or structural conditions are apt to be caused by a wider range of organism. E. coli is still the most common organism, but others have also been detected, including Klebsiella, P. mirabilis, and Citrobacter.
Fungal organisms, particularly Candida species. (Candida albicans, for example, causes the so-called "yeast infections" that also occur in the mouth, digestive tract, and vagina.)
Other bacteria associated with complicated or severe infection include Pseudomonas aeruginosa, Enterobacter, and Serratia species, gram-positive organisms (including Enterococcus species), and S. saprophyticus.

Recurring infections are often caused by different bacteria than those that caused a previous or first infection.

Even if the reinfecting bacterium is still E. coli, it may be a variant of the original infecting E. coli strain. Such strains produce substances, such as one called P fimbriae, which tend to make the bacteria more infectious. Uncommon causes of reinfection include Ureaplasma and Mycoplasma hominis, which are sometimes associated with acute urethral syndrome.

The bacteria that cause most UTIs are very common. Nearly everyone harbors them. It is not clear how they proliferate and break down the natural defenses of the body. Among the possible ways this occurs are:

Changes in the Acid-Alkaline Balance of the Urinary Tract. Changes in the amount or type of acid within the genital and urinary tracts are major contributors to lowering the resistance to infection. For example, beneficial organisms called lactobacilli increase the acidic environment in the urinary tract. Reductions in their number (which, for example, occurs with estrogen loss after menopause), increases pH and therefore the risk of infection.

Biofilm. One theory, called the biofilm mode of growth, suggests that sometimes bacteria form capsules that adhere to the urinary tract, protecting them from many of the body's normal defenses.

Symptoms

Symptoms of lower urinary tract infections usually begin suddenly and may include one or more of the following signs:

The urge to urinate frequently, which may recur immediately after the bladder is emptied.
A painful burning sensation. (If this is the only symptom, then the infection is most likely urethritis.)
Discomfort or pressure in the lower abdomen. The abdomen can feel bloated.
Cramping in the pelvic area or back.
The urine often has a strong smell, looks cloudy, or contains blood. This is a sign of pyuria, or a high white blood cell count in the urine, and is a very reliable indicator of urinary tract infections.
Occasionally, fever develops.

Symptoms of kidney infections tend to affect the whole body and be more severe than those of cystitis. They may include:

Symptoms of lower UTIs that persist longer than a week. (Sometimes lower UTI symptoms may be the only signs of kidney infection. People at highest risk for such "silent" upper urinary tract infections include patients with diabetes, impaired immune systems, or a history of relapsing or recurring UTIs.)
An increased need to urinate at night.
Chills and persistent fever (typically lasting more than 2 days).
Pain in the flank (pain that runs along the back at about waist level).
Vomiting and nausea.

UTIs in infants and preschool children tend to be more serious than those that occur in young women, in part because they are more likely to occur in the kidneys and upper urinary tract. (Older children are more likely to have lower urinary tract infections and standard symptoms.) Infants and young children should always be checked for UTIs if the following symptoms are present:

A persistent high fever of otherwise unknown cause, particularly if it is accompanied by signs of feeding problems and debility, such as listlessness and fatigue. (Studies have reported that up to 5% of infants and toddlers who are brought to the emergency room with fevers have UTIs. Scarring is a risk so very young children with UTIs need to be screened.)
Painful, frequent, and foul smelling urine. (Parents are generally unable to identify a UTI just by the smell of their child's urine. Medical tests are needed.)
Cloudy urine. (If the urine is clear, the child most likely has some other ailment, although it is not absolute proof that the child is UTI-free.)
Abdominal and low back pain may be present.
Vomiting and abdominal pain (usually in infants).
Jaundice (yellowing of the skin and the whites of the eyes) in infants, particularly if it develops after 8 days of age.

Jaundice is a condition produced when excess amounts of bilirubin circulating in the bloodstream dissolve in the subcutaneous fat (the layer of fat just beneath the skin), causing the skin and whites of the eyes to have a yellowish appearance. With the exception of normal newborn jaundice in the first week of life, all other jaundice indicates overload or damage to the liver, or inability to move bilirubin from the liver through the biliary tract to the gut.

The classic lower UTI symptoms of pain, frequency, or urgency and upper tract symptoms of flank pain, chills, and tenderness may be absent or altered in older patients with UTIs. In one study, only 20% of these patients had new urinary complaints, and many have no symptoms at all.

Symptoms of UTIs that may occur in seniors but not in younger adults may include mental changes or confusion, nausea or vomiting, abdominal pain, or cough and shortness of breath. Concomitant illness may further confuse the picture and make diagnosis difficult.

Risk Factors

After the flu and common cold, urinary tract infections (UTIs) are the most common medical complaint among women in their reproductive years. Women are 30 times more likely to have UTIs than men. At least a third of American women are diagnosed with a UTI by the time they are 24 years old. Every year, 11% of American women have at least one such infection, and up to 60% of all women will develop a UTI at some time in their lives. A third of these women will have a recurrence within a year. Furthermore, each year about 250,000 women develop kidney infections (pyelonephritis) and 100,000 are hospitalized for treatment.

According to a 2007 report from the U.S. National Institutes of Health, urinary tract infections in both women and men are the most expensive of all urologic problems. Nationally, UTIs account for about $3.5 billion a year in medical costs.

Structure of the Female Urinary Tract. In general, the higher risk in women is mostly due to the shortness of the female urethra, which is 1.5 inches compared to 8 inches in men. Bacteria from fecal matter can be easily transferred to the vagina or the urethra.

The female and male urinary tracts are relatively the same except for the length of the urethra.

Sexual Behavior. Frequent or recent sexual activity is the most important risk factor for urinary tract infection in young women. Nearly 80% of all urinary tract infections occur within 24 hours of intercourse. (Sexual activity is less associated with cystitis in women after menopause.)

UTIs are very rare in celibate women. It is important to stress, however, that UTIs are NOT sexually transmitted infections, although these infections ( Chlamydia trachomatis, gonorrhea, or herpes simplex virus) may increase the risk for UTIs.

In general, however, it is the physical act of intercourse itself that produces conditions that increase susceptibility to the UTI bacteria, with some factors increasing the risk:

Women having sex for the first time or who have intense and frequent sex after a period of abstinence are at risk for a condition called "honeymoon cystitis."
A sudden increase in the frequency of sexual intercourse poses a significant risk for UTI, particularly if a diaphragm is used.
Sexual position (such as the woman on top) can contribute to the risk.

Click the icon to see an image of a diaphragm.

Contraceptives may also contribute to risk in a number of ways:

The spring-rim of the diaphragm may bruise the area near the bladder neck, making it susceptible to bacteria.
Unlubricated condoms may injure vaginal tissue and make it vulnerable to infections. (Using a sterile water-based lubricant, such as KY jelly, may help reduce this risk. Petroleum-based lubricants should be avoided because they weaken latex condoms.)
Some women experience UTI as an allergic reaction to latex in condoms or to oral contraceptives.
Use of spermicide, such as nonoxynol-9, doubles or triples a women's risk for UTI, regardless of whether it is used with a condom or diaphragm. Spermicides also pose a risk for sexually transmitted infections, and experts warn against their use.

