FitSugar

NikePlus.com Motivates Me to Exercise

FitSugar — Thu, 12 Jul 2007 14:30:00 -0700

People exercise for different reasons, and everyone should be exercising regularly. That's easier said than done. You definitely have to have a few tricks up your sleeve to help you stay motivated. Here's one of mine.

I bought an iPod Nano ($150) and Nike + iPod Sports Kit ($30) and I use it every time I go for a run or walk. Basically you plug the receiver into your Nano, and attach the sensor to your left shoe. Nike makes special Nike + sneakers (of course), and the sensor fits snugly in the shoe under the foot bed. I like to wear whatever brand of sneaker I want, so I just use a RunAway ($7.99) - it's a waterproof capsule that holds your sensor and attaches to your laces.

Want to know how it works? Then read more

When you go for a run or walk, the sensor on your shoe monitors your time, speed, distance, and how many calories you've burned (just wish it had a heart rate monitor too). If you hit the center button on your Nano, you'll hear a voice tell you all that info (very cool). Then when you get home, just plug your Nano into your computer and all your data automatically gets sent to NikePlus.com. It keeps track of all your runs, so you can track your progress.

You can even set goals for yourself, like run 12 times in 4 weeks, or run 20 miles in 4 weeks. I set a goal to burn 1800 calories in 4 weeks and when I reached my goal I got a "Congratulations," and a little award in my virtual trophy case. It's kind of like those gold stars I put on my calendar - a little silly maybe, but very motivating.

The bottom line is you need to find what motivates you. Tracking my progress online really gets me on a regular exercise schedule, and because I can see my stats in stone, it motivates me to keep pushing my personal limits.

Speak Up: Kelly Osbourne Doesn't Weigh-In, Do You?

FitSugar — Tue, 10 Nov 2009 11:00:19 -0800

Kelly Osbourne's bod is on its way to "sick" status, thanks to her stint on DWTS. She's noticeably shed pounds from her middle, giving her an ultra-trim waistline that she's proud to show off. In fact, costume measurements for the show reveal that she's lost two inches from her waist.

Still, while she's focused and committed to getting in shape, she's not about to become a slave to the scale, noting that, "[if] I start weighing myself, I will start being like, 'Maybe I shouldn't eat so I could lose some more . . . I would get obsessed with that fact that I was losing it and I would keep at it."

Rather than fixate on pounds lost, Kelly's all about how dancing has helped her firm up, adding that, "I suddenly have muscles in my stomach that I never had before. It's all hard and it never was like that." Kelly's positive attitude and realistic weight loss goal is definitely something to be admired - clearly, she's found what works for her. But tell me, does weighing-in help you track weight loss, or like, Kelly, is it better to chart your progress without relying on the scale?

Pros and Cons of the Elliptical

FitSugar — Thu, 15 Oct 2009 05:50:09 -0700

Since running is one of my favorite forms of cardio, I'm a big fan of the treadmill when I can't get outside for a run. I'm also big into the elliptical, and by the looks of my gym, it appears tons of other people are too. While it's a popular piece of gym equipment for so many reasons, there are also some disadvantages to using one. Check out the chart below to see if an elliptical is the right machine for you.

Pros	Cons
The circular motion and the fact that you're not pounding your feet down with each step is easier on your knees than running outside on concrete or on a treadmill. The platforms for your feet are always free of rocks, trash, dog poo, and ice, so you can count on where you're stepping to be safe and clean.	Although using an elliptical is less impact on your joints, it also requires less effort, so people complain that it's too easy. Since your feet need to stay on those little platforms, you feel like you have less control over your movements, and it's less natural for someone who's used to running.

To see the rest of the pros and cons, read more.

Pros

Cons

You control the pace by moving your legs slower or faster.
By increasing the resistance of the foot pedals you can make your workout more challenging for your legs and booty. You can also pedal backward to focus on working your backside.
You can also get an arm and upper back workout by adjusting the tension of the handles.
Since you're inside, you can watch TV to beat boredom.
The readout keeps track of your workout data including time, speed, distance, and calories burned, so you can monitor your progress.
Whether it's a torrential downpour outside or it's nighttime, you can always get in your workout.
It's a safe way to burn calories if you're afraid to exercise outside in your neighborhood.

Since you're in control of how fast your legs are moving, it's easier to slack off as compared to using a treadmill, which keeps the same pace.
Since they're a one-size-fits-all kind of machine, someone who's got a naturally shorter stride may end up hyper-extending their knees, which could lead to injury.
If you don't belong to a gym, ellipticals aren't cheap and you'll end up spending around $2,000 for a good one.
Just like any other piece of cardio equipment, the repetition of doing the same thing over again can be so boring that you cut your workout short.
The readout on the machine may not be accurate.
Ellipticals require electricity, so they're not exactly the greenest type of exercise. Plus, if there's a power outage, you can't work out.

Source: Flickr User Jill Clardy

Glaucoma

FitSugar — Wed, 08 Oct 2008 17:35:34 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

Bimatoprost (Lumigan) has been approved as a first-line treatment for open-angle glaucoma.

Glaucoma Cases Increasing Worldwide

About 60 million people worldwide will have glaucoma by 2010, and the number will increase to nearly 80 million by 2010, according to a recent study in the British Journal of Ophthalmology.

Weightlifting May Increase Glaucoma Risk

Weightlifting can cause a temporary increase in intraocular eye pressure (IOP), and holding your breath while lifting weights further increases IOP, suggests a 2006 study in the Archives of Ophthalmology. Doctors should ask patients with normal-tension glaucoma if they engage in weightlifting exercise.

IOP and Posture

IOP increases in some people when they are lying prone during sleep, yet glaucoma exams measure IOP in patients while they are sitting upright and awake, notes a 2006 study in the Archives of Ophthalmology. The researchers caution that posture may affect the interpretation of IOP readings.

Pregnancy and Glaucoma

The course of glaucoma is unpredictable during pregnancy -- IOP may remain stable in some women and increase in others, indicates a 2006 study. Although glaucoma eye drops can increase the risk of some pregnancy problems, especially during the first trimester, some pregnant women may need to continue to take glaucoma medication. Be sure your ophthalmologist carefully evaluates your individual case and explains the risks and benefits of taking medication during pregnancy.

Diabetes and Glaucoma

Type 2 diabetes increases the risk for open-angle glaucoma (the most common type of glaucoma). People with type 2 diabetes need to get regular glaucoma screenings.

Glaucoma Surgery

Tube shunts may work better than trabulectomy surgery for some patients with glaucoma, suggests a 2007 study.
Phacoviscocanalostomy, a surgery procedure that combines phacoemulsification (used for cataract surgery) and viscocanalostomy (used for glaucoma surgery), is safe and effective for patients who have both glaucoma and cataracts, indicates a 2006 study.

Introduction

Glaucoma is defined as a disease of the optic nerve, in which the nerve cells in the front of the optic nerve (the ganglion cells) die. The process is irreversible. Previously, it was believed that glaucoma was almost always due to increased intraocular pressure. However, glaucoma has been observed in many patients with normal and even low eye pressure, so the definition now rests on the damage to the optic nerve.

The Aqueous Humor. In understanding of glaucoma, it is important to first consider aqueous humor, the clear, watery fluid that circulates continuously through the front (anterior) chamber of the healthy eye and is a primary focus of glaucoma research. (This fluid is not related to tears, nor is it the dense jelly-like substance called vitreous humor that is contained in the rear chamber.) It serves two important functions in the eye:

It nourishes the area around the colored iris and behind the cornea.
It exerts pressure to help maintain the eye’s shape.

Draining the Fluid and Intraocular Pressure. The aqueous fluid is continuously produced within the front of the eye, causing pressure known as intraocular pressure (IOP). To offset the in-flowing fluid and to maintain normal IOP, the fluid drains out between the iris and cornea (an area known as the drainage angle). It does so through two channels within this angle:

The trabecular meshwork, a sponge-like, porous network, and its connecting passageways are referred to as the "conventional" outflow pathway. Most of the eye fluid outflow occurs in this region and flows from the trabecular meshwork to a group of vessels encircling the anterior chamber, called Schlemm's canal. From here, the fluid enters collection chambers and then flows out into the general blood circulatory system of the body.
The uveoscleral pathway is located behind the trabecular meshwork and is called the "unconventional" pathway. Up to 30% of the fluid flows out through this channel.

Intraocular Eye Pressure. Previously, it was believed that glaucoma was almost always due to an abnormal rise in intraocular pressure.

Glaucoma is a condition of increased fluid pressure inside the eye. The increased pressure causes compression of the retina and the optic nerve which can eventually lead to nerve damage. Glaucoma can cause partial vision loss, with blindness as a possible eventual outcome.

Increased IOP is, indeed, present in most cases of glaucoma, but some patients have normal IOP, which is usually maintained at measurements of 10 - 20 mm Hg. Measurements above this, however, do not necessarily predict glaucoma. For example, only about 10% of people with IOP levels between 21 - 30 mm Hg will actually develop glaucoma. This still puts such individuals at considerable risk for glaucoma, however.

Most people with glaucoma have the form called primary-open-angle glaucoma (also called chronic open-angle glaucoma). Open-angle glaucoma is essentially a plumbing problem.

The disease process may occur as follows:

The drainage angle remains open, but tiny drainage channels in the trabecular meshwork pathway become clogged. This pathway is responsible for most aqueous humor fluid outflow. An imbalance then occurs as fluid continues to be produced but does not drain out efficiently. Experts have still not definitely determined the precise area in the pathway where the blockage is most likely to occur. (In rare instances the pressure is high because the eye produces too much aqueous humor.)
The fluid in the eye’s anterior chamber builds up and increases pressure within the eye. This is called intraocular pressure (IOP).
The intraocular pressure exerts force on the optic nerve at the back of the eye.
Over time, the persistent pressure or other factors irreversibly damages the delicate long fibers of the optic nerve, called axons, which convey images to the brain.
As these axons die, the small cup-like head of the optic nerve may eventually collapse into an enlarged irregular shape.

Optic nerve damage is the basic glaucoma condition. If it is untreated, eventually the nerve deteriorates until a person loses sight, first in the peripheral vision (the vision in the "corner of the eyes"). If it becomes severe, the person loses central vision (in the middle of the eyes), and may eventually become blind. (Blindness is fortunately nearly always preventable with early treatment.)

Primary open-angle glaucoma tends to start in one eye but eventually involves both. In about half of patients the damage in the eye is diffuse, that is the nerve damage is generalized. In the other half the disease is localized, causing wedge-shaped abnormalities in the nerve fiber layers of the retina.

Intraocular eye pressure is normal (between 12 - 22 mmHg) in about 25 - 30% of U.S. glaucoma cases, a condition known as normal-tension glaucoma. (In Japan, the rates may be as high as 70%.) Other factors are present that cause optic nerve damage but do not affect IOP.

Closed-angle glaucoma (also called angle-closure glaucoma) is responsible for 15% of all cases. It is less common than open-angle glaucoma in the U.S., but it constitutes about half of the world's glaucoma cases because of its higher prevalence among Asians. The iris is pushed against the lens, sometimes sticking to it, closing off the drainage angle. This can occur very suddenly, resulting in an immediate rise in pressure. It often occurs in genetically susceptible people when the pupil shrinks suddenly. Closed-angle glaucoma can also be chronic and gradual, a less common condition.

Congenital glaucoma, in which the eye's drainage canals fail to develop correctly, is present from birth. It is very rare, occurring in about 1 in 10,000 newborns. This may be an inherited condition and often can be corrected with microsurgery.

The Light-Processing Parts. To understand sight, one begins with light and its passage through the eye's sensitive camera-like structures:

Light first passes through the cornea, a clear tissue at the front of the eye.
Behind the cornea, the iris (the colored tissues of the eye) opens and closes like a camera shutter to regulate the passage of light.
The lens, located behind the iris, focuses the light, which then hits the retina.
The retina is an electric fragile membrane of nerve cells called photoreceptors that receive light and translate it into signals.
A layer of cells, called the retinal ganglia, receive signals from the retina. These nerve cells are the front ends of the optic nerve cable, which, in turn, receive the signals.
The optic nerve is actually a cable of about 1.2 million nerve fibers called axons. It carries the signals to the brain, which interprets them as images.
They exit the eye through the optic disc, located in the back of the eye.

The Supportive Chambers. To help support and protect these sensitive structures, the eye contains two fluid-filled chambers:

The posterior (rear) chamber is the large area behind the iris.
Fluid passes from the posterior into the anterior (forward) chamber located in the bulging area between the iris and the front of the eye.

