FitSugar

Factors Contributing to Overweight Pets

FitSugar — Tue, 10 Apr 2007 07:30:00 -0700

I was watching the Martha Stewart Show recently while I was on the treadmill at the gym. On this episode she had her veterinarian, Dr. Marty Goldstein, as a guest to talk about overweight pets. It was interesting to hear Dr. Goldstein's opinion on the three factors that can contribute to overweight pets because (in my opinion) they are rather similar to the factors that can contribute to overweight humans...

To read what they are read more

Diet: First and foremost, a pet's diet must be regulated. The order of ingredients on a nutrition label is so important because whatever is listed first is the most prominent ingredient. The serving size your pet should get might be far different from the recommended amount on the bag or can. Above all, limit treats. Many people question whether wet food is better than dry food. It generally takes more processing of the food to get it into a bag than into a can. Processing destroys the vitamins, enzymes and natural integrity of the food; processing makes it less whole, so generally wet food is healthier.
Metabolic Deficiency: There are natural fat burning enzymes called L-Carnitine and chromium picolinate, which you can get at health food stores. They work well and are all natural. Before giving your pet any sort of supplement or medicinal remedy, consult your veterinarian.
Exercise: The best exercise for a dog is jogging with him or having him retrieve a stick or ball. Twenty to thirty minutes of really good exercise a day is recommended, the more the better. For cats, increase play and encourage movement around the house.

I know the whole diet and exercise bit seems like common sense at this point, but it never hurts to reiterate it, does it? Helping your pet lose weight may also lead to helping you lose weight too. Want to really make your dog run? Consider getting a Chuck it ($7.60) ball launcher to make your dog go the distance to retrieve the ball. Buy it from Amazon.com. If you go this route, be sure to get yourself moving as the Chuck It really takes all the effort out of throwing the ball. For a sure way to get both your heart rates up: Do rounds of jumping jacks after you chuck the ball until Fido brings it back to you.

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Exercise With Your Dog and Lose More Weight

FitSugar — Fri, 06 Feb 2009 13:30:00 -0800

I love to take my pooch Bonnie out for walks and jogs because I know we both benefit from the fresh air and exercise. It turns out though, people who exercise with dogs can help you drop more pounds than a person who exercises alone. In a study at Northwestern Memorial Hospital’s Wellness Institute in Chicago, 92 overweight and obese people were tracked for a year. At the end of the year, 61 percent of the pet owners were still participating in the study, compared with 58 percent of those without pets. The pet owners exercised 3.9 hours a week compared to 3.5 hours a week for those without dogs. Those who owned dogs spent two-thirds of their total physical activity time with their furry companions. Since the people in this study who worked out with their dogs exercised for a longer period of time each week, they lost more weight. This proves that a pet dog can help motivate you to work out and keep up with your exercise plan, to help you reach your weight goals.

This is by no means urging you to get a dog for the sole purpose of encouraging you to get off the couch and get moving. It is saying that a pet can be considered part of your support group when it comes to leading an active and healthy lifestyle.

So tell me, does your pet dog encourage you to exercise more?

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Asthma in children and adolescents

FitSugar — Wed, 08 Oct 2008 17:35:28 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Warning

In 2007, the FDA requested the manufacturers of omalizumab (Xolair) to include a “boxed warning” emphasizing that this drug may cause a severe and life-threatening allergic reaction (anaphylaxis). Health care providers need to carefully observe patients for 2 hours after they receive an omalizumab injection. However, because an allergic reaction can occur up to 24 hours after the injection, patients need to know the signs and symptoms of anaphylaxis and how to self-administer emergency treatment. Omalizumab is approved for patients ages 12 and older who have moderate-to-severe asthma related to allergies.

Drug Approval

In 2006, budesonide/formoterol (Symbicort) was approved for patients age 12 years and older. Symbicort combines a corticosteroid and a long-acting beta2-agonist into a single inhaler.

Inhaled Corticosteroids

Inhaled corticosteroids may help reduce wheezing in young children with breathing problems, but they do not help prevent the development of asthma, according to several 2006 studies in the New England Journal of Medicine.
Inhaled corticosteroids work better than a corticosteroid/long-acting beta2-agonist combination or a leukotrine receptor antagonist drug in treating children with mild-to-moderate asthma, suggests a 2007 study in the Journal of Allergy and Clinical Immunology.

Long-Acting Beta2-Agonists

Long-acting beta2-agonist drugs such as salmeterol (Serevent Diskus) and formoterol (Foradil Aerolizer) may worsen asthma symptom severity and increase the risk for asthma-related death, indicates a 2006 review in the Annals of Internal Medicine.
Products that contain salmeterol and formoterol now have strengthened warning labels detailing these risks.

Childhood Asthma Statistics

Asthma death rates among children have largely declined since 1999 while doctors’ office visits for asthma treatment have more than doubled, indicates a recent report from the U.S. Centers for Disease Control and Prevention.

Introduction

The word asthma originates from an ancient Greek word meaning panting. Essentially, asthma is an inability to breathe properly. When any person inhales, the air travels through the following structures:

Air passes into the lungs and flows through progressively smaller airways called bronchioles. The lungs contain millions of these airways.
All bronchioles lead to alveoli, which are microscopic sacs where oxygen and carbon dioxide are exchanged.

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.

Asthma is a chronic condition in which these airways undergo changes when stimulated by allergens or other environmental triggers. Such changes appear to be two specific responses:

The hyperreactive response (also called hyperresponsiveness)
The inflammatory response

These actions in the airway cause patients to cough, wheeze, and experience shortness of breath (dyspnea), the classic symptoms of asthma.

In the hyperreactive response, smooth muscles in the airways constrict and narrow excessively in response to inhaled allergens or other irritants. Airways in everyone's lungs respond by constricting when exposed to allergens or irritants but there are major differences in the hyperreactive response that occurs in people with asthma:

When people without asthma breathe in and out deeply, the airways relax and open in order to rid the lungs of the irritant.
When people with asthma try to take those same deep breaths, their airways do not relax but instead narrow, causing the patients to pant for breath. Smooth muscles in the airways of people with asthma may have a defect, perhaps a deficiency in a critical chemical that prevents the muscles from relaxing.

The hyperreactive stage is followed by the inflammatory response, which generally contributes to asthma in the following way:

The immune system responds to allergens or other environmental triggers by delivering white blood cells and other immune factors to the airways.
These so-called inflammatory factors cause the airways to swell, fill with fluid, and produce a thick sticky mucus.

Click the icon to see an image of a normal versus asthmatic bronchiole.

This combination of events results in wheezing, breathlessness, inability to exhale properly, and a phlegm-producing cough.

Inflammation appears to be present in the lungs of all patients with asthma, even those with mild cases, and plays a key role in all forms of the disease.

Causes

Asthma occurs in about 5 million American children. Each year about 200,000 of them are hospitalized. It is the most common chronic childhood illness. About half of all cases of asthma develop before the age of 10, and about 80% of patients develop symptoms before they are 5 years old.

The mechanisms that cause asthma are complex and vary among population groups and even individuals. For example, asthma in children is highly associated with allergies. However, only a minority of children with allergies have asthma, and allergic response cannot explain all cases of asthma. Other factors, such as genetics or environmental conditions are probably involved in the development of asthma. Most likely, several genes combine to make a child susceptible to environmental triggers, not only allergens but also possibly infections, dietary patterns, or air pollution. Physical factors, particularly having smaller lungs, affect the chances for later asthma.

Asthma and allergies often coexist, and the allergic response plays a strong role in childhood asthma. About 70 - 85% of children with asthma also have allergies. Some studies suggest that children who have allergies are also at greater risk for developing asthma as adults. A 2006 study found that children who are allergic to dust mites are three times more likely to later develop asthma than children who were not allergic.

However, the evidence is clearly mixed. Several other 2006 studies suggested that avoiding dust mites does not help prevent asthma and, in fact, early exposure to dust mites may even protect children from developing asthma and allergic responses. Some experts think that giving immunotherapy (“allergy shots”) to children with allergies may help prevent asthma development.

An asthma attack can be induced or aggravated by direct irritants to the lungs. Studies indicate that the more indoor allergens a child is allergic to, the higher the risk for severe asthma. Important irritants or allergens include the following:

Dust mites, specifically mite feces, which are coated with enzymes that contain a powerful allergen. These are the primary allergens in the home.
Animal dander. Cats harbor significant allergens, which can even be carried on clothing; dogs usually present fewer problems.
Molds.
Cockroaches. Cockroaches are major asthma triggers and may reduce lung function even in people without a history of asthma.
Pollen. An asthma attack from an allergic response to pollen is more likely to occur during extreme air changes, such as thunderstorms. Major weather changes, such as El Nino, can affect the timing of allergy seasons because they cause seasonal changes (and pollen) to start earlier.
Food allergies. About 8 - 10% of children with asthma also have food allergies. These children also appear to have a high risk for very serious reactions to such foods. In infants and toddlers, allergy to eggs appears to be a predictor of asthma.
Fossil Fuels. Certain chemicals may trigger allergic rhinitis. Some experts believe that refined fossil fuels, such as diesel fuel and particularly kerosene, may be important triggers for allergic rhinitis. In people who already have allergies or asthma, exposure to such fossil fuels may worsen symptoms.

The Allergic Response. The allergic process, called atopy, and its connection to asthma are not completely understood. It involves various airborne allergens or other triggers that set off a cascade of events in the immune system leading to inflammation and hyperreactivity in the airways. One description is as follows:

The conductor in an orchestra of immune factors that contribute to allergies and asthma appears to be a category of white blood cells known as helper T cells, in particular a subgroup called Th2 cells.
Th2 cells overproduce interleukins (ILs), immune factors that are molecular members of a family called cytokines, which are involved in the inflammatory process.
Interleukins 4, 9, and 13, for example, may be responsible for a first-phase asthma attack. These interleukins stimulate the production and release of antibody groups known as immunoglobulin E (IgE). (People with both asthma and allergies appear to have a genetic predisposition for overproducing IgE.)
During an allergic attack, these IgE antibodies can bind to special cells in the immune system called mast cells, which are generally concentrated in the lungs, skin, and mucous membranes. This bond triggers the release of a number of active chemicals, importantly potent molecules known as leukotrienes. These chemicals cause airway spasms, overproduce mucus, and activate nerve endings in the airway lining.
Another cytokine, interleukin 5, appears to contribute to a late-phase inflammatory response. This interleukin attracts white blood cells known as eosinophils. These cells accumulate and remain in the airways after the first attack. They persist for weeks and mediate the release of other damaging particles that remain in the airways.

Researchers are investigating the role that T cells play in asthma. T cells are white blood cells that are involved in the immune response. Researchers had focused on the T cell called type 2 helper (ThH2) cells. However, a 2006 breakthrough study in the New England Journal of Medicine suggested that a different type of T cell may play a stronger role in asthma than previously thought.

Researchers discovered that these cells, called natural killer T cells, are far more common in the lungs of people with asthma than in the lungs of healthy people. Natural killer T cells are very rare, but researchers found them in 60% of people with moderate-to-severe persistent asthma. While this research is preliminary, it may explain why corticosteroid drugs do not work well for some patients with asthma: Steroid drugs target Th2 and other inflammatory cells, not natural killer T cells. Researchers think that further investigation of natural killer T cells may lead the way to new types of asthma drugs. If these cells prove to be involved in asthma, then drugs that eliminate them might become an important new treatment.

Over the course of years the repetition of the inflammatory events involved in asthma can cause irreversible structural and functional changes in the airways, a process called remodeling. The remodeled airways are persistently narrow and can cause chronic asthma. Researchers are trying to determine how this process occurs:

Interleukins. Some researchers are looking at potent immune factors, including interleukins 11 and 13. They have been linked to a number of processes possibly involved in remodeling, including scarring in the airways and overgrowth of cells in the smooth muscles that line the airways.

Growth Factors. Compounds known as vascular endothelial growth factor (VEGF) have been observed in the airways of patients with asthma. VEGF is a powerful promoter of cell growth in blood vessel linings and some researchers believe it may be major factor in remodeling.

About one-third of all persons with asthma share this condition with another member of their immediate family. Asthma may be more likely to be passed to children from the mother than from the father. Both allergies and asthma are strongly associated with hereditary factors, sharing certain genetic markers, but they are not always inherited together.

Research on the genetics of these conditions is confusing. Of some significant promise, researchers have identified a gene (ADAM33), which has been linked to asthma. The gene regulates one of the enzymes called metalloproteases, which are involved with the smooth muscle in the airway. A mutation of this gene could play a role in airway changes that occur after inflammation.

The role of early childhood respiratory and intestinal infections is very complex. Viral respiratory infections certainly worsen existing asthma, but the most common ones are unlikely to be causes of childhood asthma. In fact, early respiratory and intestinal infections may offer some protection against asthma.

Early Respiratory Infections as Causes of Asthma. Studies suggest that most respiratory infections are not important causes of asthma in children, except in certain cases. An important exception is the respiratory syncytial virus (RSV), which has been implicated in the development of asthma. RSV is the major viral cause of infant pneumonia. Studies also indicate that infants who have reduced lung function within a few days after birth are at increased risk of developing asthma by the time they are 10 years old.

Common Respiratory Infections Worsen Asthma. Common respiratory infections viruses that cause colds (such as the rhinovirus) may in some cases be associated with the development of asthma. A 2007 study suggested that children who have a wheezing rhinovirus during infancy are at increased risk for developing asthma by age 6. Even if these viruses do not directly cause asthma, they can worsen asthma in children who already have it. Rhinovirus has been reported to be the most common infection associated with asthma attacks. In one study, it was associated with 61% of asthma worsening in children. Some research suggests that colds promote inflammation in patients with existing asthma and increase the intensity of airway responsiveness for weeks.

The Hygiene Theory: Early Infections as Protection Against Asthma. Another blames the dramatic increase in asthma on the reductions in childhood infections that have occurred with modern hygiene and antibiotic use. The basic theory rests on the idea that infections stimulate production of specific immune factors called Th1 cells. As these cells build up, they replace other immune factors called Th2 cells, which react to allergens -- a less serious threat to the body. Without infections to stimulate the production of the Th1 infection fighters, the Th2 allergen fighters are not replaced, and they persist at high levels, making the growing child more susceptible to allergies and asthma.

A number of different studies support this theory:

Some studies suggest that being part of a large family or attending day care increases the risk for early respiratory infections but reduces the risk of childhood asthma. The occasional cold, then, may be protective.
In one study, researchers measured levels of bacterial byproducts called endotoxins in the mattress dust of 812 children. Those with the highest levels had 80% lower rates in allergies and asthma.
Another study further found a strong association between allergy development and the absence of certain beneficial bacteria (called probiotics) carried in the infant's intestines. Infants who were born in more hygienic environments tended to lack these bacteria. Antibiotic overuse and modern hygiene may be reducing these helpful organisms. (Probiotics can be obtained in active yogurt cultures and in supplements, which are being studied for protection.)

The standard vaccinations against serious childhood infections, according to several important studies, pose no risk for asthma. One of the studies even reported some lower risk for asthma and allergies in the second and third years after vaccinations. Infections killed thousands of children every year before immunization became widespread. Asthma, although serious, is rarely fatal in children. No one should stop giving their children vaccinations against childhood killers.

GERD. At least half of patients with asthma also have gastroesophageal reflux disease (GERD), the cause of heartburn. It is not entirely clear which condition causes the other or whether they are both due to common factors.

Heartburn is a condition where the acidic stomach contents back up into the esophagus causing pain in the chest area. This reflux usually occurs because the sphincter muscle between the esophagus and stomach is weakened. Standing or sitting after a meal can help reduce the reflux which causes heartburn. Continuous irritation of the esophagus lining as in gastroesophageal reflux disease is a risk factor for the development of adenocarcinoma.

Some theories for the causal connection between GERD and asthma are:

Acid leaking from the lower esophagus in GERD stimulates the vagus nerve, which runs through the gastrointestinal tract. This stimulated nerve, in turn, triggers the nearby airways in the lung to constrict, causing asthma symptoms.
Acid back-up that reaches the mouth may be inhaled into the airways (aspirated). Here, the acid triggers a reaction in the airways that cause asthma symptoms.

GERD is sometimes hard to detect and might be suspected as a contributor in the following patients:

Those who do not respond to asthma treatments.
Those whose asthma attacks follow episodes of heartburn.
Those whose attacks are worse after eating or exercise.
Those whose coughs follow episodes of acid reflux. (One study found that GERD was associated with about half of the episodes of coughs and wheezes in patients with asthma.)

Treating GERD symptoms with anti-acid drugs may resolve asthma in some (but not all) patients who share both conditions. A small 2005 observational study found that while GERD was common in patients with asthma, treatment of GERD had no effect on asthma symptoms. [See In-Depth Report #85: Heartburn and gastroesophageal reflux disease.]

Sinusitis. Almost half of children and adults with allergic asthma have sinus abnormalities, and in various studies, between 17 - 30% of patients with asthma develop true sinusitis. The presence of sinusitis, however, does not appear to increase the severity of asthma.

Click the icon to see an image of sinusitis.

Parental Migraines and Childhood Asthma. Some studies have reported a link between childhood asthma and parental migraines, with one small study suggesting that children are about five times more likely to develop asthma if their parents have a history of migraines.

Exercise-induced asthma (EIA) is a limited form of asthma in which exercise triggers coughing, wheezing, or shortness of breath.

About 10% of adults and some fewer children have aspirin-induced asthma (AIA). With this condition, asthma gets worse when patients take aspirin. Aspirin is one of the drugs known as nonsteroidal anti-inflammatory drugs (NSAIDs). Although aspirin is used to reduce inflammation in other disorders, it appears to have the opposite effect in many asthma cases. It is not wholly known why this occurs. AIA often develops after a viral infection. It is a particularly severe asthmatic condition and is associated with up to 25% of asthma-related hospitalizations. In about 5% of cases, aspirin is responsible for a syndrome that involves multiple attacks of asthma, sinusitis, and nasal congestion. Such patients also often have polyps (small benign growths) in the nasal passages.

Patients with aspirin-induced asthma (AIA) should avoid aspirin and most likely NSAIDs, including ibuprofen (Advil) and naproxen (Aleve).

Acetaminophen (Tylenol) has been the traditional alternative for relief of minor pain for patients who are aspirin-sensitive. Unfortunately, recent evidence has muddied these recommendations. Moreover, some asthmatic episodes have been linked to high consumption of acetaminophen among adults. And a study of children with asthma reported that those who took ibuprofen were less likely to be hospitalized for asthma than those taking acetaminophen. This is of particular concern, since acetaminophen is the pain reliever of choice in small children.

Asthma occurs primarily at night (nocturnal asthma) in as many as 75% of patients with the condition. Attacks often occur between 2 - 4 a.m. Factors that might play role in nocturnal asthma may include one or more of the following:

Chemical and temperature changes in the body during the night that increase inflammation and narrowing of the airways
Delayed allergic responses from exposure to allergens during the day
The wearing off of inhaled medications toward the early morning
An increase in acid reflux (back up of stomach acid) that causes airways to narrow
Postnasal drip that occurs during sleep
Conditions relating to sleep, such as sleep apnea or sleeping on one's back, which may worsen any asthma attack that occurs at night

Some experts believe that nocturnal asthma may actually be a unique form of asthma with its own specific biologic mechanisms that occur only at night and which reduce natural steroid hormones (which block inflammation).

Exercise-induced asthma (EIA) is a limited form of asthma in which exercise triggers coughing, wheezing, or shortness of breath. This condition generally occurs in children and young adults, most often during intense exercise in cold dry air. Symptoms are generally most intense about 10 minutes after exercising and then gradually resolve.

EIA is triggered only by exercise and is distinct from ordinary allergic asthma in that it does not produce a long duration of airway activity, as allergic asthma does. (However, some people have both forms of asthma.) People who have only EIA do not appear to require long-term maintenance therapy. A study of military recruits with EIA also reported that the condition does not hinder a person's overall physical performance.

Medications. Cromolyn, a mild anti-inflammatory drug, or short-acting beta2-agonists have been the treatments of choice for preventing EIA. Newer approaches for people who work out regularly include pretreatment with long-acting beta2-agonists, such as salmeterol (Serevent) or the regular use of inhaled corticosteroids.

Hints for Reducing EIA. EIA occurs only after exercise and is more likely to occur with regular paced activities in cold, dry air. The following are some suggestions for reducing its impact:

Warm-up and cool-down periods are important.
Patients with EIA might do better with activities that involve short bursts of exercise (tennis, football) than with exercises involving long-duration regular pacing (cycling, soccer, and distance running).
Breathing through a scarf or through the nose helps warm up the airways.
Restricting dietary salt might help reduce EIA.

Click the icon to see an image of exercise-induced asthma.

Prognosis

Asthma is the third major cause of hospitalization in children under age 15. The condition can be very serious in children, particularly those younger than age 5, because their airways are very narrow.

The severity of asthma is graded as mild intermittent and mild, moderate, and severe persistent. A patient in any of these categories, even mild intermittent, can still experience a severe and even life-threatening attack. According to one report, 30% of asthma deaths occur in patients with mild asthma.

Asthma is rarely fatal in children, with only 187 asthma deaths reported in 2002 in children under age 18. In fact, a 2006 study from the U.S. Centers for Disease Control and Prevention reported that asthma death rates for children have steadily declined since 1999. (During the same time, the number of doctor visits for asthma treatment more than doubled.) Even low mortality numbers are unacceptable, however, since asthma deaths are largely preventable.

Factors associated with an increased risk of death from asthma in children include:

Previous life-threatening episodes of asthma
Lack of adequate and ongoing health care. (Most likely the reason for the higher fatalities rates in minority children.)
Significant behavioral problems
Underestimating the severity of an acute attack poses the greatest threat. Unfortunately, one study of children found that nearly 40% of them were unaware of asthmatic symptoms when they occurred.

African American children have more than six times the death rate of Caucasians in the age groups of 4 years and younger and 15 - 24 years. Hispanic children also have a higher risk.

The following signs and symptoms may indicate a life-threatening situation:

As the chest labors to bring enough air into the lungs, breathing often becomes shallow.
Lacking sufficient oxygen, the skin becomes bluish.
The flesh around the ribs of the chest appears to be sucked in.
The patient may begin to lose consciousness.

Asthma often progresses very slowly to a serious condition or may develop to a fatal or near-fatal attack within a few minutes. It is very difficult to predict when an attack will become very serious. Early symptoms or lack thereof do not always reflect the ultimate severity of an attack. Some studies even suggest that people at high risk for fatal or near-fatal asthma attacks are those with poor awareness of their own reduced ability to breathe and who are slow in seeking help. Monitoring peak flow rates is, therefore, an important management component, since it provides a more accurate assessment of lung function than symptoms alone.

In a 2003 study, researchers followed people with asthma for longer than 30 years. About a third of children had outgrown their asthma in adulthood. In general, the more severe the childhood asthma, the greater the likelihood that it will persist. For example, only 23% of children who experienced wheezy bronchitis (wheezing during respiratory infections) suffered from frequent or persistent asthma in adulthood.

There is evidence that severe asthma can cause long-lasting damage and possibly permanent scarring in some patients. The risk for such injury is highest, however, when asthma strikes children in the first 3 - 5 years. There does not appear to be any significant risk for long-term lung damage for children who develop mild-to-moderate persistent asthma between ages 5 - 12. Children adapt well to living with asthma, and even with severe asthma they can function as well as healthy children in virtually all areas of life.

Studies are mixed over the effects of emotional disorders on the severity of asthma. One study indicated that parents of children with asthma may suffer greater psychological stress than their children. A 2000 study reported that mild-to-moderate asthma does not significantly affect the psychological well-being of most children ages 5 - 12. Teenagers and preteens may have particular difficulty coping with what they perceive as the social stigma of asthma. Parents and older children should not hesitate to seek help from support groups, doctors, friends, or family members. Support programs may help children to better manage their asthma and even reduce hospitalization.

Although there have been few studies on the effects of asthma on schooling, a 2000 study reported that nocturnal (nighttime) asthma affected school attendance and performance in children and work attendance in their parents.

Risk Factors

Asthma affects about 5 million American children between the ages of 5 - 14. Asthma has dramatically increased worldwide over the last few decades, in both developed and developing countries. From 1980 - 1994, asthma increased 160% in American children younger than 4 years and has also dramatically risen worldwide. Experts are puzzling over the cause of this phenomenon. Possible causes and risk factors that are suspects in the dramatic rise in asthma in children include:

Survival rates are now higher in low-birth-weight babies, who may be more susceptible to asthma.
Declining rates in nursing may be a contributor. Breast milk contains important anti-inflammatory substances, such as omega-3 fatty acids, which might protect against asthma.
Western dietary habits (which commonly include more fast foods and less fruits, vegetables, fiber, minerals, and other nutrients) may contribute to the development of childhood asthma.
Children are spending more time indoors watching television, playing video games, or using the computer and are, therefore, overexposed to indoor allergens.
The trend of making homes more energy-efficient may result in dust mites being trapped inside them.

Among younger children, asthma develops twice as frequently in boys as in girls, but after puberty it may be more common in girls.

Urban Life. Urban life is strongly associated with a higher risk. Although poverty plays a significant role, urban life has been associated with a higher risk for asthma in any income group and among both children and adults. In some urban areas, as many as 25% of children have asthma or show signs of wheezing. In fact, it may be greatly underdiagnosed in city children. A 1999 study reported that almost a third of children in inner-city kindergartens had asthma symptoms without a diagnosis of the disorder; 10% had actually been diagnosed with asthma, mainly because their symptoms were severe.

Ethnicity. Since 1980, asthma rates have risen the most dramatically among African American children, and they have significantly higher rates of asthma than Caucasian children. Hispanic children are also at higher risk. Both groups of minority children are more likely to have fatal asthma than Caucasian children.

Some studies indicate that the difference in risk exists simply because African Americans and other minority groups are more likely to live in urban areas. Poverty and lack of access to health care also play a role. However, Caucasian children who live in cities also face a high risk for asthma, and rural African American children do not.

Urban life and socioeconomic factors, however, may not fully explain the ethnic disparity.

Low Birth Weight. Infants of low birth weight are at higher risk for lung problems and asthma.

Winter Birth. Children born in the winter may have a greater risk for asthmatic allergies to cockroaches than children born at other times of the year.

Vitamin D. A 2006 study suggested a link between vitamin D intake during pregnancy and development of early childhood asthma. Pregnant women who had a higher intake of vitamin D were less likely to give birth to children who developed asthma.

Breast Feeding. Most studies on breastfeeding report some protection against wheezing and asthma in the first year of life. Breastfeeding has many other benefits for the child as well. The American Academy of Pediatrics recommends exclusively breastfeeding for the child's first 6 months of life.

Complications of Pregnancy. According to a 2000 study, complications of pregnancy, specifically those involving the mother's uterus (such as post-birth hemorrhage, pre-term contractions, insufficient placenta, and restricted growth of the uterus), are associated with an increased risk of childhood asthma. Another study reported that delivery procedures such as Cesarean section, the use of vacuum extraction or forceps also raised the risk of childhood asthma.

In both adults and children, the incidence of obesity and asthma has been increasing over recent years. Studies report a strong association between the two conditions. Some experts suggest that excess weight pressing on the lungs may trigger the hyperreactive response in the airways typical of asthma. Others believe that asthma leads to obesity by inhibiting physical activity, although several studies have found no difference in activity levels between people with or without asthma. Some studies suggest that many obese people may be misdiagnosed as having asthma when they are simply short of breath, possibly because of the increased effort required for breathing.