Pregnancy. Although pregnancy does not increase the rates of asymptomatic bacteriuria, it does increase the risk that it will progress to a full-blown infection. About 2 - 11% of pregnant women have asymptomatic bacteriuria and, of those, 13 - 27% will develop a kidney infection late in their term. (However in early pregnancy, frequent urination -- a common symptom of UTI -- is most likely due to pressure on the bladder.)

Although all pregnant women should be tested for UTIs, women at highest risk have the following conditions or situations:

Diabetes
Sickle cell trait
Low-income
Have had many children
History of childhood UTIs
Have undergone a cesarean section with catheterization of the bladder
Have received epidural anesthesia

Women who have had a UTI before or during pregnancy also have a higher risk of developing recurrent urinary tract infections after delivery. About 25 - 33% of women who experience bacteriuria during pregnancy will have another urinary tract infection, sometimes as many as 10 - 14 years later.

Menopause. The risk for UTIs, both symptomatic and asymptomatic, is highest in women after menopause. Studies indicate that between 20 - 25% of women over 65 years old have UTIs, and 10 - 15% have asymptomatic bacteriuria (compared to 2 - 5% of young women). Sexual activity plays a lesser role in UTIs in older women than in younger women. In general, biologic changes due to menopause put older women at particular risk for primary and recurring UTIs:

With estrogen loss, the walls of the urinary tract thin, weakening the mucous membrane and reducing its ability to resist bacteria. The bladder may lose elasticity and fail to empty completely.
Estrogen loss has also been associated with reduction in certain immune factors in the vagina that help block E. coli from adhering to vaginal cells.
Levels of lactobacilli (protective bacteria) decline after menopause, perhaps also due to drops in estrogen.

Some women carry the blood group P1, which, as they get older, is associated with high levels of specific cells in the vagina and urethra that bind to a specific strain of E. coli that is resistant to normal infection-fighting mechanisms.

Other Risk Factors in Women. Women who have skin allergies to ingredients in soaps, vaginal creams, bubble baths, or other chemicals that are used in the genital area are at high risk for UTIs. In such cases, the allergies may cause small injuries that can introduce bacteria.

Most women who have had one UTI have occasional recurrences. About 25 - 50% of these women can expect another infection within a year of the previous one.

Between 3 - 5% of women, however, have ongoing, recurrent urinary tract infections, which follow the resolution of a previous treated or untreated episode. The major groups of women who are at highest risk for recurrent infections are young highly sexually active women and postmenopausal women. It might be argued that nearly all women who have a urinary tract infection are at risk for another, particularly if they are not treated for the first one.

Lifestyle Factors Increasing the Risk for Recurrence. Why urinary tract infections become chronic and recurring in many women is not entirely clear, but researchers are identifying certain lifestyle factors that may increase the risk in specific women:

Engaging in sexual intercourse more than four times a month.
Recent changes in sexual partners.
Having a mother with a history of UTIs.
Having a first UTI before age 15.
Use of spermicides.
Smoking and taking tub baths may also increase the risk for recurrent urinary tract infections, but they are less significant than other risk factors.

Biologic and Physical Factors. Some women may also have certain biologic or anatomical factors that increase the risk for recurring UTIs:

Having a shorter than average distance between the urethra and the anus.
Certain women may carry a compound called sialosyl galactosyl globoside (SGG) on the surface of kidney cells, which is a highly powerful receptor for E. coli bacteria.
Certain women have a genetic susceptibility to becoming infected in the vaginal area with greater numbers of disease-causing organisms that adhere to the lining.
Certain women may be deficient in human beta-defensin-1 (HBD-1), believed to be a naturally occurring antibiotic.

Risk Factors for Recurrence in the Aging Woman. In addition to menopause, other very strong risk factors for recurrences in older women include urinary incontinence and previous operations on the genital or urinary tracts. Additional risk factors for UTIs in older women include diabetes, vaginal itching or dryness, having had children, and poor overall health.

Each year, about 3% of American children develop urinary tract infections. During the first few months of life, UTIs are more common in boys than in girls. Boys who are uncircumcised are about 10 - 12 times more likely than circumcised boys to develop UTIs by the time they are 1 year old. After the age of 2 years, UTIs are far more common in girls. Throughout childhood, the risk of UTIs is about 2% for boys and 8% for girls. As with adults, Escherichia coli (E. coli) is the most common cause of UTIs in children.

Vesicoureteral Reflux (VUR). Vesicoureteral reflux (VUR) affects about 10% of all children. It is the source of urinary tract infections in 30 - 50% of childhood cases. This is a structural defect of the valve-like mechanism between the ureter and bladder that allows urine to flow backward, carrying infection from the bladder up into the kidneys. VUR also puts children at risk for recurrence. Such recurrences nearly always occur within the first 6 months after the first UTI.

Click the icon to see an image of vesicoureteral reflux.

Men become more susceptible to UTIs after 50 years of age, when they begin to develop prostate problems. Benign prostatic hyperplasia (BPH), enlargement of the prostate gland, can produce obstruction in the urinary tract and increase the risk for infection. In men, recurrent urinary tract infections are also associated with prostatitis, an infection of the prostate gland that is caused by E. coli. Although only about 20% of UTIs occur in men, these infections can cause more serious problems than they do in women. Men with UTIs are far more likely to be hospitalized than women. [See In-Depth Report #71: Benign prostatic hyperplasia.]

Hospitalizations and Catheters. About 40% of all infections that develop in hospitalized patients are in the urinary tract. The organisms that cause infections in hospitals (called nosocomial infections) are usually different from those that commonly cause UTIs. They are also more likely to be resistant to standard antibiotics. Hospitalized patients at highest risk for such infections are those with in-dwelling urinary catheters, patients undergoing urinary procedures, long-stay elderly men, and patients with severe medical conditions.

About 80% of UTIs in the hospital are due to catheters. Nearly all patients who need urinary catheters develop high levels of bacteria in their urine, and the longer the catheter is in place, the higher the risk for infection. Catheterized patients who develop diarrhea are nine times more likely to develop UTIs than are patients without diarrhea. In most cases of catheter-induced UTIs, the infection produces no symptoms. Because of the risk for wider infection, however, anyone requiring a catheter should be screened for infection. Catheters should be used only when necessary and should be removed as soon as possible.

Nursing Homes. All older adults who are immobilized, catheterized, or dehydrated are at increased risk for UTIs. Nursing home residents, particularly those who are incontinent and demented, are at very high risk. Up to 40% of elderly patients who live in nursing homes will contract a urinary tract infection.

Some people have structural abnormalities of the urinary tract that cause urine to stagnate or flow backward into the upper urinary tract. Such conditions include:

A prolapsed bladder (cystocele) can result in incomplete urination so that urine collects, creating a breeding ground for bacteria.
Tiny pockets called diverticula sometimes develop inside the urethral wall and can collect urine and debris, further increasing the risk for infection.

Click the icon to see an image of a cystocele.

Antibiotics often eliminate lactobacilli, the protective bacteria, along with harmful bacteria. This causes an overgrowth of E. coli in the vagina. In one study, the risk for UTI increased during the 15 - 28 days that women were taking antibiotics. In fact, some research suggests that taking antibiotics for a urinary tract infection increases the risk for a subsequent infection.