Causes

No single factor has been identified as a cause of primary open-angle glaucoma. A number of conditions, alone or in combination, are needed to trigger the processes leading to pressure in the first place and then to the nerve damage that destroys sight. The damage done to the optic nerve in glaucoma is triggered in most cases by the excessive pressure on the optic nerve that, over time, causes damage. Because optic nerve damage occurs in patients with normal as well as high intraocular pressure, however, researchers are investigating several other abnormal events that occur and can damage the optic nerve.

A number of genes have now been identified as possible factors in many cases of glaucoma. A gene called MYOC is of particular interest. Defects in this gene occur in between 3 - 6% of patients with adult-onset and juvenile open-angle glaucoma. They appear to overproduce a sticky protein called myocilin, which clogs the trabecular meshwork. The genes WDR36 and OPTN may cause primary open-angle glaucoma. Researchers hope that identification of genes will help improve screening of high-risk patients.

Specific syndromes have been identified with glaucoma. Many have an inherited component, although in most cases other factors must be present to activate the disease process.

Pseudoexfoliation Syndrome. Pseudoexfoliation (PEX) syndrome (also known as exfoliation syndrome) is the most common identifiable condition associated with glaucoma. In one study, 9% of patients with open-angle glaucoma had the syndrome. PEX occurs when dandruff-like matter flakes off the outer layer of the lens and collects in the drainage angle. The substance is composed of proteins produced by the lens, iris, and other parts of the eye. People can have this condition and not develop glaucoma, but they are at high risk. In one Australian study, 14% of the people with this condition had glaucoma compared to 2% of those without exfoliation. PEX has a strong genetic component but other factors (possibly sunlight, an autoimmune response, or slow virus) may be needed to trigger the disease.

Pigment Glaucoma. Pigment glaucoma starts with a condition called pigment dispersion syndrome, an inherited condition in which granules of pigment (the substance that colors the iris) flakes off into the intraocular fluid. In about 30% of cases, these fragments clog the trabecular meshwork and pressure builds up, causing glaucoma. In one study, 2% of patients had this form of glaucoma.

Irido Corneal Endothelia Syndrome. In irido corneal endothelial syndrome (ICE), cells on the back surface of the cornea spread to the drainage angle, sometimes forming scars that connect the iris to the cornea.

Neovascular Glaucoma. Neovascular glaucoma is always associated with other disorders, usually diabetes, that result in abnormal formation of new blood vessels on the iris and in the drainage system.

Aniridia. Aniridia is a rare inherited disorder (in which the iris is abnormal and increases the risk for glaucoma) that is difficult to treat. (A surgical approach called goniosurgery may help prevent glaucoma in young people with aniridia.)

Congenital Glaucoma. When an infant is born with glaucoma (congenital glaucoma), it is usually caused by an inherited abnormality in the drainage canal. Researchers have identified the gene responsible for 85% of these cases.

A natural process called apoptosis (cellular self-destruction) may contribute to damage in the retinal ganglion nerve cells, the nerve cells that are the front line of the optic nerve. Cell death can occur with or without elevated eye pressure. It is not clear what triggers apoptosis and cell death in such cases, but there are a number of suspects.

Excess Glutamate. Researchers have observed abnormally high levels of glutamate in people and animals with glaucoma. Glutamate is an amino acid that excites nerve cells. In the eye this occurs during vision. Some experts theorize that in glaucoma, either reduced blood flow or increased pressure on nerve cells triggers the release of excess glutamate. In large amounts, glutamate causes the nerve cells to fire intensively, which eventually destroys them.

Reduced Blood Flow. Researchers have observed reduced blood flow to the optic nerve in patients with glaucoma associated with both high and normal IOP. Less blood flow suggests oxygen loss, which may play a role in the destructive process. Some studies suggest that the greatest risk factor for nerve damage in patients is when blood pressure to the eye drops during the night. Ocular pressure at this time is highest, so the risk for nerve damage becomes intensified. Of interest in this regard are reports finding a significant reduction in eye blood pressure at night in patients with normal-tension glaucoma.

Excess Nitric Oxide. Elevated levels of nitric oxide, another nerve-stimulating compound, also plays a role in the nerve-damaging process. Nitric oxide is critical for nerve function and flexible blood vessels, but excess amounts may be toxic to nerves.

Glaucoma and Alzheimer's Disease. Some research has pointed out similarities in the process leading to cell death in glaucoma and Alzheimer's disease. Specifically, in both diseases activation of certain enzymes called caspases occurs and leads to accumulation of fragments of beta amyloid, an insoluble protein that forms sticky patches.

Autoimmunity. Some experts are studying the possibility that normal tension glaucoma may be an autoimmune disease; that is, factors in the immune system, including antibodies, attack cells in the person's own body as if they were foreign substances. In the case of glaucoma, such antibodies would damage parts of the optic nerve.

H. pylori Infection. Some research indicates that glaucoma is associated with Helicobacter (H.) pylori, the bacterium implicated as a major cause of peptic ulcers. Studies have reported over 87% of patients with glaucoma are infected with this bacterium.

People with acute closed-angle glaucoma often have a structural defect that causes a narrow angle between the iris and cornea where the aqueous humor circulates. Conditions that suddenly dilate the pupils may cause this shallow angle to close and precipitate attacks of acute glaucoma in susceptible people. Such conditions may include:

Certain drugs such as antihistamines, tricyclic antidepressants, some asthma medications (nebulized ipratropium), some anti-seizure drugs (topiramate)
Darkness
Emotional stress

When intraocular pressure leading to glaucoma is caused by other diseases or conditions, it is known as secondary glaucoma. Secondary glaucoma may be chronic or acute, mild or severe.

Medical Conditions. A number of diseases can contribute to the development of intraocular pressure leading to glaucoma:

Diseases that affect blood flow to the optic nerve (diabetes, high blood pressure, migraine; people with type 2 diabetes should be regularly screened for glaucoma.)
Hypothyroidism
Sleep apnea
Physical injury in the eye
Extreme nearsightedness (myopia)
Previous eye surgery
Other disorders, including leukemia, sickle cell anemia, and some forms of arthritis

Corticosteroids. Corticosteroids, commonly called steroids, have multiple effects on the trabecular meshwork and may even cause genetic changes. In fact, studying the effects of steroids on the eye is helping researchers understand the glaucoma disease process. Steroids pose a higher or lower risk depending on the form:

Taking topical steroid treatments in the eye poses the highest risk. It must be monitored carefully since, in some cases, damage may be permanent.
Taking oral corticosteroids, particularly in high doses or for long periods, increases the chance of glaucoma. In such cases, the eye disorder typically develops almost immediately and reverses within 2 weeks after the drug has been withdrawn.
Inhaled steroids were not thought to cause glaucoma, but there is some risk in people with a family history of glaucoma and other risk factors.

Symptoms

Chronic glaucoma is insidious. If the pressure increases slowly, it will not produce any symptoms until it has done irreversible damage. In such cases, people may notice visual problems at first only when light is dim. Patients are often sensitive to glare. Eventually they may lose contrast sensitivity; that is, they might have trouble differentiating between varying shades and brightness.

In acute closed-angle glaucoma, the pressure inside the eye increases quickly, and the symptoms are dramatic. Intense pain in the eyebrow area and blurred vision develop usually in one eye, and the patient often feels like the eye will burst (although it won't). The eye usually reddens. A person may see rainbow-like halos around lights. Sometimes nausea and vomiting occur. These symptoms may occur on and off and not appear as a full attack. In either case, they indicate a medical emergency. In chronic closed-angle glaucoma, the process is gradual and painless.

Although congenital glaucoma is usually present at birth, symptoms generally don’t develop in the infant for a few months. If parents notice that an infant’s eyes are enlarging, becoming cloudy, often watering, or tending to close in the presence of light, they should have an ophthalmologist examine the child’s eyes. Port-wine stains on an infant’s face could indicate the Sturge-Weber syndrome, a disorder that occasionally causes glaucoma.

Outlook

Worldwide, glaucoma ranks as one of the leading causes of blindness. Even if people with glaucoma do not become blind, vision can be impaired. In developed countries, most people get treatment in time to preserve their vision. Even so, glaucoma causes between 3 - 6% of blindness cases in Caucasians, and even more cases in African Americans.

In a 20-year study of Caucasian patients with glaucoma, blindness in at least one eye occurred in 27% of patients and blindness in both eyes occurred in 9% of patients. The blindness rates in African Americans are most likely higher. In fact, glaucoma is the leading cause of blindness in African Americans. Despite this higher prevalence, this ethnic group receives surgical treatment at half the rate of Caucasians.

The Process Leading to Vision Loss. Chronic glaucoma is often called “the silent thief of sight," because the afflicted person has no warning sign, no hint that anything is wrong. Untreated, the destruction develops slowly over time:

Over years or decades, the increased pressure compresses nerves at the back of the eyes.
Glaucoma gradually destroys first the outer fibers of the optic nerve, which reduces peripheral vision (the top, sides, and bottom areas of vision), but not central vision.
By the time a person notices that peripheral vision has been lost, permanent damage has already occurred.
If the eye pressure remains high, the destruction can progress until tunnel vision develops, and the person is only able to see objects that are straight ahead.
The last nerve fibers destroyed are those responsible for central vision; if this occurs, the glaucoma victim becomes totally blind.

Although there is no cure for open-angle glaucoma, a number of treatments are available that lower intraocular pressure and slow progression of vision loss.

Risk Factors for Vision Loss. Estimates of progression rates in vision deterioration range from 9 - 30% over a 2 - 7 year period.

According to a study on patients with elevated IOP, for every 1-mm Hg increase in IOP, there is a 10% higher risk of disease progression. A very elevated IOP (above 30 mm Hg) is certainly hazardous. An elevated IOP that is below 30 mm Hg, however, is not necessarily the most important factor in determining the risk for disease progression. Some evidence suggests that frequent and large daily fluctuations in intraocular pressure, not simply high IOP, are associated with the greatest risk for loss of vision. Having normal-tension glaucoma with optic nerve damage also carries a high risk for progression, even if eye pressure is reduced.

In any case, factors other than IOP play a role in increasing the chances for progression and vision loss in patients with slightly elevated IOP and normal tension glaucoma:

Both eyes affected
Pseudoexfoliation (PEX) syndrome. PEX occurs when proteins produced in the eye flake off the outer layer of the lens and collects in the drainage angle.
Bleeding in a specific region called the peripapillary nerve fiber layer
Thin corneas. (People who have thick corneas and elevated IOP may only need to be monitored if they have no other risk factor for vision loss.)
Larger cup-to-optic disc ratio. (The cup of the optic disc is the center portion, which enlarges as nerve damage progresses.)

Non-eye related factors associated with disease progression include being elderly, African American, female, or having a history of migraines.

Acute closed-angle glaucoma is a medical emergency; if the high pressure is not reduced within hours, it may permanently damage vision. Anyone who experiences its symptoms should immediately contact an ophthalmologist or go to a hospital emergency room.

Risk Factors

About 2 million Americans have open-angle glaucoma, but an exact count is unclear. Experts estimate that by 2010, over 60 million people worldwide will have glaucoma, with 74% of these cases due to open-angle glaucoma. Half of people with glaucoma are unaware of this problem because the condition causes no symptoms.

Elevated intraocular pressure in the eye occurs in 5 - 10 million Americans, but only about 10% of such people develop glaucoma because of this pressure. And, in 15% of actual glaucoma cases, IOP is normal. Major studies are helping to clarify the people who are at highest risk for glaucoma and optic nerve damage, including those with normal tension glaucoma.

Elderly. The prevalence of chronic glaucoma increases with age. In a major study, 0.6% of people age 60 - 64 had primary open-angle glaucoma. Among people who were 10 years older, the prevalence had more than doubled to 1.3%, and among those who were age 80 - 84, it had more than doubled again to 3%.

People of African Descent. Across all age groups, according to a 2000 report, the prevalence of glaucoma in African Americans is about 3.5% compared to about 1% in Caucasians. In addition, U.S. studies suggest that glaucoma develops earlier in African American population groups (starting at age 45 instead of age 60 in Caucasians). And, their risk for blindness once they have glaucoma is 14 - 17 times that of Caucasians with glaucoma. African American men are at higher risk than women. African American children who are extremely near-sighted and have relatives with glaucoma should begin regular eye examinations for glaucoma as early as possible.

In a major glaucoma study in Barbados, where most people are of African descent, over 10% of those age 50 and older had open angle glaucoma, and over 15% were afflicted after age 70. About half of the cases had normal or lower eye pressure. An interesting 2001 study suggested that African Americans tend to have significantly thinner central corneas than Caucasians. This could lead to misleadingly lower pressure scores in African American patients who actually may have high IOPs.