In any case, there is evidence that losing weight can relieve asthma symptoms. Some evidence also suggests that people who are overweight (body mass index greater than 25) have more difficulty getting their asthma under control. Weight loss in anyone who is obese and has asthma or shortness of breath reduces airway obstruction and improves lung function. [See In-Depth Report #53: Weight control and diet.].

Damp Homes. Studies suggest that children who live in damp homes have a much higher risk for asthma.

Mental Health. Research indicates that poor mental health of parents and children are significant predictors of more severe symptoms in childhood asthma. A 2000 study suggested that high stress levels can predict the onset and severity of asthma in children genetically at risk for the condition.

Symptoms

In children with asthmatic symptoms, it is important to first consider as a possible cause inhaled foreign objects such as peanuts; viral infections such as croup; and bacterial infections, which may be accompanied by high fever and progress rapidly. Any child who has frequent coughing or respiratory infections should be checked for asthma.

The classic symptoms of an asthma attack include:

Wheezing when breathing out is nearly always present during an attack. Usually the attack begins with wheezing and rapid breathing, and, as it becomes more severe, all breathing muscles become visibly active.
Shortness of breath (dyspnea). Shortness of breath is a major source of distress in patients with asthma, although severe dyspnea does not always reflect a serious attack or reduced lung function.
Coughing. In some people, the first symptom of asthma is a nonproductive cough.
Chest tightness or pain. Initial chest tightness without any other symptoms may be an early indicator of a serious attack.
Neck muscles may tighten, and talking may become difficult or impossible.
Rapid heart rate
Sweating
Chest pain occurs in about 75% of patients. It can be very severe, although its intensity is not necessarily related to the severity of the asthma attack itself.

The end of an attack is often marked by a cough that produces thick, stringy mucus. After an initial acute attack, inflammation persists for days to weeks, often without symptoms. (The inflammation itself must still be treated, however, because it usually causes relapse.)

Diagnosis

The doctor will consider a diagnosis of asthma if a child has a history of periodic attacks of shortness of breath, coughing, and wheezing, perhaps accompanied by tightness in the chest. The parent should describe the pattern of symptoms and possible precipitating factors, including:

Whether symptoms are more frequent during the spring or fall (allergy seasons)
Whether exercise, a respiratory infection, or exposure to cold air has ever triggered an attack
Any family history of asthma or allergic disorders such as eczema, hives, or hay fever

A number of disorders may cause some or all of the symptoms of asthma. Panic disorder can coincide with asthma or be confused with it. Other diseases that must be considered during diagnosis are pneumonia, bronchitis, severe allergic reactions, psychosomatic illnesses, and certain rare disorders (such as tapeworm and trichomoniasis).

If symptoms and a patient's history are indicative of asthma, the doctor will usually perform tests known as pulmonary function tests to confirm the diagnosis and determine the severity of the disease.

Using a spirometer, an instrument that measures the air taken into and exhaled from the lungs, the doctor will determine several values:

Vital capacity (VC), which is the maximum volume of air that can be inhaled or exhaled.
Peak expiratory flow rate (PEFR), commonly called the peak flow rate, which is the maximum flow rate that can be generated during a forced exhalation.
Forced expiratory volume (FEV1), the maximum volume of air expired in 1 second.

If the airways are obstructed, these measurements will fall. Depending on the results, the doctor will take the following steps:

If measurements fall, the doctor typically asks the patient to inhale a bronchodilator. This drug is used in asthma to open the air passages. The measurements are taken again. If the measurements are more normal, the drug has most likely cleared the airways, and a diagnosis of asthma is strongly suspected.
If measurement results fail to show airway obstruction, but asthma is still suspected, the doctor may perform a challenge test. It involves administering a specific drug (histamine or methacholine) that usually increases airway resistance only when asthma is present.

The patient may be given skin or blood allergy tests, particularly if a specific allergen is suspected and available for testing. Allergy skin tests may be the best predictive test for allergic asthma, although they are not recommended for people with year-round asthma.

One of the most common methods of allergy testing is the scratch test or skin prick test. The test involves placing a small amount of the suspected allergy-causing substance (allergen) on the skin (usually the forearm, upper arm, or the back), and then scratching or pricking the skin so that the allergen is introduced under the skin surface. The skin is observed closely for signs of a reaction, which usually includes swelling and redness of the site. With this test, several suspected allergens can be tested at the same time, and results are usually available within about 20 minutes.

Tests that either rule out other diseases or obtain more information about the causes of asthma include the following:

A complete blood count
Chest and sinus x-rays
Computed tomography (CT) scans. CT scans may be helpful in certain cases, such as for determining wall thickness in airways in patients who are difficult to treat, which could signify a higher risk for lung damage.
Examination of the patient's sputum for eosinophils (white blood cells that in high levels are associated with severe allergic asthma).
Researchers are investigating measurements of certain chemicals in sputum or exhaled air that indicate airway inflammation. Such chemical markers include nitric oxide and hydrogen peroxide. For example, high levels of nitric oxide may prove to be a simple and noninvasive way of diagnosing asthma.

Treatment

Treating an Acute Attack in the Hospital. An acute attack may require hospitalization. Laboratory tests, an electrocardiogram (ECG), and a chest x-ray are performed to determine lung function, oxygen levels, and other indications of severity or rule out other causes. Depending on the results, the following treatments may be given:

Beta2-agonists are the standard therapy. They are typically administered with a nebulizer (a device that administers the drug in a fine spray). Studies suggest, however, that even very small children may be able to use metered-dose inhalers (MDIs), which are just as effective and more convenient than nebulizers. (Intravenous delivery is not recommended in most cases.)
An anticholinergic drug (ipratropium) is sometimes added to improve symptoms.
A corticosteroid (commonly called a steroid) given within the first hour helps reduce the need for hospitalization. Steroids may be administered intravenously, as a shot, or orally. Children may respond well to oral steroids.
Oxygen is usually administered, and can be life saving in severe cases.
Infusions of magnesium sulfate open airways and are an important emergency treatment for adults. Its benefits for children need to be further demonstrated.
In life-threatening situations, the patient may require mechanical ventilation.

Antibiotics are not useful for asthma attacks if there is no strong evidence of the presence of a bacterial infection. Viral infections, most often colds and the flu, are more likely to trigger an asthma attack. In such cases, antibiotics are not helpful and may have adverse effects.

Discharge and Relapse After Hospitalization. It typically takes about 3 - 4 hours to determine if a patient can be safely sent home or if they need to stay. Patients are generally discharged when:

Symptoms are gone or minimal, and
The peak expiratory flow rate is 70% or more of the predicted rate

Despite reasonable precautions, between 12 - 16% of patients relapse within 2 weeks of leaving the hospital. Receiving a steroid shot at discharge or taking an oral corticosteroid for a few days can reduce this risk.

Avoiding allergens, following appropriate drug treatments, and home monitoring are key elements in preventing dangerous asthma attacks and hospitalization. In addition, good communication between the doctor and patient is a key factor in a successful management program.

Medications for asthma fall into two categories:

Rescue Medications. Medications that open the airways (bronchodilators, or inhalers) are used to quickly relieve any moderate or severe asthma attack. These drugs are usually short-acting beta-adrenergic agonists (beta2-agonists). Other drugs used in special cases include corticosteroids taken by mouth and anticholinergic drugs. None of these drugs have any effect on the disease process itself. They are only useful for treating symptoms.
Maintenance Medications. Simply coping with asthma symptoms without also controlling the damaging inflammatory response is a common and serious error. For adults and children over age 5 with moderate-to-severe persistent asthma, experts now recommend inhaled corticosteroids and long-acting beta2-agonists.

Parents can greatly reduce the frequency and severity of their children’s asthma attacks by understanding the difference between coping with asthma attacks and controlling the disease over time. Unfortunately, many patients do not understand the difference between medications that provide rapid, short-term relief and those that are used for long-term symptom control. Many patients with moderate or severe asthma overuse their short-term medications and underuse their corticosteroid medications. The overuse of bronchodilators can have serious consequences; not using steroids can lead to permanent lung damage.

Patients need to understand that asthma symptoms can change quickly over time and that treatment strategies may need to change in response. In 2005, the two leading U.S. allergy associations published joint guidelines on controlling asthma. The guidelines emphasize that asthma treatment decisions need to be made on an individual basis. It is important that patients have a close relationship with their doctor. The doctor needs to evaluate a patient’s asthma symptoms at each visit to determine any need for changes in medication. According to the guidelines, asthma management is classified as either “well-controlled” or “not well-controlled.” The doctor may need to change some medications, or increase or decrease the dosage, depending on whether a child’s asthma is well-controlled or not well-controlled.

These are the signs of well-controlled asthma:

Asthma symptoms occur twice a week or less
Rescue bronchodilator medication is used twice a week or less
Symptoms do not cause nighttime or early morning awakening
Symptoms do not limit work, school, or exercise activities
Peak flow meter readings are normal or the patient’s personal best
Both the doctor and the patient consider the asthma to be well controlled


Classification	Symptom Frequency	Children Age 5 Years and Younger: Recommended Treatment	Children Older Than 5 Years: Recommended Treatment
Mild intermittent	At least 2 days per week. At least 2 nights per month.	No daily medication.	No daily medication. If severe attacks occur, systemic corticosteroids recommended.
Mild Persistent	More than 2 days per week, but less than once per day. More than 2 nights per month.	Preferred treatment: Low-dose inhaled corticosteroids with nebulizer, or MDI with holding chamber with or without face mask. Alternative treatment: Cromolyn or leukotriene-antagonist.	Preferred treatment: Low-dose corticosteroids. Alternative treatment: Cromolyn, leukotriene modifier, nedocromil, OR sustained release theophylline.
Moderate Persistent	Daily daytime symptoms. More than 1 night per week.	Preferred treatment: Low-dose inhaled corticosteroids and long-acting beta2-agonists OR medium-dose inhaled corticosteroids. Alternative treatment: Low-dose inhaled corticosteroids and either leukotriene receptor antagonist or theophylline. If needed (especially if severe attacks occur): Medium-dose inhaled corticosteroids and long-acting beta2-agonists; medium-dose inhaled corticosteroids and either leukotriene receptor antagonist or theophylline.	Preferred treatment: Low-to-medium dose inhaled corticosteroids and long-acting beta2-agonists. Alternative treatment: Low-to-medium dose inhaled corticosteroids and either leukotriene receptor antagonist or theophylline, or increased medium dose inhaled corticosteroids. If needed (especially if severe attacks occur): Increase dosage of medium-dose inhaled corticosteroids with add-on long-acting beta2-agonists. Alternatively, increase dosage of medium-dose inhaled corticosteroids plus either leukotriene receptor antagonist or theophylline.
Severe Persistent	Continual daytime symptoms. Frequent nighttime symptoms.	Preferred treatment: High-dose inhaled corticosteroids and long-acting beta2-agonists plus (if needed) oral corticosteroids.	Preferred treatment: High-dose inhaled corticosteroids combined with long-acting inhaled beta2-agonists. Add, if needed: Oral corticosteroids. Repeat attempts should be made to reduce use of systemic corticosteroid and maintain control with inhaled corticosteroid.
Adapted from National Asthma Education and Prevention Program (NAEPP) Expert Panel Report: Guidelines for the Diagnosis and Management of Asthma – Update on Selected Topics 2002 (EPR-2 Update).

Most asthma drugs are inhaled using various forms of inhalers or nebulizers. Inhaled drugs must be used regularly as prescribed and the patient carefully trained in their use in order for them to be effective and safe. Studies suggest that many children fail to use the devices properly, although newer devices are easier to use than others. The basic devices are the metered-dose inhaler (MDI), breath-actuated inhalers, dry powder inhalers, and nebulizers.

MDIs have used chlorofluorocarbons (CFCs) as their propellants. CFCs are damaging to the environment and are now being replaced with other propellants (hydrofluoroalkane) that are more environmentally safe, and do not chill the device as CFCs do. Devices that don't use any propellants are also now available.

Metered-Dose Inhaler. The standard device for administering any asthma medication is the metered-dose inhaler (MDI). This device, particularly when used with a spacer, allows precise doses to be delivered directly to the lungs. (The spacer is a tube that is attached to the inhaler. It serves as a holding chamber for the medication that is sprayed by the inhaler.) MDI-delivered drugs must be used regularly as prescribed and the patient carefully trained in their use in order for them to be effective and safe. Some patients hold the MDI too close to their mouths, or even inside them. Others may exhale too forcefully before inhalation.

The spacer helps improve medication delivery by allowing the patient additional time to inhale. They vary, however, in their effectiveness. It should be noted that MDIs can continue to deliver propellant even after the drug has been used up. Patients should track their medicine and throw the device away when the last dose has been administered.

Nebulizers (not MDIs) are typically used in very small children, both at home and in the emergency room. However, recent studies suggest spacers may be better than nebulizers for children and shorten the time spent in emergency rooms. Studies also indicate that with the use of a face mask and a spacer, the MDI works well even for infants in the emergency room and may prove to be useable at home.

Click the icon to see an illustrated series detailing a metered dose inhaler.

Breath-Actuated Inhalers. Breath-actuated rotary inhalers (Easi-Breathe and Autohaler) deliver the drug directly to the back of the throat as the user inhales. Their primary advantage over the MDI is their ease of use. They also do not use CFCs as propellants. In comparison studies, patients have been very successful with the breath-actuated inhalers. They are not recommended for children under 8 years old.

Dry Powder Inhalers. Dry powder inhalers (DPIs) deliver a powdered form of beta2-agonists or corticosteroids directly into the lungs. Such devices include Rotahaler, Spinhaler, Turbohaler, Clickhaler, Easyhaler, Diskhaler, Discus, Twisthaler, Spiros, and others. DPIs are as effective as the older devices, and generally have a better taste and are easier to manage. They may differ among themselves, however, in their ability to deliver drugs into the airways. In one study, for example, the Turbohaler was easier to use than the Diskhaler and so achieved better delivery.

Humidity or extreme temperatures can affect DPIs' performance, so they should not be stored in humid places (bathroom cabinets) or locations subject to high temperatures (glove compartments during summer months).

Dry-powder may cause tooth erosion. Children are advised to rinse their mouths out right after using these inhalers and to brush twice a day with a fluoride toothpaste.

Other Hand-Held Inhalers. Respimat delivers a fine-mist spray that is created by forcing the liquid medication through nozzles. It does not use any propellant.

Nebulizers. A nebulizer is a machine that delivers a fine spray of medication-containing liquid. Nebulizers are often used for children younger than 3 years and sometimes for older children who have difficulty using the MDI. It takes 5 - 10 minutes to administer medication using a nebulizer. Because the spray is less targeted than with the inhaler, it must deliver large amounts of the drug. This increases the risk for toxicity and severe side effects. Nebulizers should not be used by children who can manage an inhaler. Their use has been associated with a higher rate of hospitalizations and longer duration of symptoms than inhalers. A 2007 study also suggested that the misuse of home nebulizers may be an important factor in asthma deaths in children and young adults. If children must use an albuterol nebulizer, parents should be sure that it does not contain the preservative benzalkonium, which actually narrows the airways.

Click the icon to see an illustrated series detailing the use of a nebulizer.

Asthma triggers a vicious emotional-physical cycle:

Breathlessness and wheezing incite a fear of suffocation and death, even in very small children.
This anxiety produces further constriction on the muscles surrounding the airways, which makes breathing even more difficult.

Caregivers must first focus on alleviating their own anxiety, which can heighten a child's own fears. The next step is to help the child relax. One method for this is as follows:

The child sits comfortably, bending slight forward with the eyes closed.
The hands are placed gently over the navel.
The child is then told to pretend the stomach is a balloon.
The "balloon" must be "blown up" by inhalation, not exhalation. The child can tell if this working because the hands will move slightly apart.
When the child breathes out, the "balloon" will be made flat.

This exercise both relaxes the child and discourages shallow, oxygen-poor breathing. Massaging the child in gentle circles on the chest is relaxing and may also loosen mucus.

Other recommendations include:

A child may also find relief by lying stomach-down on several pillows so that the head is slightly lower than the chest while the caregiver gently pats the back between the shoulder blades.
Warm liquids, such as soup or hot cider, are effective in loosening mucus and may also relax bronchial muscles. Cold fluids, like cold air, should be avoided.
Overhydration (too much liquid) can be harmful, however, so these drinks should not be forced on the child.
Warm, moist air from vaporizers can greatly ease and moderate asthma attacks.
Daily massages and breathing and relaxation techniques to reduce stress can be very helpful.

Many adults self-manage their asthma using daily monitoring of peak air flow with adjustments of the medications as needed. This involves the use of a peak flow meter, which measures peak expiratory flow rate (PEFR).

Click the icon to see an image of a peak flow meter.

Studies suggest, however, that for most children with asthma, an educational program is just as effective for managing the condition as monitoring. Most children do not need to monitor their peak air flow on any regular basis.

Quick-Relief Medications

These medications quickly control acute asthma attacks.

Beta2-agonists do not reduce inflammation or airway responsiveness but serve as bronchodilators, relaxing and opening constricted airways during an acute asthma attack. A short-acting inhaled beta2-agonist, taken as needed, is often the only medication used by children with chronic mild asthma.

Asthma is a disease in which inflammation of the airways causes airflow into and out of the lungs to be restricted. When an asthma attack occurs, mucus production is increased, muscles of the bronchial tree become tight, and the lining of the air passages swells, reducing airflow and producing the characteristic wheezing sound.

Specific short-acting beta2-agonists include:

Albuterol (Proventil, Ventolin), called salbutamol outside the U.S., is the standard short-acting beta2-agonist in America. Other similar beta2-agonists are isoproterenol (Isuprel, Norisodrine, Medihaler-Iso), metaproterenol (Alupent, Metaprel), pirbuterol (Maxair), terbutaline (Brethine, Brethaire, Bricanyl), and bitolterol (Tornalate). Isoetharine (Bronkometer, Bronkosol) is available in nebulizers.
Newer beta2-agonists, including levalbuterol (Xopenex), have more specific actions than the standard drugs. Xopenex is administered with a nebulizer, and studies have indicated that it is as effective as albuterol with fewer side effects. The original formulation of Xopenex was administered with a nebulizer. A new metered-dose inhaler formulation was launched at the end of 2005. It is approved for children age 4 years and older.

Short-acting bronchodilators are generally administered through inhalation and are effective for 3 - 6 hours. They relieve the symptoms of acute attacks, but they do not control the underlying inflammation. If asthma continues to worsen with the use of these drugs, a doctor may prescribe corticosteroids or other drugs to treat underlying inflammation.

Side Effects of Beta2-Agonists. Side effects of all beta2-agonists may include:

Anxiety
Tremor
Restlessness
Headache
Fast and irregular heartbeats. A doctor should be notified immediately if this side effect occurs.
These drugs should be taken with caution by children with diabetes or a history of seizures.
Beta2-agonists have serious interactions with certain drugs and parents should tell the doctor about any other medications their child is taking.

Loss of Effectiveness and Overdose. There has been some concern that short-acting beta2-agonists become less effective when taken regularly over time, increasing the risk for overuse. Over time, some patients may become tolerant to many effects of short-acting beta2-agonists. The degree to which this affects the airways is uncertain. In some studies, the duration of action has declined but the peak effect appears to be preserved, making these drugs still useful for acute attacks. Regular use of long-acting beta2-agonists may increase the chances of a reduced effect from the short-acting forms.

A 2005 landmark study suggested that patients’ differing clinical response to albuterol may be based on their genotype. Albuterol targets the beta-adrenergic receptor. In the Beta-Adrenergic Response by Genotype (BARGE) trial, researchers studied the effects of albuterol on patients with two different forms of this receptor. The results suggested that patients with the arginine form of the receptor did not respond to albuterol. These patients’ asthma symptoms actually improved when albuterol was not used. By contrast, patients with the glycine form of the receptor had improved asthma control with albuterol.

Inhaled ipratropium bromide (Atrovent) acts as a bronchodilator over time. Ipratropium bromide alone is only modestly beneficial for acute asthma attacks. In fact, the drug is not approved specifically for asthma. Some parents report benefit for treating wheezing in infants. It is also sometimes used in the emergency room to treat children with severe asthma to enhance the effects of intravenous beta2-agonists.

Common oral corticosteroids include prednisone/prednisolone, dexamethasone, methylprednisolone, and hydrocortisone. They reduce inflammation very effectively. A 2006 study indicated that oral prednisolone worked better than inhaled fluticasone for treating mild-to-moderate asthma attacks in children in emergency rooms. However, children often have difficulty taking these drugs because they have a bitter taste and can cause vomiting. Taking oral dexamethasone for 2 days may be as effective and more tolerable than the standard 5-day regimen of prednisone/prednisolone. Prolonged use of oral steroids has widespread and sometimes serious side effects, so they are not generally give to children for longer than a few days.

[See In-Depth Report #4: Asthma in adults.]

Long-Term Relief Medications

These medications are taken on a regular basis to prevent asthma attacks and control chronic symptoms.

Corticosteroids, also called glucocorticoids or steroids, are powerful anti-inflammatory drugs. Steroids are not bronchodilators (they do not relax the airways) and have little effect on symptoms. Instead, they work over time to reduce inflammation and prevent permanent injury in the lungs. They can also help prevent asthma attacks from occurring. Many studies have shown that the use of inhaled corticosteroids in patients with moderate-to-severe asthma significantly reduces the rate of rehospitalizations and deaths from asthma.

Inhalation of corticosteroids makes it possible to provide effective local anti-inflammatory activity in the lungs with minimal systemic effects. (By contrast, oral steroids have considerable side effects throughout the body.) Inhaled corticosteroids are recommended as the primary therapy under the following circumstances:

For any asthmatic condition more serious than occasional episodes of mild asthma. (Low-doses of inhaled steroids may even be safe and effective for some people with mild asthma, particularly those who find themselves using beta2-agonists daily.)
When treatment with bronchodilators is not effective.

Examples of inhaled corticosteroids:

Inhaled steroids include fluticasone (Flovent), budesonide (Pulmicort), triamcinolone (Azmacort and others), and flunisolide (AeroBid). In general, the newer drugs are more powerful than the older generation of inhaled drugs. Budesonide (Pulmicort Respules) is available in a jet nebulizer for children from 12 months to 8 years. It is the first such medication to be approved for children in this age group.
The FDA approved a new inhaled corticosteroid, mometasone furoate (Asmanex) was approved in 2005 for patients age 12 and older.
The older corticosteroid inhalants are beclomethasone (Beclovent, Vanceril) and dexamethasone (Decadron Phosphate Respihaler and others). They are less powerful than the newer steroids when delivered with standard inhalers. New inhalers that use very fine sprays (QVAR, Autohaler) to deliver the drugs deep into the lungs may prove to be as effective as the newer, more potent steroids.
Inhalers that combine both long-acting beta2-agonists and corticosteroids are also available. These include Symbicort (budesonide/formoterol), which was approved in 2006 for patients ages 12 years and older.

Expert guidelines recommend inhaled corticosteroids as the preferred first-line therapy for children with mild-to-moderate asthma. Nevertheless, they are still significantly underprescribed in the patients who need them most. An important 2007 study of 6 - 14 year old children with asthma compared inhaled corticosteroid therapy (fluticasone) with an inhaled corticosteroid/long-term beta2 agonist (fluticasone/salmeterol) and a leukotrine receptor antagonist (montelukast). The results indicated that fluticasone alone worked better than the other two treatments.

Researchers have been investigating whether early treatment with corticosteroids can help prevent the development of asthma in at-risk children. Two important 2006 studies in the New England Journal of Medicine suggested that while inhaled corticosteroids helped ease symptoms and reduce breathing problems in pre-school children at risk for asthma, they did not help protect against asthma development.

For now, experts caution against corticosteroids for infants and toddlers with mild asthma and urge close monitoring especially for children under age 5 with severe asthma who are receiving high doses. Because the newer potent drugs, particularly fluticasone, may produce major side effects similar to oral steroids, it is important when treating all children to aim for the lowest effective dose possible. Fortunately, studies suggest that low doses of fluticasone may achieve the same benefits as with high ones, thus reducing risks for serious side effects. Better delivery methods may also allow lower doses.

Side effects of inhaled steroids may include:

The most common side effects are throat irritation, hoarseness, and dry mouth. These effects can be minimized or prevented by using a spacer device and rinsing the mouth after each treatment.
Rashes, wheezing, facial swelling (edema), fungal infections (thrush) in the mouth and throat, and bruising are also possible but not common with inhalators.
Some children experience changes in mood, memory, and behavior. These changes are not permanent.
Some studies have suggested a higher risk for gum inflammation.
Oral steroids reduce bone density. Research reports that inhaled steroids -- both older and newer drugs -- may also affect bone growth and density. However, a number of studies report only a slight effect (about half an inch) on children's growth, which may be only temporary. It is still unknown if these drugs have any significant long-term effect on bone density. Calcium supplements may help prevent bone loss that is due to inhaled steroids.
It is not yet known whether inhaled steroids affect lung growth in very young children. Steroids administered using nebulizers are of particular concern.
There is also some concern that the stronger drugs, particularly fluticasone, suppress the adrenal system to a greater degree than other steroid inhalants. This effect, in turn, reduces levels of natural steroids -- notably cortisol, the major stress hormone. (This is a serious side effect of oral steroids).

Long-acting beta2-agonists are used in combination with inhaled corticosteroids for treating children with moderate-to-severe asthma. These drugs include include salmeterol (Serevent Diskus) and formoterol (Foradil Aerolizer). A single inhaler (Advair Diskus) that combines both salmeterol and the corticosteroid fluticasone is available for children age 4 years and older, and an inhaler (Symbicort) combining formoterol and the corticosteroid budesonide is approved for children age 12 years and older.

Long-acting beta2-agonists are used for preventing an asthma attack (not for treating attack symptoms). The effects of one dose of a long-acting beta2-agonist last for about 12 hours, so they are particularly effective during the night. These drugs also may be used for prevention of exercise-induced asthma in people and to protect against aspirin-induced asthma.

However, research indicates that long-acting beta2-agonists can worsen asthma by increasing symptom severity. These drugs may also increase the risk for asthma-related deaths. Experts are still trying to determine when long-acting beta2-agonists should be added to an asthma treatment plan. If a child’s symptoms do not improve or if symptoms worsen with this type of drug, the doctor will recommend discontinuing it. Patients should not, however, stop taking this drug or other asthma medications without first talking with their doctors.

Side Effects. Side effects of long-acting beta2-agonists are similar to the short-acting drugs.

Specific Warning on Salmeterol and Formoterol. In 2003 a "black box" warning was added to product packaging for drugs that contain salmeterol, including Serevent Diskus, and Advair Diskus. Serevent and Advair are approved for patients age 12 years and older. The warning was based on a study that demonstrated more serious and even fatal asthma episodes in patients who used the drug than in patients who used a placebo.

In 2006, the FDA updated the warning to include formoterol (Foradil Aerolizer, approved for patients 5 years and older). Warnings for salmeterol and formoterol products emphasize that these medicines can increase the risk of severe asthma episodes. Long-acting beta2-agonists require up to 20 minutes to achieve effectiveness, and there is a danger of overdose if a patient is not aware of this delay and takes additional doses to achieve faster relief. The FDA recommends that patients:

Use long-acting beta2-agonists only if other medicines (such as steroids) have not helped control asthma.
Use a short-acting bronchodilator, not a long-acting beta2-agonist, to treat sudden wheezing.
Do not use long-acting beta2-agonists to treat wheezing that is getting worse. Call your doctor if this situation occurs.
Do not stop using any asthma medicines without first talking to your doctor.