Diabetes. Diabetes puts women at significantly higher risk for asymptomatic bacteriuria. The longer a woman has diabetes, the higher the risk. (Control of blood sugar has no effect on this condition.) The risk for UTI complications is also higher in people with diabetes. In fact, certain UTI-related abscesses are reported only in patients with diabetes. These patients are also at higher risk for fungal-related UTIs.

Kidney Problems. Nearly any kidney disorder increases the risk for complicated UTIs.

AIDS and Immunosuppressed Patients. Any infection is dangerous in people whose immune systems are damaged, and UTIs are no exception, particularly pyelonephritis.

Sickle-Cell Anemia. Patients with sickle-cell anemia are particularly susceptible to kidney damage from their disease, and UTIs put them at even greater risk.

Kidney Stones. In some cases, kidney stones can cause urinary tract obstruction that leads to infection, particularly pyelonephritis. Symptoms of severe urinary tract infection in people with a history of kidney stones may indicate obstruction, which is a serious condition.

Click the icon to see an image of kidney stones.

Zinc. High doses of zinc supplements may increase the risk for urinary tract infections and other urologic problems, according to a 2007 study. Researchers found that hospitalizations for urinary complications were far more common among patients who took high doses of zinc than those who did not take this mineral supplement. Patients in the study took 80 mg of zinc daily. In general, the recommended daily amount for zinc is 8 mg/day for women and 11 mg/day for men. Higher doses of zinc are sometimes prescribed for people with certain medical conditions, such as age-related macular degeneration (an eye disease). However, no one should take more than 40 mg/day of zinc without talking to a doctor.

Complications

Urinary discomfort and emotional distress are the primary concerns in most women with recurrent UTIs. One study reported significant impairment of a woman's quality of life during symptom periods, which affected social function, vitality, and emotional well-being.

Nearly all urinary tract infections are mild, treatable, and have no long-term consequences. Serious physical complications can occur in some cases, however, most often in hospitalized patients.

Obstruction and Widespread Infection. Very severe upper urinary tract infections may cause obstruction that results in widespread and even life-threatening infection. Patients who develop UTIs in the hospital are at higher risk for such infections than those outside the hospital. In one particularly dangerous form of kidney infection that obstructs the ureter, mortality rates exceed 40%. This specific condition should be suspected in people with diabetes who have severe UTIs.

Kidney Damage. In high-risk adults, recurrent UTIs may cause scarring in the kidneys, which over time can lead to hypertension and eventual kidney failure. People with UTIs who develop serious kidney disease from UTIs are likely to have other predisposing diseases or structural abnormalities. (Recurrent urinary tract infections, even in the kidney, almost never lead to progressive kidney damage in otherwise healthy women.)

Urge Incontinence. Recurrent UTIs may increase the risk for urge incontinence after menopause. (People with urge incontinence experience leakage and the need to urinate frequently.) [See In-Depth Report #50: Urinary incontinence.]

Kidney Stones. Kidney stones can be caused by urinary tract infections (as well as increase the risk for UTIs in the first place). Those known as struvite stones are almost always caused by urinary tract infections due to bacteria that secrete certain enzymes. These enzymes raise urine concentrations of ammonia, which composes the crystals forming struvite stones. The stone-promoting bacterium is usually Proteus, but others include Pseudomonas, Klebsiella, Providencia, Serratia, and staphylococci.

Urinary tract infections during pregnancy pose particular risks for both mother and child:

If asymptomatic bacteriuria is not detected and treated promptly in pregnant women, as many as 25% develop kidney infection (pyelonephritis), which in turn increases the risk for premature birth, infant mortality, and later chronic kidney disease.
Even if kidney infection does not develop, untreated UTIs occurring in the first and third trimester of pregnancy slightly increase the risk for mental retardation and developmental delay in the infant.
Certain strains of E. coli can increase the risk for complications during pregnancy, including miscarriage or premature delivery, even if pyelonephritis does not develop.
Infants of women who harbor Ureaplasma urealyticum also have an increased risk for respiratory infections.

Urinary tract infections are a major cause of hospitalization in children. Untreated, they can be very serious, particularly in children under 4 years old. Fortunately, with prompt treatment, childhood cases of upper urinary tract infections rarely cause any serious consequences.

Spread of Infection. Widespread infection is a major complication of a primary infection. Although laboratory tests in some infants with UTI may suggest the presence of meningitis (inflammation of the spinal column), in most of these UTI cases the outcome is good with treatment, and there appear to be no neurological symptoms afterward.

Kidney Scarring. Kidney scarring is the major concern in children who develop serious or recurrent UTIs. Scarring in young growing kidneys is much more serious than in the mature kidney. Over the years, it increases the risk for hypertension and kidney failure. In one study, evidence of scarring developed in 6% of children who had been hospitalized for a urinary tract infection. Children most at risk for this complication include:

Children with vesicoureteral reflux (VUR). (Carefully managed vesicoureteral reflux without scarring is not associated with serious complications.)
Abnormally structured urinary tracts
Recurrent kidney infections
A delay in treating an acute UTI

One encouraging study followed children with evidence of kidney scarring for 16 - 26 years. On average, their total kidney function was well preserved, although the scarred kidney had signs of lower function and patients with scarring in both kidneys were at higher risk for future problems. Earlier studies have shown poorer results, which suggests that outcomes are now improving with early detection and better follow-up.

Women with diabetes have more frequent and more severe UTIs than women without the disease. They also are more frequently hospitalized for kidney infections. In fact, the most serious, but rare, complications of urinary tract infections (pyelonephritis, widespread infections, abscesses, inflammation of the bladder wall) occur mostly in patients with diabetes.

Diagnosis

In younger women, UTI symptoms plus positive results on an over-the-counter dipstick test are often enough to make a diagnosis. Symptoms include frequent urination and vaginal burning, without other complications such as fever, chills, and pain in the kidney. In such cases, young women can usually receive treatment by calling a health professional (usually a nurse) who will prescribe antibiotics. A good response to antibiotic therapy usually eliminates the need for further tests.

This course is recommended only for nonpregnant women at low risk for recurrent infection who do not have symptoms suggesting other problems, such as vaginitis. In some centers, women who are treated over the phone have to be younger than 55 years old; other patients need to see a doctor for evaluation. Pregnant women should be screened for E. coli because of the risk of complications, including miscarriage, from certain strains of these bacteria.

About half of women with symptoms of a UTI actually have some other condition, such as irritation of the urethra, vaginitis, interstitial cystitis, or sexually transmitted diseases (STDs). Some of these problems may also accompany or lead to UTIs.

Vaginitis. Vaginitis is a common vaginal infection that can be caused by a fungus (candidiasis) or bacteria. Occasionally, the infection causes frequent urination, mimicking cystitis. The typical symptoms of vaginitis are itching and an abnormal discharge.

Sexually Transmitted Diseases. Women with painful urination whose urine does not exhibit signs of bacterial growth in culture may have a sexually transmitted disease. The most common culprit is the organism Chlamydia trachomatis. Other STDs that may be responsible include gonorrhea and genital herpes.