Family History. Glaucoma tends to run in families. Brothers and sisters of patients with open angle glaucoma are 5 times more likely to develop glaucoma by the time they are 70 years old than people whose siblings do not have the disease. Previous studies have also found that people with family histories of glaucoma are more likely to already have some vision loss when they are first diagnosed with glaucoma.

Effects of Blood Pressure. The association between a person's blood pressure and intraocular pressure in the eye is not entirely clear. A number of studies have found a higher risk for glaucoma in people with high blood pressure. A 2002 study suggested, however, that people with blood pressure that is low relative to their intraocular pressure may be at higher risk for glaucoma. The same study found no higher risk for glaucoma in people with hypertension, and in fact, high blood pressure was associated with a lower risk.

Having Certain Medical Disorders. Individuals with certain medical or physical conditions, including diabetes, migraine, nearsightedness, and sleep apnea, appear to have a higher risk. Conditions that require the use of any oral or inhaled steroid, particularly high doses for prolonged periods of time, can cause glaucoma. Previous eye surgery also puts people at risk.

Weightlifting. According to a 2006 study, holding your breath while weightlifting can increase the risk for developing normal-tension glaucoma. Weightlifting causes temporary increases in eye pressure; holding your breath during this exercise leads to even greater intraocular pressure.

Risk Factors for Closed-Angle Glaucoma. Chronic closed-angle glaucoma tends to be more common in people of Asian and African descent. Those who have this condition are often extremely farsighted. Acute closed-angle glaucoma occurs much more frequently in women than in men.

Risk Factors for Normal Tension Glaucoma. Risk factors for normal tension glaucoma include Japanese ancestry and a family history of the disease. It is more common in women than in men. A family history of cardiovascular disease also increases the risk.

Risk Factors for Pigmentary Glaucoma. Pigmentary glaucoma occurs three times more often in men then in women and at a younger age.

Risk Factors for Irido Corneal Endothelial Syndrome. This condition occurs more often in light-skinned women.

Diagnosis

A diagnosis of glaucoma no longer simply relies on the presence of pressure within the eye. It requires that there be optic nerve damage or a strong suggestion of damage, which can be clearly seen during a dilated eye examination of the optic nerve. In general, the hallmark sign of this condition is a loss of peripheral vision. With peripheral vision loss, a person can see in front of him- or herself but has lost the vision to the side.

The optic nerve carries the information of vision from the eye to the brain.

Because chronic glaucoma has no warning symptoms, half of its victims are unaware that they have the condition. Early diagnosis, however, is the key to successful treatment of glaucoma. One study reported that the more years since the last visit to an eye professional, the greater the risk for having visual loss.

Everyone over age 65 and African Americans over 40 years old should have periodic eye exams, including tests for glaucoma, every other year.
African Americans between ages 20 - 39 should have eye examinations every 3 - 5 years.
Other people at higher risk (people with diabetes, history of eye injuries, a family history of glaucoma, or those taking corticosteroid medications) should have eye examinations every year after age 35.
People with known glaucoma should have frequent examinations to check peripheral vision and to be sure treatment is maintaining a safe eye pressure. After such examinations, the ophthalmologist will assess current treatment and make necessary adjustments.

Doctors determine the intraocular pressure (IOP) of the aqueous humor inside the eye using tonometry, which measures the force necessary to make an indentation in the eye. There are several methods:

In the Schiotz method, the doctor first anesthetizes the eye with drops, then presses very lightly against it with tonometer, a tiny smooth instrument that is used to measure the pressure.
In the applanation method, the doctor touches a strip of orange-dyed paper to the side of the eye. The stain helps with the examination and rinses out with tearing. The doctor uses a slit-lamp, which is moved forward toward the patient's face until the tonometer touches the eye.
The noncontact approach applies a puff of air and measures the force needed to indent the eye.

Attempting to close the eyelids during the test can increase eye pressure and produce errors in the results.

In general, normal IOP is usually maintained at measurements of 10 - 20 mm Hg. Glaucoma pressure over 21 mm Hg indicates a potential problem. The test is not completely accurate, however. Only about 10% of people with IOP levels between 21 - 30 mm Hg will actually develop glaucoma and optic nerve damage. On the other hand, many people with glaucoma have normal pressure, at least for part of the time.

Changes in posture may also affect IOP. A 2006 study indicated that IOP increases during sleep or when a person is lying down. As IOP tests are generally given in a doctor’s office when a patient is sitting up, they may not provide a completely accurate evaluation of eye pressure.

The cornea thickness may be an important indicator of disease progression in patients with elevated IOP. According to some research, patients with thinner corneas have a significant risk for developing damage from glaucoma, while those with thicker corneas have a low risk.

In order to determine early damage in the optic nerve, a number of diagnostic instruments have been developed to assess the nerve fiber layers at the back of the eye (the fundus) and to check for optic disk cupping. (The cup of the optic disc is the center portion, which enlarges as nerve damage progresses.) The two most common procedures for identifying nerve damage are ophthalmoscopy and fundus photography. Other instruments have been developed, including those that use laser technology and computers, but none have proved to be infallible. No test has proven to be completely accurate, however, and none is routinely performed by all eye professionals.

In order to be accurate, the tests require a skilled professional and there are certain common factors:

The pupils must also be widely dilated using eye drops before the procedure.
Even mild cataracts and a slightly less-than-optimally dilated pupil can degrade the results. Such conditions are common in elderly people, who are the most likely to develop glaucoma.
If the back of the eye is lightly pigmented (colored), the area under observation is less distinct.
If the glaucoma is diffuse and there is a generalized loss of nerve fiber (which occurs in half of patients), it is more difficult to detect than if the glaucoma is more localized.

If IOP is low or normal and tests report optic nerve damage and peripheral visual loss, doctors should also check for other conditions before starting any treatment for glaucoma. Such problems include steroid use, anemia, and previous hemorrhage or severe low blood pressure.

Ophthalmoscopy. The eye professional (or even a primary care doctor) uses an ophthalmoscope to peer through the pupil directly at the optic nerve. The examiner can then check the shape and color of the nerve fibers to evaluate whether they have been damaged by the high pressure of glaucoma. Damaged nerve fibers may be indicated by:

An asymmetrical or elongated cupped optic nerve
The optic nerve color may be pale or an unhealthy-pink

If results show no optic nerve damage in patients who have mild elevations in pressure, the ophthalmologist may want to retest frequently but delay drug treatment, unless the patient has significant risk factors.

Fundus Photography. Fundus photography may be used to take pictures of the optic nerve and can reveal changes years in advance of vision loss. It is an unpleasant procedure requiring drops and a bright flash. This procedure has the same limitations as ophthalmoscopy.

Laser Polarimetry. Polarimetry uses laser technology to scan the eye and does not require any response from the patient. It is reported to be able to measure nerve fiber thickness in the eye and so be able to reveal early signs of deterioration. Preliminary studies have indicated that it has a diagnostic accuracy of over 90% for both confirming and ruling out glaucoma. One study, however, reported that laser polarimetry was sensitive enough to detect glaucoma in only up to 57% of patients with early glaucoma, 71% of those with moderate disease, and 81% of those with severe glaucoma. More research is needed.

Other Devices. Computer-assisted devices, such as the confocal scanning laser ophthalmoscope, are now available that may be useful for evaluating the retinal nerve layer. Another instrument, the optical coherence tomograph, measures the echo time delay of light that is scattered back from different layers in the retina. The value of these tests has not yet been determined.

If there is indication of optic nerve damage, the eye professional will conduct tests of the visual fields (the areas that the patient can see). In most people with glaucoma, the first areas to become noticeably impaired are the peripheral visual fields (areas of sight that are not directly in front of a person but more to the sides).

Click the icon to see an image of the visual field test.

Standard Perimetry Tests. Perimetry tests are used to check peripheral vision. One variation of this test is as follows:

A person sits closely facing a large computer-like monitor.
Small bright white lights flicker on and off hundreds of times, at different places on the screen, while the patient clicks a button whenever one of the lights is seen.
The machine prints out a report that maps any blanked-out areas in the person’s vision.

The test is complex and lengthy; elderly people and those with short attention spans may be inappropriate candidates. Other perimetry tests, some requiring less time to administer and some using "virtual reality" techniques, are currently being developed.

Other Tests. Other visual field tests are being developed that can detect abnormalities years before they can be detected by standard perimetry. Experts recommend some of these tests in selected patients with suspected glaucoma.

For example, a screening test called frequency doubling technology (FDT) checks for changes in particular cells in the retina that are indications of early glaucoma. It takes less than a minute to perform.

Another test called short wave automated perimetry (SWAP) uses colors (blue-on-yellow) and also detects very early abnormalities in the visual field. Testing time is longer than with FDT, however, and the presence of certain types of cataracts can interfere with its accuracy.

ELAM-1. Endothelial leukocyte cell adhesion molecule 1 (ELAM-1) is a molecule that has been found in glaucoma but not in healthy eyes. This molecule may prove to be a "marker" and its presence may be helpful in diagnosing glaucoma.

A simple test using a penlight helps determine the risk for acute closed-angle glaucoma. A beam of light is directed from the side of the face toward the patient's iris. If no shadow appears on the nose, then most likely the angle is wide enough to dilate. Using an instrument called a gonioscope, ophthalmologists can also inspect the front of the eyes and assess the drainage angle between the cornea and the iris and the channels in the trabecular meshwork. This test can differentiate between closed- and open-angle glaucoma.

Treatment

Most treatments for glaucoma aim to reduce ocular pressure and its fluctuations. Early treatment with medications, surgery, or both can nearly always maintain safe pressure of the aqueous humor, thus preventing optic nerve damage and blindness. The choice between surgery and medications and when to start treatment is not always straightforward. For example, with the introduction of beta blockers and newer glaucoma drugs, there has been a decline in surgeries. It is not clear, however, which drugs are more effective than others and if, over time, any will actually prevent surgery. Patients should discuss all issues with their doctors and ophthalmologists.

Many people have high IOP but no sign of nerve damage. Over the course of 20 years, only between 10 - 30% of these people will actually develop glaucoma. Nevertheless, once glaucoma has destroyed optic nerve fibers, no known treatment can reverse the damage.

Indeed, studies suggest that in people with glaucoma, even very small differences in pressure may mean the difference between disease progression and stability. An important trial reported that, on average, treating patients when their glaucoma was first detected reduced IOP by 25%. In addition, treatment reduced the risk for progression by 17%. This study confirmed previous findings supporting early treatment for glaucoma. Another study found that treatment with eye drops halved the risk of developing open-angle glaucoma in African Americans who had elevated IOP. Some evidence suggests that early treatment to lower IOP may be beneficial even in patients with normal tension glaucoma.

However, not all individuals with early signs of glaucoma (elevated IOP or normal-tension glaucoma) develop optic nerve damage and serious vision problems. Nor does treatment prevent progression in a large minority of patients. Medications used for glaucoma also can carry significant side effects and risks.

Some experts suggest that treatment is warranted only in people with early signs of glaucoma who have risk factors for progressive disease and vision loss (thinner corneas, larger cup to optic disc ration, older age, and elevated pressure).

A number of effective drugs are now available for treating glaucoma. The drugs reduce pressure in the eye but all have a number of side effects that affect other parts of the body. Some of these side effects can be quite severe. Many of the drugs used for glaucoma also interact with common medications for other conditions. To compound the difficulties, many patients require multiple drugs. As a result, only about half of patients comply with their treatments.

Experts generally recommend topical drugs first (those that can be used as eye drops or ointments rather than taken by mouth).

Topical beta blockers are the standard first-line drugs, most commonly timolol (Timoptic). Newer beta blockers include betaxolol (Betoptic), levobunolol (Betagan), carteolol (Ocupress), and metipranolol (OptiPranolol). Timolol has been used for years, and these other drugs are also well tolerated.
Topical prostaglandins are alternatives if beta blockers fail. They include latanoprost (Xalatan) and unoprostone (Rescula). Of the standard drugs used for glaucoma, these drugs have the greatest effect on lowering IOPs. They also have fewer widespread effects than the beta blockers.
Topical carbonic anhydrase inhibitors (CAIs) are less effective than standard beta blockers or prostaglandins but have fewer widespread effects than the beta blockers. They may be helpful in certain cases. Topical forms are dorzolamide (Trusopt) and brinzolamide (Azopt). (Oral CAIs are available and more effective, but they have severe side effects and are rarely used for the long term.)
Alpha2-adrenergics, also called selective alpha adrenergics, are effective but may not be as well tolerated as timolol. They include brimonidine (Alphagan).
Miotics, which include pilocarpine and others, were the standard drugs before the introduction of topical beta blockers. They have now been largely replaced by timolol and others, although they are sometimes used in combinations.
Beta blockers and newer drugs (prostaglandins, topical CAIs, and selective alpha adrenergics) are now preferred over the older drugs, which include miotics, oral CAIs, and nonselective alpha adrenergics.