Cromolyn sodium (Intal) is both an anti-inflammatory drug and has antihistamine properties that block asthma triggers such as allergens, cold, or exercise. Cromolyn has been the anti-inflammatory drug of choice for prevention of asthma attacks in children over age 4 with chronic moderate asthma. It is not as effective as inhaled corticosteroids, however, for reducing hospitalization rates, improving symptoms, and reducing the use of beta2-agonists in children with persistent asthma. Still, cromolyn has a well-known long-term safety record, while the long-term adverse effects of corticosteroids in children are still not fully known. Many children who need asthma maintenance therapy will still do well on cromolyn. (It may not provide any real benefit for children under age 4.)

Nedocromil (Tilade) is similar to cromolyn and needs to be taken only once a day. It also prevents asthmatic reactions to cold and exercise. It is not used in very young children. A cromolyn nasal spray called Nasalcrom has been approved for over-the-counter purchase, but only to relieve nasal congestion caused by allergies. Patients should not use it for self-medication without the advice of a doctor.

Side Effects. Side effects of cromolyn include nasal congestion, coughing, sneezing, wheezing, nausea, nosebleeds, and dry throat. Nedocromil has an unpleasant taste, and some people have complained of nausea, headache, and spasms in the airways, but no serious side effects have been reported.

Leukotriene-antagonists (also called anti-leukotrienes or leukotriene modifiers) are oral medications that block leukotrienes. Leukotrienes are powerful immune system factors that, in excess, produce a battery of damaging chemicals that can cause inflammation and spasms in the airways of people with asthma. As with other anti-inflammatory drugs, leukotrienes are used for prevention and not for treating acute asthma attacks.

Leukotriene-antagonists include zafirlukast (Accolate), montelukast (Singulair), zileuton (Ziflo), and pranlukast (Ultair, Onon). These drugs are proving helpful for long-term prevention of asthma, including exercise-induced asthma and aspirin (or NSAID) -induced asthma. However, most studies to date have reported better success with inhaled corticosteroids than with the leukotriene-antagonists. A 2006 study of children with mild-to-moderate persistent asthma indicated that the corticosteroid fluticasone worked better than the leukotriene-antagonist montelukast in controlling symptoms. Nevertheless, some studies suggest that montelukast, which comes in a chewable tablet, may be particularly useful for managing asthma in small children (ages 2 - 5), since they have trouble with inhaled steroids.

Side Effects and Complications. Gastrointestinal distress is the most common side effect of leukotriene-antagonists. Very few other side effects have been reported. In general, these drugs appear to be safe and well-tolerated.

Of some concern are reports of Churg-Strauss syndrome in a few people taking zafirlukast or montelukast. Churg-Strauss syndrome is very rare, but it causes blood vessel inflammation in the lungs and can be life threatening. Oral steroids quickly resolve the problem. In fact, usually the syndrome has occurred in patients who were tapering off steroids and changing over to the leukotriene-antagonists. Some experts believe that, in such cases, the steroids may simply have masked the presence of the disorder, which then developed when the steroid drugs were withdrawn. Symptoms include severe sinusitis, flu-like symptoms, rash, and numbness in the hands and feet.

Other concerns are indications of liver injury in patients taking zileuton and zafirlukast when taken at higher than standard doses. No adverse effects on the liver have been reported to date with montelukast.

Theophylline (Theo-Dur, Theolair, Slo-Phyllin, Slo-bid, Constant-T, Respbid) is a mild-to-moderate bronchodilator that has been used to treat childhood asthma for more than 30 years. It is useful for treating nocturnal asthma and may also have anti-inflammatory qualities even in low doses.

Available in tablet, liquid, and injectable forms, some theophylline sustained-release tablets and capsules have a long duration of action and can therefore be taken once or twice a day with good results.

Side effects may include changes in behavior, mood, and memory. If theophylline is not taken exactly as prescribed, an overdose can easily occur. Toxicity can cause nausea, vomiting, headache, insomnia, and, in rare cases, disturbances in heart rhythm and convulsions. Contact a doctor immediately if any of these side effects occur.

The risks for these adverse effects are small if the drug is taken exactly as prescribed but the following precautions should be noted:

Infants tend to metabolize the drug extremely slowly and, therefore, should receive very low doses.
By the time children reach age 1, however, they metabolize the drug faster than adults. There is a risk, therefore, of toxic effects.
Fever and certain antibiotics may slow down the rate at which theophylline is eliminated from the body. In such cases, the doctor may want to reduce the dosage of theophylline.

If a child is taking theophylline on an ongoing basis, the doctor should monitor the drug level at the start of therapy and at regular intervals thereafter.

Omalizumab (Xolair) is FDA-approved for patients age 12 and older who have moderate-to-severe persistent asthma related to allergies. The first drug of this type to be approved for asthma, omalizumab is a monoclonal antibody (MAb), a genetically developed drug designed to attack very specific targets. Omalizumab is administered by injection every 2 - 4 weeks. It is used only to treat patients whose symptoms are not controlled by inhaled corticosteroids.

Omalizumab prevents the antibody immunoglobulin E (IgE) from triggering the inflammatory events that lead to asthmatic attacks. Studies have shown excellent benefits of the drug, including a reduced need for corticosteroids, fewer hospitalizations, and significant symptomatic improvements.

However, about 1 in 1,000 patients who take omalizumab develop anaphylaxis (a life-threatening allergic reaction). In 2007 the FDA requested the manufacturers of omalizumab to put a “boxed warning” on the medicine’s label emphasizing the drug’s risk for anaphylaxis. The boxed warning notes that patients can develop anaphylaxis after any dose of omalizumab, even if they had no reaction to a first dose. Anaphylaxis may occur up to 24 hours after the dose is given.

The FDA recommends that healthcare providers observe patients for at least 2 hours after an injection. Patients should also carry emergency self-treatment for anaphylaxis (such as an Epi-Pen) and know how to administer it. With an Epi-Pen, or similar auto-injector device, patients can quickly give themselves a life-saving dose of epinephrine.

Anaphylaxis symptoms include:

Difficulty breathing
Chest tightness
Dizziness
Fainting
Itching and hives
Swelling of the mouth and throat

[See In-Depth Report #4: Asthma in adults.]

Other Treatments

Alternative therapies are widely used by children, adolescents, and adults with asthma. In one study, nearly half of asthma or allergy sufferers resorted to alternative treatments. To date, however, evidence does not support most alternative therapies, including high-dose vitamins, urine injections, homeopathic remedies, and most herbal remedies.

Relaxation and Stress-Reduction Techniques. Patients report benefits from many stress reduction and physical techniques, such as acupuncture, hypnosis, breathing relaxation techniques, the Alexander technique, massage therapy, and meditation practices. There have been very few well-conducted studies supporting their use, however.

Acupuncture, hypnosis, and biofeedback are alternative ways to control pain. Acupuncture involves the insertion of tiny sterile needles, slightly thicker than a human hair, at specific points on the body.

Breathing Exercises. Some studies have suggested that breathing exercises or training may be helpful. A number of different methods are available. One example is the Buteyko breathing method, an experimental approach designed to increase levels of carbon dioxide in the body. To do this, patients are trained to reduce their volume of breath and to avoid hyperventilation (over-breathing). Some studies report that patients using this method reduce their use of medications and improve their quality of life. The system originated in Australia and is not yet widely available in the U.S.

Probiotics. Probiotics are beneficial bacteria that may possibly help protect against allergies and asthma. Antibiotic overuse and modern hygiene may specifically be reducing these helpful organisms. Look for probiotics in active yogurt cultures and in supplements, which are being studied for protection.

Herbal Remedies. Butterbur (also known as Petasites hybridus, butter dock, blatterdock, bog rhubarb, and exwort), is a traditional herbal remedy used for seasonal allergies and asthma. In a 2002 study, it was as effective and less sedating than a commonly prescribed antihistamine for treating seasonal allergies over a 2-week period. However, little research exists on its effect on asthma. Overall, there is scant evidence supporting the benefits of herbs and nutritional supplements for asthma control.

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.

Managing Asthma

The more allergies a child has, the more severe the asthma. Making lifestyle changes to reduce allergy attacks and other triggers is extremely important.

House dust is a reservoir for pollen and dust mites. Some experts believe that reducing household allergens and pollutants in the home could reduce asthma in children by 40%.

Controlling for Dust. Spray furniture polish is very effective for reducing both dust and allergens. Air cleaners, filters for air conditioners, and vacuum cleaners with High Efficiency Particular Air (HEPA) filters can help remove particles and small allergens found indoors. Neither vacuuming nor the use of anti-mite carpet shampoo, however, is effective in removing mites in house dust. Vacuuming actually stirs up both mites and cat allergens. If possible, avoid carpets and rugs.

Click the icon to see an image of a HEPA air filter.

Bedding and Curtains. Many experts recommend reducing exposure to dust mites by enclosing mattresses and pillows in semipermeable coverings. (Vinyl mattress covers limit airflow and may also worsen, or even cause, asthma in children. Synthetic pillows may pose a significantly higher risk for severe asthma attacks in children than feather or no pillows.) However, several 2005 studies suggested that such covers do not prevent asthma or allergies. Replace curtains with shades or blinds, and wash bedding using the highest temperature setting.

Click the icon to see an image of dust mite prevention.

One study found that children sleeping in bottom bunk beds are significantly more likely to develop asthma than siblings occupying the upper bunks. Families with children who have asthma or allergies should avoid bunk beds or be sure that children with asthma sleep in the top bunk. Even with standard beds, it may be useful to have them sleep as high off the floor as possible.

Exterminating Pests (Cockroaches and Mice). Use professional exterminators to eliminate cockroaches. (One study reported that ridding a home of cockroaches and cleaning the house using standard housecleaning techniques failed to eliminate the cockroach allergens themselves.) Exterminate mice, and attempt to remove all dust, which might contain mouse urine and dander.

Reducing Humidity in the House. Although warm, moist air from vaporizers can greatly ease and moderate asthma attacks, living in a damp house is counterproductive. Dust mites thrive in humidity and damp houses increase the risk for mold, so on-going humidifiers can be unhelpful. If they are used, humidity levels should not exceed 40%, and humidifier should be cleaned daily with a vinegar solution.

Controlling Pets. People with asthma who already have pets and are not allergic to them probably have a low risk for developing such allergies later on. When children are exposed to more than one dog or cat during their first year, they have a much lower risk for allergies and asthma.

For children who have an existing allergy to pets, however, the pets should be given away or kept outside. If this isn't possible, they should at least be confined to carpet-free areas outside the bedroom. Cats harbor significant allergens, which can even be carried on clothing; dogs usually present fewer problems. Washing animals once a week can reduce allergens. Dry shampoos, such as Allerpet, are now available for both cats and dogs to remove allergens from skin and fur and are easier to administer than wet shampoos.

Many of the same substances trigger both allergies and asthma. Common allergens include pollen, dust mites, mold and pet dander. Other asthma triggers include irritants like smoke, pollution, fumes, cleaning chemicals, and sprays. Asthma symptoms can be substantially reduced by avoiding exposure to known allergens and respiratory irritants.

Preventing Exposure to Cigarette and Cooking Smoke. Parents who smoke are strongly urged to quit. Studies indicate that exposure to second-hand smoke in the home increases the risk for asthma and asthma-related emergency room visits in children. Even smoky cooking can worsen asthma.

Parental smoking has been shown to increase the airway responsiveness of infants as early as the first 2 - 10 weeks of life. This extends even to the fetus of pregnant women who smoke. Such mothers tend to have babies born at a low birth weight, which affects lung function and increases babies' risks for asthma.

Avoiding Outdoor Allergens. The following are some recommendations for avoiding allergens outside:

Avoid scheduling camping and hiking trips during times of high pollen count (generally, May and June for grass pollen and mid-August to October for ragweed).
Patients should avoid strenuous activity when ozone levels are highest, which usually occur in early afternoon, particularly on hot hazy summer days. Levels are lowest in early morning and at dusk.
Asthma attacks are often higher during thunderstorms. Some evidence points to a build-up of ozone that accompanies such storms. Other evidence suggests that the changing airflow patterns bring a sudden downdraft of air containing concentrations of pollens, small particles and allergens.
Patients who are allergic to mold should avoid barns, hay, raking leaves, and mowing grass.
Exposure to automobile fumes may worsen asthma. Fungi in car air conditioners can also be a problem.

Reducing Exposure to Air Pollution. Children breathe faster than adults, taking in more pollutants, and therefore are particularly susceptible to soot and other small particles in the air. A 2001 study found an association between higher rates of asthma and other health problems in children who were exposed to high levels of specific pollutants (particularly sulfur dioxide and nitrogen dioxide). Diesel fuel exhaust has also been associated with worsening asthma in children.

Some experts point out that asthma rates in North America have increased over recent years while the prevalence of many common air pollutants have declined. So pollution is unlikely to be a primary cause of asthma. Regardless of whether pollution is an important cause of asthma, evidence strongly suggests that it can affect existing asthma.

Patients with asthma and chronic allergic rhinitis may require daily medications. Patients with severe seasonal allergies may be advised to start medications a few weeks before the pollen season, and to continue it until the season is over.

Immunotherapy ("allergy shots") may help reduce asthma symptoms, and the use of asthma medications, in patients with known allergies. They may also help prevent the development of asthma in children with allergies. Immunotherapy poses some risk for severe allergic reactions, especially for children with poorly controlled asthma, so it is important that the doctor carefully evaluates the child’s asthma condition.

[See In-Depth Report #77: Allergic rhinitis.]

Weight Loss. Children who are both asthmatic and overweight may reduce asthma symptoms simply with weight loss.

Fruits, Vegetables, and Whole Grains. Healthy foods are important for lung function. Specific foods that may be important for healthy lungs contain antioxidants (deep green and yellow-orange fruits and vegetables), selenium (fish, red meat, grains, eggs, chicken, liver, garlic), plant chemicals called flavonoids (apples, onions), and magnesium (green leafy vegetables, nuts, whole grains, milk, and meats).

Fish Oil. Omega-3 fatty acids, found in cold water oily fish and in supplements (preferably DHA-EPA, the important compounds in fish oil) have anti-inflammatory effects. Some evidence suggests they may be helpful for people with asthma.

Caffeine. Caffeine has properties that are similar to the asthma drug theophylline. A major analysis of studies reported that caffeine improved lung function for up to 4 hours after consumption. Although tea and coffee are the major sources of caffeine, some sodas contain it and should be avoided when children have an asthma attack. (People who are going to have their lung function tested should avoid drinking coffee, tea, or other caffeinated beverages for at least 4 hours beforehand.)

Food Allergies. Although about 70% of people with asthma believe their symptoms are aggravated by food allergies, studies indicate that this belief may be true in only 5% of cases. If young children show signs of or test positive for food allergies, however, parents should be extra cautious in preventing exposure to any asthma trigger. Some doctors now counsel all children with asthma to avoid nuts entirely, and, of course, children who experience reactions to any foods should avoid them.

Chemicals that may pose some risk for an allergic reaction are monosodium glutamate, or MSG (found in some canned soups, cheese, and certain vegetables), and sulfites (preservatives in foods, such as frozen potatoes and tuna). Contrary to what many believe, dairy products do not appear to worsen asthma symptoms in people who are not already allergic to them.

Asthma is no reason to avoid exercise. Historically, about 10% of Olympic athletes have asthma. Some studies indicate that long-term exercise may help control asthma and reduce hospitalization.

Encourage children with asthma to swim and play sports, such as baseball, that will present less difficulty for them. Intense activities lasting less than 2 minutes, such as sprinting or competitive swimming, may cause fewer problems than longer-lasting exercises.

Young people who enjoy running should probably choose an indoor track to avoid pollutants. Swimming is excellent for people with asthma. Yoga practice, which uses both stretching, breathing, and meditation techniques, may have particular benefits. One study reported that two-thirds of patients who practiced yoga regularly were able to reduce or stop taking their asthma medications.

Patients should consult their doctors before starting any exercise program. Exercise-induced asthma is a limited condition that has specific recommendations.

People with asthma should try to minimize their risk for respiratory tract infections. Washing hands is a very simple but effective preventive measure.

Patients with asthma should ask their doctor about getting the influenza ("flu") vaccine and also whether they should receive the vaccination against pneumococcal pneumonia.

Zanamivir, a new drug used for treating influenza, is considered safe for patients with asthma 12 years of age or older. In one study, patients with asthma treated with zanamivir experienced fewer flu symptoms, and their lung function improved.

People with asthma have no higher rate of anxiety or depression than the general population. However, such emotions interact with the effects of asthma and its treatments in important ways:

Negative emotions can discourage compliance with medication and the ability to cope.
Poor control of asthma symptoms, in turn, increases the risk for negative emotions.
Stress and depression have been associated with more severe symptoms and even an increased risk of fatal asthma attacks.

Some evidence suggests that stress reduction techniques, a positive attitude, and relaxation techniques may be very helpful in the long-term management of asthma.

Resources

www.lungusa.org -- The American Lung Association
www.acaai.org -- American College of Allergy, Asthma & Immunology
www.aaaai.org -- American Academy of Allergy, Asthma, and Immunology
www.nhlbi.nih.gov -- National Heart, Lung, and Blood Institute
www.asthma-carenet.org -- Childhood Asthma Research and Education Network
www.njc.org -- National Jewish Center for Immunology and Respiratory Medicine
www.aafa.org -- Asthma and Allergy Foundation of America
www.aanma.org -- Allergy and Asthma Network, Mothers of Asthmatics

References

Akinbami L; Centers for Disease Control and Prevention National Center forHealth Statistics. The state of childhood asthma, United States, 1980-2005. Adv Data. 2006 Dec 12;(381):1-24.

Bisgaard H, Hermansen MN, Loland L, Halkjaer LB, Buchvald F. Intermittent inhaled corticosteroids in infants with episodic wheezing. N Engl J Med. 2006 May 11;354(19):1998-2005.

Cates CJ, Crilly JA, Rowe BH. Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD000052.

Douwes J, van Strien R, Doekes G, Smit J, Kerkhof M, Gerritsen J, et al. Does early indoor microbial exposure reduce the risk of asthma? The Prevention and Incidence of Asthma and Mite Allergy birth cohort study. J Allergy Clin Immunol. 2006 May;117(5):1067-73.

Guilbert TW, Morgan WJ, Zeiger RS, Mauger DT, Boehmer SJ, Szefler SJ, et al. Long-term inhaled corticosteroids in preschool children at high risk for asthma. N Engl J Med. 2006 May 11;354(19):1985-97.

Haland G, Carlsen KC, Sandvik L, Devulapalli CS, Munthe-Kaas MC, Pettersen M, et al. Reduced lung function at birth and the risk of asthma at 10 years of age. N Engl J Med. 2006 Oct 19;355(16):1682-9.

Marks GB, Mihrshahi S, Kemp AS, Tovey ER, Webb K, Almqvist C, et al. Prevention of asthma during the first 5 years of life: a randomized controlled trial. J Allergy Clin Immunol. 2006 Jul;118(1):53-61.

National Asthma Education and Prevention Program Expert Panel Report: Guidelines for the Diagnosis and Management of Asthma Update on Selected Topics -- 2002. Rockville, MD. National Heart, Lung, and Blood Institute, US Dept of Health and Human Services; 2003. NIH publications 02-5074.

O'Byrne PM, Pedersen S, Busse WW, Tan WC, Chen YZ, Ohlsson SV, et al. Effects of early intervention with inhaled budesonide on lung function in newly diagnosed asthma. Chest. 2006 Jun;129(6):1478-85.

Salpeter SR, Buckley NS, Ormiston TM, Salpeter EE. Meta-analysis: effect of long-acting beta-agonists on severe asthma exacerbations and asthma-related deaths. Ann Intern Med. 2006 Jun 20;144(12):904-12.

Schuh S, Dick PT, Stephens D, Hartley M, Khaikin S, Rodrigues L, Coates AL. High-dose inhaled fluticasone does not replace oral prednisolone in children with mild to moderate acute asthma. Pediatrics. 2006 Aug;118(2):644-50.

Sorkness CA, Lemanske RF Jr, Mauger DT, Boehmer SJ, Chinchilli VM, Martinez FD, et al. Long-term comparison of 3 controller regimens for mild-moderate persistent childhood asthma: the Pediatric Asthma Controller Trial. J Allergy Clin Immunol. 2007 Jan;119(1):64-72.

Review Date:
3/26/2007
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).

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adam.com

K9 Time: Exercising With Your Pooch

FitSugar — Fri, 03 Apr 2009 08:00:00 -0700

I love running with my dog, Bonnie, because it's a way for us to both get some exercise and fresh air, and I know I appreciate the company. It makes me feel a little safer when running alone, and it also makes the time go by faster. Before you lace up your running shoes and leash up your dog too, consider these pet exercise tips.

It's not good for puppies' developing muscles and bones to run consistently for long periods of time. Wait until your dog is at least one year old or more. If she is older or overweight, running may be too hard on her joints, so stick to walking.
Consider your dog's breed. If she is a Pug or other dog with a short nose, walking might be better than running to limit breathing difficulties. If your dog is a large breed such as a Standard Poodle, running long distances may be hard on her joints, so opt for short runs.
Build up your dog's endurance gradually. Start off with short intervals of alternating between walking and running. Even though your dog may want to keep going, you don't want to overexert her too quickly and risk an injury.

To see the other tips, read more.

Don't get frustrated if your dog has a hard time staying next to you, pulls on the leash, or stops constantly to smell things. Practice makes perfect, so be patient. It may take some time for her to get used to being on a short leash and running beside you at your pace.
Asphalt and concrete can be too hot for furry feet, and rocks and gravel may cause cuts. Monitor your dog’s pads for cracking and wear.
Dogs overheat easily, so avoid exercising in hot weather. Make sure to carry water with you or exercise near water so your pup can hydrate and cool off.
Dogs like routines, so if you establish a regular exercise time, you’ll never have to self-motivate. Your dog will beg you to get up and get going.

Source

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 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.

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

Asthma in adults

FitSugar — Wed, 08 Oct 2008 17:35:00 -0700

In This Report

Highlights
Introduction
Symptoms
Causes
Prognosis
Risk Factors
Diagnosis
Treatment
Quick-Relief Medications...
Long-Term Relief Medication...
Other Treatments
Managing Asthma
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Warning

In 2007, the FDA requested the manufacturers of omalizumab (Xolair) to include a “boxed warning” emphasizing that this drug may cause a severe and life-threatening allergic reaction (anaphylaxis). Omalizumab is approved for patients who have moderate-to-severe asthma related to allergies and whose symptoms are not controlled by inhaled corticosteroids. It is given by injection in a doctor’s office every 2 - 4 weeks. The warning indicates that patients may develop anaphylaxis after any dose of omalizumab, even if they had no reaction to the initial shot. Health care providers need to observe patients carefully for 2 hours after they receive an omalizumab injection. However, because an allergic reaction can occur up to 24 hours after the injection, patients need to know the signs and symptoms of anaphylaxis and how to self-administer emergency treatment.

Anaphylaxis symptoms include:

Difficulty breathing
Chest tightness
Dizziness
Fainting
Itching and hives
Swelling of the mouth and throat

Drug Approval

In 2006, the FDA approved budesonide/formoterol (Symbicort). Symbicort combines a corticosteroid and a long-acting beta2-agonist into a single inhaler.

Long-Acting Beta2-Agonists

Long-acting beta2-agonist drugs, such as salmeterol (Serevent Diskus) and formoterol (Foradil Aerolizer), may worsen asthma symptom severity and increase the risk for asthma-related death, indicates a 2006 review in the Annals of Internal Medicine.
Products that contain salmeterol and formoterol now have strengthened warning labels detailing these risks.

Asthma and Heartburn

Studies have suggested an association between heartburn, also known as gastroesophageal reflux disease (GERD), and asthma that gets worse at night (nocturnal asthma). A 2006 study tested whether a proton pump inhibitor drug might help improve morning breathing in patients who suffer from these two conditions. The results suggested that the drug provided only a moderate benefit.

Introduction

Air passes into the lungs and flows through progressively smaller airways called bronchioles. The lungs contain millions of these airways.
All bronchioles lead to alveoli, which are microscopic sacs where oxygen and carbon dioxide are exchanged.

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.

Asthma is a chronic condition in which these airways undergo changes when stimulated by allergens or other environmental triggers. Such changes appear to be two specific responses:

The hyperreactive response (also called hyperresponsiveness)
The inflammatory response

These actions in the airway cause patients to cough, wheeze, and experience shortness of breath (dyspnea), the classic symptoms of asthma.

In the hyperreactive response, smooth muscles in the airways of the lungs constrict and narrow excessively in response to inhaled allergens or other irritants. Everyone's airways respond by constricting when exposed to allergens or irritants, but a special hyperreactive response occurs in people with asthma:

When people without asthma breathe in and out deeply, the airways relax and open to rid the lungs of the irritant.
When people with asthma try to take those same deep breaths, their airways do not relax and narrow, causing patients to pant for breath. Smooth muscles in the airways of people with asthma may have a defect, perhaps a deficiency in a critical chemical that prevents the muscles from relaxing.

The hyperreactive stage is followed by the inflammatory response, which generally contributes to asthma in the following way:

In response to allergens or other environmental triggers, the immune system delivers white blood cells and other immune factors to the airways.
These so-called inflammatory factors cause the airways to swell, to fill with fluid, and to produce a thick sticky mucus.
This combination of events results in wheezing, breathlessness, inability to exhale properly, and a phlegm-producing cough.

Click the icon to see an image of a normal bronchiole versus an asthmatic bronchiole.

Inflammation appears to be present in the lungs of all patients with asthma, even those with mild cases, and plays a key role in all forms of the disease.

Symptoms

Asthma symptoms vary in severity from occasional mild bouts of breathlessness to daily wheezing that persists despite taking large doses of medication. After exposure to asthma triggers, symptoms rarely develop abruptly but progress over a period of hours or days. Occasionally, the airways have become seriously obstructed by the time the patient calls the doctor.

The classic symptoms of an asthma attack include:

Wheezing when breathing out is nearly always present during an attack. Usually the attack begins with wheezing and rapid breathing, and, as it becomes more severe, all breathing muscles become visibly active.
Shortness of breath (dyspnea). Shortness of breath is a major source of distress in patients with asthma. However, the severity of this symptom does not always reflect the degree to which lung function is impaired. Some patients are not even aware that they are experiencing shortness of breath. Such patients are at particular risk for very serious and even life-threatening asthma attacks, since they are less conscious of symptoms. Those at highest risk for this effect tend to be older, female, and to have had the disease for a longer period of time.
Coughing. In some people, the first symptom of asthma is a nonproductive cough. Some patients find this cough even more distressing than wheezing or sleep disturbances.
Chest tightness or pain. Initial chest tightness without any other symptoms may be an early indicator of a serious attack.
Neck muscles may tighten, and talking may become difficult or impossible.
Rapid heart rate.
Sweating.
Chest pain occurs in about 75% of patients. It can be very severe, although the pain's intensity is not necessarily related to the severity of the asthma attack itself.

The end of an attack is often marked by a cough that produces thick, stringy mucus. After an initial acute attack, inflammation lasts for days to weeks, often without symptoms. (The inflammation itself must still be treated, however, because it usually causes relapse.)