Interstitial Cystitis. Interstitial cystitis (IC) is an inflammation of the bladder wall that occurs almost predominantly in women. The average age of patients with IC is 40 years old, but 25% of cases occur in women under age 30. Symptoms are very similar to cystitis, but no bacteria are present. Pain during sex is a very common complaint in these patients, and stress may intensify symptoms.

Bladder Cancer. Bladder cancer is a rare cause of painful urination and is more common in men than in women.

Kidney Stones. The pain of kidney stones along with blood in the urine can resemble the symptoms of pyelonephritis. There are no bacteria present with kidney stones, however.

Thinning Urethral and Vaginal Walls. After menopause, the vaginal and urethral walls become dry and fragile, causing pain and irritation that can mimic a UTI.

Disorders in Children that Mimic UTIs. Problems that might cause painful urination in children include reactions to chemicals in bubble bath, diaper rashes, and infection from the pinworm parasite.

Prostate Conditions in Men. Prostate conditions, including prostatitis (inflammation of the prostate) and benign prostatic hyperplasia, can cause symptoms similar to urinary tract infections.

Click the icon to see an image of benign prostatic hypertrophy.

During an exam, the doctor should examine the pelvic and vaginal area in women. Men require a digital rectal examination to determine if prostate enlargement is present. The doctor will also examine the male genitals for signs of infection. In both men and women, the doctor should also check the abdomen and areas around the kidneys for swelling and tenderness.

With the exception of skin cancer, prostate cancer is the most common type of cancer among men in the United States. Early detection may result from a blood test called a PSA (prostate-specific antigen) or a digital rectal exam. The digital rectal exam checks the rear surface of the prostate gland for any abnormalities. A lump or hardness found during the exam might be a sign of prostate cancer.

Dipstick tests, available over the counter, are quite reliable in making a reasonable diagnosis of UTIs in women with symptoms. Dipstick tests may also be useful for identifying UTIs in children and infants. The test uses a chemical on a stick that when dipped in urine reacts to nitrites, substances produced by many of the bacteria that cause UTIs. A positive test (which indicates that an infection is present) often eliminates the need for urine cultures, a more expensive test used to detect bacteria. A negative dipstick test helps to avoid unnecessary antibiotics, which are contributing to the growing problem of antibiotic resistance. These tests are not entirely accurate, however, and studies report that they may miss up to 25% of actual UTIs. If a woman has persistent UTI symptoms, and the dipstick test is negative, she should check with her doctor to see if more accurate tests are needed.

A urine sample is needed for most extensive testing. In most cases, the doctor requests a clean-catch sample. There are also other methods for collecting urine, depending on the patient's condition.

Clean-Catch Sample. A clean-catch sample for UTI depends on a sample free of contaminants normally present at the opening of the urethra (white blood cells and bacteria unrelated to UTIs). To obtain an untainted urine sample, doctors usually request a so-called midstream, or clean-catch, urine sample. To provide this, the following steps are taken:

Patients must first wash their hands thoroughly, then wash the penis or vulva and surrounding area four times, with front-to-back strokes, using a new soapy sponge each time.
The patient must then begin urinating into the toilet and stop after a few drops.
The patient then positions the container to catch the middle portion of the stream. Ideally, this urine will contain only the bacteria and other evidence of the urinary tract infection.
The patient then urinates the remainder into the toilet.
The patient securely screws the container cap in place without touching the inside of the rim.

The sample is generally given to the doctor or sent to the laboratory for analysis.

Incontinence Pads. Testing and diagnosing UTIs in elderly patients who are incontinent is especially difficult, because of the similarities in symptoms. Researchers have found that pressing a dipstick into an incontinence pad is an effective way to screen for urinary tract infections in incontinent patients.

Collection with a Catheter. Some patients (small children, elderly people, or hospitalized patients) cannot provide a urine sample. In such cases, a catheter may be inserted into the bladder to collect urine. This is the best method for providing a contaminant-free sample.

A urinalysis involves a physical and chemical examination of urine. In addition, the urine is spun in a centrifuge to allow sediments containing blood cells, bacteria, and other particles to collect. This sediment is then examined under a microscope. A urinalysis offers a number of valuable clues for an accurate diagnosis:

Color and cloudiness of urine
Acidity
White blood cells (leukocytes). A high count of white cells in the urine is referred to as pyuria. (A leukocyte count over 10 per microliter is considered to indicate pyuria.) Pyuria is usually sufficient for a diagnosis of UTI in nonhospitalized patients if other standard symptoms (or just fever in small children) are also present.

Treatment can be started without the need for further tests if the following urinalysis results are present in patients with symptoms and signs of UTIs:

A high white cell count
Cloudy urine

A urine culture uses a urine specimen that is placed on an agar plate, then incubated in the laboratory for 24 - 48 hours. It is then examined for the presence of bacterial growth. Urinary tract infection is nearly always caused by a single species of bacteria, notably E. coli. Cultures have limitations, however. If a mix of different species is found, the test is considered contaminated and is redone. In addition, even if E. coli is identified, researchers are also looking for variants of these bacteria. Certain types may indicate a higher risk for a second infection, while others may even be protective against recurring infections. Furthermore, some organisms, such as Chlamydia, which is a sexually transmitted organism, may not be detected.

A urine culture is usually performed if the dipstick results are positive, but even if the results are negative, a culture may still be helpful under certain circumstances:

If urinalysis or dipstick is negative but the patient has UTI symptoms, particularly if the patient has recurring infections or is in a high-risk group.
If the doctor suspects complications.
In girls less than 2 years of age with a high fever of unknown origin that lasts 2 days or more.

Even if bacteria are present in the culture, a diagnosis of UTI depends on symptoms and gender:

The presence in a culture of at least 100,000 bacteria per milliliter of urine usually provides conclusive evidence of infection in women with symptoms.
A count of 100,000 bacteria per milliliter in a woman without symptoms indicates asymptomatic bacteriuria. The decision to treat depends on the woman's risk factors for complications.
In young women with symptoms of cystitis, a diagnosis of infection can reasonably be made with counts as low as 1,000 bacteria per milliliter.
Men are considered to have an infection with a count of only 1,000.

If doctors suspect that bacteria other than E. coli may be present, a Gram stain is used to help predict the species. This is a staining procedure used to make bacteria visible through a microscope. Many bacteria are categorized by the terms Gram-positive and Gram-negative.

Bacteria that turn pink from staining are called Gram-negative
Those that turn blue are called Gram-positive

Escherichia coli bacteria are Gram-negative and the most common cause of UTIs. If doctors suspect that bacteria other than E. coli are causing a UTI, a Gram stain is useful for identifying other species.

Because of the expense and the limited accuracy of imaging procedures, these techniques are used only for the following:

Serious and recurrent cases of pyelonephritis
When structural abnormalities are suspected
If infections do not respond to treatment
If a doctor suspects obstruction or an abscess
After a first urinary tract infection in children age 2 - 24 months to detect possible obstruction or vesicoureteral reflux. Tests include ultrasound and a voiding cystourethrogram and possibly scans. Some evidence suggests that ultrasound is probably not necessary, but at this time it is recommended by major medical groups.