Combinations. Combinations of these drugs can be very effective, because they tend to have different actions. Single medications that contain two drugs are becoming available. For example, Cosopt combines timolol and dorzolamide; Timpilo is a combination of timolol and pilocarpine. Studies of these and other combinations compared to each other to single drugs are ongoing. To date, results on any superior combinations have been mixed. It should be noted that the side effects of each drug apply to any combination.

Treating the Pregnant Patient. Considerations for a pregnant woman with glaucoma can be complicated. All of the drugs used for glaucoma are absorbed by the body, cross the placenta, and are excreted in breast milk. Many have effects that can interfere with or adversely affect pregnancy.

Women should discuss going off medication, particularly during the first trimester, and be monitored during that time for increasing eye pressure. IOP tends to drop during pregnancy, although usually not to a significant degree. In addition, changes in IOP and visual loss vary greatly. Some women experience no IOP change or visual loss during pregnancy, while others may experience an increase in IOP or worsening of visual loss. It is important that your ophthalmologist carefully considers your individual case and discusses with you the risks and benefits of continuing glaucoma medication during pregnancy.

If women need to take medications, they should try to achieve the lowest dose possible. Some drugs have fewer side effects than others. Pregnant women must also be very careful about administering eye drops to allow as little medication as possible to enter the body. When taking eye drops, press your index finger against the corner of the eye near your nose. This helps prevent the eye drop from passing down into the tear duct where it is easily absorbed through the rest of the body. Even this approach, however, does not guarantee complete safety. Women with glaucoma who are planning to become pregnant might want to consider surgery before they conceive.

The object of standard glaucoma surgery is to reduce pressure in the eye by increasing the outflow of the aqueous fluid. Two methods are commonly used:

Filtration surgery (trabeculectomy). This uses standard surgical instruments to open a passage in the eye for draining fluid.
Laser trabeculoplasty. This procedure uses a laser to burn 80 - 100 tiny holes in the drainage area.

Both are effective, but certain patient groups may respond to one more than the other. For example, African Americans may do better with laser surgery while trabeculectomy may be a better choice for Caucasians with no serious medical problems.

In general, surgery is a last resort. Doctors may, however, recommend surgery before drug therapies for patients unlikely to comply with difficult drug regimens or for patients who may have severe reactions from the glaucoma drugs. Women who plan on becoming pregnant should also discuss surgery with their doctor.

Some studies indicate that laser treatment performed as the initial treatment for glaucoma is as effective as medications in some cases. Findings in 2003 from a major comparison study suggested that 4 years after surgery there was little difference in visual field loss between trabeculectomy and medical treatment. There was, however, a higher risk for cataracts and loss of vision sharpness with surgery. On the other hand, side effects from medications may be ongoing and troublesome. It is important to note that even surgery does not cure glaucoma, and over half of patients will require medication within 2 years. Experts who are against early surgeries also argue that studies on their success often omitted serious postoperative problems, such as late-onset infection, and quality of life assessments.

Medications

Nearly all glaucoma medications are prescribed for reducing eye pressure. Lowering IOP is even proving to be beneficial for about two-thirds of patients with normal-pressure glaucoma.

Topical beta adrenoceptor blockers (common called beta-blockers) are the drugs most often prescribed to treat glaucoma. They lower the pressure inside the eye by inhibiting the production of aqueous humor.

Brands. These drugs are categorized as either nonselective or selective beta-blockers:

Nonselective adrenoceptor beta-blockers. Timolol (Timoptic, Betimol) has been the standard beta-blocker for years. Newer nonselective drugs include levobunolol (Betagan), carteolol (Ocupress), and metipranolol (OptiPranolol). A few studies suggest some are more beneficial than timolol with similar side effects.
Selective beta1-adrenoceptor blockers. Betaxolol (Betoptic) and levobetaxolol (Betaxon) are selective beta-blockers. These drugs appear to have fewer adverse effects on the heart than the nonselective beta-blockers, although they still have widespread effects. Studies also suggest that they slow progression more than timolol, although timolol is more effective at lowering IOP. selective beta-blockers may also have nerve-protecting properties.

All beta-blockers are effective and generally well tolerated. Because they cause less eye irritation than many other glaucoma medications, they are often prescribed for patients who also have cataracts.

Side Effects and Complications. After the beta-blocker is administered, only a tiny amount of the drug is absorbed by the cornea. Most of it enters in the bloodstream. These drugs, therefore, can cause side effects in parts of the body other than the eyes ("systemic" side effects):

Common systemic side effects include reduced sexual drive, fatigue, depression, anxiety, severe nausea and vomiting, and breathing difficulties.
Beta-blockers affect the heart. They lower heart rate and reduce blood pressure. (The newer selective beta-1 blockers may not have as bad effects on the heart as the nonselective beta-blockers.) They may also cause unhealthy cholesterol and triglyceride changes.
All beta-blockers can worsen severe asthma or other lung diseases. Beta-blockers should only be used very cautiously or not at all by anyone with asthma, emphysema, bronchitis, or heart disease. In one study, lung function was reduced in 40% of elderly people who took timolol, even those without previous symptoms of lung problems. (Selective beta-blockers may produce fewer of these adverse effects.)
If the patient is switching to a beta-blocker from other glaucoma medication, there may be a sudden rise in eye pressure. It is important that the pressure be checked shortly after the other drug has been withdrawn.
When beta-blockers are used to treat one eye, the other (contralateral) eye also experiences a lesser, but still significant reduction in IOP.

Interactions with Other Medications. The effects of the eye medication may be additive to other oral medications, such as oral beta-blockers, calcium-channel blockers, or the antiarrhythmic drug quinidine. People with diabetes who take insulin or hypoglycemic medications should realize that timolol side effects may resemble and mask the symptoms of hypoglycemia (low blood sugar).

Prostaglandins are hormone-like substances that help open blood vessels. Drugs that resemble prostaglandins increase outflow of aqueous humor (the watery substance in the eye). Drainage of aqueous humor helps reduce intraocular pressure.

Brands. Latanoprost (Xalatan) and unoprostone (Rescula) are the standard brands. Latanoprost was the first prostaglandin to be approved as first-line treatment for elevated eye pressure. Two newer prostaglandins, travoprost (Travatan) and bimatoprost (Lumigan), may help some patients who do not respond to latanoprost. These drugs may also benefit patients with normal-tension glaucoma. Latanoprost, travoprost, and bimatoprost need to be taken only once daily. Unoprostone needs to be taken twice a day and is not as effective as others, but it still can reduce IOP significantly and is the least expensive of these drugs.

Latanoprost has been shown to reduce pressure by between 45 - 70%. Some, but not all studies, have suggested that newer prostaglandins travoprost (Travatan) and bimatoprost (Lumigan) are more effective than latanoprost, but the older drug appears to be better tolerated. All of these drugs may be work better than timolol in lowering IOP. The newer prostaglandins may be especially superior to timolol in treating African American patients. In comparison studies, latanoprost achieved better IOP pressure reduction than brimonidine. Studies have suggested that bimatoprost is more effective in lowering eye pressure than a combination of timolol and dorzolamide (Cosopt). Studies have been mixed on whether latanoprost is superior to the combination.

Side Effects. These drugs do not slow down the heart rate and also appear to be safe for people with asthma. Side effects include itching, redness, and burning during administration. Muscle and joint pain may also occur. All of these drugs may permanently change eye color from blue or green to brown. To date, such color changes do not seem to be hazardous. (The only significant problem may be cosmetic in people who treat only one eye, since the color may differ from the other.) These drugs can increase blood flow in the eye and also make eyelashes become thicker and longer in some patients. (These latter effects are more common with bimatoprost and travoprost than with latanoprost.)

Carbonic anhydrase inhibitors (CAIs) decrease eye pressure by reducing the fluid in the chambers of the eye (aqueous humor). Research suggests that CAIs reduce aqueous humor fluid by as much as 40%. These drugs are used for glaucoma when other drugs do not work. They may be combined with other medications.

CAIs may also improve blood flow in the retina and optic nerve (beta-blockers do not). Improving blood flow can keep the disease from getting worse.

Brands and Side Effects. CAIs are available in the following forms:

Eye-drop CAIs include dorzolamide (Trusopt) and brinzolamide (Azopt). About 10% of patients report fatigue, stinging in the eye, and loss of appetite using dorzolamide. Taste changes can occur. Research suggests that dorzolamide can be helpful for children with glaucoma, including those younger than 6 years old. Brinzolamide is a newer medication that was chemically designed to be closer in pH to human tears and may cause less stinging than dorzolamide.
Oral forms include acetazolamide (Diamox), methazolamide (Neptazane), and dichlorphenamide (Daranide). Although they are more effective than eye drops, they have significantly more side effects and are rarely used for long-term treatment. The oral forms have very unpleasant side effects that include frequent urination, depression, stomach problems, fatigue, weight loss, sexual dysfunction, and, in infants, failure to thrive. Long-term use of the oral forms, in rare cases, can cause serious anemia and kidney problems, including the risk for stones. They can also produce a toxic reaction when taken with large doses of aspirin.

Adrenergic agonists activate muscles in the eye that dilate pupils and, therefore, increase outflow of aqueous fluid. Newer variations called alpha 2-adrenergic agonists reduce production of aqueous humor and also increase outflow through the uveoscleral pathway (the alternative channel to the trabecular meshwork). Older adrenergic agonists include epinephrine.

Alpha 2-Adrenergic Agonists. Apraclonidine (Iopidine) and brimonidine (Alphagan) are alpha 2-adrenergic agonists. These have generally been used before glaucoma surgery, but a number of studies are indicating that they may even be useful as primary therapy when used in combination with beta-blockers or other standard drugs.

Brimonidine is proving to be particularly effective for long-term therapy. (Apraclonidine is used for the short term.) It also may have nerve-protecting properties and may be safer than other drugs during pregnancy and for patients with asthma.

The most common side effects of brimonidine and apraclonidine are dry mouth and altered taste. They also commonly trigger an allergic reaction that causes red and itching eyes and lids, a major drawback. Brimonidine causes less of an allergic response than apraclonidine. Unlike apraclonidine, however, it can cause lethargy and mild low blood pressure. It also appears to remain effective longer.

Miotics, also called cholinergic agonists, narrow the iris muscles and constrict the pupil. This action pulls the iris away from the trabecular meshwork and allows the aqueous humor to flow out through the drainage channels, reducing the pressure inside the front of the eye.

Brands. Pilocarpine (Pilocar, Adsorbocarpine, Almocarpine, Isoptocarpine, Ocusert) was the most widely used anti-glaucoma drug before timolol was introduced. It is the preferred miotic. Because pilocarpine is used up by the body fairly quickly, however, patients must take it several times a day; many people, therefore, fail to take their medication regularly. A combination of timolol or latanoprost with pilocarpine is more effective than either drug used alone. Carbachol is another miotic.

Demecarium (Humorsol), isoflurophate (Floropryl), and echothiophate (Phospholine) are a group of long-acting drugs known as anticholinesterase miotics. Because of their potential for serious side effects, however, some authorities even prefer surgery to their use.

Epinephrine and its derivatives are the older anticholinergics. Epinephrine is now rarely prescribed because of side effects. Dipivefrin (Dipivefrin), a newer form of epinephrine, remains inactive until it reacts with enzymes in the cornea. It is effective in low doses and causes few systemic side effects.

Side Effects. Side effects include:

Teary eyes, brow-aches, eye pain, and allergic reactions.
A miotic narrows the pupil and so can cause nearsightedness. Vision can also become dim and it may difficult to see in darkened rooms or at night, when driving could be hazardous. A gel form administered once a day or wafer placed under the lid once a week may help reduce these side effects.
The anticholinesterase miotics increase the risk of cataract development and are therefore used mostly in patients in whom cataracts have already been removed. Retinal detachment is an uncommon but dangerous side effect in susceptible individuals. Excessive use of these miotics may cause toxic reactions, including convulsions, muscular paralysis, and even death from respiratory failure.
Epinephrine can produce burning in the eyes, enlarged pupils, and allergic reactions. Occasionally it can cause anxiety and headaches. Rare side effects include high blood pressure and disturbances in heart rhythm. It is rarely prescribed now. Although dipivefrin, the newer form of epinephrine, has fewer systemic side effects, it still causes problems in the eyes similar to those of epinephrine.