Causes

Asthma has dramatically risen worldwide over the past decades, particularly in developed countries, and experts are puzzled over the cause of this increase. The mechanisms that cause asthma are complex and vary among population groups and even from individual to individual. Many asthma sufferers have allergies, and some researchers are targeting common factors in both these conditions. Not all people with allergies have asthma, however, and not all cases of asthma can be explained by allergic response.

Asthma is most likely to be caused by a convergence of factors that can include genes and various environmental and biologic triggers (infections, dietary patterns, hormonal changes in women, and allergens).

Nearly half of adults with asthma have an allergy-related condition, which, in most cases developed first in childhood. (In patients who first develop asthma during adulthood, the allergic response usually does not play a strong causal role.) Important irritants or allergens include:

Dust mites, specifically mite feces, which are coated with enzymes that contain a powerful allergen. These are the primary allergens in the home.
Animal dander.
Pollen. An asthma attack from an allergic response to pollen is more likely to occur during extreme air changes, such as thunderstorms. Major weather changes, such as El Nino, can affect the timing of allergy seasons. For example, in 1998, when the effects of El Nino were very strong, allergy and asthma attacks occurred earlier and were markedly increased.
Molds. A 2002 study suggested that molds might produce a worse asthma attack in adults than other allergens.
Fungi.
Cockroaches. Cockroaches are major asthma triggers and may reduce lung function even in people without a history of asthma.
Fossil Fuels. Certain chemicals may trigger allergic rhinitis. Some experts believe that refined fossil fuels, such as diesel fuel and particularly kerosene, may be important triggers for allergic rhinitis. And, in people who already have allergies or asthma, exposure to such fossil fuels may worsen symptoms.

The Allergic Process. The allergic process, called atopy, and its connection to asthma is not completely understood. It involves various airborne allergens or other triggers that set off a cascade of events in the immune system leading to inflammation and hyperreactivity in the airways. One description is as follows:

The conductor in an orchestra of immune factors that contribute to allergies and asthma appears to be a category of white blood cells known as helper T cells, in particular a subgroup called Th2 cells.
Th2 cells overproduce interleukins (ILs), immune factors that are molecular members of a family called cytokines, which are involved in the inflammatory process.
Interleukins 4, 9, and 13 may be responsible for a first-phase asthma attack. These interleukins stimulate the production and release of antibody groups known as immunoglobulin E (IgE). (People with both asthma and allergies appear to have a genetic predisposition for overproducing IgE.)
During an allergic attack, these IgE antibodies can bind to special cells in the immune system called mast cells, which are generally concentrated in the lungs, skin, and mucous membranes. This bond triggers the release of several active chemicals, importantly potent molecules known as leukotrienes. These chemicals cause airway spasms, overproduce mucus, and activate nerve endings in the airway lining.
Another cytokine, interleukin 5, appears to contribute to a late-phase inflammatory response. This interleukin attracts white blood cells known as eosinophils. These cells accumulate and remain in the airways after the first attack. They persist for weeks and mediate the release of other damaging particles that remain in the airways.

The Immune Response. Researchers are investigating the role that T cells play in asthma. T cells are white blood cells that are involved in the immune response. Researchers had focused on the T cell called type 2 helper (Th2) cells. However, a 2006 breakthrough study in the New England Journal of Medicine suggested that a different type of T cell may play a stronger role in asthma than previously thought.

Growth Factors. Compounds known as vascular endothelial growth factor (VEGF) have been observed in the airways of patients with asthma. VEGF is a powerful promoter of cell growth in blood vessel linings, and some researchers believe it may be major factor in remodeling.

About one-third of all persons with asthma share this condition with another member of their immediate family. Asthma may be more likely to pass to children from their mother than from their father. Both allergies and asthma are strongly associated with hereditary factors, sharing certain genetic markers, but they are not always inherited together.

Hormones or changes in hormone levels appear to play a role in the severity of asthma in women.

Menstrual-Related Asthma. Between 30 - 40% of women with asthma experience fluctuations in severity that are associated with their menstrual cycle. One study indicated that women with menstrually associated asthma tend to have the following characteristics:

Older age
Had asthma for a long time
Had severe asthma attacks that were likely to occur 3 days before and 4 days into the menstrual period

Oral contraceptives (OCs) theoretically should help asthma sufferers by leveling out hormonal changes, but they do not appear to have much effect. (There have been a few reports of asthma exacerbation with OCs, but these are uncommon events.)

Asthma during Pregnancy. During pregnancy, one-third of women with asthma suffer more from the condition, one-third suffer less, and one-third experience no difference in severity. Some studies suggest that expectant mothers carrying a female baby tend to have more severe asthma symptoms than do those who are bearing a male.

Menopause and Asthma. Around the time of menopause (called perimenopause) when estrogen declines, the risk for hospitalization in women with asthma increases fourfold compared to previous years. Studies have not demonstrated that hormone replacement therapy (HRT), which contains estrogen, has much benefit.

About 10% of adults and some fewer children have aspirin-induced asthma (AIA). With this condition, asthma gets worse when patients take aspirin. Aspirin is one of the drugs known as nonsteroidal anti-inflammatory drugs (NSAIDs). Although aspirin is used to reduce inflammation in other disorders, it appears to have the opposite effect in many asthma cases. It is not wholly known why this occurs. AIA often develops after a viral infection. It is a particularly severe asthmatic condition, associated with up to 25% of asthma-related hospitalizations. In about 5% of cases, aspirin is responsible for a syndrome that involves multiple attacks of asthma, sinusitis, and nasal congestion. Such patients also often have polyps (small benign growths) in the nasal passages.

Patients with aspirin-induced asthma (AIA) should avoid aspirin and most likely other NSAIDs, including ibuprofen (Advil) and naproxen (Aleve).

Exercise-induced asthma (EIA) is a limited form of asthma in which exercise triggers coughing, wheezing, or shortness of breath.

Asthma occurs primarily at night (nocturnal asthma) in as many as 75% of patients with asthma. Attacks often occur between 2 and 4 a.m. Factors that might play role in nocturnal asthma may include one or more of the following:

Chemical and temperature changes in the body during the night that increase inflammation and narrowing of the airways
Delayed allergic responses from exposure to allergens during the day
The wearing off of inhaled medications toward the early morning
An increase in acid reflux (back up of stomach acid) that causes airways to narrow
Postnasal drip that occurs during sleep
Conditions relating to sleep, such as sleep apnea or sleeping on one's back, which may worsen any asthma attack that occurs at night

Some experts believe that nocturnal asthma may actually be a unique form, with its own specific biologic mechanisms that occur only at night and which reduce natural steroid hormones (which block inflammation).

Infections. The role of infections in asthma is complicated. Respiratory infections may play a role in some cases of adult-onset asthma, but may be protective against asthma in small children. (In both children and adults with existing allergic asthma, however, an upper respiratory tract infection often worsens an attack.)

Researchers are particularly interested in the organisms Chlamydiapneumoniae and Mycoplasmapneumoniae adenovirus. They are major causes of both mild and serious respiratory infections and are becoming important suspects in many cases of severe adult asthma. (If such respiratory infections occur in young children, they are unlikely to affect adult-onset asthma.)

In one study, patients whose asthma occurred after infections had more severe conditions than those whose asthma was due to other causes. The infection-initiated asthma, however, lasted only 5.6 years compared to 13.3 years in the non-infection group.

In any age group, respiratory infections worsen existing asthma in people who have it already. Rhinovirus (the common cold virus) has been reported to be the most common infection associated with asthma attacks. In one study, it was associated with 61% of asthma exacerbations in children and 44% in adults. Some research suggests that colds promote allergic inflammation and increase the intensity of airway responsiveness for weeks.

GERD. At least half of patients with asthma have gastroesophageal reflux disease (GERD), the cause of heartburn. It is not entirely clear which condition causes the other or whether they are both due to common factors.

Heartburn is a condition where the acidic stomach contents back up into the esophagus causing pain in the chest area. This reflux usually occurs because the sphincter muscle between the esophagus and stomach is weakened. Standing or sitting after a meal can help reduce the reflux that causes heartburn. Continuous irritation of the esophagus lining as in gastroesophageal reflux disease is a risk factor for the development of adenocarcinoma.

Some theories for the causal connection between GERD and asthma are:

Acid leaking from the lower esophagus in GERD stimulates the vagus nerve, which runs through the gastrointestinal tract. This stimulated nerve triggers the nearby airways in the lung to constrict, causing asthma symptoms.
Acid backup that reaches the mouth may be inhaled into the airways (aspirated). Here, the acid triggers a reaction in the airways that cause asthma symptoms.

GERD is sometimes hard to detect and might be a contributor in the following patients:

Those who do not respond to asthma treatments
Those whose asthma attacks follow episodes of heartburn
Those whose attacks worsen after eating or exercise
Those whose coughs follow episodes of acid reflux. (One study found that GERD was associated with about half of the episodes of coughs and wheezes in patients with asthma.)

Treating GERD symptoms with anti-acid drugs may resolve asthma in some (but not all) patients who share both conditions. A small 2005 study found that while GERD was common in patients with asthma, treatment of GERD had no effect on asthma symptoms. A 2006 study indicated that the proton pump inhibitor esomeprazole (Nexium) slightly helped patients who had both GERD and asthma symptoms that occurred at night. [See In-Depth Report #85: Heartburn and gastroesophageal reflux disease.]

Click the icon to see an image of sinusitis.

EIA is triggered only by exercise and is distinct from ordinary allergic asthma in that it does not produce a long duration of airway activity, as allergic asthma does. (It should be noted that some people have both forms of asthma.) People who have only EIA do not appear to require long-term maintenance therapy. A study of military recruits with EIA also reported that the condition does not hinder a person's overall physical performance.

Medications

Cromolyn, a mild anti-inflammatory drug, or short-acting beta2-agonists have been the treatments of choice for preventing EIA. Newer approaches for people who work out regularly include pretreatment with long-acting beta2-agonists, such as salmeterol (Serevent), or the regular use of inhaled corticosteroids.

Hints for Reducing EIA

EIA occurs only after exercise and is more likely to occur with regularly paced activities in cold, dry air. The following are some suggestions for reducing its impact:

Warm-up and cool-down periods are important.
Patients with EIA might do better with activities that involve short bursts of exercise (tennis, football) than with exercises involving long-duration regular pacing (cycling, soccer, and distance running).
Breathing through a scarf or through the nose helps warm up the airways.
Some evidence suggests that restricting dietary salt might help reduce EIA.

Click the icon to see an image of exercise-induced asthma.

Prognosis

About 450,000 American adults are admitted to an emergency room with asthma each year. The number of deaths from asthma increased from about 2,900 in 1908 to a high of 5,667 in 1996. The numbers appear to be declining slightly, and in 2002 about 4,260 people died because of asthma. Death from asthma is still a very uncommon event, considering that an estimated 20 million people in the U.S. have this condition. Most deaths from asthma, even when they occur in elderly adults, are preventable. It is very rare for a person who is receiving proper treatment to die of asthma. And, studies suggest that the use of inhaled corticosteroids can reduce the risk for death by 90%. In spite of this and similar research, these important drugs are greatly underused.

About 55% of U.S. deaths from asthma occur among the elderly (over age 65), and an estimated 25% occur in adults aged 45 - 64. Women have a higher risk for fatal asthma than men. Being poor is also a significant risk factor for severe asthma. Hispanics and African Americans are at higher risk for death from asthma than Caucasians. Other specific risk factors for fatal asthma include:

Previous history of respiratory failure
Frequent visits to the emergency room
Lack of continuous care and poor compliance with medications
Having stopped treatment, particularly withdrawal from corticosteroids
Having an emotional or psychiatric disorder. (Some evidence suggests that depression, anxiety, and stressful life situations can worsen asthma.)
Being a drug abuser
Being in a lower socioeconomic and educational group

The following signs and symptoms may indicate a life-threatening situation:

As the chest labors to bring enough air into the lungs, breathing often becomes shallow.
Lacking sufficient oxygen, the skin becomes bluish.
The flesh around the ribs of the chest appears to be sucked in.
The patient may begin to lose consciousness.

It should strongly be noted that early symptoms or lack thereof do not always reflect the ultimate severity of an attack. In fact, some studies suggest that people at high risk for fatal or near-fatal asthma attacks are those with poor awareness of their own reduced ability to breathe and who are therefore slow in seeking help. Those at highest risk for this effect tend to be older, female, and have had the disease for a longer period of time. Monitoring peak flow rates is an important management component since it provides a more accurate assessment of lung function than symptoms alone.

The severity of asthma is graded using the following categories: mild intermittent and mild, moderate, and severe persistent. A patient in any of these categories, even mild intermittent, can still experience a severe and even life-threatening attack. In fact, according to one report, 30% of asthma deaths occur in patients with mild asthma.

Asthma is usually chronic, although it occasionally goes into long periods of remission. Long-term outlook generally depends on severity:

In mild-to-moderate cases, asthma can improve over time, and many adults even become symptom free.
Even in some severe cases, adults may experience improvement depending on the degree of obstruction in the lungs and the timeliness and effectiveness of treatment.
In about 10% of severe persistent cases, changes in the structure of the walls of the airways lead to progressive and irreversible problems in lung function, even in aggressively treated patients.

Lung function declines faster than average in people with asthma, particularly in those who smoke and in those with excessive mucus production (an indicator of poor treatment control). Overall, one study reported that 72% of men and 86% of women with asthma had symptoms 15 years after an initial diagnosis. Only 19% of these people, however, were still seeing a doctor, and only 32% used any maintenance medication.

Patients who develop occupational asthma often experience asthmatic symptoms for years, even after avoiding the harmful triggers. Improvement does occur over time in most people who leave such jobs.

Emotional Problems. Even when it is not life-threatening, asthma is debilitating and frightening. It significantly lowers the quality of life.

Sleep Disorders. Sleeplessness and daytime sleepiness are common problems. Studies indicate that between 80 - 93% of people with asthma have sleeping problems about three times a week. In one poll, 40% missed work an average of 11 days a year because of sleep disturbance. Asthma has been associated with snoring and obstructive sleep apnea, a condition in which blockage of the upper airway causes the sleeper to temporarily stop breathing, then resume with a gasp, often many times during each hour of sleep.

Asthma and Pregnancy. Uncontrolled asthma in pregnant women puts them at higher risk for complications that can include early labor, hypertension, gestational diabetes, and hemorrhage. Asthma also places the babies at risk for lower birth weight and breathing disorders. Teenage mothers with asthma face higher risks than older women. Fortunately, studies indicate that most asthma drugs are safe to take during pregnancy, and good control of asthma reduces these risks to normal levels.

New guidelines released in 2005 by the National Asthma Education and Prevention Program (NAEPP) emphasize that most asthma medications are safe for pregnant women. The guidelines recommend that pregnant women with asthma have albuterol available at all times. Inhaled corticosteroids should be used for persistent asthma. Patients whose persistent asthma does not respond to standard dosages of inhaled corticosteroids may require a higher dosage or the addition of a long-acting beta agonist to their drug regimen. For severe asthma, oral corticosteroids may be required. The NAEPP notes that while it is not clear if oral corticosteroids are safe for pregnant women, uncontrolled asthma poses an even greater risk for a woman and her fetus.

Heart Disease. There have been some reports of an association between asthma and a heightened risk for heart disease. Some experts believe that the inflammatory process may be the common factor linking the two conditions, although there is no evidence to date confirming any causal association.

Risk Factors

According to a major national 2001 survey, American adults have a 10% lifetime risk for developing asthma. As of 2002, an estimated 20 million adults had the disorder. Between 1980 - 1996 the prevalence of asthma increased by nearly 74%, but it may be stabilizing. Other respiratory diseases, sinusitis, and ear infections are also on the rise, suggesting that airborne or environmental factors may be at work that affects all of these conditions, including asthma.

Before puberty, asthma occurs more often in males, but after adolescence, it appears to be more common in females. In adults with similar cases of actual airway obstruction, women are likely to report more severe symptoms than men are. In addition, women may be at much greater risk of death from asthma than men.

In both adults and children, the incidence of obesity and asthma has been increasing in parallel over recent years. Studies report a strong association between the two conditions. Some experts suggest that excess weight pressing on the lungs may trigger the hyperreactive response in the airways typical of asthma. Others believe that asthma leads to obesity by inhibiting physical activity, although several studies have found no difference in activity levels between people with or without asthma. Some studies suggest that many obese people may be misdiagnosed as having asthma when in fact they are simply short of breath, possibly because of the increased effort required for breathing.

In one study of elderly people with severe adult-onset asthma, smoking was the most significant risk factor for developing this condition. Smoking, in any case, contributes to decline in lung function in everyone.

Urban Life and Poverty. African Americans have higher rates of asthma than Caucasians or other ethnic groups. They are also more likely to die of the disease. Ethnicity and genetics, however, are less likely to play a role in these differences than socioeconomic differences, such as having less access to optimal health care. Poverty is a consistent risk factor in most studies. Both the elderly and the urban poor have the highest risk for severe asthma and death. Urban life, in fact, has been associated with a higher risk for asthma in all income groups and among both children and adults. Twin studies also suggest that people who have lower educational levels (as well as those who exercise less) are at higher risk for adult-onset asthma, further suggesting a link to lower economic status.

Geographical Differences. Asthma rates vary widely among different populations regardless of socioeconomic or other factors. For example, asthma and hospitalization rates are dramatically higher in New York Puerto Ricans than in Hispanic Americans who live in Los Angeles or the Southwest. Among the U.S. states, rates are lowest in Louisiana and highest in Maine.

There are significant differences among nations. In a 2001 study of 22 nations, the countries with the highest asthma rates were Britain, Ireland, Australia, New Zealand, and the U.S. (According to another study, asthma rates are also significantly higher in Canadian adults than they are in comparable European groups.) Low rates were reported in Iceland, Norway, Spain, Germany, Italy, Algeria, India, and Eastern European nations. The reasons for these variations are still unknown.

Diagnosis

When asthma is suspected, the patient should describe for the doctor any pattern related to the symptoms and possible precipitating factors, including:

Whether symptoms are more frequent during the spring or fall (allergy seasons).
Whether exercise, a respiratory infection, or exposure to cold air has ever triggered an attack.
Any family history of asthma or allergic disorders, such as eczema, hives, or hay fever.
Any occupational or long-term exposure to chemicals. Early detection of occupational asthma is very important. If symptoms improve on weekends and vacation and are worse at work, the job is likely to be the source of the asthma, although this is not always the case. Asthma is common, and exacerbation at work may be coincidental.

A number of disorders may cause some or all of the symptoms of asthma:

Asthma and chronic obstructive lung diseases (chronic bronchitis and emphysema) affect the lungs in similar ways and, in fact, may all be present in the same person. Unlike other chronic lung conditions, asthma usually first appears in patients younger than age 30 and with chest x-rays that are normal. Still, it may be difficult to distinguish these disorders in some adults with late onset asthma.
Panic disorder can coincide with asthma or be confused with it.
Gastroesophageal reflux disorder (GERD) is a common companion in asthma and may affect treatment.
Other diseases that must be considered during diagnosis are pneumonia, bronchitis, severe allergic reactions, pulmonary embolism, cancer, heart failure, tumors, psychosomatic illnesses, and certain rare disorders (such as tapeworm and trichomoniasis).

If symptoms and a patient's history suggest asthma, the doctor will usually perform tests known as pulmonary function tests to confirm the diagnosis and determine the severity of the disease.

Using a spirometer, an instrument that measures the air taken into and exhaled from the lungs, the doctor will determine several values:

1. Vital capacity (VC), which is the maximum volume of air that can be inhaled or exhaled.

2. Peak expiratory flow rate (PEFR), commonly called the peak flow rate, which is the maximum flow rate that can be generated during a forced exhalation.

3. Forced expiratory volume (FEV1), which is the maximum volume of air expired in one second.

Spirometry is a painless study of air volume and flow rate within the lungs. Spirometry is frequently used to evaluate lung function in people with obstructive or restrictive lung diseases such as asthma or cystic fibrosis.

If the airways are obstructed, these measurements will fall. Depending on the results, the doctor will take the following steps:

If measurements fall, the doctor typically asks the patient to inhale a bronchodilator. This drug is used in asthma to open the air passages. The measurements are taken again. If the measurements are more normal, the drug likely has cleared the airways and a diagnosis of asthma is strongly suspected.
If measurement results fail to show airway obstruction, but asthma is still suspected, the doctor may perform a challenge test. This involves administering a specific drug (histamine or methacholine) that usually increases airway resistance only when asthma is present. The challenge test may be quite useful in ruling out occupational asthma. It is not always accurate, particularly in patients whose only symptom is persistent coughing.
Administering cold air is another method for inducing airway resistance. This test is very accurate for ruling out asthma, but it is not sensitive enough to accurately identify adults who actually have asthma.

The patient may be given skin or blood allergy tests, particularly if a specific allergen is suspected and available for testing. Allergy skin tests may be the best predictive tests for allergic asthma, although they are not recommended for people with year-round asthma.

Click the icon to see an image of allergy testing.

Tests that either rule out other diseases or obtain more information about the causes of asthma include:

A complete blood count.
Chest and sinus x-rays.
Computed tomography (CT) scans. CT scans may be helpful in certain cases, such as for determining wall thickness in airways in patients who are difficult to treat, which could signify a higher risk for lung damage.
Examination of the patient's sputum for eosinophils (white blood cells that in high levels are associated with severe allergic asthma). One 2002 study suggested that treatment goals based on achieving a normal eosinophil count might effectively manage asthma.
Researchers are investigating measurements of certain chemicals in sputum or exhaled air that indicate airway inflammation. Such chemical markers include nitric oxide and hydrogen peroxide. For example, high levels of nitric oxide in exhaled air is proving to be a simple and noninvasive way of diagnosing asthma.
If aspirin-induced asthma (AIA) is suspected, a non-invasive test called acoustic rhinometry may be useful. A solution of lysine acetylsalicylic acid (L-ASA) is instilled into the patient's nostril. Patients who experience symptoms such as sneezing, itching, congestion, and secretion are likely to have AIA.

Treatment

Beta2-agonists are the standard therapy. They may be administered with a nebulizer (a device that administers the drug in a fine spray) or given hourly with an inhaler. Studies are suggesting the use of an inhaler is equally or possibly more effective than a nebulizer. Intravenous delivery is not recommended in most cases.
A corticosteroid (commonly called a steroid) given within the first hour helps reduce the need for hospitalization. Steroids are typically administered intravenously or as an injection in adults. Lower doses work as well as higher ones in these situations.
Intravenous magnesium opens airways and is an important emergency treatment for patients with very severe asthma.
Oxygen is usually administered, and can be life-saving in severe cases.
In life-threatening situations, the patient may require mechanical ventilation.
Antibiotics are not useful for asthma attacks if there is no strong evidence of the presence of a bacterial infection. (Viral infections, most often colds and the flu, are more likely to trigger an asthma attack. In such cases, antibiotics do not appear to be beneficial and may have adverse effects.)

Discharge and Relapse After Hospitalization. It typically takes 3 - 4 hours to determine if a patient can be safely sent home or if they need to stay in the hospital. Patients are generally discharged under the following circumstances:

When symptoms are gone or are minimal, and
The peak expiratory flow rate is 70% or more of the predicted rate

Discharged patients generally take oral corticosteroids for 5 - 7 days. Despite reasonable precautions, about 20% of patients relapse within 2 weeks, although the risk is very low if they keep taking their medication after they leave.

Avoiding allergens, following appropriate drug treatments, and home monitoring are key elements in preventing dangerous asthma attacks and hospitalization. A combination of medications is important for both treating and preventing asthma attacks. In addition, good communication between the doctor and patient is a key factor in a successful management program. Written action plans, which instruct individual patients how to properly respond to changes in their unique symptoms, are a very important element in successful self-management of asthma.

Medications for asthma fall into two categories:

Rescue Medication. Medications that open the airways (bronchodilators, or inhalers) are used to quickly relieve any moderate or severe asthma attack. These drugs are usually short-acting beta-adrenergic agonists (beta2-agonists). Other drugs used in special cases include corticosteroids taken by mouth and anticholinergic drugs. None of these drugs have any effect on the disease process itself. They are only useful for treating symptoms.
Maintenance Medication. Simply coping with asthma symptoms without also controlling the damaging inflammatory response is a common and serious error. For adults and children over age 5 with moderate-to-severe persistent asthma, experts now recommend inhaled corticosteroids and long-acting beta2-agonists.

Patients can greatly reduce the frequency and severity of asthma attacks by understanding the difference between coping with asthma attacks and controlling the disease over time. Unfortunately, many patients do not understand the difference between medications that provide rapid short-term relief and those that are used for long-term symptom control. Many patients with moderate or severe asthma overuse their short-term medications and underuse their corticosteroid medications. The overuse of bronchodilators can have serious consequences; not using steroids can lead to permanent lung damage.

Patients need to understand that asthma symptoms can change quickly over time and that treatment strategies may need to change. In 2005, the two leading U.S. allergy associations published joint guidelines on controlling asthma. The guidelines emphasize that asthma treatment decisions need to be made on an individual basis. It is important that patients have a close relationship with their doctor. The doctor needs to evaluate a patient’s asthma symptoms at each and every visit to determine if there should be any changes in medication.

According to the guidelines, asthma management is classified as either “well-controlled” or “not well-controlled.” Your doctor may need to change some of your medications, or increase or decrease the dosage, depending on whether your asthma is well-controlled or not well-controlled.

These are the signs of well-controlled asthma:

Asthma symptoms occur twice a week or less
Rescue bronchodilator medication is used twice a week or less
Symptoms do not cause nighttime or early morning awakening
Symptoms do not limit work, school, or exercise activities
Peak flow meter readings are normal or the patient’s personal best
Both the doctor and the patient consider the asthma to be well controlled

Most asthma drugs are inhaled using various forms of inhalers or nebulizers. Inhaled drugs must be used regularly as prescribed and the patient carefully trained in their use in order for them to be effective and safe. The basic devices are the metered-dose inhaler (MDI), breath-actuated inhalers, dry powder inhalers, and nebulizers.

MDIs have used chlorofluorocarbons (CFCs) as their propellants. CFCs are damaging to the environment. CFCs are now being replaced with other propellants (such as hydrofluoroalkane) that are equally effective to CFCs, are environmentally safe, and do not chill the device as CFCs do. Devices that don't use propellants at all are also now available.

Metered-Dose Inhaler. The standard device for administering any asthma medication has been the metered-dose inhaler (MDI). This device, particularly when used with a holding chamber, allows precise doses to be delivered directly to the lungs.

Click the icon to see an image of a holding chamber.

MDI-delivered drugs must be used regularly as prescribed, and the patient carefully trained in their use, for the drugs to be effective and safe. Some patients hold the MDI too close to their mouths, or even inside them. Others may exhale too forcefully before inhalation. The holding chamber, or spacer, allows the patient additional time to inhale the medication, improving delivery. They vary, however, in their ability to deliver medication. Often MDIs continue to deliver propellant after the drug has been used up. Patients should track their medicine and throw the device away when the last dose has been administered.

Click the icon to see an illustrated series detailing metered dose inhaler use.

Dry Powder Inhalers. Dry powder inhalers (DPIs) deliver a powdered form of beta2 agonists or corticosteroids directly into the lungs. They also do not use CFCs. Such devices include Rotahaler, Spinhaler, Turbohaler, Clickhaler, Easyhaler, Diskhaler, Discus, Twisthaler, Spiros, and others. DPIs are as effective as the older devices, and generally have a better taste and are easier to manage. They may differ among themselves, however, in their ability to deliver drugs into the airways. In one study, for example, the Turbohaler was easier to use than the Diskhaler, achieving better delivery. The Discus is another effective DPI. It has a dose counter and protects against exhalation effects.