Ultrasound. Ultrasound is a noninvasive, risk-free imaging test that can be used to screen for hydronephrosis (obstructions of the flow of urine), kidney stones that predispose to infection, and kidney abscesses. In men, ultrasound can detect enlargement or abscesses of the prostate and, when combined with x-rays, is an accurate method for detecting incomplete emptying of the bladder, a common cause of UTI in men over age 50. In children with urinary tract infections, it also can be used to detect vesicoureteral reflux, the defect of the valve-like mechanism between the ureter and bladder. Ultrasounds are not as accurate as voiding cystourethrograms.

Nuclear Scans. Imaging techniques called nuclear scans may be useful in certain complicated cases, such as detecting kidney scarring after pyelonephritis in children. They produce better images and expose the patient to far less radiation than x-rays. One such scan called dimercaptosuccinic acid (DMSA) scintigraphy uses injections of tiny amounts of radioactive tracers. A scanning machine (scintillation or gamma camera) is then used to detect pictures of the tracer in the kidney. This information is recorded on a computer screen or on film.

Magnetic Resonance Imaging (MRI) or Computed Tomography (CT). Magnetic resonance imaging (MRI) and computed tomography (CT) scans are noninvasive advanced imaging techniques that are sometimes used when nuclear scans are inconclusive. A CT scan is useful for ruling out kidney stones or obstructions in women with recurrent UTIs.

X-Rays. Special x-rays can be used to screen for structural abnormalities, urethral narrowing, or incomplete emptying of the bladder, which can cause stagnation of urine and predispose to infection.

Voiding cystourethrogram is an x-ray of the bladder and urethra. To obtain a cystourethrogram, a dye, called contrast material, is injected through a catheter inserted into the urethra and passed through the bladder.
An intravenous pyelogram (IVP) is an x-ray of the kidney. For a pyelogram, the contrast matter is injected into a vein and eliminated by the kidneys. In both cases, the dye passes through the urinary tract and reveals any obstructions or abnormalities on x-ray images. Due to the possible risks to the fetus, x-rays are not performed on pregnant women.

Click the icon to see an image of a voiding cystourethrogram.

Click the icon to see an image of an intravenous pyelogram.

Cystoscopy. Cystoscopy is used to detect structural abnormalities, interstitial cystitis, or masses that might not show up on x-rays during an IVP. The patient is given a light anesthetic, and the bladder is filled with water. The procedure uses a cystoscope, a flexible, tube-like instrument that the urologist inserts through the urethra into the bladder.

Click the icon to see an image of cystoscopy.

No noninvasive test will differentiate between upper and lower urinary tract infections. This is a particular problem because of the high percentage of women whose cystitis symptoms mask infections that also exist in the upper tract.

Antibiotic Trial. The best current test for pyelonephritis is the short-term antibiotic therapy given for cystitis. If the infection returns within 2 weeks after treatment, upper urinary tract infection is usually present.

Blood Cultures. If symptoms are severe, blood cultures will be taken to determine if the infection is in the bloodstream and threatening other parts of the body.

Treatment

Although antibiotics should be used as a cure for most urinary tract infections, severe symptoms can persist for several days until treatment effectively eliminates the bacteria. A number of options are available for relieving symptoms until the antibiotics take action.

Important Note. All of the drugs discussed below treat only symptoms and are not cures. They should never be used to replace antibiotics.

Phenazopyridine (Pyridium, Uristat, Barodium, Eridium, AZO Standard) relieves pain and burning caused by the infection. It should not be taken for more than 2 days and should be discontinued when symptoms are relieved.

Side effects include headache and stomach distress. The drug turns urine a red or orange color, which can stain fabric and be difficult to remove. In rare cases, it can cause serious side effects, including shortness of breath, a bluish skin, a sudden reduction in urine output, shortness of breath, and confusion. In such cases, patients should immediately call the doctor.

Methenamine (Atrosept, Prosed, Urised) or flavoxate (Urispas) reduce bladder spasms, which may occur with some UTIs. These drugs can have severe side effects, however, that the patient should discuss with the doctor.

Medications

Antibiotics are the mainstay treatment for all UTIs. A variety of antibiotics are available, and choices depend on many factors, including whether the infection is complicated or uncomplicated or primary or recurrent. Treatment decisions are also based on the type of patient (man or woman, a pregnant or nonpregnant woman, child, hospitalized or nonhospitalized patient, person with diabetes). Treatment should not necessarily be based on the actual bacteria count. For example, if a woman has symptoms, even if bacterial count is low or normal, infection is probably present and antibiotic treatment should be considered.

Bacterial Resistance to Antibiotics. Antibiotic-resistant strains of E. coli, the most common cause of UTIs, are increasing. The prevalence of such bacteria has dramatically increased worldwide, in large part due to widespread use of antibiotics in humans and animal feed. In a 2003 report, 42% of E. coli were resistant to one or more of the 12 antibiotics that researchers investigated. As more bacteria have become resistant to the standard UTI treatment trimethoprim-sulfamethoxazole (TMP-SMX), more doctors have been prescribing quinolone antibiotics to treat UTIs. A 2006 study found that quinolones have now overtaken TMP-SMX as the most commonly prescribed antibiotic for UTIs. Experts are concerned that resistance may develop to these drugs as well.

Beta-Lactams

The beta-lactam antibiotics share common chemical features and include penicillins, cephalosporins, and some newer similar drugs. Their primary actions to interfere with bacterial cell walls. Many have been important in the treatment of urinary tract infections.

Penicillins (Amoxicillin). Until recent years, the standard treatment for a UTI was 10 days of amoxicillin, a penicillin antibiotic, but it is now ineffective against E. coli bacteria in up to 25% of cases. A combination of amoxicillin-clavulanate (Augmentin) is sometimes given for drug-resistant infections. Amoxicillin or Augmentin may be useful for UTIs caused by Gram-positive organisms, including Enterococcus species and S. saprophyticus.

Cephalosporins. Antibiotics known as cephalosporins are also alternatives for infections that do not respond to standard treatments or for special populations. They are often classed as:

First generation, including cephalexin (Keflex), cefadroxil (Duricef, Ultracef), and cephradine (Velosef).
Second generation, including cefaclor (Ceclor), cefuroxime (Ceftin), cefprozil (Cefzil), and loracarbef (Lorabid).
Third generation, including cefpodoxime (Vantin), cefdinir (Omnicef) cefditoren (Sprectracef), cefixime (Suprax), and ceftibuten (Cedex). Ceftriaxone (Rocephin) is an injected cephalosporin. These are effective against a wide range of Gram-negative bacteria.

Other Beta-Lactam Drugs. Other beta-lactam antibiotics have been developed. For example, pivmecillinam (a form of mecillinam), is commonly used in Europe for UTIs. It appears to be safe during pregnancy.

Trimethoprim-Sulfamethoxazole (TMP-SMX)

The typical treatment is a 3-day course of the combination drug trimethoprim-sulfamethoxazole, commonly called TMP-SMX (Bactrim, Cotrim, Septra). A 1-day course is somewhat less effective but poses a lower risk for side effects. Longer courses (7 - 10 days) work no better than the 3-day course and have a higher rate of side effects. TMP-SMX should not be used in patients whose infections occurred after dental work or in patients allergic to sulfa drugs. Allergic reactions can be very serious. Trimethoprim (Proloprim, Trimpex) is sometimes used alone in those allergic to sulfa drugs. TMP-SMX can interfere with the effectiveness of oral contraceptives. High rates of bacterial resistance to TMP-SMX exist in many parts of the United States. Still, even when regional rates approach 30%, cure rates with TMP-SMX reach 80 - 85%.