Cannabinoids. Cannabinoids, compounds in marijuana (cannabis), are being studied for their effects on glaucoma. For example, oral or inhaled tetrahydrocannabinol (THC), the active ingredient in marijuana, has been shown to reduce IOP in 60 - 65% of patients. The effects of smoking marijuana on IOP last only 3 hours, however. THC also increases the release of glutamate -- a nerve-protecting chemical. Experts are hoping that topical use of THC or other cannabinoids may help prevent optic nerve damage without the widespread effects of oral or inhaled administration.

Reasons for Noncompliance. Studies indicate that more than 40% of patients miss 10% of their doses, and 15% of patients miss more than 50% of their doses. Noncompliance is very high for many reasons:

People with chronic glaucoma who are on medication must use eye drops or take pills one or more times a day, usually for the rest of their lives.
Many people require a multi-drug regimen, two or more different kinds of medications that can be used in various combinations, such as eye drops, ointments, or time-release wafers inserted under the eyelid. Such regimens can be very confusing.
The side effects of the drugs are more unpleasant than the disease itself, which has no symptoms until vision is lost. Because the treatment does not usually produce any noticeable improvement, the consequence of not taking the drugs (blindness) may seem far in the future.
Skipping even a few doses can greatly increase the risk of visual loss. It is essential that patients tell their doctor if they are not regularly taking their medication. Otherwise, the doctor may increase the dosage, thereby causing unwelcome side effects.

Patients who do not regularly take their glaucoma medication are at high risk for blindness. If you have problems taking your medications or sticking to the dosing regimen, talk with your doctor.

Hints for Managing a Regimen.

Pharmaceutical manufacturers use colored tops, yellow for timolol, for example, and green for pilocarpine, to help prevent mix-ups. Creating a chart scheduling each drug by color can be helpful.
Small electronic timers are available that will signal times for taking the medications. The timing of these combinations is important. For example, the combination of pilocarpine with latanoprost is most effective when pilocarpine is taken four times a day and when the bedtime dose is administered an hour after latanoprost.
Some patients may be candidates for single medications that combine two drugs, such as Cosopt, which contains both dorzolamide and timolol. This medication requires only one drop twice per day. Patients who need additional glaucoma drugs, however, will need to take these two drugs separately.
When using any drug for a long period of time, side effects are a potential problem. If they become intolerable, patients should discuss with the doctor reducing the dosage or trying other drugs.

Administering Eye Drops. A common reason that medicine does not work is that patients do not take it correctly. Patients should ask the ophthalmologist to watch while they place the drops in their own eyes to make sure the procedure is being done correctly. The following are some recommended steps:

If you use both ointments and eye drops, take the eye drops first.
Wash your hands before applying eye drops.
Hold the bottle upside down.
Tilt your head back and, with one hand, pull the lower eyelid down to form a pocket.
With your other hand, hold the bottle as close as possible to your eye. Don’t let the bottle directly touch your eye or eyelid.
After you have placed the drop, close your eye or press your index finger against the corner of the eye near your nose. Gently move the lower lid upward until the eye is closed. Keep your eye closed for at least 1 minute. This prevents the drop from draining out.
Wait at least 5 minutes before applying another drop or a different medication

In this emergency situation, ophthalmologists may administer a combination of two or more anti-glaucoma medications to reduce eye pressure quickly before it can damage the optic nerve and cause visual loss. Apraclonidine (Iopidine) is a powerful drug used before and after laser surgery to prevent an increase in fluid pressure and is more effective than other medications. In addition to standard drugs, doctors may also administer glycerin (Glyrol, Osmoglyn) by mouth or mannitol or acetazolamide intravenously. Surgery is almost always performed once the pressure is reduced.

Most rare forms of glaucoma respond to the same medications and surgery used for open angle glaucoma. Irido corneal endothelial syndrome (ICE) is difficult to treat and if surgery is required, filtering surgery is the best choice. Neovascular glaucoma is also very hard to treat; researchers are investigating drainage implants for this disorder.

Surgery

If medications do not control eye pressure, or if they create intolerable side effects, surgery may be necessary in a small percentage of people with chronic glaucoma. It may be particularly helpful for patients with pseudoexfoliation glaucoma.

The standard procedures are usually one of the following:

Filtration surgery (trabeculectomy). This procedure opens the full thickness of the drainage area.
Laser trabeculoplasty. This procedure partially opens the drainage area. It does not reduce pressure to the extent of trabeculectomy but it has fewer adverse effects.

African Americans may respond better to initial laser surgery than to conventional trabeculectomy, while the opposite may be true in Caucasians. Some experts now recommend that, in most circumstances, African Americans should start with laser surgery and Caucasians who have no serious medical problems should have trabeculectomy first.

In addition, a number of experimental and less invasive procedures are under development.

The Procedure. Filtration surgery has been used for more than 100 years with only minor modifications. It employs conventional surgical techniques known as full-thickness filtering surgery or guarded filtering surgery (trabeculectomy).

The surgeon creates a sclerostomy, a passage in the sclera (the white part of the eye) for draining excess eye fluid.
A flap is created that allows fluid to escape but which does not deflate the eyeball.
The surgeon may also remove a tiny piece of the iris (called an iridectomy) so that fluid can flow backward into the eye.
A small bubble called a bleb nearly always forms over the opening, which is a sign that fluid is draining out. Although surgeons aim for a thick bleb, which poses less risk than a thin one for later leakage, paradoxically the ideal operation would have no bleb at all.

The procedure has a high success rate. About 50% of patients no longer need medication after surgery. Thirty-five to 40% of those who still need medication have better control of their glaucoma.

A new instrument called a trabectome has allowed for a less invasive type of trabulectomy surgery The trabectome procedure appears to be a safe and simple way to lower eye pressure. It can be performed before a traditional trabulectomy, if needed. Results from a small study, presented at the 2005 meeting of the American Academy of Ophthalmology, showed that the new approach successfully reduced eye pressure in 90% of patients with open-angle glaucoma.

Side Effects. Many of the serious side effects or complications that occur with filtration surgery involve blebs (blister-like bumps).

Bleb Leaks and Infections. Blebs, particularly thin ones, commonly leak. Leakage can occur early on or sometimes as late as months or years after surgery. Untreated, such leaks can be serious and even cause blindness. Late-onset leakage significantly increases the risk for infection as well as a number of other serious conditions, including bleeding, a flattening of the eye ball, and harmful inflammation. Surgical repair is the most effective way of managing leaking blebs, although drug therapies, pressure patching, and other nonsurgical techniques may be tried first. Due to the dangers of leaking blebs, experts recommend lifelong monitoring after surgery. Unfortunately, the incidence of late-onset leaking blebs is increasing due to the use of drugs used in filtration surgery to prevent scarring, another complication.
Scarring. In up to 20% of cases, scars form around the incision, closing up the drainage channels and causing pressure to rebuild. These scars are formed from fibroblasts, which are immature collagen cells that form at the surgical site. Scarring is a particular problem in young patients, African Americans, patients who have taken multiple drugs, have had an inflammatory disease, or have had cataract surgery. Releasing the surgical stitches used in the procedure may help prevent scarring and pressure build-up. A second procedure called bleb needling sometimes can open up the scarred area and restore drainage. With this technique, the tip of a very fine hypodermic needle is used carefully to cut loose the particles closing off the drainage area. A new technique that does not require sutures may prove to be effective and have fewer complications.
Cataracts. The procedure is highly associated with the development of cataracts over time. Because cataracts are associated with glaucoma anyway, it is not entirely clear whether the cataracts are caused by the surgery or would develop in any case.

Click the icon to see an illustrated series detailing cataract surgery.

Supportive Medication for Preventing Scarring. Specific drugs, usually mitomycin C, are often used in conjunction with the procedure to prevent scarring and closure. A large review of studies of mitomycin C supported its effectiveness in increasing surgical success in nearly all patients. Fluorouracil (5-FU) appears to be similar in effectiveness but has a high risk for complications and is not used as often as in the past.

The Procedure. Laser trabeculoplasty involves the following steps:

The procedure uses an instrument, usually a YAG laser, to burn 80 - 100 tiny holes in the drainage area.
A tiny scar forms, which increases fluid outflow.
The procedure takes 15 minutes, causes almost no discomfort, and has very few complications.

In a 2-year study, laser surgery of the trabecular meshwork reduced pressure by a third in 70 - 97% of patients. Patients still need to take anti-glaucoma eye drop medications every day.

Laser surgery is not a cure. Within 2 - 5 years, about half of patients need either additional surgery or new medications.

Complications. In about 35% of patients, pressure increases after surgery. In most cases it is temporary, but in rare cases the increased pressure is permanent and vision loss can occur. Use of the drug apraclonidine (Iopidine) or pilocarpine can help prevent this elevated pressure. About a third of patients also develop adhesive-like substances called peripheral anterior synechiae that cause the iris to stick to part of the cornea.

Drainage implants, also known as tube shunts, may be used to drain fluid in certain cases, such as if glaucoma is not responsive to any standard procedure or is caused by certain conditions. A 2007 study suggested that tube shunts work better than filtration surgery (trabulectomy) for some patients. In the study, patients who received tube shunts had more stable IOP over the course of a year than patients who underwent trabulectomy.

Candidates. Success rates are highest (75% pressure control over 5 - 7 years) in appropriate patients. Drainage implants may be useful in the following conditions:

Glaucoma caused by swelling in the iris
Glaucoma caused by abnormal vessel formations
Iridocorneal endothelial (ICE) syndrome

The Procedure. In general, the procedure involves:

An implant, most commonly a 1/2 inch silicone tube, is inserted into the eye's front chamber (anterior). The Molteno implant used with mitomycin C is currently the most effective approach, with reported success rates of 80%. Other implants, such as the Ahmed implant, may have fewer complications.
The tube drains the fluid onto a tiny plate that is sewn to the side of the eye.
Fluid collects on the plate and then is absorbed by the tissues in the eye.

Complications. Complications include:

Hypotony (very low eye pressure) is a serious complication that has been reduced using better techniques and improved implants.
Cataracts, detached retina, breakdown of the cornea, and bleeding are potentially significant complications.
There is also a risk for eye movement disorders, such as strabismus (crossed eyes) or diplopia (double-vision).

The implant often becomes blocked and repeated operations are needed. Some researchers are studying the use of a drug called tissue plasminogen activator (tPA) to open up tubes that have been blocked by blood or blood factors. (This so-called clot-busting drug is normally used to break up blood clots during heart attacks.) In one 2002 study, tPA prevented such blocks in 89% of eyes. Unfortunately, significant complications rates were high (11%).

Deep sclerectomy and viscocanalostomy are less invasive techniques than filtering surgery that leave the anterior chamber (front of the eye) intact and avoid creation of blebs.

In deep sclerectomy, the surgeon removes a deep piece of the sclera (the white part of the eye), part of the trabecular meshwork, and the front of Schlemm's canal (the vessels that return fluid into the bloodstream).

In both deep sclerectomy and viscocanalostomy, the surgeon first creates a flap in the outer part of the sclera (the white part of the eye) and then removes a deep piece of the sclera underneath. This opens up Schlemm's canal (the vessels that return fluid into the bloodstream) and exposes a layer above the anterior chamber called Descemet's membrane. A space has also been created between the inner and outer layers of the sclera.
In deep sclerectomy, this space now serves as a tiny reservoir for aqueous fluid that flows through the membrane and pools here. The fluid then flows out without the surgeon having to open the anterior chamber (as in standard filtering surgery).
In viscocanalostomy, the surgeon typically injects gel-like materials into the ends of Schlemm's canal in order to enlarge the canal for fluid outflow and lower IOP. The tiny reservoir is sewn tightly up.

Many variations are under investigation. In general, the procedures have fewer complications afterward than standard filtering surgery, although they require excellent surgical skill. Nonpenetrating techniques do not lower IOPs as much as conventional surgery does, however. In time, however, these nonpenetrating techniques are expected to be as effective as filtration surgery.