Humidity or extreme temperatures can affect these inhalers' performance, so they should not be stored in humid places (bathroom cabinets) or locations subject to high temperatures (glove compartments during summer months).

Dry-powder may cause tooth erosion, and children are advised to rinse their mouths out right after using a DPI and to brush twice a day with a fluoride toothpaste.

Other Hand-Held Inhalers. Respimat delivers a fine-mist spray that is created by forcing the liquid medication through nozzles. It does not use any propellant.

Nebulizers. A nebulizer is a device that administers the drug in a fine spray that the patient breathes in. They are mostly used in hospital settings or when the patient cannot use an inhaler. Nebulizers may be important for delivering newer drugs used in asthma treatment.

Click the icon to see an illustrated series detailing nebulizer use.

People who self-manage their asthma using daily monitoring of peak air flow and adjusting their medications as needed have fewer hospitalizations, fewer unplanned doctors visits, and, generally, a better quality of life than those who rely only on the occasional doctor or emergency room visit to control symptoms. Doctors recommend that patients with even mild asthma monitor their own conditions.

In general, monitoring involves the following steps:

A peak flow meter is the standard monitoring device for measuring peak expiratory flow rate (PEFR).

Click the icon to see an image of a peak flow meter.

Patients with severe asthma should take PEFR readings two or three times a day. The overall goal should be to achieve less than a 20% (and ideally only 10%) variation in readings between evening and morning rates. For mild-to-moderate asthma, a single determination each morning usually suffices, but patients should check with their doctors.
It is important to use the meter at the same times each day and to stand or sit in the same position to keep an accurate record.
Patients should keep an ongoing record of their peak flow readings to help them detect worsening of their condition.
They should also record attacks, exposure to any allergens or triggers, and medications taken.
After about 2 months, patients and doctors can use the recorded data for administering medications effectively and to recognize problems before they become serious.

In general, many people fail to monitor their asthma. Experts believe that, ideally, portable monitors should be available to measure forced expiratory volume (FEV1), a more accurate gauge of lung function, and the results should be electronically transmitted to the doctor.

New monitoring devices are showing promise in accomplishing one or more of these goals, although they are not covered by most insurers. For example, the AirWatch is a handheld digital monitor that measures and displays the rate of airflow and compares it to the rates from previous days. Once a month, or whenever there is a problem, the patient plugs the device into a standard telephone jack, and the daily readings are sent to an automated data center that creates tables and charts for the patient and the doctor.


Medication Purpose	Drug Class	Generic Name	Brand Names	Administration
Quick-Relief Medications (control acute attacks)	Short-Acting Beta2 Agonists	Albuterol	Proventil, Ventolin, AccuNeb	Inhaler, nebulizer
		Levalbuterol	Xopenex	Nebulizer
		Metaproterenol	Alupent	Inhaler
		Pirbuterol	MaxAir	Inhaler
		Ipratropium / Albuterol	Combivent	Inhaler
	Anticholinergics	Ipratropium	Atrovent	Inhaler
		Tiotropium	Spiriva	Inhaler
	Systemic Corticosteroids	Cortisone	Cortone	Pill
		Dexamethasone	Decadron	Pill
		Hydrocortisone	Cortef	Pill
		Methylprednisolone	Medrol	Pill
		Prednisolone	Orapred, Prelone	Syrup
		Prednisone	Various	Pill
		Triamcinolone	Aristocort	Pill
Long-Term Relief Medications (prevent attacks and control chronic symptoms)	Inhaled Corticosteroids	Beclomethasone	QVAR	Inhaler
		Budesonide	Pulmicort	Inhaler, nebulizer
		Budesonide / Formoterol	Symbicort	Inhaler
		Flunisolide	AeroBid	Inhaler
		Fluticasone	Flovent	Inhaler
		Fluticasone / Salmeterol	Advair	Inhaler
		Mometasone	Asmanex	Inhaler
		Triamcinolone	Azmacort	Inhaler
	Long-Acting Beta2-Agonists	Formoterol	Foradil	Inhaler
		Salmeterol	Serevent	Inhaler
	Anti-inflammatories	Cromolyn	Intal	Nebulizer
		Nedocromil	Tilade	Inhaler
	IgE-inhibitor	Omalizumab	Xolair	Injectable
	Leukotriene Modifiers	Montelukast	Singulair	Pill
		Zafirlukast	Accolate	Pill
		Zileuton	Zyflo	Pill
	Methylxanthine	Theophylline	Uniphyl, Quibron, Theo-24	Pill, syrup

Quick-Relief Medications

These medications quickly control acute asthma attacks.

Beta2-agonists do not reduce inflammation or airway responsiveness but serve as bronchodilators, relaxing and opening constricted airways during an acute asthma attack. They are used alone only for patients with mild and intermittent asthma. Patients with more severe cases should use them in combination with other drugs.

Specific short-acting beta2-agonists include:

Albuterol (Proventil, Ventolin), called salbutamol outside the U.S., is the standard short-acting beta2-agonist in America. Other similar beta2-agonists are isoproterenol (Isuprel, Norisodrine, Medihaler-Iso), metaproterenol (Alupent, Metaprel), pirbuterol (Maxair), terbutaline (Brethine, Brethaire, Bricanyl), and bitolterol (Tornalate). Isoetharine (Bronkometer, Bronkosol) is available in nebulizers.
Newer beta2-agonists, including levalbuterol (Xopenex), have more specific actions than the standard drugs. Studies have indicated that levalbuterol is as effective as albuterol with fewer side effects. The original formulation of Xopenex was administered with a nebulizer. A new metered-dose inhaler formulation became available in late 2005.

Short-acting bronchodilators are generally administered through inhalation and are effective for 3 - 6 hours. They relieve the symptoms of acute attacks, but they do not control the underlying inflammation. If asthma continues to worsen with the use of these drugs, patients should discuss corticosteroids or other drugs to treat underlying inflammation.

Side Effects of Beta2-Agonists. Side effects of all beta2-agonists include the following:

Anxiety
Tremor
Restlessness
Headache
Fast and irregular heartbeats. A doctor should be notified immediately if this side effect occurs, particularly in people with existing heart conditions. Such patients face an increased risk for sudden death from cardiac related causes. This risk is higher with oral or nebulized drugs, but there have also been reports of heart attacks and angina in some patients using inhaled beta2-agonists.

Beta2-agonists have serious interactions with certain other drugs, such as beta-blockers, and patients should tell the doctor about any other medications they are taking. Individuals with diabetes, existing heart disease, high blood pressure, hyperthyroidism, an enlarged prostate, or a history of seizures should take these drugs with caution.

Loss of Effectiveness and Overdose. There has been some concern that short-acting beta2-agonists become less effective when taken regularly over time, increasing the risk for overuse. Over time some patients may become tolerant to many effects of short-acting beta2-agonists. The degree to which this affects the airways is uncertain. In some studies, the duration of action has declined but the peak effect appears to be preserved, making these drugs still useful for acute attacks. Regular use of long-acting beta 2-agonists may reduce the effect of short-acting forms.

Patients who perceive beta2-agonists as being less effective may overuse them. Overdose can be serious and in rare cases even life-threatening, particularly in patients with heart disease.

Inhaled ipratropium bromide (Atrovent) acts as a bronchodilator over time. Ipratropium bromide alone is only modestly beneficial for acute asthma attacks. Moreover, the drug is not approved specifically for asthma. It may, however, have benefits in certain cases:

It may be useful for certain older patients with asthma who also have emphysema or chronic bronchitis.
A combination with a beta2-agonist might be helpful for patients who do not initially respond to treatment with a beta2-agonist alone.

Common oral corticosteroids include prednisone, prednisolone, methylprednisolone, and hydrocortisone. They very effectively reduce inflammation but are generally used only after hospitalization for an acute attack. In some severe cases, they may be used as maintenance.

Adverse effects of prolonged use of oral steroids include cataracts, glaucoma, osteoporosis, diabetes, fluid retention, susceptibility to infections, weight gain, hypertension, capillary fragility, acne, excess hair growth, wasting of the muscles, menstrual irregularities, irritability, insomnia, and psychosis. Osteoporosis is a common and particularly severe long-term side effect of prolonged steroid use. Medications that can prevent osteoporosis include calcium supplements, parathyroid hormone, bisphosphonates, or hormone replacement therapy in post-menopausal women.

Osteoporosis is a condition characterized by progressive loss of bone density, thinning of bone tissue, and increased vulnerability to fractures. Osteoporosis may result from disease, dietary or hormonal deficiency or advanced age. Regular exercise and vitamin and mineral supplements can reduce and even reverse loss of bone density.

Long-term use of oral steroid medications suppresses secretion of natural steroid hormones by the adrenal glands. After withdrawal from these drugs, this so-called adrenal suppression persists, and it can take the body a while (sometimes up to a year) to regain its ability to produce natural steroids again. There have been a few cases of severe adrenal insufficiency that occurred when switching from oral to inhaled steroids, which, in rare cases, has resulted in death.

No one should stop taking any steroids without consulting a doctor first. If the doctor orders steroids withdrawn, regular follow-up monitoring is necessary. Patients should discuss with their doctor measures for preventing adrenal insufficiency during withdrawal, particularly during stressful times when the risk increases.

Long-Term Relief Medications

These medications are taken on a regular basis to prevent asthma attacks and control chronic symptoms.

Inhalation of corticosteroids makes it possible to provide effective local anti-inflammatory activity in the lungs with minimal systemic effects. (By contrast, steroids taken by mouth have considerable side effects throughout the body.) Inhaled corticosteroids are recommended as the primary therapy under the following circumstances:

For any asthmatic condition more serious than occasional episodes of mild asthma. (Low-doses of inhaled steroids may even be safe and effective for some people with mild asthma, particularly those who find themselves using beta2-agonists daily.)
When treatment with bronchodilators is not effective.

Examples of inhaled corticosteroids:

The most recent generation of inhaled steroids include fluticasone (Flovent), budesonide (Pulmicort), triamcinolone (Azmacort and others), and flunisolide (AeroBid). In general, these newer steroids are more powerful than the older generation of inhaled drugs. These steroids are sometimes combined with a long-acting beta2-agonist in a single inhaler.
The FDA approved a new inhaled corticosteroid, mometasone furoate (Asmanex) in 2005.
The older corticosteroid inhalants are beclomethasone (Beclovent, Vanceril) and dexamethasone (Decadron Phosphate Respihaler and others). They are less powerful than the newer steroids when delivered with standard inhalers. New inhaler systems include QVAR, which uses extra fine formulations of beclomethasone to allow deep delivery into the lungs. Such systems may prove to be as effective as the newer, more potent steroids. Beclomethasone is believed to be safe during pregnancy.
Inhalers that combine both long-acting beta2-agonists and corticosteroids are also available. These include Symbicort (budesonide/formoterol), which in 2006 was approved for patients ages 12 years and older.

Traditionally, patients have been advised to take corticosteroids on a daily basis. However, a 2005 study suggested that intermittent corticosteroid therapy may be appropriate for some patients with mild persistent asthma. In the Improving Asthma Control Trial (IMPACT), researchers found that patients with mild persistent asthma who used an inhaled corticosteroid (budesonide) on an as-needed basis to control acute symptoms had similar lung function and quality of life outcomes as patients who used the drug daily. The researchers emphasize that patients with severe asthma should adhere to a daily dosage schedule, and that all patients with asthma should consult with their doctor to discuss any changes in medication regimen.

Optimal timing of the dose is important and may vary depending on the medication. Most of the newer inhaled steroids and even some older ones are now available as a single daily dose.

Inhaled steroids are generally considered safe and effective and only rarely cause any of the more serious side effects reported with prolonged use of oral steroids. Side effects of inhaled steroids are the following:

The most common side effects are throat irritation, hoarseness, and dry mouth. These effects can be minimized or prevented by using a spacer device and rinsing the mouth after each treatment.
Rashes, wheezing, facial swelling (edema), fungal infections (thrush) in the mouth and throat, and bruising are also possible but not common with inhalators.
A 2001 study reported a higher risk for cataracts in patients over age 40. (No higher risk was observed in younger people.)
Some studies report a higher risk for bone loss in patients who take inhaled steroids regularly, a side effect which is known to occur with oral steroids. A number of bone-preserving medications are now available that might safely offset this effect.
There is some concern that the more potent drugs, particularly fluticasone, suppress the adrenal system (which secretes natural steroids) to a greater degree than other steroid inhalants. (This is a serious side effect of oral steroids.)

Long-acting beta2-agonists are used in combination with inhaled corticosteroids for treating patients with moderate-to-severe asthma. These drugs include salmeterol (Serevent Diskus) and formoterol (Foradil Aerolizer). Combination single inhalers are available. One combines salmeterol and the corticosteroid fluticasone (Advair Diskus), and another combines formoterol and the corticosteroid budesonide (Symbicort).

Long-acting beta2-agonists are used for preventing an asthma attack (not for treating attack symptoms). The effects of one dose of a long-acting beta2-agonist last for about 12 hours, so these medicines are particularly effective during the night. These drugs also may be used for prevention of exercise-induced asthma in people and to protect against aspirin-induced asthma.

However, research indicates that long-acting beta2-agonists can worsen asthma by increasing symptom severity. These drugs may also increase the risk for asthma-related deaths. Experts are still trying to determine when long-acting beta2-agonists should be added to an asthma treatment plan. If your symptoms do not improve or if symptoms worsen with this type of drug, your doctor will recommend discontinuing it. Do not, however, stop taking this drug or other asthma medications without first talking with your doctor.

Side Effects. Side effects of long-acting beta2-agonists are similar to the short-acting drugs.

Specific Warning on Salmeterol and Formoterol. In 2003, a "black box" warning was added to product packaging for drugs that contain salmeterol, including Serevent Diskus, and Advair Diskus. The warning was based on a study that demonstrated more serious and even fatal asthma episodes in patients who used the drug than in patients who used a placebo. The risk for serious asthma episodes with salmeterol appears to be highest in African Americans and elderly patients with severe asthma.

In 2006, the FDA updated the warning to include formoterol (Foradil Aerolizer). Warnings for salmeterol and formoterol products emphasize that these medicines can increase the risk of severe asthma episodes. If these episodes occur, they can be fatal. Long-acting beta2-agonists require up to 20 minutes to achieve effectiveness, and there is a danger of overdose if a patient is not aware of this delay and takes additional doses to achieve faster relief. The FDA recommends that patients:

Use long-acting beta2-agonists only if other medicines (such as steroids) have not helped control asthma.
Use a short-acting bronchodilator, not a long-acting beta2-agonist, to treat sudden wheezing.
Do not use long-acting beta2-agonists to treat wheezing that is getting worse. Call your doctor if this situation occurs.
Do not stop using any asthma medicines without first talking to your doctor.

Cromolyn sodium (Intal) is both an anti-inflammatory drug and has antihistamine properties that block asthma triggers such as allergens, cold, or exercise. Nedocromil (Tilade) is similar to cromolyn. A cromolyn nasal spray called NasalCrom has been approved for over-the-counter purchase, but only to relieve nasal congestion caused by allergies. Patients should not use it for self-medication without the advice of a doctor.

Candidates. Cromolyn is often used in children with allergic asthma, but it has also been an important treatment for exercise-induced asthma (EIA) in all age groups, for pregnant women, and possibly for preventing allergic asthma in adults as well as children. Both cromolyn and nedocromil appear to be useful for patients with aspirin-induced asthma. These drugs do not effectively treat asthma once an attack is underway. They also have very little long-term benefits on lung function compared to inhaled corticosteroids.

Leukotriene-antagonists include zafirlukast (Accolate), montelukast (Singulair), zileuton (Ziflo), and pranlukast (Ultair, Onon). These drugs are proving to be effective for long-term prevention of asthma, including exercise-induced asthma and aspirin (or NSAID)-induced asthma. Most studies to date still report better success with inhaled corticosteroids than with the leukotriene-antagonists. Their anti-inflammatory actions are different from those of steroids, however, and combinations of the two drugs are being tried. A 2002 analysis of 13 studies, however, reported only modest benefits when anti-leukotrienes were added to corticosteroids. The combination did improve asthma control in some of the studies, but they did not reduce corticosteroid use. (In all but one of these studies the subjects were adults.)

Of some concern are reports of Churg-Strauss syndrome in a few people taking zafirlukast or montelukast. Churg-Strauss syndrome is very rare, but it causes blood vessel inflammation in the lungs and can be life threatening. Oral steroids quickly resolve the problem. Usually the syndrome has occurred in patients who were tapering off steroids and changing over to the leukotrienes-antagonists. Some experts believe that, in such cases, the steroids may simply have masked the presence of the disorder, which then developed when the steroid drugs were withdrawn. Symptoms include severe sinusitis, flu-like symptoms, rash, and numbness in the hands and feet.

Theophylline. Theophylline (Theo-Dur, Theolair, Slo-Phyllin, Slo-bid, Constant-T, Respbid) relaxes the muscles around the bronchioles and also stimulates breathing. One study reported that it may also have anti-inflammatory qualities even in low doses. Available in tablet, liquid, and injectable forms, some theophylline sustained-release tablets and capsules have a long duration of action and can, therefore, be taken once or twice a day with good results.

If theophylline is not taken exactly as prescribed, an overdose can easily occur. Toxicity can cause nausea, vomiting, headache, insomnia, and, in rare cases, disturbances in heart rhythm and convulsions. Contact a doctor immediately if any of these side effects occur.

The risks for these adverse effects are small if the drug is taken exactly as prescribed, but the following precautions should be noted:

Chronic smokers metabolize theophylline much more quickly and require higher doses of the drug than nonsmokers; prolonged-release versions are helpful for such people.
Too much caffeine can increase the concentration of this drug and the amount of time it stays in the body.
Theophylline also interacts with many other drugs that are taken for other common medical conditions, including asthma. Exercise caution when using beta2-agonists and theophylline together.
No one with a peptic ulcer should take theophylline. The elderly and anyone with heart disease, liver disease, hypertension, seizure disorders, or heart failure, should take theophylline with caution. Of special note, people with heart conditions who take theophylline orally face an increased risk for sudden death from heart-related causes.

However, about 1 in 1,000 patients who take omalizumab develop anaphylaxis (a life-threatening allergic reaction). In 2007 the FDA requested the manufacturers of omalizumab put a “boxed warning” on the medicine’s label emphasizing the drug’s risk for anaphylaxis. The boxed warning notes that patients can develop anaphylaxis after any dose of omalizumab, even if they had no reaction to a first dose. Anaphylaxis may occur up to 24 hours after the dose is given.

The FDA recommends that health care providers observe patients for at least 2 hours after an injection. Patients should also carry emergency self-treatment for anaphylaxis (such as an Epi-Pen) and know how to administer it. With an Epi-Pen, or similar auto-injector device, patients can quickly give themselves a life-saving dose of epinephrine.

Anaphylaxis symptoms include:

Difficulty breathing
Chest tightness
Dizziness
Fainting
Itching and hives
Swelling of the mouth and throat

Other Treatments

Various drugs are being investigated for asthma treatment. Some of these drugs have anti-inflammatory effects, which may help reduce dependence on corticosteroids. For example, etanercept (Enbrel), which blocks the inflammatory protein called tumor necrosis factor alpha, is being investigated for patients whose asthma has not responded to other drugs. The humanized monoclonal antibody daclizumab has also improved asthma control in patients with treatment-resistant asthma, as well as patients with moderate to severe chronic persistent asthma. Certain antibiotics, such as clarithromycin (Biaxin), may improve lung function in patients with asthma who show evidence of infection with the bacterial organisms Mycoplasma or Chlamydiapneumoniae. Dapsone, a drug known as a sulfone, is also under investigation.

Alternative therapies are being widely used by children, adolescents, and adults with asthma. In one study, nearly half of asthma or allergy sufferers resorted to alternative treatments. To date, however, evidence does not support any value from most alternative therapies, including high-dose vitamins, urine injections, homeopathic remedies, and most herbal remedies.

Relaxation and Stress-Reduction Techniques. Patients report benefits from many stress reduction techniques, such as acupuncture, hypnosis, breathing relaxation techniques, massage therapy, and meditation practices.

Acupuncture, hypnosis and biofeedback are all alternative ways to control pain. Acupuncture involves the insertion of tiny sterile needles, slightly thicker than a human hair, at specific points on the body.

The Buteyko Breathing Method. The Buteyko breathing method is an experimental approach designed to increase levels of carbon dioxide in the body. To do this, patients are trained to reduce their volume of breath and to avoid hyperventilation (over-breathing). Some studies have reported that patients using this method reduce their use of medications and improve their quality of life. The system originated in Australia and is not yet widely available in the U.S.

Probiotics. Probiotics are beneficial bacteria that may help protect against allergies and asthma. Antibiotic over-use and modern hygiene may specifically be reducing these helpful organisms. Probiotics can be obtained in active yogurt cultures and in supplements, which are being studied for protection.

Herbal Remedies. There have been few rigorous studies on herbal remedies for asthma. Butterbur (also known as Petasites hybridus, butter dock, blatterdock, bog rhubarb, and exwort) is one traditional herbal remedy used for treating seasonal allergies and asthma. In a 2002 study, it appeared as effective and less sedating than a commonly prescribed antihistamine for treating seasonal allergies over a 2-week period, but there has been little research on its effect on asthma.

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.

Managing Asthma

Avoidance or control of the triggers that lead to asthma attacks is as much a priority as treatment of the disease.

Controlling Pets. Patients who already have pets and are not allergic to them probably have a low risk for developing allergies. If pets trigger asthma, however, they should be kept outside. If this isn't possible, they should at least be confined to carpet-free areas outside the bedroom. Cats harbor significant allergens, which can even be carried on clothing; dogs usually present fewer problems. Washing animals once a week can reduce allergens. Dry shampoos, such as Allerpet, are now available for both cats and dogs that remove allergens from skin and fur and are easier to administer than wet shampoos.

Controlling for Dust. Spray furniture polish is very effective for reducing both dust and allergens. Air cleaners, filters for air conditioners, and vacuum cleaners with High Efficiency Particle Arresting (HEPA) filters can help remove particles and small allergens found indoors. Neither vacuuming nor the use of anti-mite carpet shampoo, however, is effective in removing mites in house dust. In fact, vacuuming stirs up both mites and cat allergens. If possible, avoid carpets and rugs.

A HEPA (High Efficiency Particle Arresting) filter can remove the majority of harmful particles, including mold spores, dust, dust mites, pet dander and other irritating allergens from the air. Along with other methods to reduce allergens, such as frequent dusting, the use of a HEPA filtration system can be a helpful aid in controlling the amount of allergens circulating in the air. HEPA filters can be found in most air purifiers, which are usually small and portable.

Reducing Humidity in the House. Although warm, moist air from vaporizers can greatly ease and moderate asthma attacks, living in a damp house is counterproductive. Dust mites thrive in humidity and damp houses increase the risk for mold, so on-going humidifiers can be unuseful. If they are used, humidity levels should not exceed 40% and they should be cleaned daily with a vinegar solution.

Gas Stoves, Kerosene, and Cooking. People with asthma should choose electric ovens rather than gas, which release nitrogen dioxide, a substance that can aggravate asthma symptoms. Even smoky cooking can worsen asthma. Kerosene (used in space heaters and lamps) may also produce allergic reactions.

Exterminating Pests (Cockroaches and Mice). Use a professional exterminator to eliminate cockroaches. (One study reported that ridding a home of cockroaches and cleaning the house using standard housecleaning techniques failed to eliminate the cockroach allergens themselves.) Exterminate mice and attempt to remove all dust, which might contain mouse urine and dander.

Avoiding Smoking and Cigarette Smoke. Cigarette smoke can accelerate the decline in lung function related to asthma. Even exposure to secondhand smoke can double the risk of asthma-related emergency room visits. In one study, it was the most frequently cited trigger of asthma symptoms. Everyone should quit smoking and encourage others around them to quit. [For help in quitting, see In-Depth Report # 41: Smoking.]

Click the icon to see an image of common asthma triggers.

Avoiding Outdoor Allergens. The following are some recommendations for avoiding allergens outside:

Avoid scheduling camping and hiking trips during times of high pollen count (generally, May and June for grass pollen and mid-August to October for ragweed).
Avoid strenuous activity when ozone levels are highest, which usually occur in early afternoon, particularly on hot hazy summer days. Levels are lowest in early morning and at dusk.
Asthma attacks are often higher during thunderstorms. It is not clear why. Some evidence points to a build-up of ozone that accompanies such storms. One study suggested that changing airflow patterns bring a sudden downdraft of air containing concentrations of pollens, small particles and allergens.
Patients who are allergic to mold should avoid barns, hay, raking leaves, and mowing grass. Exposure to automobile fumes may worsen asthma. Fungi in car air conditioners can also be a problem.

Click the icon to see an image of fungus.

Reducing Exposure to Air Pollution. A number of studies have linked air pollution to asthma. An important 2000 study found a strong association between higher mortality rates from heart and lung diseases and high levels of specific pollutants (ozone, carbon monoxide, sulfur dioxide, and nitrogen dioxide). Some experts point out that asthma rates in North America have increased over recent years while the prevalence of many common air pollutants have declined. Nevertheless, evidence strongly suggests that air pollution can worsen existing asthma and patients should take precautions if they are exposed to polluted air.

A number of studies have estimated that between 2 - 26% of adult-asthma cases are related to work history. Some experts encourage doctors to suspect occupational factors in all cases of adult-onset asthma. Although workers who have allergies, who smoke, or both are at higher risk than others, any worker exposed to occupational triggers may be at risk for asthma.

Work-related asthma is one of two types:

Work-aggravated asthma, in which existing asthma symptoms are triggered by irritants at the workplace
Occupational asthma, which is new-onset asthma strongly associated with conditions at work

Occupational asthma is further categorized as:

Nonlatent (symptoms occur right after exposure to an irritant, usually high concentrations of gas, fumes, dust, or chemicals)
Latent (symptoms develop after prolonged exposure to substances in the workplace)

Occupational Triggers. Over 250 substances have been identified as potential occupational triggers of asthma, and the list is growing. A few of these chemicals and substances include:

Isocyanates used in the manufacture of polyurethane, paints, steel, and electronics
Trimellitic anhydrides (TMA) used in many plastics and epoxies
Western red cedar, oak, redwood, and mahogany
Metal salts (platinum, nickel, and chrome) and metal working fluids
Vegetable dusts (soybeans, grains, flour, cotton, and gums)
Biologic organisms (Bacillus subtilis, pancreatic enzymes)
Xylanase used in the baking industry
Pharmaceuticals (penicillin, phenylglycine acid chloride)
Glutaraldehyde used to sterilize medical equipment
Red dye made from the cochineal insect
Diacetyl, the main chemical in artificial butter flavoring used in popcorn

Workers in these industries and others, including farmers, hairdressers, and those who work in the garment industries are at risk for asthma.

Preventing Occupational Asthma. In people whose asthma is caused by workplace conditions, improved ventilation or face masks may help.

Sometimes, however, even low levels of chemical substances can trigger an asthma attack. In such cases, leaving the job is the only way to prevent the condition from getting worse. Because such a step can be emotionally and financially threatening, workers should be sure that occupational substances are the cause of the asthma by having a complete check-up by a lung specialist.