Fluoroquinolones (Quinolones)

Fluoroquinolones (also simply called quinolones) are now becoming as widely used as TMP-SMX. These drugs interfere with the bacteria's genetic material so they cannot reproduce. They are the standard alternatives to TMP-SMX. Examples of quinolones include ofloxacin (Floxacin), ciprofloxacin (Cipro), norfloxacin (Noroxin), levofloxacin (Levaquin), gatifloxacin (Tequin), and sparfloxacin (Zagam). These antibiotics are effective against a wide range of organisms but are expensive and, in general, used in the following circumstances:

In patients with complicated or catheter-induced UTIs
In patients who do not respond or who are allergic to TMP-SMX
In communities where there are high rates of bacteria resistant to TMP-SMX
In elderly patients. A 2001 study of older women with UTIs (mean age 80), about half of whom were living in nursing homes, found that 96% responded to ciprofloxacin, compared with 87% to TMP-SMX.

Pregnant women should not take fluoroquinolone antibiotics. They also have more adverse effects in children than other antibiotics and should not be the first-line option in most situations.

Antibiotics Used Specifically for UTIs

Nitrofurantoin. Nitrofurantoin (Furadantin, Macrodantin) is a relatively inexpensive antibiotic that is used specifically for urinary tract infections. It is an effective alternative to TMP-SMX or a quinolone. Unlike many of the other drugs, however, it must be given 7 - 10 days, even in cases of simple cystitis. (Shorter course treatments are being investigated.) It is not useful for treating kidney infections. Nitrofurantoin frequently causes stomach upset and interacts with many drugs. Other chronic or serious medical conditions may also affect its use. It should not be used in pregnant women within 1 - 2 weeks of delivery, in nursing mothers, or in those with kidney disease.

Fosfomycin. The antibiotic fosfomycin (Monurol), which comes in an orange-flavored, soluble powder, is proving to be another good alternative. It can be an effective 1-dose treatment for many women, including those who are pregnant. To date, bacterial resistance rates to this antibiotic are very low.

Tetracyclines

Tetracyclines inhibit bacterial growth. They include doxycycline, tetracycline, and minocycline. Long-term treatment with tetracycline or doxycycline may be used for infections that are caused by Mycoplasma or Chlamydia. Tetracyclines have unique side effects among antibiotics, including skin reactions to sunlight, possible burning in the throat, and tooth discoloration.

Aminoglycosides

Aminoglycosides (gentamicin, kanamycin, tobramycin, amikacin) are given by injection for very serious bacterial infections. They can be given only in combination with other antibiotics. Gentamicin is the most commonly used aminoglycoside for serious UTIs. They can have very serious side effects, including damage to hearing, sense of balance, and kidneys.

UTIs in low-risk women can often be successfully treated over the phone. In such cases, a health professional provides the patients with 3-day antibiotic regimens without even requiring an office urine test. This course is recommended only for women at low risk for recurrent infection and who do not have symptoms suggesting other problems, such as vaginitis.

Antibiotic Regimen. Oral antibiotic treatment cures 94% of uncomplicated urinary tract infections, although the rate of recurrence remains high. The following antibiotics are commonly used for uncomplicated UTIs:

The standard regimen has traditionally been a 3-day course of trimethoprim-sulfamethoxazole, commonly called TMP-SMX (Bactrim, Cotrim, Septra). TMP-SMX combines an antibiotic with a sulfa drug. A single dose of TMP-SMX is sometimes prescribed in mild cases, but cure rates are generally lower than with the 3-day regimens.
Fluoroquinolone antibiotics, also called quinolones, have usually been a second choice. However, in geographic areas that have a high resistance to TMP-SMX, quinolones are now the first-line treatment for UTIs. Ciprofloxacin (Cipro) is the quinolone antibiotic most commonly prescribed. Quinolones are usually given over a 3–day period. Pregnant women should not take these drugs.
Nitrofurantoin (Furadantin, Macrodantin) is a third option. This drug must be given for longer than 3 days.
Fosfomycin (Monurol) is not as effective as other antibiotics but may be used during pregnancy. Resistance rates to this drug are very low.
Many other effective antibiotics are available, including amoxicillin (with or without clavulanate) and cephalosporins. Doxycycline is often effective but cannot be given to children or pregnant women.

After a week of antibiotic treatment, most patients are free of infection. If the symptoms do not clear up within the first few days of therapy, doctors generally suggest that women discontinue their antibiotic and provide a urine sample for culturing in order to identify the specific organism causing the condition.

Treatment for Relapsing Infection. A relapsing infection (caused by treatment failure) occurs within 3 weeks in about 10% of women. Relapse is treated similarly to a first infection, but the antibiotics are continued for at least 2 weeks. (Relapsing infections may be due to structural abnormalities, abscesses, or other problems that may require surgery, and such conditions should be ruled out.)

Preventive antibiotics may be required for women who experience two or more symptomatic UTIs within 6 months or three or more over the course of a year. A woman's own perception of discomfort can generally guide her decisions on whether to use preventive antibiotics or not. All women should use lifestyle measures to prevent recurrences.

Intermittent Self Treatment. Many, if not most, women with recurrent UTIs can effectively self-treat recurrent UTIs without going to a doctor. In general, this requires the following steps:

As soon as the patient develops symptoms, she takes the antibiotic. Infections that occur less than twice a year are usually treated as if they were an initial attack, with single-dose or three-day antibiotic regimens.
At that time, she also performs a clean-catch urine test and sends it to the doctor for culturing to confirm the infection.

A doctor should be consulted under the following circumstances:

If symptoms have not completely resolved within 48 hours
If there is a change in symptoms
If the patient suspects that she is pregnant
If the patient has more than four infections a year

Women who are not good candidates for self-treatment are those with impaired immune systems, previous kidney infections, structural abnormalities of the urinary tract, or a history of infection with antibiotic-resistant bacteria.

Postcoital Antibiotics. If recurrent infections are clearly related to sexual activity and episodes recur more than two times within a 6-month period, a single preventive dose taken immediately after intercourse is very effective. Antibiotics for such cases include TMP-SMX, nitrofurantoin, cephalexin, or a fluoroquinolone (such as ciprofloxacin). (Fluoroquinolones are not appropriate during pregnancy.)

Continuous Preventive Antibiotics (Prophylaxis). Continuous preventive (prophylactic) antibiotics are an option for some women who do not respond to other measures. With this approach, low-dose antibiotics are taken continuously for 6 months or longer.

Typical prophylactic regimens include one dose of nitrofurantoin (50 mg), 1/2 tablet of TMP-SMX, or cephalexin (250 mg) daily. Taking the antibiotic at bedtime may be most effective. Studies suggest that continuous prophylactic antibiotics reduces recurrences by up to 95% and may prevent kidney infection.