Cataracts and Glaucoma. For patients with both glaucoma and cataracts, experts recommend the following:

In patients with cataracts and poorly controlled glaucoma, a two-step procedure for both eye conditions is needed. Typically the patient will first have a trabeculectomy for glaucoma, followed by cataract surgery such as phacoemulsification (lens removal through ultrasound). Fluid leakage and the presence of blood in the back chamber of the eye are potential complications of this combined procedure.
Phacoemulsification is sometimes combined with viscocanalostomy in a procedure called phacoviscocanalostomy. A 2006 study suggested this approach is safe and effective. The study followed patients for 7 years after they underwent phacoviscocanalostomy and found that no serious complications occurred.
In patients who have cataracts plus either closed-angle glaucoma or open angle glaucoma that is stabilized with medication, the cataract may be able to be extracted and medication continued for the glaucoma.

A major 2002 analysis suggested that the combined approach generally offers better control over eye pressure for patients with both cataracts and glaucoma. However, it is still unclear which specific type of surgical procedure works best. [See In-Depth Report #26: Cataracts.]

Diode laser transscleral cyclophotocoagulation (TSCPC), also called laser cycloablation, reduces aqueous production by destroying the muscles that control the lens for near and far vision (the ciliary body ). There is a chance of vision loss with this procedure, so it is reserved for people with end-stage glaucoma or those who fail to benefit from any other therapies. Nevertheless, researchers continue to explore the possibilities for this effective procedure, especially for people who may not have access to expensive medications. Studies have suggested it may even be suitable as first-line surgery for some patients.

For an acute closed-angle glaucoma attack, emergency microsurgery is usually necessary after reducing pressure with medications.

Iridotomy or Iridectomy. Either laser (iridotomy) or conventional (iridectomy) surgery may be used. With either procedure an ophthalmologist makes a tiny opening in the iris to let the aqueous humor flow out more freely. Because acute glaucoma commonly occurs later in the other eye, surgeons will often recommend surgery in the unaffected eye to prevent a second attack.

Laser iridotomy almost never requires hospitalization, and postsurgical treatment includes only aspirin and eye drops. It has almost completely replaced conventional surgery, which requires anesthesia and hospitalization.

Vision will be blurred, and recovery can take 4 - 8 weeks. Once surgery has been performed, such patients can usually use previously restricted anticholinergic medications, such as antihistamines and certain antidepressants, with safety.

Phacoemulsification and Intraocular Lens Implantation. Phacoemulsification and intraocular lens implantation, a procedure ordinarily used for cataracts, may prove to be beneficial for some patients with acute angle-closure glaucoma requiring surgery. [See In-Depth Report #26: Cataracts.]

Lifestyle Changes

Studies suggest that patients with glaucoma who exercise regularly (at least 3 times a week) may be able to reduce their intraocular pressure by an average of 20%. If they stop exercising for more than 2 weeks, pressure increases again. In one study, those who walked briskly 4 times a week for 40 minutes were able to go off their medications. (Although not confirmed by any evidence, yoga or other exercises that involve head-down or inverted positions may be harmful for patients with glaucoma and should be discussed with the doctor.)

Exercise has no effect on closed-angle glaucoma. It may, in fact, increase eye pressure in patients with pigmentary glaucoma. Vigorous high-impact exercise may cause more pigment to be released from the iris in these patients. Patients should talk to their doctor about an appropriate exercise program.

Antioxidants in Foods and Supplements. Diet most likely plays very little role in glaucoma. For example, a 2003 study found no association between important nutrients associated with protection against other eye disorders, including vitamins C, E, A, and carotenoids.

Caffeine. Some studies have shown that large amounts of caffeine drunk in a short period of time can elevate eye pressure for up to 3 hours. One study suggested that such changes in eye pressure could be significant in patients with both normal eye pressure and high IOP.

Fluids. Drinking large amounts (a quart or more) of any liquid within a short time, about 30 minutes, appears to increase pressure. Patients with glaucoma should have plenty of fluids, but they should drink them in small amounts over the course of a day.

Glaucoma can cause the eyes to be very sensitive to light and glare. Medications can worsen this problem. Sunglasses solve this problem and are important for prevention of cataracts. Protective sunglasses do not have to be expensive. Sunglasses are classified into three categories based on protection against ultraviolet radiation (UV) A or B:

Cosmetic-purpose sunglasses block at least 70% UVB and up to 60% UVA. People should avoid these glasses if they have any risk for cataracts or eye problems.
General-purpose sunglasses block at least 95% UVB and a minimum of 60% UVA. At the very least, people should purchase general purpose sunglasses and they should be labeled "Meets ANSI Z80.3 General Purpose UV Requirements.” Labels should indicate that sunglasses block UV radiation up to 400 nm.
Special-purpose sunglasses block at least 99% UVB and a minimum of 60% UVA rays. These are the optimal sunglasses for people at risk for eye disease. Special purpose glasses should wrap around the head and block light coming from above, below, and both sides of the glasses. They should also fit snugly on the nose.
Lenses that are simply dark but not coated with UV-absorbing material may increase the risk of cataracts because the pupil widens to compensate for the shaded glass. This may allow more harmful ultraviolet waves to enter the eye. Polarized glasses cut glare but have no effect on UV radiation. Mirror finishes without additional processing for UV blockage also are not fully protective. There is some controversy over whether blue light is harmful to the eyes. Some people prefer amber lenses, which block out the blue spectrum.

Meditation, biofeedback, and relaxation methods can help counteract stress, and there are some reports that they may help some people with open-angle glaucoma. A number of herbal and nontraditional remedies have been advertised as glaucoma remedies. A few studies have reported that the herbal remedy ginkgo biloba may have properties that offer benefits to patients with glaucoma, including increasing blood flow in the eye without altering overall blood pressure, heart rate, or intraocular pressure. More research is, however, needed.

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.

The following is of special concern for people with glaucoma:

Bilberry, a European blueberry (Vaccinium myrtillus), is sold in natural food stores as a glaucoma remedy. Studies indicate that it may help some people improve night vision and glare, but it is not at all effective in preventing or treating glaucoma.

Resources

www.glaucoma.org -- Glaucoma Research Foundation
www.nei.nih.gov -- National Eye Institute
www.glaucomafoundation.org -- The Glaucoma Foundation
www.aao.org -- American Academy of Ophthalmology
www.glaucomaweb.org -- American Glaucoma Society
www.lighthouse.org -- Lighthouse International

References

Bottaro M, Ritch R. Intraocular pressure variation during weight lifting. Vieira GM, Oliveira HB, de Andrade DT. Arch Ophthalmol. 2006 Sep;124(9):1251-4.

Brauner SC, Chen TC, Hutchinson BT, Chang MA, Pasquale LR, Grosskreutz CL. The course of glaucoma during pregnancy: a retrospective case series. Arch Ophthalmol. 2006 Aug;124(:1089-94.

Gedde SJ, Schiffman JC, Feuer WJ, Herndon LW, Brandt JD, Budenz DL. Treatment outcomes in the tube versus trabeculectomy study after one year of follow-up. Am J Ophthalmol. 2007 Jan;143(1):9-22.

Hara T, Hara T, Tsuru T. Increase of peak intraocular pressure during sleep in reproduced diurnal changes by posture. Arch Ophthalmol. 2006 Feb;124(2):165-8.

Higginbotham EJ. Managing glaucoma during pregnancy. JAMA. 2006 Sep 13;296(10):1284-5.

Pasquale LR, Kang JH, Manson JE, Willett WC, Rosner BA, Hankinson SE. Prospective study of type 2 diabetes mellitus and risk of primary open-angle glaucoma in women. Ophthalmology. 2006 Jul;113(7):1081-6.

Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006 Mar;90(3):262-7.

Wishart MS, Dagres E. Seven-year follow-up of combined cataract extraction and viscocanalostomy. J Cataract Refract Surg. 2006 Dec;32(12):2043-9.

Review Date:
3/3/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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

A.D.A.M. Copyright

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

adam.com

Keep Track of Your Diet and Exercise Goals With Fitbook

FitSugar — Thu, 23 Apr 2009 13:00:00 -0700

If you're serious about getting in shape and eating right, documenting your plan of action and your daily progress is a great way to meet your goals. I found an easy way to keep track of all your stats - the fitbook ($20). It's 12-week fitness journal and food diary that's 5.5 square inches, so it's small enough to tuck in your purse or gym bag. It's made of 100 percent recycled paper, and comes with a little pen to jot down your info. It has neat little charts so you can see how much you've worked out, what you've eaten, your weekly weight, and your body fat percentage.

A fit and healthy lifestyle doesn't come easy to many people. It takes discipline and a lot of planning, so using a journal like this one is a great way to set yourself up for success. Plus research shows that those who write down their goals are 75 percent more likely to achieve them.

If you want to take a peek inside this neat little fitbook then read more.

View 7 Photos ›

If your goals will take more than 12 weeks to accomplish, or you have some friends who want to get on the fitbook boat, you can purchase a set of four for $75. Since we're all pinching pennies, if you don't want to splurge on a fitbook then you can download my fitness and food journals for free.

Nearsightedness

admin — Wed, 03 Sep 2008 17:53:52 -0700

Overview

Definition
Alternative Names
Causes, incidence, and risk factors
Symptoms
Signs and tests
Treatment
Expectations (prognosis)
Complications
Calling your health care provider
Prevention

Illustrations

Visual acuity test

Normal, near, and farsightedness

Lasik eye surgery - series

HEALTH GUIDE REFERENCE FROM A.D.A.M

Definition

Nearsightedness is when the eyes focus incorrectly, making distant objects appear blurred.

Alternative Names

Myopia; Shortsightedness

Causes, incidence, and risk factors

A nearsighted person sees near objects clearly, while objects in the distance are blurred. As a result, someone with myopia tends to squint when viewing far away objects. This characteristic is the basis of the word "myopia," which comes from two Greek words: myein, meaning shut, and ops, meaning eye.

A nearsighted person can easily read the Jaeger eye chart (the chart for near reading), but finds the Snellen eye chart (the chart for distance) difficult to read. This blurred vision results when the visual image is focused in front of the retina, rather than directly on it.

Nearsightedness occurs when the physical length of the eye is greater than the optical length. For this reason, it often develops in the rapidly growing school-aged child or teenager, and progresses during the growth years, requiring frequent changes in glasses or contact lenses. It usually stops progressing as a person finishes growing in his or her early twenties.

Nearsightedness affects males and females equally. Those with a family history of nearsightedness are more likely to develop it. Most eyes with nearsightedness are entirely healthy, but a small number of people with myopia develop a form of retinal degeneration.

Symptoms

Blurred vision or squinting when trying to see distant objects (children often cannot read the blackboard, but can easily read a book)
Eyestrain
Headaches (uncommon)

Signs and tests

A general eye examination, or standard ophthalmic exam may include:

Measurement of the pressure of fluid in the eyes
Refraction test, to determine the correct prescription for glasses
Retinal examination
Slit-lamp exam of the structures at the front of the eyes
Test of color vision, to look for possible color blindness
Tests of the muscles that move the eyes
Visual acuity, both at a distance (Snellen), and close up (Jaeger)

Treatment

You can compensate for nearsightedness by wearing eyeglasses or contact lenses, which shift the focus point to the retina. There are several surgical procedures that reshape the cornea, shifting the focus point from in front of the retina to the retina.

Radial keratotomy is a surgical procedure that was popular in the recent past. Now it has been almost completely replaced by LASIK, in which an excimer laser is used to reshape the cornea.

Expectations (prognosis)

Early diagnosis of nearsightedness is important, because a child can suffer socially and educationally by not being able to see well at a distance.

Complications

Complications can occur in people who use contact lenses (corneal ulcers and infections)
Complications of laser vision correction are uncommon, but can be serious
People with myopia can, in rare cases, develop retinal detachments or retinal degeneration

Calling your health care provider

Call for an appointment with your ophthalmologist if your child shows these signs, which may indicate a vision problem:

Having difficulty reading the blackboard in school or signs on a wall
Holding books very close when reading
Sitting close to the television

Call for an appointment with your ophthalmologist if your child is having difficulties at school that may be caused by a vision problem.

Call for an appointment with your ophthalmologist if you or your child is nearsighted and experiences:

Flashing lights
Floating spots
Sudden loss of any part of the field of vision

Prevention

There is no way to prevent nearsightedness. Reading and watching television do not cause nearsightedness. In the past, dilating eye drops were proposed as a treatment to slow the development of nearsightedness in children, but they have never been proved effective.

The use of glasses or contact lenses does not affect the normal progression of myopia -- they simply focus the light so the nearsighted person can see distant objects clearly.