If the diagnosis of occupational asthma is certain, patients should obtain advice on available compensation plans for disability. The effects of workplace asthma can be permanent. However, in one study, 70% of people with asthma experienced significant improvement in symptoms after leaving the job.

Immunotherapy ("allergy shots") may help reduce asthma symptoms, and the use of asthma medications, in patients with known allergies. They may also help prevent the development of asthma in children with allergies. Immunotherapy poses some risk for severe allergic reactions, however, especially for children with poorly controlled asthma.

[See In-Depth Report #77: Allergic rhinitis; and Report #5: Asthma in children and adolescents.]

Preventing and Treating Respiratory Infections. Respiratory infections, including the common cold, can act with allergies to worsen asthma. People with asthma should try to minimize their risk for respiratory tract infections. Washing hands is a very simple but effective preventive measure.

Patients with asthma should ask their doctors about the flu vaccine and also whether they should receive the vaccination against pneumococcal pneumonia.

Zanamivir, a new drug used for treating influenza, is considered safe for patients with asthma 12 years of age or older. In one study, patients with asthma who were treated with zanamivir experienced fewer flu symptoms and had improved lung function. [See In-Depth Report #94: Colds and influenza.]

Managing Hormonal-Related Asthma. Women who suspect that menstrual-related changes may influence asthma severity should keep a diary recording their menstrual dates and times of asthma attacks. In some cases, adjusting medications in anticipation of menstruation may help prevent attacks. Some small studies have suggested that hormonal drugs called gonadotropin-releasing hormone (GnRH) analogues may help women with severe premenstrual asthma. Such drugs reduce or suppress estrogen levels, however, and can have severe side effects. More research is needed to determine if the disadvantages outweigh the benefits.

Weight Loss. People who have asthma and who are overweight may help reduce asthma symptoms with weight loss.

Vitamin D. There may be an association between a lack of vitamin D and asthma. Some research suggests that children are less likely to develop asthma at a young age if their mothers consume a high intake of vitamin D during pregnancy. Vitamin D is available from dietary sources or vitamin supplements.

Fish Oil. Omega-3 fatty acids, found in cold water oily fish and in supplements (preferably DHA-EPA, which are the important compounds in fish oil) have anti-inflammatory effects. Some evidence suggests they may be helpful for people with asthma, although it is weak.

Caffeine. Caffeine has properties that are similar to theophylline, a drug used to treat asthma. A major analysis of studies reported that caffeine improved lung function for up to 4 hours after consumption. (People who are going to have their lung function tested should avoid drinking coffee, tea, or other caffeinated beverages for at least 4 hours beforehand.)

Alcohol. In adults, some research suggests that alcohol intake may influence allergy severity. One study found that as little as one drink a day is enough to worsen dust mite allergies.

Role of Food Allergies. Although 67% of people with asthma believe their symptoms are aggravated by food allergies, studies indicate that this belief may be true in only 5% of cases. The primary suspects are monosodium glutamate, or MSG (found in some canned soups, cheese, and certain vegetables), and sulfites (preservatives in wine and foods that include processed frozen potatoes and tuna). Contrary to what many people believe, dairy products do not appear to worsen asthma symptoms in people who are not already allergic to them.

Asthma is no reason to avoid exercise. Historically, about 10% of Olympic athletes have asthma. Some studies indicate that long-term exercise even helps control asthma and reduce hospitalization. Patients should consult their doctors before embarking on any exercise program, however. Uncontrolled asthma can be dangerous and, in rare cases, can be fatal for athletes, even some with mild asthma. Use of the inhaler is extremely important.

People who enjoy running should probably choose an indoor track to avoid pollutants. Swimming is excellent for people with asthma. Yoga practice, which uses both stretching, breathing, and meditation techniques, may have particular benefits. One study reported that two-thirds of patients who practiced yoga regularly were able to reduce or stop taking their asthma medications.

Exercise-induced asthma is a limited condition that has specific recommendations.

People with asthma have no higher rate of anxiety or depression than the general population. However, such emotions interact with the effects of asthma and its treatments in important ways:

Negative emotions can discourage compliance with medication and the ability to cope
Poor control of asthma symptoms, in turn, increases the risk for negative emotions
Stress and depression have been associated with more severe symptoms and even an increased risk of fatal asthma attacks

Some evidence suggests that stress reduction techniques, a positive attitude and relaxation techniques can be very helpful in the long-term management of asthma. [See In-Depth Report #31: Stress.]

Resources

www.lungusa.org -- The American Lung Association
www.acaai.org -- American College of Allergy, Asthma & Immunology
www.aaaai.org -- American Academy of Allergy, Asthma & Immunology
www.nhlbi.nih.gov -- National Heart, Lung, and Blood Institute
http://asthma.nationaljewish.org -- National Jewish Medical and Research Center
www.aafa.org -- Asthma and Allergy Foundation of America
www.aarc.org -- American Association for Respiratory Care

References

Glassroth J. The role of long-acting ß-agonists in the management of asthma: Analysis, meta-analysis, and more analysis. Ann Intern Med 2006 Jun 20; 144:936-7.

Kiljander TO, Harding SM, Field SK, Stein MR, Nelson HS, Ekelund J, et al. Effects of esomeprazole 40 mg twice daily on asthma: a randomized placebo-controlled trial. Am J Respir Crit Care Med. 2006 May 15;173(10):1091-7.

Review Date:
3/27/2007
Reviewed By:
Harvey Simon, MD, 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.

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

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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

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Bipolar disorder

FitSugar — Wed, 08 Oct 2008 17:35:00 -0700

In This Report

Highlights
Introduction
Risk Factors
Causes
Prognosis
Diagnosis
Treatment
Medications
Other Treatments
Therapy and Lifestyle Chang...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

In 2007, the FDA approved risperidone (Risperdal) for short-term treatment of manic or mixed episodes of bipolar I disorder in children ages 10 - 17. Risperidone (an atypical antipsychotic) and lithium (a mood stabilizer) are the two drugs currently approved for treating pediatric patients with bipolar disorder.

Drug Warnings

Olanzapine (Zyprexa, Symbex) causes a greater risk for high blood sugar than other atypical antipsychotics, according to updated information added to the drug’s warning label. Olanzapine also causes weight gain and can increase the risk for unhealthy cholesterol levels.
All atypical antipsychotics increase the risk for diabetes. Patients who take these drugs should receive regular screenings for changes in blood sugar levels. Patients should also have their cholesterol levels monitored.

Bipolar Disorder in Children and Adolescents

Diagnoses of bipolar disorder in children have increased 40-fold in the past decade, according to an analysis in the Archives of General Psychiatry. There is debate whether bipolar disorder in children was under-diagnosed in the past or is being over-diagnosed now.
Bipolar symptoms in children differ from those of adults, with some symptoms overlapping with behavioral and conduct disorders. New guidelines from the American Academy of Child and Adolescent Psychiatry (AACP) caution that a diagnosis of bipolar disorder must be carefully made, especially considering the risks associated with drug therapy. The AACP also advises that there are currently no established criteria for diagnosing bipolar disorder in preschoolers.

Bipolar Depression

The antidepressants bupropion (Wellbutin) and paroxetine (Paxil) do not increase the risk for mania, but neither do they help ease depression any more than mood stabilizers, suggests a 2007 study in the New England Journal of Medicine.
Intensive psychotherapy in combination with medication can help improve depression outcomes, indicates a 2007 study in the Archives of General Psychiatry.

Introduction

Bipolar disorder, or manic-depressive illness, is characterized by moods that swing between two opposite poles:

Periods of mania with exaggerated euphoria, irritability, or both
Episodes of depression

Although chemical imbalances in the brain are a key component of bipolar disorder, it is a complex condition that involves genetic, environmental, and other factors.

Bipolar disorder is classified according to the pattern and severity of the symptoms as bipolar disorder I, bipolar disorder II, or cyclothymic disorder. Patients with one type may develop another. Nevertheless, they are distinct enough to merit separate classifications, and some experts believe these conditions are actually separate disorders with different biologic factors that account for their differences.

Bipolar Disorder I. Bipolar disorder I is characterized by at least one manic episode, with or without major depression, that lasts for at least 7 days. In 60 - 70% of cases, manic episodes precede or follow depressive episodes in a regular pattern. Episodes are more acute and severe than in the other two categories.

Without treatment, patients average four episodes of dysregulated mood each year. With mania, either euphoria or irritability may mark the phase. In addition, there are significant negative effects (such as sexual recklessness, excessive and impulsive shopping, and sudden traveling) on a patient's social life, performance at work, or both. Untreated mania lasts at least a week, and it can last for months. Typically, depressive episodes tend to last 6 - 12 months, if left untreated.

Bipolar Disorder II and Hypomania. Bipolar disorder II is characterized by episodes of predominantly depressive symptoms, with occasional episodes of hypomania, which last for at least 4 days. Hypomania is similar to mania, but the symptoms (typically euphoria) are less severe and do not last as long.

Patients do not experience manic or mixed episodes, and most return to fully functional levels between episodes. However, bipolar II patients have a more chronic course, significantly more depressive episodes, and shorter periods of being well between episodes than patients with type I have. It is highly associated with the risk for suicide.

Cyclothymic Disorder. While cyclothymic disorder is not as severe as either bipolar disorder II or I, the condition is more chronic. Hypomanic symptoms tend toward irritability as compared to the more euphoric symptoms of bipolar II. (One report, in fact, referred to these patients as having "darker" natures, while bipolar II patients were "sunnier.")

The disorder lasts at least 2 years, with single episodes persisting for more than 2 months. Cyclothymic disorder may be a precursor to full-blown bipolar disorder in some people or it may continue as a low-grade chronic condition.

Symptoms of the Depression Phase. The symptoms of depression experienced in bipolar disorder are almost identical to those of major depression, the primary form of unipolar depressive disorder. They include:

Sad mood
Fatigue or loss of energy
Sleep problems such as insomnia, excessive sleeping, or shallow sleep with frequent awakenings
Appetite changes
Diminished ability to concentrate or to make decisions
Agitation or markedly sedentary behavior
Feelings of guilt, pessimism, helplessness, or low self-esteem
Loss of interest or pleasure in life
Thoughts of, or attempts at, suicide

Distinguishing Between Unipolar and Bipolar Depression. It is often difficult to differentiate between unipolar and bipolar depression, particularly in patients with bipolar II disorder. They may differ in the following ways:

Bipolar depression typically lasts 2 - 3 months -- not as long as in major depression (although left untreated some bipolar disorder episodes can last 6 - 12 months or longer).
People with unipolar depression can still experience a variety of other moods, but none meet the criteria for a manic state.
Depressive symptoms in those with bipolar disorder tend to vary. For example, some patients experience increased sleep, gain weight, and feel a heaviness and slowness in their bodies. Other patients with bipolar depression experience impaired sleep, but unlike patients with unipolar depression, they do not feel sleepy the next day.
Bipolar depressive episodes tend to develop more gradually than do those caused by major depression.

Symptoms of the Acute Manic Phase. The acute pure manic phase is always characterized by mood elevation, presented in the following ways:

Exaggerated euphoria (a feeling of great happiness or well-being)
Irritability
Both euphoria and irritability

The episode lasts for at least few days but, in some cases, the episode may last weeks or even months and may be severe enough to require hospitalization.

Other symptoms must also be present to make a diagnosis. Some mental health professionals use the mnemonic device DIGFAST to identify them. In general, for a diagnosis of mania, a patient must have experienced either euphoria with three DIGFAST symptoms or irritability with four of these symptoms:

D. Distractibility. This is the most common symptom, and it is usually characterized by the inability to pay attention to any activity for very long.
I. Insomnia in mania typically means having high energy and requiring less sleep. (This differs from insomnia in depression, in which the patient has low energy plus an inability to sleep.)
G. Grandiosity. Patients with this symptom have an inflated sense of themselves, which, in severe cases, can be delusional. Close to 60% of all manic patients experience feelings of being all-powerful. Sometimes they feel that they are godlike or have celebrity status.
F. Flight of ideas. Thoughts literally race.
A. Activity. The patient may show an increase in intensity in goal-directed activities, which are related to social behavior, sexual activity, work or school.
S. Speech. The patient may talk excessively.
T. Thoughtlessness. Excessive involvement in high-risk activities is present (such as unrestrained shopping, promiscuity). Mood disturbance may be severe enough to damage one's job or social functioning or one's relationships with others. Some patients require hospitalization to prevent harm to others or to themselves.

Some patients with bipolar I may experience psychotic symptoms, including thought disorders, hallucinations, and catatonia (a state in which the patient goes into a stupor for long periods, which may give way to short periods of extreme excitement).

Hypomania. With hypomania the symptoms of mania are milder and of shorter duration (but they last at least 4 days). They do not affect social or work life as dramatically.

Mixed Mania State Symptoms. Mixed mania (also called mixed episodes or dysphoric mania) are manic episodes that also have a depressive component. In such a state, mania is present to a significant degree, but depression is present most of the day and nearly every day. Such mixed symptoms occur for at least a week.

Depressive Mixed State Symptoms. Depressive mixed state is characterized by major depression as the primary emotional state with manic features (such as irritability, distractibility, and racing thoughts). Such patients may receive an inaccurate diagnosis of unipolar depression.

Risk Factors

Between 1 - 2 million Americans may suffer from bipolar disorder. Researchers estimate that about 1% of Americans experience bipolar disorder during the course of their lifetime, but some studies indicate that prevalence may be as high as 4%. There is differing opinion on how to diagnose and categorize bipolar symptoms, which affects these estimates. The majority of people with bipolar disorder also have other psychiatric disorders, particularly anxiety and substance abuse.

Bipolar disorder affects both sexes equally, but there is a higher incidence of rapid cycling, mixed states, and cyclothymia in women. Early-onset bipolar disorder tends to occur more frequently in men and it is associated with a more severe condition. Men with bipolar disorder also tend to have higher rates of substance abuse (drugs, alcohol) than women.

Bipolar disorder frequently occurs within families, although genetic factors account for only about 60% of cases. Family members of patients with bipolar disorder also have a higher than average incidence of other psychiatric problems. They include schizophrenia, schizoaffective disorder, anxiety disorders, ADHD, and major depression.

Causes

No single cause may ever be found for bipolar disorder. Instead, a combination of biologic, genetic, and environmental factors appears to trigger and perpetuate the chemical imbalances in the brain that shape this complex disorder. Biologic factors observed or considered in bipolar disorder, as detected by use of imaging scans and other tests, include:

Oversecretion of cortisol, a stress hormone
Excessive influx of calcium into brain cells
Abnormal hyperactivity in parts of the brain associated with emotion and movement coordination
Low activity in parts of the brain associated with concentration, attention, inhibition, and judgment
A superfast "biologic clock"

The so-called biologic clock is a tiny cluster of nerves called the supra chiasmatic nucleus, or SCN. The SCN is located in the center of the brain in the hypothalamus region. It regulates a person's circadian rhythm, the daily cycle of life, which influences sleeping and waking.

The genetics of bipolar disorder are the most intensively studied of all psychiatric diseases. Multiple genes, involving several chromosomes, have been linked to its development. Bipolar disorder also may share these genetic factors with other disorders, including schizophrenia, epilepsy, and panic disorder. It is not clear if some of these disorders are variations of a single disease or separate disorders.

Bipolar Disorder and Schizophrenia. Researchers have been investigating whether common biologic factors are involved with schizophrenia, severe bipolar disorder, and other psychoses. Schizophrenia and bipolar disorder often show up in the same family. Researchers are identifying a number of common genetic and biologic pathways that they both share. Bipolar Disorder and Epilepsy. Neurotransmitters called gamma aminobutyric acid (GABA) and norepinephrine have been implicated in mania:

GABA helps prevent nerve cells from over-firing
Norepinephrine is a hormone that involves stress

Some research has associated similar biologic mechanisms in patients with epilepsy and bipolar disorder. As in epilepsy, the more episodes a bipolar disorder patient experiences early in the course of the disease, the more frequent and severe later episodes will be. Antiseizure drugs, in fact, can play an important role in the treatment of bipolar disorder.

Panic Disorder and Bipolar Disorder. Researchers are also studying the common biologic and genetic factors between panic disorder and bipolar disorder. While specific genes have not yet been identified, some researchers studying these illnesses now believe that they may represent different forms of a shared, complex condition.

Prognosis

Bipolar disorder can be severe and long-term, or it can be mild with infrequent episodes. Patients with the disease may experience symptoms in very different ways. A typical bipolar disorder patient averages 8 - 10 manic or depressive episodes over a lifetime. However, some people experience more and some fewer episodes.

Typical Bipolar Cycles. In most cases of bipolar disorder, the depressive phases far outnumber manic phases, and the cycles of mania and depression are neither regular nor predictable. Many patients experience mixed mania, or a mixed state, in which both mania and depression coexist for at least 7 days.

Rapid Cycling. About 15% of patients with the disorder have a temporary, complicated phase known as rapid cycling. With this phase the manic and depressive episodes alternate at least four times a year and, in severe cases, can even progress to several cycles a day. Rapid cycling tends to occur more often in women and in those with bipolar II. Typically, rapid cycling starts in the depressive phase, and frequent and severe episodes of depression may be the hallmark of this event. This phase is difficult to treat, particularly since antidepressants can trigger the switch to mania and set up a cyclical pattern.

Differences Between Children and Adults. Research suggests that symptoms of bipolar disorder in children and adolescents differ from those of adults. While adults with bipolar disorder usually have distinct and persistent periods of mania and depression, children with bipolar disorder fluctuate rapidly in their mood and behavior. Mania in children is characterized by irritability and belligerence whereas adults tend to experience euphoria. Children with bipolar depression are frequently angry and restless, and may have additional mood and behavioral disorders such as anxiety, attention deficit hyperactivity disorder, conduct disorder, and substance abuse problems.

Medical evidence has shown that patients with bipolar disorder have higher death rates from suicide, heart problems, and death from all causes than those in the general population. Patients who get treatment, however, experience great improvement in survival rates, including deaths from suicide and heart disease.

Bipolar disorder usually first occurs between the ages of 15 - 30 years, with an average age of onset at 25 years. However, bipolar disorder can affect people of all ages, including children. Bipolar disorder that occurs late in life often accompanies medical and neurological problems (particularly cerebrovascular disease, such as stroke). It is less likely to be associated with a family history of the disorder than earlier-onset bipolar disorder.

Patients with bipolar disorder, especially type II or cyclothymic disorder, have frequent episodes of major depression. Anxiety disorders also commonly coexist in these patients. For example, the occurrence of panic disorder in patients with bipolar disorder is 26 times that of the general population. Patients with bipolar disorder, particularly those with type II, are also subject to phobias. In one study, the presence of anxiety disorders was also associated with longer and more severe bipolar depressive episodes and with a higher risk for suicide.

Symptoms of bipolar disorder in children are often confused with attention-deficit hyperactivity disorder (ADHD). Furthermore, the two conditions can coincide. In one study, 65% of adolescents with bipolar disorder met criteria for ADHD. The risk for both diagnoses is highest in white males. Symptoms are also more severe in people with both conditions. Some researchers believe that many of these disorders may actually be variations of a single disease.

The risk for suicide is very high in patients who suffer from bipolar disorder and who do not receive medical attention. Between 10 - 15% of patients with bipolar disorder I commit suicide, with the risks being highest during episodes of depression or mixed mania (simultaneous depression and mania). Some studies suggest that the risk for suicide in patients with bipolar disorder II is even higher than it is for those with bipolar disorder I or major depressive disorder. Patients who also suffer from an anxiety disorder are also at greater risk for suicide. (Rapid cycling, although a more severe variation of bipolar disorder, does not appear to increase the suicide risk in patients with bipolar disorder.)

Many pre- and early adolescent children with bipolar disorder are more severely ill than are adults with the disease, and the risk for suicide is high. They have a higher risk for mixed mania, multiple and frequent cycles, and a long duration of illness without well periods.

Studies suggest that patients with bipolar disorder may have varying degrees of problems with short- and long-term memory, speed of information processing, and mental flexibility. Such problems persist even between episodes. They tend to be more severe when a person has more manic episodes. Medications used for bipolar disorder could be responsible for some of these abnormalities, although some evidence suggests that such traits may have a biologic basis. These mental difficulties may make it harder for these patients to comply with medications or to participate in complex psychotherapies.

A small percentage of bipolar disorder patients demonstrate heightened productivity or creativity during manic phases. More often, however, the distorted thinking and impaired judgment that are characteristic of manic episodes can lead to dangerous behavior, including:

Spending money with reckless abandon, causing financial ruin in some cases
Angry, paranoid, and even violent behaviors
Openly promiscuous behavior

Such behaviors are often followed by low self-esteem and guilt, which are experienced during the depressed phases. During all stages of the illness, patients need to be reminded that the mood disturbance will pass and that its severity can be diminished by treatment.

Cigarette smoking is prevalent among patients with bipolar disorder, particularly those who have frequent or severe psychotic symptoms. Some experts speculate that, as in schizophrenia, nicotine use may be a form of self-medication because of its specific effects on the brain.

Up to 60% of patients with bipolar disorder abuse other substances (most commonly alcohol, followed by marijuana or cocaine) at some point in the course of their illness.

The following are risk factors for alcoholism and substance abuse in patients with bipolar disorder:

Having mixed-state episodes rather than ones of pure mania
Being a man with bipolar disorder

Patients do not manifest their negative behaviors (such as spending sprees or even becoming verbally or physically aggressive) in a vacuum. They have a direct effect on others around them. It is very difficult for even the most loving of families or caregivers to be objective and consistently sympathetic with an individual who periodically and unexpectedly creates chaos around them.

Many patients and their families find it difficult to accept that these episodes are part of an illness and not simply extreme, but normal, characteristics. Such denial is often strengthened by patients who are highly articulate and deliberate, and who can intelligently justify their destructive behavior, not only to others, but also to themselves.

Family members may also feel socially alienated by the fact of having a relative with mental illness, and feel forced to conceal this information from acquaintances.

The economic burden of bipolar disorder is significant. It is estimated that the disorder costs the U.S. workplace about $14.1 billion annually in lost productivity, mostly due to poor functioning on the job. According to a 2006 study sponsored by the U.S. National Institute of Mental Health, bipolar disorder accounts for twice as much lost productivity as major depressive disorder (MDD), despite the fact that MDD is more prevalent. Each worker with bipolar disorder loses about 66 workdays a year compared with 27 workdays a year for workers with MDD. Research suggests that bipolar disorder’s depressive episodes impair productivity more than its manic episodes.

People with mental illness have a higher incidence of many medical conditions, including heart disease, asthma and other lung problems, gastrointestinal disorders, skin infections, diabetes, hypertension, migraine headaches, hypothyroidism, and cancer. Patients with bipolar disorder are also less likely to receive medical care than people without mental disorders. Substance abuse, including smoking, alcoholism, and drug abuse, also contributes to many of these problems as well as reduced access to care. Medications used for bipolar disorder can also increase the risk for medical problems.

However, people with bipolar disorder and other mental illness have a higher risk for a number of these conditions independent of these factors.

Diabetes. Diabetes is diagnosed almost three times more often in people with bipolar disorder than it is in the general population. Many patients with bipolar disorder are overweight, with about 25% meeting the criteria for obesity. Being overweight is a significant risk factor for diabetes and so it may be the common factor in both diseases. Drugs used to treat bipolar can also cause weight gain and diabetes. Common genetic factors in diabetes and bipolar disorder may cause a rare disorder called Wolfram syndrome and other problems with carbohydrate metabolism.

High Blood Pressure. Patients with bipolar disorder may be at a higher risk for high blood pressure (hypertension) than patients without the disorder. The high prevalence of hypertension among patients with bipolar disorder may also account for their greater risk for illness and death from heart-related conditions.

Migraine Headaches. Migraines are common in patients with a number of mental illnesses, but they are particularly common among patients with bipolar II disorder. Patients with bipolar II suffer from migraine more frequently than patients with bipolar I, suggesting that different biologic factors may be involved with each bipolar form.

Hypothyroidism. Hypothyroidism (low thyroid levels) is a common side effect of lithium, the standard treatment for bipolar. However, evidence also suggests that patients, particularly women, may be at higher risk for low thyroid levels regardless of which medications they use. Hypothyroidism may, in fact, be a risk factor for bipolar disorder in some patients.

Diagnosis

Bipolar disorder is more common than previously thought, but this illness, particularly bipolar disorder II, is still poorly recognized in the family-practice setting. It is estimated that only a third of affected people are accurately diagnosed.

When making a diagnosis of bipolar disorder, it is important that the doctor rule out other conditions that may be causing symptoms of bipolar disorder.

Distinguishing Mania from Normal Euphoria or Joy. A major difficulty with a diagnosis of bipolar disorder is the tendency for a patient to be unable to recognize his or her own condition, particularly when in the manic state. The patient often denies their symptoms, which may be perceived as positive feelings. The doctor should take a careful and complete history of any and all episodes of depression, mania, or both. Hypomania, the less severe variant of mania, may be particularly difficult to distinguish from normal joy or euphoria. It can often be distinguished by the following characteristics:

Hypomania persists for at least 4 days
Patients with hypomania are easily distracted and overly talkative
Patients with hypomania have difficulty functioning

Distinguishing Unipolar from Bipolar Depression. People with bipolar disorder are more likely to seek help because of a depressive episode and may not have a manic episode until they have experienced three or more depressive episodes. In such cases, the condition is often diagnosed as major depression. An accurate diagnosis is important because patients with bipolar disorder who are inappropriately medicated solely with antidepressants have a higher incidence of rehospitalization than do other bipolar disorder patients.

Bipolar disorder should be suspected in patients who have been treated for depression and who had a fast and good response, followed by the return of depression and failure to respond to other antidepressant treatment.

A family history of manic-depressive illness may make a doctor suspicious, but a diagnosis of bipolar disorder cannot be established until a manic or hypomanic episode has occurred. Patients with bipolar II disorder and those with depressive mixed state are most likely to be misdiagnosed with depression.

Attention Deficit Hyperactive Disorder (ADHD). Children or adolescents with bipolar disorder may be inappropriately diagnosed with attention-deficit hyperactivity disorder. ADHD and bipolar disorder often cause inattention and distractibility, and the two disorders may be difficult to distinguish, particularly in children. In some cases, ADHD in children or adolescents can even be a marker for an emerging bipolar disorder. The primary distinction between bipolar disorder and ADHD is the presence of a manic or hypomanic episode, which occurs in patients with bipolar disorder but not those with ADHD.

Schizophrenia. Severe manic episodes that include delusions and hallucinations may be easily confused with schizophrenia. (African-American men are more likely to be diagnosed with schizophrenia than with bipolar disorder.) The key factors that distinguish bipolar disorder from schizophrenia include:

The presence of one or more manic or hypomanic episodes in bipolar disorder, but not in schizophrenia
A flat emotional expression, with no variability in the voice among people with schizophrenia
People with bipolar disorder are typically very expressive

Substance Abuse. Up to 60% of patients with bipolar disorder abuse alcohol and drugs at some point during their illness. Both diagnosis and treatment are difficult in such cases, since substance abuse is often a method of self-treatment, and withdrawal can produce symptoms of mania or severe depression. The effects of cocaine in a heavy user can also produce abnormal mood swings that closely resemble those of bipolar disorder.