Adverse effects mostly include gastrointestinal problems and yeast infections. (Taking probiotic supplements or eating yogurt may help prevent yeast infections.) Although there is concern that continuous risk increases the risk for bacteria that are resistant to the antibiotics, studies to date have not reported any significant risk even up to 5 years of use.

Treating Uncomplicated Kidney Infections. Patients with uncomplicated kidney infections (pyelonephritis) may be treated at home with oral antibiotics. Such patients are healthy and nonpregnant. They typically are experiencing fever, chills, and flank pain. However, they are not nauseous or vomiting and show no symptoms or signs of kidney involvement or complicated infection.

The standard treatment for uncomplicated pyelonephritis is a 14-day course of oral antibiotics, usually trimethoprim-sulfamethoxazole (TMP-SMX) or a fluoroquinolone. Sometimes patients with uncomplicated pyelonephritis are first given an antibiotic injection, if indicated.

Oral amoxicillin or amoxicillin-clavulanate (Augmentin) may be prescribed for women with bacteria (Gram-positive organisms, including Enterococcus species and S. saprophyticus) that do not respond to standard regimens.

A urine culture may be obtained within 1 week of completion of therapy and again 4 weeks later.

Treating Moderate-to-Severe Kidney Infections. Patients with moderate-to-severe acute kidney infection and those with severe symptoms or other complications may need to be hospitalized. In such cases, antibiotics (ceftriaxone and gentamicin) are usually given intravenously for 3 - 5 days or until symptoms are relieved and patients have not shown any signs of fever for 24 - 48 hours.

If fever and back pain persist after 72 hours of antibiotic administration, the doctor will usually order imaging tests to see if abscesses, obstructions, or other abnormalities are present.

Treating Chronic Kidney Infections. Patients with chronic pyelonephritis are often treated with long-term antibiotics, even during periods when they have no symptoms.

The two approved treatments for interstitial cystitis are pentosan polysulfate (Elmiron), and dimethyl sulfoxide (DMSO). Patients generally prefer Elmiron because it can be taken by mouth. A DMSO solution is instilled into the bladder through a catheter. Elmiron is a type of blood thinner that helps to coat the bladder lining and prevent infections. It may take several months before having an effect on symptoms, but the benefits increase the longer the drug is used.

Doctors sometimes also prescribe other types of medications to help interstitial cystitis symptoms. These drugs include antihistamines, such as hydroxyzine (Atarax), and low doses of the tricyclic antidepressant amitriptyline (Elavil). Drugs that reduce bladder spasms (hyoscine, oxybutynin) are also sometimes used. Other treatments are being investigated, including hyperbaric oxygen therapy. This treatment involves having a patient breathe pure oxygen inside a sealed pressurized chamber.

Some doctors think that interstitial cystitis may be related to immune disorders. Researchers are investigating various drugs that block immune and inflammatory responses.

Treating the Pregnant Woman. Pregnant women should be screened for UTIs, since they are at high risk for UTIs and their complications. The antibiotics used during pregnancy are amoxicillin, ampicillin, nitrofurantoin, or an oral cephalosporin. Fosfomycin (Monurol) is not as effective as others but may be used during pregnancy. Pregnant women should not take fluoroquinolones.

Pregnant women with even asymptomatic bacteriuria (evidence of infection but no symptoms) have a 30% risk for acute pyelonephritis in their second or third trimester. They need screening and treatment for this condition. In such cases, they should be treated with a short course of antibiotics (3 - 5 days). For an uncomplicated UTI, pregnant women may need longer-term antibiotics (7 - 10 days).

Treating Women with Diabetes. Women with diabetes have more frequent and more severe UTIs than women without the disease. Many experts recommend that patients with diabetes and UTI, even an uncomplicated infection, be treated with antibiotics for 7 - 14 days. People with diabetes have higher than average rates of asymptomatic bacteriuria, but it is unclear whether they should be screened and treated for this condition. A 2003 study indicated that treating this condition had little value in these women and did not prevent complications.

Treating Urethritis in Men. Urethritis in men has typically been treated with a 7-day regimen of doxycycline. Some research suggests that a single dose of azithromycin may be just as effective while causing fewer side effects. One-dose treatment also improves compliance, so cure rates may even be better than with a long-term regimen. However, once an infection spreads to the prostate gland it is harder to treat, so most doctors still prefer the longer regimen. Patients with urethritis should also be tested for an accompanying sexually transmitted disease such as gonorrhea.

Treating Children with UTIs. Children with UTIs are generally treated with TMP-SMX or cephalexin (Keflex). These drugs are usually taken by mouth in either liquid or pill form. Doctors sometimes give them as a shot or IV. Children usually respond to treatment within a few days. Antibiotic resistance to cephalosporin antibiotics such as cephalexin is increasing, and some doctors prefer to prescribe an aminoglycoside antibiotic. Gentamicin (Garamycin) is the aminoglycoside antibiotic that is most commonly used. It is given intravenously.

Vesicoureteral reflux (VUR) is a concern for children with UTIs. About a third of children with UTIs develop this condition, in which urine backs up into the kidneys. VUR can lead to kidney infection (pyelonephritis), which can cause kidney damage. Either long-term antibiotics or surgery are options to correct vesicoureteral reflux (VUR) and prevent infection. Many experts recommend surgery over antibiotics, especially due to concerns of antibiotic resistance. Antibiotic treatment usually continues for years with the idea that the condition will resolve when the child has grown. However, a 2006 study suggested that long-term antibiotics are not useful for preventing VUR. Furthermore, the study found that mild-to-moderate VUR does not increase the likelihood of UTIs or pyelonephritis.

Children with acute kidney infection are treated with oral cefixime (Suprax) or a short course (2 - 4 days) of an intravenous (IV) antibiotic (typically gentamicin, given in one daily dose). An oral antibiotic then follows the IV.

Preventing Catheter-Induced Infections

Catheter-induced urinary tract infections are very common, and preventive measures are extremely important. Catheters should not be used unless absolutely necessary, and they should be removed as soon as possible. Reducing the risk for infections during long-term catheter use, however, remains problematic.

Catheter Coatings. Catheter coatings, such as silver nitrate, antibiotics, and other substances, are being tested and are showing some benefits, but the problem is still not resolved. One promising catheter (LoFric) uses a so-called hydrophilic coating consisting of PVP (polyvinyl pyrrolidone) and salt. It attracts water to the catheter surface, putting up a water barrier to reduce friction. In a 2003 study, it was associated with significantly fewer UTIs.

Intermittent Use of Catheters. If a catheter is required for long periods, it is best to use it intermittently if possible (as opposed to an indwelling catheter). Some doctors recommend replacing it every 2 weeks to reduce the risk of infection and irrigating the bladder with antibiotics between replacements.

Daily Hygiene. A typical catheter is one that has been preconnected and sealed and uses a drainage bag system. To prevent infection, some of the following tips may be helpful:

Drink plenty of fluids, including 3 glasses of cranberry juice a day.
The catheter tube should be free of any knots or kinks.
Clean the catheter and the area around the urethra with soap and water daily and after each bowel movement. (Women should be sure to clean front to back.)
Wash hands before touching the catheter or surrounding area.
Never disconnect the catheter from the drainage bag without careful instructions from a health professional on strict methods for preventing infection.
Keep the drainage bag off the floor.
Stabilize the bag against the leg using tape or some other system.