Review Date: 11/13/2007

Reviewed By: Manju Subramanian, M.D., Assistant Professor in Ophthalmology, Vitreoretinal Disease and Surgery, Boston University Eye Associates, Boston, MA. Review provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

adam.com

Source Doc: 1_001023

Start a Biggest Loser Competition in Your Office

FitSugar — Fri, 13 Mar 2009 11:00:00 -0700

The office is often a place where people end up gaining weight. What with all the sitting around all day, snacking at your desk, office parties, ordering food as a group, and the baked goodies co-workers bring in, it's no wonder extra pounds start to creep onto the scale. So instead of getting fatter at your job, lose weight together by starting a Biggest Loser-style competition in your office.

To find out how read more.

Choose a starting date where everyone gets weighed. Record the numbers on a chart (post it or have a responsible person hold onto it).
Then choose to do weekly weigh-ins or just do one big weigh-in on the last day.
Choose an end date. Make the competition for a short amount of time - I'd say two to four months long in order to see some real progress.
Then of course, figure out what the Biggest Loser will win. Everyone can put in $10 to $20 and the winner receives the grand total, or you can wager something, like everyone chips in to get the winner a massage or lunch out at their favorite restaurant.

Keep in mind that it doesn't matter how many pounds you lose - it's the percentage of weight you lose as compared to your body weight. Although it is a competition, you can encourage each other to eat healthier by having office potlucks and ditching the 3 p.m. runs to Dunkin Donuts. You can also motivate each other to work out by exercising at the office or hitting the gym together on your lunch break.

A little healthy competition can be just the thing to help you ditch your old habits, and even if you don't win, you'll feel good knowing you're getting healthier.

Source

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

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 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.

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 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.

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.

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).

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. Some asthmatic episodes have been linked to high consumption of acetaminophen among adults.

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.]

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.

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. (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.

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.

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 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.]

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

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 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.

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.

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.

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. 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.

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.

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.

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, 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.

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 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.)

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. 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.

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. 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.

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 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.

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.

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.

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 medicine 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, 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.

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).

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.

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.

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.

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

Cholesterol

FitSugar — Wed, 08 Oct 2008 17:34:59 -0700

In This Report

Highlights
Introduction
Cholesterol's Effect on the...
Cholesterol's Effect on the...
Risk Factors
Symptoms
Diagnosis
Lifestyle Changes
Treatment
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

New Guidelines for Children and Adolescents

In 2007, the American Heart Association (AHA) established new guidelines for assessing and treating high cholesterol in children and adolescents. According to the AHA’s scientific statement:

LDL (“bad") cholesterol goals for children should be 190 mg/dL or less for children without heart disease risk factors and 160 mg/dL or less for children with heart disease risk factors.
Children who are overweight or obese, as well as those with a family history of high cholesterol and heart disease, should get their cholesterol levels checked.
For overweight and obese children with cholesterol imbalances, diet changes and exercise should be tried before drug treatment. For children with cholesterol imbalances who have a family history of cholesterol and heart problems, statins are the best first-line drug therapy.

Herbs and Supplements

Garlic, whether raw or in supplement form, does not help lower LDL in patients with moderately high LDL levels, according to a 2007 Archives of Internal Medicine Study.
Policosanol, a dietary supplement derived from sugar cane, has no effect on cholesterol, indicates a 2006 Journal of the American Medical Association (JAMA) study.

Diet Plans

In a 2007 JAMA comparison study of four diet plans (Atkins, Ornish, Zone, and LEARN), the low-carbohydrate Atkins diet was best at raising HDL (“good cholesterol”) levels and lowering triglyceride levels, but did not affect LDL levels. The low-fat Ornish diet was best at lowering LDL levels.
The Mediterranean diet works better than a low-fat diet in quickly lowering cholesterol as well as blood pressure and blood sugar, suggests a 2006 Annals of Internal Medicine study.

Drug Research

In contrast to research findings released last year, rosuvastatin (Crestor) does not appear to reverse heart disease, according to a 2007 JAMA study. However, the statin drug did help slow the progression of arterial thickening.

Introduction

Lipids are the building blocks of the fats and fatty substances found in animals and plants. They are microscopic layered spheres of oil, which, in animals, are composed mainly of cholesterol, triglycerides, proteins (called lipoproteins), and phospholipids (molecules made up of phosphoric acid, fatty acids, and nitrogen). Lipids do not dissolve in water and are stored in the body to serve as sources of energy.

Cholesterol is a white, powdery substance that is found in all animal cells and in animal-based foods (not in plants). In spite of its bad press, cholesterol is an essential nutrient necessary for many functions, including:

Repairing cell membranes
Manufacturing vitamin D on the skin's surface
Producing hormones, such as estrogen and testosterone
Possibly helping cell connections in the brain that are important for learning and memory

Regardless of these benefits, when cholesterol levels rise in the blood, they can have dangerous consequences, depending on the type of cholesterol. Although the body acquires some cholesterol through diet, about two-thirds is manufactured in the liver, its production stimulated by saturated fat. Saturated fats are found in animal products, meat, and dairy products.

Saturated fats are found predominantly in animal products, such as meat and dairy products, and are strongly associated with higher cholesterol levels. Tropical oils -- such as palm, coconut, and coconut butter -- are also high in saturated fats.

Triglycerides are composed of fatty acid molecules. They are the basic chemicals contained in fats in both animals and plants.

Lipoproteins are protein spheres that transport cholesterol, triglyceride, or other lipid molecules through the bloodstream. Most of the information about the effects of cholesterol and triglyceride actually concerns lipoproteins.

Lipoproteins are categorized into five types according to size and density. They can be further defined by whether they carry cholesterol or triglycerides.

Cholesterol-Carrying Lipoproteins. These are the lipoproteins commonly referred to as cholesterol.

Low density lipoproteins (LDL). (Often called the "bad" cholesterol.)
High-density lipoproteins (HDL), the smallest and most dense. (Referred to as the "good" cholesterol.)

Triglyceride-Carrying Lipoproteins.

Intermediate density lipoproteins (IDL). They tend to carry triglycerides.
Very low density lipoproteins (VLDL). These tend to carry triglycerides.
Chylomicrons (largest in size and lowest in density).

Lipoprotein(a). Lipoprotein(a), or lp(a) has a size and density somewhere between LDL and HDL. The molecules carry a protein that may interfere with the body's ability to dissolve blood clots. Lipoprotein(a) is being investigated as a possible marker or cause of heart disease.

Remnant Lipoproteins. Remnant lipoproteins are byproducts of chylomicrons, very low-density lipoproteins (VLDL), or both. Some research indicates that high levels may be an important risk factor for coronary artery disease, particularly in patients who have otherwise normal cholesterol levels.

Reducing LDL and total cholesterol levels, while at the same time boosting HDL levels, can prevent heart attacks and death in all people (with or without heart disease). Reducing LDL is the primary goal of most cholesterol therapy.

Blood tests can easily measure both HDL and overall cholesterol levels. It is very difficult to measure LDL levels by themselves, but LDL levels can be reliably calculated by subtracting HDL and triglyceride levels from total cholesterol. The exact formula is:

LDL = TOTAL CHOLESTEROL - HDL - TRIGLYCERIDES/5.

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.

The 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)

Two or more of these risk factors increases by 20% the chance of having a heart attack within 10 years.

The LDL cholesterol level is one of the most important factors in determining whether a patient needs cholesterol therapy and whether the treatment 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.


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

The following chart summarizes all goals.


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 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 an optimal goal. 160 mg/dL or below for people at less risk (one or zero risk factors); 130 mg/dL is an optimal goal. Anything above 160 is high, with levels above 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.

Although current guidelines as described in the table are extremely useful, they do have pitfalls. For example, the following cholesterol levels pose some dilemmas:

Low LDL levels (protective) accompanied by low HDL, high triglycerides, or both (harmful)
High total cholesterol (harmful) accompanied by high HDL (protective)

Would individuals with these cholesterol balances be at high risk or low risk for developing heart disease? To resolve this dilemma, experts have devised a calculation for a risk ratio by dividing the total cholesterol by either total HDL or LDL. It is not clear at this point which ratio is a better predictor of heart disease, although the HDL ratio may be superior. Using this ratio, the following results indicate better to worse outlook:

The ideal ratio is 3.5 or below.
A ratio of 4.5 carries an average risk.
Ratios of 5 or higher are potentially dangerous.

For example, if a person has a high total cholesterol of 280 mg/dL but a high HDL level of 70 mg/dL, the risk ratio is 4, which actually carries a lower than average risk. The use of this ratio may predict coronary artery disease more accurately than using total cholesterol levels alone. Still, the primary goal of lipid-lowering therapy is reducing LDL levels. Evidence strongly suggests that the lower the LDL levels, the lower the risk for heart disease.

Cholesterol's Effect on the Heart

Coronary artery disease, commonly known as heart disease, is the leading cause of death in the U.S. and was responsible for nearly 500,000 deaths in 2003.

Atherosclerosis is a common disorder of the arteries. Fat, cholesterol, and other substances collect in the walls of arteries. Larger accumulations are called atheromas or plaque and can damage artery walls and block blood flow. Severely restricted blood flow in the heart muscle leads to symptoms such as chest pain.

As many as half of these deaths were probably due to unhealthy cholesterol and lipid levels. Strong evidence points to LDL as the villain and HDL as a hero in the process. The role of other lipids, notably triglycerides, is not entirely clear.

Unhealthy cholesterol, particularly low-density lipoprotein (LDL), forms a fatty substance called plaque, which builds up on the arterial walls. Smaller plaques remain soft, but older, larger plaques tend to develop fibrous caps with calcium deposits.

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

The long-term result is atherosclerosis, commonly called hardening of the arteries. The heart is endangered in two ways by this process:

Eventually these calcified and inelastic arteries become narrower (a condition known as stenosis). As this process continues, blood flow slows and prevents sufficient oxygen-rich blood from reaching the heart. This condition leads to angina (chest pain) and, in severe cases, to heart attack.

Click the icon to see an image of a heart attack.

Smaller unstable plaques may rupture, triggering the formation blood clots on their surface. The blood clots block the arteries and are important causes of heart attack.

This process is accelerated and enhanced by other risk factors, including high blood pressure, smoking, obesity, diabetes, and a sedentary life style. When more than one of these risk factors is present, the risk is compounded.

The effects of cholesterol on the heart may involve more than just the arteries. There is some evidence that unhealthy levels may affect the heart muscles and increase the risk for heart failure. High cholesterol levels may even reduce the protection that aspirin provides for people with heart disease.

On an encouraging note, mortality rates associated with coronary artery disease have declined dramatically during the past 30 years. Some experts estimate that about 30% of the decline is due to better cholesterol management and statin drugs.

Studies consistently report a higher risk for death from heart disease with high total cholesterol levels (200 mg/dL and higher). The higher the cholesterol, the greater the risk. One study reported that men with total cholesterol levels higher than 240 mg/dL had a risk nearly two to four times that of men whose cholesterol was below 200 mg/dL. On average, every time a person's cholesterol level drops by a point, the risk of heart disease drops by 2%.

The primary villain in the cholesterol story is low-density lipoprotein (LDL). In a major study, the lowest incidence in heart disease was found among people with the lowest LDL levels. Lowering LDL is the primary goal of cholesterol drug and lifestyle therapy.

Low-density lipoprotein (LDL) transports about 75% of the blood's cholesterol to the body's cells. It is normally harmless. However, if it is exposed to a process called oxidation, LDL can penetrate and interact dangerously with the walls of the artery, producing a harmful inflammatory response. Oxidation is a natural process in the body that occurs from chemical combinations with unstable molecules. These molecules are known as oxygen-free radicals or oxidants.

When LDL collects on arterial walls these oxidants are released from the wall membranes.
Oxidants are missing an electron and tend to bind with other molecules in the body, a process called oxidation.
When the oxidation process modifies LDL, it signals the immune system that a harmful molecule has appeared.

Inflammation and Plaque. In response to oxidized LDL, the body releases various immune factors aimed at protecting the damaged walls. Unfortunately, in excessive quantities they cause inflammation and promote further injury to the areas they target:

White blood cells and other factors gather and form a fatty substance called plaque. (Of interest in this process is an enzyme called lipoprotein-associated phospholipase A2, which binds to oxidized LDL. Studies report that this enzyme may play a major role in the release of plaque-forming inflammatory factors.)
Other immune factors also cause inflammation and injure the endothelium, the layer of cells that line blood vessels.

Click the icon to see an image of the cut section of an artery.

Immune factors that increase the risk for blood clots are also mobilized.
Oxidized LDL plays another dangerous role by reducing levels of nitric oxide, a chemical that helps relax the blood vessels and allow blood to flow freely.

High density lipoprotein (HDL) appears to benefit the body in two ways:

It removes cholesterol from the walls of the arteries and returns it to the liver.