Other Causes of Mood Swings. Other conditions that can cause mood swings include:

Thyroid disorders
Adrenal disorders (Addison's disease or Cushing syndrome)
Vitamin B12 deficiency
Neurologic disorders such as Huntington's disease, epilepsy, brain tumors, encephalitis, or multiple sclerosis
Medications, including corticosteroids and certain drugs used to treat anxiety and Parkinson's disease

Patients should be tested for drugs or alcohol if the doctor suspects that they have been using these substances. Blood tests for thyroid function should also be performed.

Noninvasive imaging tests of the brain using magnetic resonance imaging (MRI) and positron-emission tomographic (PET) scans are being evaluated in clinical trials for detecting abnormalities in the brain. The results of these tests may eventually help identify bipolar disorder and test the effectiveness of various treatments. However, imaging tests do not currently play a role in diagnosing bipolar disorder.

The number of children diagnosed with bipolar disorder has increased dramatically during the past decade. Psychiatrists debate whether bipolar disorder was formerly under-diagnosed in children or whether it is being over-diagnosed now. Part of the controversy concerns the diagnostic criteria used for children and adolescents. Some bipolar symptoms, such as irritable mania, share characteristics with common childhood anger outbursts or behavioral disorders such as conduct disorder and attention deficit hyperactivity disorder. In addition, many children with bipolar disorder also have behavioral and developmental disorders. These overlapping conditions can complicate diagnosis.

The American Academy of Child and Adolescent Psychiatry (AACP) recommends that doctors use specific screening questions to diagnose bipolar disorder. These questions are designed to evaluate periods of mood changes associated with sleep disorders and restlessness. Doctors should also ask about family histories of mood disorders. The AACP cautions that the validity of diagnosing bipolar disorder in children younger than 6 years old has not been established.

Bipolar disorder is treated with powerful psychiatric drugs that can cause serious side effects. It is very important to make sure that a child’s symptoms are due to bipolar disorder, rather than emotional or behavioral issues, before prescribing these medications.

Treatment

Bipolar disorder is a recurrent disease that can be unpredictable. The major goals of treatment are to:

Treat and reduce the severity of acute episodes of mania or depression when they occur
Reduce the frequency of episodes
Avoid cycling from one phase to another
Help the patient function as best as possible between episodes

The doctor will first try to determine what may have triggered the attack and identify any accompanying medical or emotional problems that might interfere with or complicate treatment.

Some experts think that the best way to treat bipolar disorder is through a disease management model, similar to those used for treating diabetes and asthma. In this “collaborative care” model, patients are treated by a multi-disciplinary team of psychiatrists and nurses. The nurses provide patient education on medication side effects, early warning signs of symptoms, and coping skills. In several 2006 studies, patients who received this treatment model reported fewer symptoms, more productive time at work, better relationships with family members, and general improvement in quality of life.

The treatments for bipolar disorder, while very effective, pose some specific challenges for the patient:

Mood variations in bipolar disorder are not predictable, so it is sometimes difficult to tell if a patient is responding to treatment or naturally emerging from a bipolar phase.
A patient with bipolar disorder cannot always reliably inform the doctor about the state of the illness.
The patient is likely to need more than one medication during the course of the disease. This increases the risk for distressing side effects. Noncompliance is common.
Patients often have more than one medical problem and need different drugs to treat each condition. Such medications may interact with drugs used to treat bipolar disorder or increase side effects. For example, children with bipolar disorder have a higher risk for attention deficit-hyperactivity disorder, which is treated with stimulants that can complicate bipolar treatment.
Family members who have not been educated about the disorder may interfere with the treatment.
Treatment strategies for children and the elderly have not been intensively studied and have not been clearly defined.
Treatments may be costly.

The following are the treatment options for most patients with bipolar disorder, depending on the bipolar disorder phase or episode. Patients should understand that, even with aggressive therapy, either mania or depression recurs in almost three-quarters of patients.

Drugs Used in Bipolar Disorder. Mood stabilizing drugs are the mainstay for patients with bipolar disorder. They are defined as drugs that are effective for acute episodes of mania and depression and that can be used for maintenance. The standard first-line mood stabilizers are lithium and valproate. Both drugs stimulate the release of the neurotransmitter glutamate, although they appear to work through different mechanisms. Other drugs may also be used.

Lithium. Lithium has been used for years for bipolar disorder. It remains the best drug for people with pure mania characterized by euphoria and pure depression. Although imperfect, it is also an effective long-term drug for many patients with other bipolar subtypes.
Antiseizure Drugs. Valproate (valproic acid) carbamazepine (Tegretol, Carbatrol, Equetro), oxcarbazepine (Trileptal), and lamotrigine (Lamictal) are the most established antiseizure drugs. Other anti-seizure drugs used or investigated for bipolar include gabapentin (Neurontin), zonisamide (Zonegran) and topiramate (Topamax). To date, it is not clear if any of these newer drugs are useful for the treatment of acute mania.
Atypical Antipsychotics. Drugs known as atypical antipsychotics are used to treat schizophrenia and also have mood stabilizing properties that are applicable to bipolar disorder. They may be used either alone or in combination with lithium or valproate. Clozapine (Clozaril) was the first of these drugs, but it has not yet been approved for treatment of bipolar disorder. The newer atypical antipsychotics include olanzapine (Zyprexa), risperidone (Risperdal), quetiapine (Seroquel), ziprasidone (Geodon), and ariprazole (Abilify).

Such drugs may be used in combination with each other. Additional drugs, such as conventional antipsychotics, antidepressants, antianxiety drugs, or experimental drugs are used as necessary.

Electroconvulsive Therapy. Electroconvulsive therapy is a very effective treatment that may be administered in certain patients for acute episodes or for maintenance.

Non-Medical Treatments. In addition to medical treatments, psychotherapy and sleep management are also parts of bipolar disorder treatment. They can help reduce symptoms and prevent relapse.

The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), an ongoing trial supported by the National Institute of Mental Health, is the largest treatment study ever conducted for bipolar disorder. With plans to enroll approximately 5,000 patients, STEP-BD aims to evaluate all the best-practice treatment options used for bipolar disorder, including mood-stabilizing medications, antidepressants, and atypical antipsychotics. It will also evaluate psychosocial interventions, including cognitive behavioral therapy, family-focused therapy, interpersonal and social rhythm therapy, and psychoeducation. Results of STEP-BD may clarify the best treatments for bipolar disorder.

Step 1. Determine the Need for Hospitalization and Eliminate Triggers. The first step in treating an acute manic episode is to rule out any life-threatening conditions and eliminate any triggers, such as antidepressants or other substances that can elevate moods.

Patients often require hospitalization at the onset of acute mania. The need for hospitalization depends on a number of factors:

Whether the patient is at risk for suicide or for harming others
The availability of social and emotional support at home

Step 2. Control Symptoms of Acute Manic with a Mood Stabilizer. Doctors often try different drugs to control a manic episode. If a current drug does not work well, another type of drug may be added or substituted. It may take several weeks for a mood stabilizer to take effect, and other drugs may be needed.

The following is an example of a stepped approach recommended by some experts:

Initiating a mood-stabilizing drug is the critical first step. Either valproate or lithium is the standard first drug for most manic episodes. Lithium is effective in 60 - 80% of all hypomanic and manic episodes. Carbamazepine is usually used in place of valproate to treat patients with multiple manic episodes, mixed episodes, and rapid cycling. Combinations of these mood stabilizers may be used if the patient does not respond to a single drug.
If the patient does not respond fully within a week, atypical antipsychotics may be added to one or more mood stabilizers. Atypicals include olanzapine (Zyprexa), risperidone (Risperdal), quetiapine (Seroquel), apriprazole (Abilify), and ziprasidone (Geodon). Clozapine (Clozaril), the oldest atypical drug, also works well but it is not generally used because of its potential for severe side effects and the need for weekly monitoring of white blood cell counts.

Step 3. Addition of Other Treatments. Other treatments may be added to speed recovery, treat any psychosis, and achieve remission. They include:

Older antipsychotic drugs (also called typical antipsychotics), such as haloperidol (Haldol), may be used for acute mania. They can cause severe side effects, however, particularly extrapyramidal effects, which disrupt motor control. They are not generally used on a long-term basis for treating bipolar disorder.
Benzodiazepines, such as clonazepam (Klonopin) or lorazepam (Ativan), are anti-anxiety drugs that may be particularly beneficial if the patient is experiencing severe mania.
Electroconvulsive therapy. This treatment helps patients who do not respond to medication and may even be life-saving in elderly patients with severe late-onset mania.

Step 4. Terminate Some Drug Treatments. Drugs may be stopped under the following circumstances:

When side effects are intolerable
When the patient does not respond to the maximum dose
When the patient improves and recovery is sustained

In cases of improvement and sustained recovery, the neuroleptic or benzodiazepine is slowly withdrawn and only the mood-stabilizing drug is continued.

Step 5. Continuation of Mood Stabilizers. Mood stabilizers are typically continued for about 8 weeks, unless the patient shows signs of shifting to another mood state. If the patient remains stable at that time, the doctor may decide to continue maintenance treatment or to gradually withdraw medications.

Depressive episodes pose a particular challenge. They are a significant cause of suffering, yet the use of standard antidepressants poses a significant risk for triggering mania. It is also not clear if standard antidepressants work for bipolar depression. In fact, depressive episodes are very difficult and patients who do not respond to mood stabilizers may endure prolonged depressive episodes up to 2 - 3 months.

Lithium or lamotrigine are the standard first-line treatments for depressive episodes. Many studies indicate that lithium works better for controlling manic states, and that lamotrigine works better for bipolar depression.

If improvement does not occur within 2 - 4 weeks, an antidepressant may be added. Antidepressants alone are not recommended. The first choices for antidepressants are bupropion (Wellbutrin) or paroxetine (Paxil). Alternatives include one of the selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac), a newer antidepressant such as venlafaxine (Effexor), or a monoamine oxidase inhibitor (MAOI).

Several studies have found no additional benefits from antidepressants. Many studies indicate that antidepressants may cause patients to “switch” to a manic state. Any patient with bipolar disorder who takes antidepressants and who develops symptoms of hypomania should stop taking these drugs, because hypomania is often a sign of impending mania. All antidepressants should be tapered after the mood has been stabilized for a month.

An atypical antipsychotic combined with a mood stabilizer is another treatment option. In 2003, the Food and Drug Administration (FDA) approved a drug (Symbyax) that combines the atypical antipsychotic olanzapine and the SSRI antidepressant fluoxetine. Symbyax was the first drug to be specifically approved for treatment of bipolar depression. In 2006, quetiapine (Seroquel), which is approved for treatment of bipolar mania, received an additional approval for treatment of bipolar depression.

Other Treatments. Cognitive-behavioral therapy or other psychotherapy programs may help patients endure depressive episodes by developing ways to manage negative thoughts and behaviors. Electroconvulsive therapy is another option for depression that does not respond to less intense approaches.

The first step in treating rapid cycling is to try to identify and resolve other factors, such as drug abuse or hypothyroidism, which may have caused this condition. Many patients may require a combination of medications to control rapid cycling:

Antidepressants, particularly SSRIs, may prompt rapid cycling and should be tapered off.
Lithium or valproate is a first-line treatment for rapid cycling.
Lamotrigine is an alternative treatment for rapid cycling.
Atypical antipsychotics (olanzapine, aripiprazole, ziprasidone, risperidone) are approved to treat mixed episodes. These drugs are used either alone or in combination with lithium or valproate.
One biological mechanism involved with rapid cycling is an excessive influx of calcium into brain cells. Cardiovascular drugs called calcium channel blockers may be beneficial for ultra-rapid cycling.
Low thyroid (hypothyroidism) is involved in some cases of rapid cycling. In these cases, levothyroxine, a synthetic derivative of the thyroid hormone T4 (thyroxine), has helped stabilize rapid-cycling patients.
Electroconvulsive therapy can be useful in emergency situations.

In addition, other measures should be taken:

Patients should avoid anti-anxiety drugs, alcohol, caffeine, and stimulants.
Patients should avoid exposure to bright light.
All efforts should be made to help the patient sleep normally.

Drugs Used During Maintenance. Relapse occurs in most patients after treatment of acute attacks, and patients who are at high risk for recurring episodes should consider life-long maintenance therapy. This usually involves mood-stabilizing drugs:

Lithium is a first-line mood stabilizer used in maintenance therapy. The anti-epileptic drug valproate is also a first-line treatment. In general, the two work equally well, although valproate may be better for patients who have had multiple manic episodes. There are some differences in side effects, but the drop-out rates between the drugs are similar. Lithium has proved effective for preventing relapses of manic episodes, but may not work as well for controlling depressive symptoms.
Lamotrigine, an anti-epileptic drug, was approved in 2003 for long-term maintenance treatment. It is also used as a first-line drug for treating depressive episodes.
Carbamazepine and oxcarbazepine are other anti-epileptic drugs used as alternative maintenance treatments.
Atypical antipsychotics may be used for maintenance, particularly in combination with a mood stabilizer. In 2004, olanzapine became the first atypical antipsychotic to be approved specifically for maintenance treatment.

The general recommendations for maintenance therapy with lithium are as follows:

The earlier lithium is started in the disease process, the better. Studies suggest that patients on long-term lithium therapy have survival rates comparable to the general population, but those who permanently drop out of therapy have significantly lower survival rates due to an increased suicide risk.
Lithium still works for patients who discontinue and then restart treatment later on. In such cases, however, there may be a greater need for drug combinations. In addition, patients who stop and start again may be at higher risk for hospitalization than those who use the drug continuously.
For those who want to stop, a gradual discontinuation (over 15 - 30 days) may help to delay recurrence. Stopping lithium quickly poses a high risk for relapse and even for suicide.

Information on clinical care of pregnant women with bipolar disorder remains very limited. In fact, in one survey, almost half of women with bipolar disorder were discouraged by their doctors from becoming pregnant. Nevertheless, after careful counseling about medications, possibilities for relapse, and disease severity, nearly two-thirds of them decided to attempt pregnancy.

Risks for Bipolar Episodes. Some studies suggest the following risks for bipolar episodes during and after pregnancy:

In women who discontinue lithium during pregnancy, the chance for recurrence of bipolar disorder is the same as in non-pregnant women, which is over 50%.
Pregnant women with bipolar disorder are at particularly high-risk for recurrence in the period after childbirth. In one study, symptoms recurred in 74% of women after delivery, and another 20% were hospitalized within 90 days after giving birth. The risk for depressive or mixed states is particularly high.

Drugs for Bipolar and Pregnancy. It is not ethical to test drugs during pregnancy, so all known effects of bipolar drugs are reported anecdotally. It is well-known, however, that most mood stabilizers used for bipolar disorder carry a high risk for the fetus, particularly if they are taken during the first trimester. Taking mood stabilizers at the time of delivery may help reduce the risk of manic episodes occurring after the baby is born. However, caution is still advised. Reported effects of drugs taken during pregnancy include:

Lithium can pass through the placenta and affect the fetus. When possible, patients should avoid taking lithium during pregnancy, especially during the first 3 months. Studies report that lithium use during the first trimester may cause heart defects and thyroid problems in the baby. If taken immediately before childbirth, lithium can also cause muscle weakness and drowsiness in newborn infants. Women who must take lithium during pregnancy should take the lowest possible dosage and stop the drug 1 - 2 days before delivery. Mothers who are taking lithium should not nurse their babies, since lithium is concentrated in breast milk.
The antiseizure drugs valproate and carbamazepine both greatly increase the risk for physical malformations, developmental delay, and spina bifida in babies. They appear to have minimal effect on breastfeeding, however. Lamotrigine can cause cleft lip and palate birth defects if taken during the first trimester.
Small studies have suggested that the atypical antipsychotic olanzapine does not increase the risk for birth defects. However, it does pose a great risk for excess weight gain that could be unhealthy during pregnancy. Less is known about the effects of other atypical antipsychotics during pregnancy.

Electroconvulsive Therapy (ECT). In spite of its bad press, ECT appears to be very beneficial for women with bipolar disorder who become pregnant. The patient should discuss this option with her doctor.

Doctors are still trying to decide the best treatment of bipolar disorder in children and adolescents. The drugs used for bipolar disorder have considerable side effects, which may be even more severe in younger people. Parents should consider the potential risks and benefits of treatment for their children.

Until recently, lithium was the only drug approved for treating bipolar disorder in children (age 12 years and older). In 2007, the FDA approved the atypical antipsychotic risperidone (Risperdal) for short-term treatment of manic or mixed episodes of bipolar I disorder in children ages 10 - 17.

Lithium is generally used as the first-line treatment, with valproate and risperidone (or other atypical antipsychotics) as alternatives. If treatment with a single drug does not work, a combination of drugs may be used.

Lithium and valproate are the drugs most studied in children and adolescents. However, side effects of these drugs in children may include severely impaired thinking, acne, increased urination, weight gain (lithium), and menstrual irregularities and polycystic ovary syndrome (valproate). Side effects of risperidone may include drowsiness, fatigue, increased appetite, nausea, dizziness, dry mouth, tremor, and rash.

Pediatric prescriptions for atypical antipsychotics have been increasing in recent years. However, the safety and effectiveness of these drugs for children and adolescents has not been established. They appear to work well in the short-term, but a 2006 study noted that there is little available evidence concerning their long-term effects.

Psychotherapy is also an important addition to drug treatment. Therapy that includes the entire family is important. Electroconvulsive therapy (ECT) may benefit adolescents with bipolar I disorder who suffer severe episodes of mania or depression and who have not been helped by medication.

Medications

Lithium (Carbolith, Duralith, Lithobid, Lithizine, Eskalith, Lithane) is one of the standard mood stabilizing drugs for bipolar disorder. Lithium is extremely helpful for most patients and it significantly reduces the rate of hospitalizations in bipolar disorder. Some studies report the following advantages of lithium:

Lithium is effective in 60 - 80% of all hypomanic and manic episodes. (Valproate may be better in patients with multiple manic episodes, mixed episodes, and rapid cycling.)
It helps to prevent relapses.
It helps psychosocial functioning.
It may help reduce the risk for suicide regardless of its effects on stabilizing mood.
It works well for most patients even if they have discontinued taking it and wish to restart treatment.

Administration of Lithium. Lithium may take weeks to become totally effective, so patients should not expect an immediate response during an acute episode. Doctors may take different approaches to administering the drug:

Some doctors initially administer lithium in two low doses and gradually increase the dosage over time until an effective (therapeutic) level is achieved.
Another approach is to administer a higher dose initially and measure blood levels of the drug after 24 hours. The doctor uses this information combined with a chart called a nomogram to calculate the doses most likely to be therapeutic.

In addition to drugs, several factors may affect lithium levels:

Seasonal change -- lithium levels may be higher in summer.
Menstrual cycle -- lithium levels may drop during the premenstrual phase.
Weight loss
Changes in salt intake
Dehydration
Diarrhea

Lithium levels should be monitored regularly. Side effects can occur at therapeutic levels or at those only slightly higher than desired. Blood tests that measure drug levels should be conducted frequently during acute attacks and about every 3 months during maintenance therapy.

Lithium Toxicity. Evidence of moderate toxicity include:

Trembling hands
Nausea
Increased urine output
Blurred vision
Some loss of coordination

Severe reactions occurring at higher blood levels, include:

Vomiting
Convulsions
Uncontrolled jerky movements in arms and legs
Stupor
Coma

Very high blood levels of lithium can be fatal. If overdose occurs, drugs should be stopped immediately and one or more of the following steps taken, depending on the severity:

Patients are given fluids and drugs to increase excretion of lithium salts.
Gastric lavage, a procedure that rinses the stomach, may be used to treat very recent overdoses.
Hemodialysis, a procedure that filters lithium out of the blood, may also be performed in severe cases.

Side Effects. Even for patients who do not experience a severe response, long-term use of lithium is not without problems. Weight gain is one of the main reasons why some patients want to stop taking the drug. Other side effects include:

An unpleasant taste in the mouth
Hair loss
Skin eruptions that can resemble acne and make psoriasis worse
Low thyroid function
An increased risk for diabetes
A blunted sexual drive
Dulled emotions and lack of mental clarity
Memory loss
Lack of motor coordination
Increased sensitivity to light

In some cases, light sensitivity may slightly affect a person's ability to recognize colors. More seriously, it can cause problems with night driving. This effect occurs regardless of how long a person has been on the drug. Experts recommend that patients wear sunglasses outside and avoid extensive exposure to bright light.

Drug Interactions. Because lithium is eliminated from the body by the kidneys, any drugs or dietary factors that slow the kidneys' actions may increase lithium blood levels and should be used with great caution. Such drugs include:

Nonsteroidal anti-inflammatory drugs (NSAIDs)
Thiazide diuretics
ACE inhibitors

There have been reports of interactions between lithium and certain drugs commonly used in combination, including:

Antipsychotics
Anticonvulsants
Calcium-channel blockers

The risks associated with these drug interactions are very low, but caution is needed.

Patients should be sure to contact their doctor if they have any suspicious symptoms or illnesses.

Noncompliance. Noncompliance is common. One study of lithium users found that patients took their medication only 34% of the time. Another reported that nearly a third of patients eventually went off the drug.

Side effects are certainly one reason for noncompliance. Some patients regret the loss of their manic episodes and the exhilaration and creativity that sometimes accompany them. In one small study of artists with bipolar disorder, however, only 25% felt their work had declined, while another 25% found no change in their creative output, and 50% believed that lithium had improved their output.

Despite side effects and other concerns, this important drug saves lives. Doctors are confident that lithium, which has been in use for more than 50 years, can be taken safely, even for life, by most patients.

Antiseizure drugs, also called anti-epileptics or anticonvulsants, affect the neurotransmitter gamma aminobutyric acid (GABA), which helps prevent nerve cells from over-firing. These drugs may be an alternative for patients (especially substance abusers) who do not tolerate or respond to lithium. They also may be used in combination with lithium, atypical antipsychotics, or other drugs.

Standard Antiseizure Drugs.

Valproate (Depakote), also called valproic acid or divalproex, is now a first option for many bipolar disorder patients. It works well for many patients with mania, rapid-cycling, and mixed states, as well as for patients who are substance abusers. Valproate also helps migraine headaches, a common problem among patients.
Lamotrigine (Lamictal) is approved for maintenance treatment of adults with bipolar I disorder. It appears to be particularly helpful for patients with rapid cycling and bipolar II disorder, in whom depression remains problematic after taking other mood stabilizers.
Carbamazepine (Epitol, Tegretol), a standard alternative antiseizure drug used for mood stabilizing, is usually the second anti-seizure medication of choice. In 2004, the FDA approved an extended release form of carbamazepine (Equetro). Another drug, oxcarbazepine (Trileptal), is similar to carbamazepine.
Other anti-seizure drugs used or investigated for bipolar include gabapentin (Neurontin), zonisamide (Zonegran) and topiramate (Topamax). To date, it is not clear if any of these newer drugs are useful for the treatment of acute mania.

General Side Effects. The side effects given here are associated with valproate. Other antiseizure drugs have similar effects and some specific ones of their own. Most are usually minor, occurring early in therapy and then subsiding. Valproate side effects include:

Gastrointestinal problems such as nausea, vomiting, and heartburn
Headaches
Visual disturbances
Ringing in the ear
Hair loss
Weight gain (a significant problem with valproate)
Agitation
Odd movements
Menstrual irregularities and a higher risk for polycystic ovary syndrome (PCOS)
Birth defects when taken by pregnant women
Cognitive impairment and symptoms of Parkinson's disease

Very serious side effects are possible. Stevens-Johnson syndrome (SJS) is a rare but severe and potentially life-threatening, rash that can develop as a side effect of carbamazepine, lamotrigine, oxcarbazepine and other anticonvulsants. Because this is a very serious condition, these drugs are discontinued at the first sign of rash. The risk of serious skin reactions is 10 times higher for patients of Asian ancestry than Caucasians. The FDA recommends that people of Asian ancestry get a genetic test before starting carbamazepine to determine if they are at risk for this side effect.

Other serious side effects, also rare, may include liver damage, convulsions, coma, and pancreatitis.

Atypical antipsychotics are standard drugs for schizophrenia. They are now proving to be beneficial for bipolar disorder when used alone or in combination with the mood stabilizers that treat mania. These drugs include clozapine (Clozaril) (the first atypical antipsychotic), olanzapine (Zyprexa), risperidone (Risperdal), paliperidone (Invega), quetiapine (Seroquel), aripiprazole (Abilify), and ziprasidone (Geodon).

Olanzapine was the first atypical antipsychotic approved for treatment of bipolar disorder. In 2000, the FDA approved it to treat bipolar mania and mixed states. In 2004, the drug became the first atypical antipsychotic approved for bipolar maintenance treatment.
Symbyax, a drug that combines olanzapine and the antidepressant fluoxetine, was approved in 2003 for treatment of bipolar depression.
Risperidone, ziprasidone, and ariprazole are approved for treatment of bipolar mania and mixed states. Paliperidone (Invega), which is chemically related to risperidone, was approved in 2007 for treatment of schizophrenia but has not yet been approved for bipolar disorder.
Quetiapine is approved for treatment of bipolar mania and bipolar depression, making it the only drug approved for treating both manic and depressive states.
Clozapine has not been approved for treatment of bipolar disorder, but has shown promise in investigational studies. However, this drug has more significant side effects than other atypical antipsychotics. It poses a risk of white blood cell reduction (agranulocytosis).

Side Effects. Although atypical antipsychotics have fewer severe side effects than standard antipsychotics, many patients fail to comply with regimens containing them. Common side effects include:

Nasal congestion or runny nose
Drooling
Dizziness
Headache
Drowsiness -- however, these drugs may also cause restlessness and insomnia.
Constipation
Rapid heart beat
Difficulty urinating
Skin rash
Increased body temperature
Confusion, short-term memory problems, disorientation, and impaired attention
Weight gain -- risk is highest with clozapine and olanzapine, lowest with aripiprazole and ziprasidone

More serious risks include:

Diabetes (See Diabetes Risk and Atypical Antipsychotics)
Weight gain and metabolic problems. The risk is highest for olanzapine, and lowest for aripiprazole and ziprasidone.
Unhealthy cholesterol levels. Particularly with olanzapine, increased risk for high levels of trigylcerides and total cholesterol.
Seizures
Heat stroke
Sudden drop in blood pressure (hypotension)
A significant drop in white blood cell count (neutropenia) and neutrophils (agranulocytosis) occurs in 1% or more of patients, generally in the first 6 months after starting treatment. Patients should have their white blood count and absolute neutrophil count regularly monitored if they take clozapine.
Extrapyramidal side effects, which are lack of motor coordination and involuntary movements
Cataracts and worsening of any existing glaucoma
Increased prolactin levels -- prolactin is a hormone associated with infertility and impotence. High levels can cause menstrual abnormalities and may increase the risk for osteoporosis and possibly breast cancer.

Diabetes Risk and Atypical Antipsychotics. In 2003, the FDA requested that the strongest warning be added to the product labels of all atypical antipsychotics. This so-called black box warning advises that these drugs can increase the risk of high blood sugar (hyperglycemia) and diabetes. (Olanzapine is more likely to cause high blood sugar levels than other atypical antipsychotic medicines.) The FDA recommends that:

Patients with an established diagnosis of diabetes who begin atypical antipsychotic treatment should be regularly monitored for worsening of blood sugar control.
Patients with risk factors for diabetes (obesity, family history of diabetes) should undergo fasting blood sugar testing at the beginning of atypical antipsychotic treatment and periodically during treatment.
All patients treated with atypical antipsychotics should be monitored for high blood sugar (hyperglycemia) symptoms.
Patients who develop hyperglycemia symptoms should undergo fasting blood sugar testing.