Antibiotics for Catheter-Induced Infections

Patients using catheters who develop UTIs with symptoms should be treated for each episode with antibiotics and the catheter should be removed, if possible. A major problem in treating catheter-related UTIs is that the organisms involved are constantly changing. Because there are likely to be multiple species of bacteria, experts generally recommend an antibiotic that is effective against a wide variety of microorganisms. These medications include those in the fluoroquinolone group and drug combinations such as ampicillin plus gentamicin or imipenem plus cilastatin.

Although high bacteria counts in the urine (bacteriuria) occur in most catheterized patients, administering antibiotics to prevent a UTI is rarely recommended. Many catheterized patients do not develop symptomatic urinary tract infections even with high bacteria counts. If bacteriuria occurs without symptoms, antibiotic therapy has little benefit if the catheter is to remain in place for a long period.

Catheterization is accomplished by inserting a catheter (a hollow tube, often with an inflatable balloon tip) into the urinary bladder. This procedure is performed for urinary obstruction, following surgical procedures to the urethra, in unconscious patients (due to surgical anesthesia, coma, etc.), or for any other problem in which the bladder needs to be kept empty (decompressed) and urinary flow assured. Catheterization in males is slightly more difficult and uncomfortable than in females because of the longer urethra.

Other Treatments

The following are hygiene tips. Although there is no evidence that good hygiene makes a real difference in preventing UTIs, it is always a wise practice.

Clean the genital and urinary areas from front to back with soap and water after each bowel movement.
Keep the genital and anal areas clean before and after sex. Urinate before and after intercourse to empty the bladder and cleanse the urethra of bacteria.
Avoid tight-fitting pants.
Wear cotton-crotch underwear and panty hose, changing both at least once a day. (Mild detergents are best for washing underwear.)
Take showers rather than baths.
Avoid bath oils, feminine hygiene sprays, douches, and powders. As a general rule, do not use any product containing perfumes or other possible allergens near the genital area. Douching in is never recommended. It may destroy the natural antiviral organisms normally present in the vagina, making women more susceptible to human papillomavirus (HPV), a risk factor for cervical cancer.
Choose sanitary napkins instead of tampons (which some doctors believe encourage infection). Napkins and tampons, in any case, should be changed after each urination.
Urinate frequently.

Appropriate hygiene and cleanliness of the genital area may help reduce the chances of introducing bacteria through the urethra. Females are especially vulnerable to this, because the urethra is in close proximity to the rectum. The genitals should be cleaned and wiped from front to back to reduce the chance of dragging E. coli bacteria from the rectal area to the urethra.

The following recommendations may reduce the risks from sexual activity:

In women using contraceptives, consider alternatives, particularly if exposed to spermicides from condoms or diaphragms. Discuss the best contraceptive choice with a doctor.
Avoid sex with multiple partners. This can cause many health problems, including sexually transmitted diseases and UTIs.

Postmenopausal women with recurrent UTIs may consider the use of an estrogen vaginal cream or estrogen-releasing vaginal ring (Estring). Estrogen may resist infection by increasing the number of lactobacilli, the microorganism that fights infection by lowering the vaginal pH levels and preventing E. coli from adhering to vaginal cells. Estrogen creams and estrogen-releasing rings may help reduce the risk of recurring urinary tract infections. Oral hormone replacement therapies that contain estrogen do not seem to provide the same benefit as the topical forms. Estrogen HRT carries many health risks, including an increased risk for breast cancer and heart disease. It is not clear if vaginal forms of estrogen are associated with these risks.

Many doctors believe that emptying the bladder frequently will help prevent bladder irritation and therefore recommend drinking plenty of water daily and urinating often.

Cranberries, blueberries, and lignonberry, a European relative of the cranberry, are three fruits that may have protective properties. Researchers are finding that red pigments in these closely related fruits called tannins (or proanthocyanadins) prevent E. coli bacteria from adhering to cells in the urinary tract, thereby inhibiting infection. Fructose, which is commonly used to sweeten fruit juices, may also interfere with bacterial adhesion.

Cranberry juice offers well-known protection against urinary tract infections. In one study, only 15% of elderly women who drank cranberry juice daily for 6 months experienced UTIs, compared with 28% of women who did not drink the juice. Its effects were stronger in helping the body rid itself of infections than in preventing them in the first place, but it showed benefits in both situations.

Studies suggest that for protection, it is necessary to drink at least one to two cups of 30% cranberry or lignonberry juice daily, or to take at least 300 - 400 mg in tablet form twice daily.

Important research has targeted probiotics (essentially friendly organisms), which may protect against infections in the genital and urinary tracts. They may have other health benefits as well. The best-known probiotics are the lactobacilli strains, such as acidophilus, which is found in yogurt and other fermented milk products (kefir). The probiotics bifidobacteria and GG lactobacilli may prove to be even more important. Other probiotics include the lactobacilli rhamnosus, casel, plantarium, bulgaricus, and salivarius, and also Enterococcus faecium and Streptococcus thermophilus.

Lactobacilli have the potential to help protect women from UTIs in a number of ways:

Maintain a low pH environment
Hinder E. coli growth
Produce hydrogen peroxide, which produces an environment hostile for bacteria

In a 2003 study, drinking fermented milk reduced the risk for UTIs. Not all studies show benefits from drinks containing lactobacilli, but more research is warranted.

Researchers are studying several different herbal treatments for urinary tract infections. Studies on these herbs have only been conducted on animals and cell samples -- not in humans:

Forskolin, an extract from the Indian coleus plant, may help flush out bacteria hiding in the lining of the bladder.
Green tea contains compounds that may help prevent inflammation in bladder cells.
St. John’s wort, a popular herbal remedy for depression, may help relieve pain associated with interstitial cystitis.

It is important to inform your doctor of any herbs, dietary supplements, or vitamins and minerals that you take or are considering taking. Some of these remedies may actually increase your chance of developing urinary tract infections. For example, high doses of zinc have been associated with increased risk of UTIs.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

Biofeedback is a technique that provides visual and auditory clues in response to specific exercises. Some research indicates that biofeedback teaches children who are prone to UTIs to relax and control their pelvic muscles, resulting in fewer recurrences of infection.

Resources

http://kidney.niddk.nih.gov -- National Kidney and Urologic Diseases Clearinghouse
www.urologyhealth.org -- American Urological Association
www.acog.org -- American College of Obstetricians and Gynecologists
www.ichelp.com -- Interstitial Cystitis Association

References

Bishop BL, Duncan MJ, Song J, Li G, Zaas D, Abraham SN. Cyclic AMP-regulated exocytosis of Escherichia coli from infected bladder epithelial cells. Nat Med. 2007 May;13(5):625-30. Epub 2007 Apr 8.

Johnson AR, Munoz A, Gottlieb JL, Jarrard DF. High dose zinc increases hospital admissions due to genitourinary complications. J Urol. 2007 Feb;177(2):639-43.

Litwin MS, Saigal CS, editors. Urologic Diseases in America. US Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. Washington, DC: US Government Printing Office, 2007; NIH Publication No. 07–5512.

Review Date:
6/15/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com