Antidepressants are sometimes used for depressive episodes in bipolar disorder, but their use is controversial. They may trigger mania in 12 - 28% of patients. In addition, a number of studies report no additional benefits from antidepressants. Specific antidepressants may be beneficial in certain circumstances. However, any patient on antidepressants who develops symptoms of hypomania should stop taking these drugs, since hypomania is often a sign of impending mania. All antidepressants should be tapered off after the mood has been stabilized for a month.

Bupropion. The antidepressant bupropion (Wellbutrin) appears to pose a lower risk for triggering mania than do other antidepressants. Side effects include restlessness, agitation, sleeplessness, headache, rashes, stomach problems, and in rare cases, hallucinations and bizarre thinking. Initial weight loss occurs in about 25% of patients. High doses may cause seizures. This side effect is uncommon and tends to occur in patients with eating disorders (anorexia or bulimia) or those with risk factors for seizures.

Selective Serotonin Reuptake Inhibitors. Serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac), citalopram (Celexa), sertraline (Zoloft), and paroxetine (Paxil), are sometimes used to treat bipolar depression, but their benefits have not yet been established. They may be useful in patients whose depression does not respond to lithium. They do not appear to be useful as an add-on treatment to lithium. Another antidepressant, venlafaxine (Effexor), may also be used in patients with severe cases of depression who do not respond to other treatments.

Side effects of SSRIs include:

Nausea and gastrointestinal problems, which usually wear off over time
Agitation, insomnia, mild tremor, and impulsivity
Dry mouth, which can increase the risk for cavities and mouth sores
Headache
Sexual dysfunction

Some weight loss may occur during the first few weeks of treatment, but over time patients on maintenance treatment typically return to their pretreatment weight.

Monoamine Oxidase Inhibitors (MAOIs). Older drugs known as monoamine oxidase inhibitors (MAOIs), particularly tranylcypromine (Parnate) are recommended for depression that does not respond to newer antidepressants. MAOIs can interact with certain foods and cause severe high blood pressure. Such foods have high tyramine content and include aged cheeses, most red wines, vermouth, dried meats and fish, canned figs, fava beans, and concentrated yeast products. MAOIs can also have severe interactions with certain drugs, including some common over-the-counter cough medications. In such cases, severe high blood pressure or dangerous reactions can occur. It is important that patients discuss with their doctor any other medications they are taking.

Other Treatments

Electroconvulsive therapy (ECT) is a non-drug treatment for bipolar disease and other mental disorders, such as severe depression. It is commonly called shock therapy. ECT has received bad press since it was introduced in the 1930s. But, over the years it has been refined, and is now considered a very safe treatment.

Research suggests ECT may be particularly beneficial for:

Patients who need immediate stabilization of their condition and who cannot wait for medications to work
Most patients with mania -- especially elderly patients with severe mania
Patients who suffer suicidal thoughts and guilt during the depressive phase
Pregnant patients
Patients who cannot tolerate drug treatments
Patients with certain types of heart problems
Young patients

In a review of studies, about 80% of ECT-treated patients experienced improvement, and for some, it is the only treatment that works.

The Procedure. ECT is performed on an outpatient basis and does not require hospitalization. In general, the ECT procedure is performed as follows:

A muscle relaxant and short-acting anesthetic are given to the patient.
A small amount of electricity is sent to the brain, causing a generalized seizure that lasts for about 40 seconds.
The response to ECT is usually very fast, and the patient often needs less medication afterward.

Side Effects. Side effects of ECT may include temporary confusion, memory lapses, headache, nausea, muscle soreness, and heart disturbances. Taking the drug naloxone immediately before ECT may help reduce its effects on concentration and some (but not all) forms of memory impairment. Concerns about permanent memory loss appear to be unfounded.

Biologic Effects of ECT on Bipolar Disorder. The precise way that ECT benefits patients with bipolar disorder is not clear. ECT may help by:

Causing changes in the brain's physiology. For example, ECT may increase the permeability of the blood-brain barrier, produce an antiseizure effect (similar to the effects of antiseizure drugs used as mood stabilizers), and reduce blood flow in parts of the brain associated with improved mood.
Causing various hormonal changes, particularly with thyroid-related hormones.
Balancing dopamine levels. This brain chemical plays an important role in bipolar disorder as well as other conditions for which ECT is sometimes recommended, including delusional depression.
Stimulating growth of neurons in the hippocampus (the area in the brain responsible for memory).

Some studies are finding that maintenance electroconvulsive therapy (ECT) may be helpful for patients who do not respond to medications. In one study of patients with bipolar disorder, those who had intractable recurrent episodes received monthly ECT treatments for more than a year and a half. Without ECT, those patients spent an average of almost half a year in the hospital, suffering at least three episodes annually. After ECT, all the rapid cyclers achieved full or partial remission.

Transcranial Magnetic Stimulation. Repeated transcranial magnetic stimulation (rTMS) is also being studied for unipolar and bipolar depression. Unlike ECT, this procedure does not appear to cause seizures, memory lapses, or impaired thinking. The only common side effect is a mild headache.

Therapy and Lifestyle Changes

Psychotherapy is an important addition to medication. Many approaches are proving to be very useful. Trained mental health professionals can:

Educate patients about bipolar disorder and its treatments
Teach patients to recognize and manage early warning symptoms of imminent manic or depressive episodes
Help them comply with drug regimens
Monitor the patient's on-going status
Intervene early in manic and depressive episodes to reduce the severity of the attack

In addition, psychotherapy can help patients:

Adjust to the reality of the illness and understand the negative consequences of mania -- particularly important for patients who consider their mania to be positive, creative, and exhilarating
Cope with feelings of guilt and remorse that occur after manic episodes
Deal with feelings of imperfection and despair

Therapists trained in cognitive-behavioral therapy (CBT) may be particularly helpful for many patients. CBT is a structured, conscious method that aims to help a patient recognize negative thoughts and behavioral patterns and to change them. CBT is known to be helpful for other mood disorders, including depression and anxiety, and some studies suggest that it benefits bipolar disorder patients as well. For example, in one recent study, patients who were given mood stabilizers and underwent a CBT program that was specifically designed to prevent relapse experienced fewer and shorter episodes and improved social functioning compared to those on mood stabilizers alone.

Using Cognitive-Behavioral Therapy for Bipolar Disorder. Typical goals of CBT for bipolar disorder patients include learning how to:

Recognize manic episodes before they become full-blown and change behaviors during an episode
Cope with depression by developing behaviors and thoughts that may help offset the negative mood

It is very important that partners, family members, or both be involved in therapy. CBT can help them learn how to accept the condition, the need for medications, and how to protect themselves and the patient financially during manic episodes. In fact, one study indicated that when a spouse of a patient learned ways of coping with the illness, the partner's chances of sticking to a prescribed treatment improved.

Supporting the Patient. Recommendations for supporting the patient include:

Create a treatment contract as a first step. In this contract, the patient and family agree to specific steps for maintaining emotional stability. If such measures fail, all parties agree on further actions to be taken during an acute episode, including requests for hospitalization.
Be supportive. Unlike relatives of patients with alcoholism who may be encouraged to get tough, relatives of patients with bipolar disorder must be strongly supportive because of the high risk for suicide with this disorder. Simply listening attentively and being empathic can help.
Get the patient to comply with treatment, even if it means threatening a hospitalization if the patient fails to comply.
Have ready a hotline number or the telephone number of a psychiatrist authorized to commit the patient. The doctor should be willing to facilitate commitment if a patient becomes violent or the family is on the verge of collapse.
Don't feel guilty and don't make the patient feel guilty. Bipolar disorder results from an imbalance of chemicals in the brain and not from anyone's fault.

Support for the Family. Unfortunately, actions that support a bipolar disorder patient may not be intuitive, and they take their toll. Loved ones must also care for themselves or they may also follow a path to severe depression. They should to boost energy and reduce stress through:

Exercise
Meditation
Relaxation techniques
Holidays away from the patient
Involvement in hobbies
Involvement in support groups, Internet resources with chat rooms, and message boards for bipolar disorder caregivers

Interpersonal problems (such as family disputes) and disruptions in daily routines or social rhythms (such as loss of sleep or changes in meal times) may make people with bipolar disorder more susceptible to new episodes of their illness. A form of psychosocial treatment called interpersonal and social rhythm therapy (IPSRT) focuses on maintaining a regular schedule of daily activities to reduce these potential triggers and improve emotional stability. Patients also learn how to avoid problems with personal relationships. Preliminary evidence suggests that IPSRT combined with drug therapy works better than medication alone. A 2-year study of patients with bipolar 1 disorder indicated that IPSRT may help prevent new manic episodes.

Exercise. Exercise is an important part of treatment, particularly in helping manage weight gain. It also helps increase feelings of well-being.

Sleep Management. Good sleep hygiene is particularly important for patients. One study reported that techniques used to enforce healthy sleep helped reduce mood cycling.

Diet. A healthy diet low in saturated foods and rich in whole grains, fresh fruits, and vegetables is important for anyone. People with bipolar disorder should be sure to maintain a regular healthy diet. They may need to restrict calories if they are on medications that increase weight.

Some research indicates that consumption of omega-3 polyunsaturated fatty acids found in oily fish (such as mackerel, sardines, salmon, and bluefish) may help reduce the symptoms of a variety of mental illnesses, including bipolar disorder. Researchers are investigating the effects of eicosapentaneoic acid (EPA) and docosahexaenoic acid (DHA) supplements for patients who have not responded to other treatments.

Resources

www.nimh.nih.gov -- National Institute of Mental Health
www.bpkids.org -- Child & Adolescent Bipolar Foundation
www.dbsalliance.org -- Depression and Bipolar Support Alliance
www.nami.org -- National Alliance on Mental Illness
www.nmha.org -- Mental Health America
www.aabt.org -- Association for Behavioral and Cognitive Therapies
www.psych.org -- The American Psychiatric Association
www.aacap.org -- American Academy of Child and Adolescent Psychiatry

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McClellan J, Kowatch R, Findling RL; Work Group on Quality Issues. Practice parameter for the assessment and treatment of children and adolescents with bipolar disorder. J Am Acad Child Adolesc Psychiatry. 2007 Jan;46(1):107-25.

Merikangas KR, Akiskal HS, Angst J, et al. Lifetime and 12-month prevalence of bipolar spectrum disorder in the National Comorbidity Survey replication. Arch Gen Psychiatry. 2007 May;64(5):543-52.

Miklowitz DJ, Otto MW, Frank E, et al. Psychosocial treatments for bipolar depression: a 1-year randomized trial from the Systematic Treatment Enhancement Program. Arch Gen Psychiatry. 2007 Apr;64(4):419-26.

Moreno C, Laje G, Blanco C, Jiang H, Schmidt AB, Olfson M. National trends in the outpatient diagnosis and treatment of bipolar disorder in youth. Arch Gen Psychiatry. 2007 Sep;64(9):1032-9.

Morriss RK, Faizal MA, Jones AP, Williamson PR, Bolton C, McCarthy JP. Interventions for helping people recognise early signs of recurrence in bipolar disorder. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD004854.

Newcomer JW. Metabolic considerations in the use of antipsychotic medications: a review of recent evidence. J Clin Psychiatry. 2007;68 Suppl 1:20-7.

Sachs GS, Nierenberg AA, Calabrese JR, et al. Effectiveness of adjunctive antidepressant treatment for bipolar depression. N Engl J Med. 2007 Apr 26;356(17):1711-22. Epub 2007 Mar 28.

Scherk H, Pajonk FG, Leucht S. Second-generation antipsychotic agents in the treatment of acute mania: a systematic review and meta-analysis of randomized controlled trials. Arch Gen Psychiatry. 2007 Apr;64(4):442-55.

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Review Date:
12/25/2007
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

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Asthma

FitSugar — Wed, 08 Oct 2008 17:34:55 -0700

Overview

Signs and Symptoms
Causes
Risk Factors
Diagnosis
Prevention
Treatment
Other Considerations
Supporting Research

HEALTH GUIDE REFERENCE FROM A.D.A.M

Asthma is a chronic disease that involves inflammation of the lungs. Airways swell and restrict airflow in and out of the lungs, making it hard to breathe. The word asthma comes from the Greek word for "panting." People with asthma pant and wheeze because of the restricted flow of air.

Normally, when you breathe in an irritant or are subjected to stressful activity such as exercise, your airways relax and open, allowing the lungs to get rid of irritants or take in more air. With asthma, muscles in the airways tighten, and the lining of the air passages swells.

About 20 million Americans have asthma, including 9 million children. In fact, asthma is the most common chronic childhood illness. About half of all cases develop before the age of 10, and many children with asthma also have allergies.

Asthma can either be allergic or non-allergic. In allergic asthma, an allergic reaction to an inhaled irritant -- pet dander, pollen, dust mites -- triggers an attack. The immune system gets involved, but instead of helping, it causes inflammation. This is the most common form of asthma.

Non-allergic asthma does not involve the immune system. Attacks can be triggered by stress, anxiety, cold air, smoke, or a virus. Some people experience symptoms only when they exercise, a condition known as exercise-induced asthma.

While there is no cure for asthma, it can be controlled.

Signs and Symptoms

Most people with asthma may go for periods of time without any symptoms, then experience an asthma attack. Some people experience chronic shortness of breath that gets worse during an attack. Asthma attacks can last minutes to days, and can become dangerous if the airflow becomes severely restricted.

Primary symptoms include:

Shortness of breath
Wheezing -- usually begins suddenly; may be worse at night or early in the morning; can be made worse by exposure to cold air, exercise, and heartburn; is relieved by using bronchodilators (drugs that open the airways; see Medications)
Chest tightness
Cough (dry or with sputum) -- in cough-variant asthma, this may be the only symptom

If you experience any of these symptoms, seek emergency treatment:

Extreme difficulty breathing or cessation of breathing
Bluish color to the lips and face (called cyanosis)
Severe anxiety
Rapid pulse
Profuse sweating
Decreased level of consciousness (such as drowsiness or confusion)

Causes

Asthma is most likely caused by a combination of several factors. Genes play a part; you’re more likely to develop asthma if others in your family have it. Among those who are susceptible, exposure to environmental factors such as allergens (substances that cause an allergic reaction) or infections may increase the likelihood of developing asthma.

Risk Factors

The following factors may increase the risk of developing asthma:

Having allergies
Family history of asthma or allergies
Exposure to secondhand smoke
Having upper respiratory infections as an infant
Living in a large city
Gender -- among younger children, asthma develops twice as often in boys as in girls, but after puberty it may be more common in girls
Obesity
Gastroesophageal reflux (heartburn)

Triggers

Childhood asthma in particular can be triggered by almost all of the same things that trigger allergies, such as:

Sensitivity to allergens such as dust, cockroach waste, pet dander, indoor and outdoor mold, pollen
Air pollutants, such as smoke, aerosols, perfumes, diesel particles, sulfur dioxide, high ozone levels, and fumes from paint, cleaning products, and gas stoves
Changes in the weather, especially in temperature (particularly cold) and humidity

Other triggers include:

Activities that affect breathing (exercising, laughing, crying, yelling)
Stress and anxiety

Diagnosis

The symptoms of asthma can mimic several other conditions, and your doctor will take a thorough history to rule out other diseases. You may also have lung function tests to measure, among other things, how much air your lungs can hold and how much air you exhale. Your doctor may use a spirometer to measure how much air you exhale and how quickly you get air out of your lungs. Other tests may include chest and sinus x-rays, blood tests, or allergy tests.

Asthma is classified as

Mild intermittent: Having mild symptoms up to 2 days a week and 2 nights a month
Mild persistent: Having symptoms more than 2 a week but not more than one time in a single day
Moderate persistent: Having symptoms once a day and more than one night per week
Severe persistent: Having symptoms throughout the day on most days and often at night.

Prevention

Although there is no way you can prevent asthma, you can take several steps to reduce the number and frequency of attacks:

Avoid allergens and irritants as much as possible. For example, to reduce exposure to dust mites, use special mattress and pillow covers that keep allergens out and remove carpets from bedrooms. Clean your house frequently.
Exercise. Even people with exercise-induced asthma can stay active, and exercise will benefit you by strengthening your lungs and helping you maintain a proper weight. Taking precautions when it’s cold outside -- such as wearing a face mask to warm the air that you’re breathing -- can help you avoid asthma symptoms. Talk to your doctor before starting an exercise regimen.
Pay attention to your breathing. Watch for signs of an oncoming attack, such as wheezing. Your doctor may give you a machine called a peak flow meter that can detect slight differences in your breathing before you even notice them and allow you to take medication immediately to ward off an attack.
Treat attacks quickly. The sooner you treat an attack, the less severe it will be, and the less medication you’ll need.

If you have allergies, a process known as allergy desensitization may decrease the number of asthma attacks and their intensity, and lower the amount of medication you need. Desensitization includes regular injections of the allergen (substance causing the allergic reaction), with each shot containing a slightly higher amount. Gradually your immune system becomes used to the allergen and no longer attacks it. Talk to your doctor about whether desensitization is right for you.

Treatment

Avoiding asthma attacks, reducing inflammation, and preventing lung damage are the primary goals of treatment. The more you know about your condition, the more you can work closely with your doctor to develop a treatment plan. Preventing exposure to allergens or irritants and taking medication as prescribed are important for the successful control of asthma. You may need emergency medications during an asthma attack, but monitoring your breathing taking your medications every day will help you control asthma over the long term.

Severe attacks may require hospitalization for oxygen and medications that are given intravenously (IV).

Lifestyle

If you smoke, quit.
Lose weight if you are overweight; excess weight may put pressure on the lungs and trigger an inflammatory response.
Monitor your condition every day using a peak flow meter (a portable device that helps measure how your lungs are working). Keep a diary of readings to show your doctor; together, you will establish your "personal best" reading. You should call your doctor if your peak flow reading falls below 80% of your personal best and go to the hospital if it falls below 50%.
Keep a journal that logs changes or attacks -- it may help determine triggers

Medications

Medications for asthma are prescribed for two different purposes: to stop an immediate attack, and to control inflammation and reduce lung damage over the long term.

Quick relief medications -- These drugs are called bronchodilators and help open the airways when you have an attack.

Short-acting beta-adrenergic agonists start working immediately. These drugs include:

Albuterol (Proventil)
Isoproterenol (Isuprel)
Metaproterenol (Aluprent)
Pirbuterol (Maxair)
Terbutaline (Brethine)
Levalbuterol (Xopenex)

Another drug that might be prescribed to help open your airway is ipratropium (Atrovent).

Sometimes, steroids are needed for an acute asthma attack. They can take longer to work (from a couple of hours to a few days) and include:

Prednisone
Prednisolone
Methylprednisolone
Hydrocortisone

Long-term control -- These drugs are usually taken every day.

Inhaled corticosteroids reduce inflammation have fewer side effects than oral corticosteroids. They include

Beclamethasone (Qvar)
Budesonide (Pulmicort)
Flunisolide (Aerobid)
Fluticasone (Flovent)
Triamcinolone (Azmacort)

A class of drugs called leukotreine modifiers help reduce the production of inflammatory chemicals called leukotreines that cause your airways to swell. They include:

Montelukast (Singulair)
Zafirlukast (Accolate)

Cromolyn (Intal), Nedocromil (Tilade) -- These medications, which are inhaled, can help prevent mild to moderate attacks and are used to treat exercise-induced asthma.

Theophylline (TheoDur) -- This medication helps open airways and prevent asthma symptoms, especially at night. Too much can cause serious side effects, so your doctor will monitor levels in your blood.

Nutrition and Dietary Supplements

Although asthma cannot be cured by any nutritional supplement, people who have a chronic illness such as asthma should eat well-balanced meals that include plenty of fruits and vegetables. Some studies have shown that people with asthma tend to have low levels of certain nutrients, but there is no evidence that taking supplements has any benefit. Rather, an overall healthy diet will ensure you get the nutrients you need and help your body deal with a long-term condition such as asthma.

Choline (3 g per day) -- Choline, a B vitamin, may help reduce the severity and frequency of asthma attacks, and allow people with asthma to use bronchodilators less often. Some evidence indicates that higher doses (3 g per day) may be most effective. More research is needed to say for sure whether choline helps.
Magnesium -- The suggestion of taking magnesium to treat asthma comes from the fact that people who have asthma often have low levels of magnesium, and from some (but not all) studies showing that intravenous (IV) magnesium can be effective as an emergency treatment for an asthma attack. However, studies that have looked at whether taking magnesium orally was beneficial have shown mixed results. More research is needed.
Omega-3 fatty acids -- The evidence for using omega-3 fatty acids (fish oil) to treat asthma is mixed. At least a few studies have found that fish oil supplements may improve inflammation and symptoms in children and adults with asthma. But the studies have only included a small number of people, and one study found that fish oil might make aspirin-induced asthma worse. Talk to your doctor about whether a high quality fish oil supplement makes sense for you.
Quercetin -- Quercetin, a kind of antioxidant called a flavonoid, inhibits the production and release of histamine and other allergic/inflammatory chemicals in the body. Histamine contributes to allergy symptoms such as a runny nose, watery eyes, and hives. Because of that, quercetin has been proposed as a treatment for asthma, but no human studies have examined whether it works or not.
Selenium -- Studies suggest that people with asthma tend to have low levels of selenium. In addition, a population-based study suggested that eating selenium-rich foods may reduce the risk of asthma. And in one small study of 24 people with asthma, those who received selenium supplements for 14 weeks had fewer symptoms than those who received placebo. However, a recent study indicated that people who took 200 mcg of selenium per day for about eight years were more likely to develop type 2 diabetes. Talk to your doctor before taking selenium supplements.
Vitamin C (1 g per day) -- One preliminary study suggested that children with asthma experienced significantly less wheezing when the ate a diet that was rich in fruits with vitamin C. Vitamin C does have anti-inflammatory and antioxidant properties, which may help you maintain good health overall. Other studies have indicated that taking a vitamin C supplement (1 g per day) may help keep airways open, but other studies have found no benefit.
Other -- Other supplements that may have benefit for asthma include:
- Coenzyme Q 10 (CoQ10) -- if you have asthma, you may have low levels of this antioxidant in your blood. It is not known, however, whether taking CoQ10 supplements will make any difference in your symptoms.
- Lycopene and beta-carotene -- preliminary data suggests that these two antioxidants, found in many fruits and vegetables, may help prevent exercise-induced asthma.
- Vitamin B6 -- may be needed if you are taking theophylline because this medication can lower blood levels of this nutrient.
- Potassium -- levels in the body also may be lowered if you take theophylline.

Herbs

The use of herbs is a time-honored approach to strengthening the body and treating disease. Herbs, however, can trigger side effects and interact with other herbs, supplements, or medications. For these reasons, herbs should be taken with care, under the supervision of a health care practitioner.

Boswellia (Boswellia serrata, 3 mg three times per day) -- Boswellia (also known as Salai guggal), an herb commonly used in Ayurvedic medicine (a traditional Indian system of health care), has shown promise in treating asthma. In one double-blind, placebo-controlled study, people who took boswellia had fewer attacks and improved lung function. Boswellia may help leukotreine modifiers work better. However, more research is needed. People who take medication to lower their cholesterol, or people who take nonsteroidal anti-inflammatory drugs (NSAIDs) should talk to their doctor before taking boswellia.
Coleus forskohlii -- Coleus forskohlii is another herb used in Ayurvedic medicine to treat asthma. A few preliminary studies that used inhaled coleus powder seemed to relieve symptoms, but more research is needed to know for sure. People who have diabetes or thyroid conditions should not take coleus. If you take an anticoagulant (blood thinner), taking coleus may increase your risk of bleeding. Pregnant women should not take coleus.
Tylophora (Tylophora indica, 250 mg one to three times per day) -- Tylophora has also been used historically to treat asthma. Some modern scientific studies show that it can help reduce symptoms, but the studies were not the best quality. More research is needed. Tylophora may cause serious side effects at high doses, so talk to your doctor before taking it. Do not take tylophora if you are pregnant, have diabetes, high blood pressure, or congestive heart failure.
Pycnogenol (Pinus pinaster, 1 mg per pound of body weight, up to 200 mg) -- A 2002 review of studies on a standardized extract from French maritime pine bark, called pycnogenol, suggests that it may reduce symptoms and improve lung function in people with asthma. Do not use pycnogenol if you have diabetes or take medication for high blood pressure. Taking pycnogenol with an anticoagulant (blood thinner) -- including aspirin -- can increase your risk of bleeding; talk to your doctor first.
Saiboku-to -- A traditional Japanese herbal mixture called Saiboku-to has helped reduce symptoms and allowed study participants to reduce doses of corticosteroids in three preliminary trials. In test tubes, Saiboku-to has shown anti-inflammatory effects. Saiboku-to contains several herbs, including Asian ginseng (Panax ginseng), Chinese skullcap (Baikal scutellaria), licorice (Glycyrrhiza glabra), and ginger (Zingiber officinale). Talk to your healthcare provider before taking Saiboku-to as the herbs it contains can interact with other herbs and medications.

Acupuncture

Some preliminary studies indicate that acupuncture may help reduce symptoms for some people with asthma, but not all studies agree. It is important to note that acupuncture should be used in addition to, not as a replacement for, conventional medicine when treating asthma.

Homeopathy

Although very few studies have examined the effectiveness of specific homeopathic therapies, professional homeopaths may consider the following remedies for the treatment of asthma based on their knowledge and experience. Before prescribing a remedy, homeopaths take into account a person's constitutional type-- your physical, emotional, and psychological makeup. An experienced homeopath assesses all of these factors when determining the most appropriate treatment for each individual.

Arsenicum album -- for asthma that generally worsens between midnight and 2 am and is accompanied by restlessness, anxiety, chills, and thirst.
Ipecacuanha -- for those with asthma, particularly children, who have significant tightness in the chest, a chronic cough with lots of phlegm that may lead to vomiting, and worsening of symptoms in hot, humid weather.
Pulsatilla -- for asthma with yellow or greenish phlegm that gets worse in the evening, in warm, stuffy rooms, or after consuming rich, fatty foods; this remedy is most appropriate for adults or children who are tearful and clingy or sweet and affectionate.
Sambucus -- for asthma that awakens a person at night with a sensation of suffocation; symptoms worsen when the person is lying down .

Mind-Body Medicine

Because stress and anxiety can make asthma worse, incorporating stress management techniques into daily life may help reduce symptoms. These techniques do not directly treat asthma, however.

Hypnosis -- may be especially useful for children, who can readily learn the technique.
Yoga -- in addition to general relaxation and reduction of stress, several studies of people with asthma have suggested that lung function improve with the regular practice. Any benefits in breathing appear to be slight, however.
Journaling -- A study published in the New England Journal of Medicine documented the positive effect of daily journaling on people with asthma. Some theorize that journaling allows for the release of pent-up emotions and leads to overall stress reduction.

Other Considerations

Warnings and Precautions

Long-term treatment with theophylline for asthma may reduce blood levels of vitamin B6.

Prognosis and Complications

People with asthma can live normal, active lives. Because asthma is a chronic illness, it requires self-care and monitoring over the long term, as well as close contact with your doctor. Most people with asthma have occasional attacks separated by symptom-free periods. Paying attention to your mood, lowering the stress in your life, and having a good emotional support system will help you take good care of yourself.

Supporting Research

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Review Date:
9/23/2007
Reviewed By:
Steven D. Ehrlich, N.M.D., private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

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