Click the icon to see an image of the liver.

It helps prevent oxidation of LDL. HDL actually appears to have its own antioxidant properties.

HDL helps keep arteries open and reduces the risk for heart attack. High levels of high HDL (above 60 mg/dL) may be nearly as important for the heart as low levels of LDL. HDL levels below 40 mg/dL are considered to be harmful. In one study, for each 4 mg/dL decline in HDL levels there was a 10% increase in coronary artery disease.

Triglycerides are major troublemakers for the heart. They appear to interact with HDL cholesterol in such a way that HDL levels fall as triglyceride levels rise. Low HDL is known to be harmful to the heart.

The harmful imbalance of high triglycerides with low HDL levels is also associated with obesity (particularly around the abdomen), insulin resistance, and diabetes. Insulin is a hormone essential for regulating the storage and use of glucose (sugar) and amino acids (proteins) in the body. Insulin resistance occurs when there are normal levels of insulin but the body cannot use it. Insulin resistance increases the risk for developing type 2 diabetes, and it is also associated with metabolic syndrome. Both of these conditions increase the risk for heart disease.

Some evidence also suggests that high triglycerides pose other dangers, regardless of cholesterol levels. Triglycerides, for example, may be responsible for blood clots that form and block the arteries. High triglyceride levels are also associated with the inflammatory response -- the harmful effect of an overactive immune system that can cause considerable damage to cells and tissues, including the arteries.

Studies are finding an elevated risk for angina and first heart attacks in people with elevated levels of lipoprotein(a), also known as or lp(a). This lipoprotein falls somewhere between HDL and LDL in density 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. Because concentrations of lipoprotein(a) are usually inherited, they do not respond to dietary or lifestyle changes. At this time, few experts recommend drug treatments to reduce lp(a) levels. Older women, but not men, appear to be at greater risk for high lp(a) levels and their consequences.

Cholesterol's Effect on the Brain

Having adequate levels of HDL may be the most important lipid-related factor for preventing ischemic stroke, a type of stroke caused by blockage of the carotid arteries that carry blood to the brain. HDL may even reduce the risk for hemorrhagic stroke, a less common type of stroke caused by bleeding in the brain that is associated with low overall cholesterol levels.

The build-up of plaque in the internal carotid artery may lead to narrowing and irregularity of the artery's lumen, preventing proper blood flow to the brain. More commonly, as the narrowing worsens, pieces of plaque in the internal carotid artery can break free, travel to the brain, and block blood vessels that supply blood to the brain. This leads to stroke, with possible paralysis or other deficits.

The effects of high total cholesterol and LDL levels on ischemic stroke are less clear. One study suggested that the risk for ischemic stroke increases when total cholesterol is above 280 mg/dL. A 2002 study suggested that high cholesterol poses a risk for stroke only when specific proteins associated with inflammation are present.

Evidence points to high cholesterol levels, along with high blood pressure and a family history of the disease, as independent risk factors for AD. A major research target for common factors between cholesterol levels and AD has been apolipoprotein E (ApoE). ApoE plays a role in the movement and distribution of cholesterol for repairing nerve cells during development and after injury. People who carry a variant of this gene (ApoE4) are at significantly higher risk for AD.

High cholesterol may pose a risk for Alzheimer's regardless of this genetic factor, however. Some studies report that cholesterol is important within the brain for cell communication and memory.

Risk Factors

About half of all American adults have total cholesterol levels over 200 mg/dL. Over 25% have been told by doctors that they have unhealthy levels. Total cholesterol levels have been declining over the last several decades, at least among middle-aged and older adults. This decline may be partly due to the increased use of statins and other lipid-lowering medications. However, total cholesterol levels are getting higher among younger adults (ages 25 – 34 years). The major risk factor for these high rates may be the Western lifestyle. The typical high-fat/low-fiber American diet coupled with sedentary habits is largely responsible for this unfortunate trend.

Men. Heart disease is the major cause of death in men. On average, men develop coronary artery disease 10 - 15 years earlier than women do and have a greater risk for dying of heart disease at a younger age. A 2006 study suggested that high total cholesterol may also contribute to the development of high blood pressure in men.

Women. Coronary artery disease is also the number one killer of women. Women between the ages of 20 and 34, and after menopause (around age 55), have higher cholesterol levels than men. Some evidence suggests that HDL levels may be more significant in women than in men. In one study, at total cholesterol levels above 200, women with HDL levels below 50 had a higher death rate than those with levels above 50, regardless of their LDL cholesterol levels. Women also appear to be more susceptible to the high-triglyceride low-HDL syndrome, which may be a particular risk factor for heart disease.

Children and Adolescents. Children who have abnormal cholesterol levels are at increased risk of developing heart disease later in life. However, it is difficult to distinguish “normal” cholesterol levels in children. Changes in cholesterol levels occur between the ages of 8 - 18, and vary between genders and population groups. Cholesterol levels tend to naturally rise sharply until puberty, then decrease sharply, and then rise again.

In 2007, the American Heart Association established general LDL goals for children that take into account these fluctuations. The association’s LDL goals are 190 mg/dL or less for children with no additional heart disease risk factors and 160 mg/dL or less for children with additional risk factors (such as family history of high cholesterol, heart disease, and diabetes).

It is also clear that children who are overweight are at higher risk for high triglycerides and low HDL, which may be directly related to later unhealthy cholesterol levels. Studies have confirmed that childhood LDL levels and body-mass index (BMI) are strongly associated with cardiovascular risk during adulthood. The American Heart Association recommends that children who are overweight and obese, as well as those with a family history of high cholesterol, undergo cholesterol screening. Overweight and obese children who have high cholesterol should also get tested for high blood pressure, diabetes, and other conditions associated with metabolic syndrome.

As in adults, the primary source of unhealthy cholesterol levels in children comes from diets high in unhealthy fats: Saturated fats (found mainly in animal and dairy products) and trans fatty acids (found in commercial food products). Over-consumption of unhealthy fats increases the risk for both obesity and heart disease.

Less common causes of unhealthy cholesterol levels in children include:

Low-birth weight (associated with low HDL levels)
Low thyroid levels (hypothyroidism)
Kidney or liver diseases
Homozygous familial hypercholesterolemia. This is an uncommon inherited condition that causes severe cholesterol imbalances and can result in very early heart disease.
Certain medications such as specific antiseizure drugs, corticosteroids, and isotretinoin (Accutane)

Young and Middle-Aged Adults. The strongest evidence of unhealthy cholesterol levels and heart disease is in adults over age 45. However, a 2006 analysis found that while total cholesterol levels are decreasing among older adults, they are increasing in those age 25 - 34 years. Research strongly suggests that the younger a person is when unhealthy cholesterol levels develop, the greater the chance for serious heart and blood vessel problems in the future. A 2006 study in the New England Journal of Medicine indicated that keeping LDL levels low from an early age can help prevent heart disease later in life. In one important study, young men (ages 16 - 34) who had cholesterol levels at or above 240 mg/dL had two to four times the risk of dying from heart attack or other cardiac problems than did men whose cholesterol was lower than 200 mg/dL. Young men without cholesterol problems had a higher life expectancy, by up to 8 years. Other studies have suggested similar risks from unhealthy cholesterol in young women as well.

Elderly Adults. About 85% of people who die from coronary artery disease are over the age of 65. Because high cholesterol is an important risk factor for heart disease, experts strongly recommend statin or other lipid-lowering therapy for elderly people with high cholesterol levels. Surveys indicate that total cholesterol levels have been declining in older people over the last few decades. Many experts believe this is due in part to increased use of statin drugs.

In the U.S., 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, obese individuals tend to have high triglyceride levels and low HDL levels. This combination is a risk factor for heart disease. Obesity also causes other effects (high blood pressure, increase in inflammation) that pose major risks to the heart.

Obesity is a particularly hazard when it is one of the components of the metabolic syndrome, formerly known as syndrome X. This syndrome consists of obesity marked by abdominal fat, unhealthy cholesterol 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. Many experts recommend that patients with metabolic syndrome should be aggressively treated with high-dose statin therapy to lower LDL levels.

Obesity is also strongly associated with type 2 diabetes, which itself poses a significant risk for high cholesterol levels and heart disease.

Low thyroid levels (hypothyroidism) are associated with unhealthy lipid levels. (Lipids are fat molecules). Specifically, people with hypothyroidism are at higher risk for high total and LDL cholesterol, triglycerides, and other lipids associated with heart disease. Treating the thyroid condition can significantly reduce cholesterol levels. Some experts suggest that patients with high cholesterol should be evaluated for thyroid function before they are given cholesterol-lowering drugs. Research is mixed on whether mild hypothyroidism (subclinical hypothyroidism) is associated with unhealthy cholesterol levels. [See In-Depth Report #38: Hypothyroidism.]

Hypothyroidism is a decreased activity of the thyroid gland which may affect all body functions. In this condition, the rate of metabolism slows, causing mental and physical sluggishness. The most severe form of hypothyroidism is myxedema, which is a medical emergency.

Genetics play a major role in determining a person's blood cholesterol levels. Children from families with a history of premature heart disease should be tested for cholesterol levels after they are 2 years old. Genes may influence whether a person has low HDL levels, high LDL levels, high triglycerides, or high levels of other lipoproteins, such as lipoprotein(a).

Some inherited disorders and genetic abnormalities have been identified:

Familial hypercholesterolemia causes dangerous increases in cholesterol. It may be more common than previously thought. One European study reported familial hypercholesterolemia in 1 out of every 400 people.
Familial lipoprotein lipase deficiency is a very rare disorder that causes depletion of lipoprotein lipase. This is an enzyme that appears to be important in the removal of lipoproteins that are rich in triglycerides. People who are deficient in it have high levels of cholesterol and fat in their blood. A very low-fat diet is essential and is an effective treatment for these individuals.
Several studies have found a genetic mutation affecting neuropeptide Y in people with high total cholesterol and LDL levels. Neuropeptide Y is a compound in the brain that regulates appetite.
Researchers have identified a gene called APOAV, which may help detect patients at risk for elevated levels of triglycerides.

Other medical conditions strongly associated with unhealthy cholesterol levels include:

Polycystic ovarian syndrome. Women with this disorder, particularly those who are obese, appear to be at increased risk for high triglyceride and low HDL levels. This risk may be due to higher levels of the male hormone testosterone in these women.

Click the icon to see an image of a polycystic ovary.

Kidney disease

Symptoms

There are no warning signs for high LDL cholesterol levels. When symptoms finally occur, they usually take the form of angina or heart attack in response to the buildup of atherosclerotic plaque in the patient's arteries. This is definitely a condition where it pays to invest in preventive medicine before dangerous complications occur.

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.

Diagnosis

A blood test for cholesterol should include the entire lipoprotein profile: LDL, total cholesterol, HDL, and triglycerides. It is very difficult to measure LDL levels by themselves, but LDL levels can be reliably calculated using total cholesterol and HDL levels.

To obtain a reliable cholesterol reading, experts advise:

Avoid strenuous exercise for 24 hours before the test.
Do not eat or drink anything but water for 12 hours beforehand.
If the test results are abnormal, a second test should be performed between 1 week and 2 months after the first test.

Home Tests. Tests are available for home use and in public locations, such as shopping malls and pharmacies. For example, the CholesTrak Test can be taken at home with results in 10 minutes, but it measures only total cholesterol. The BioSafe Cholesterol Panel Test is also a home test, but it needs to be sent to a laboratory. This test, however, is very accurate and provides a full lipid profile.

Certain blood tests for factors associated with inflammation in the arteries indicate a higher risk for heart disease, even in people without unhealthy lipids:

C-reactive protein (CRP). CRP is regulated by a very potent immune factor called interleukin-6. Elevated levels have been strongly associated with the inflammatory response and a higher risk for heart attack, even in people with normal cholesterol levels. CRP is also associated with high blood pressure, insulin resistance (the primary problem in type 2 diabetes), and obesity.
A high white blood cell count.
Elevated fibrinogen (a factor responsible for blood clotting).
Lipoprotein-associated phospholipase A2 may prove to be another marker for inflammation and heart disease. Studies suggest that it may play some causal role in coronary artery disease.

A new type of test measures cholesterol levels in the skin. High skin levels may indicate an increased risk for atherosclerosis and serious heart disease.

General Screening Recommendations. Experts groups differ slightly on when screening should start, but the following are generally accepted recommendations:

Periodic cholesterol testing in all adults starting at age 20. Adults with normal cholesterol levels do not need to have the test repeated for 5 years unless changes occur in lifestyle (including weight gain and diet). Adults with risk factors for heart disease or stroke should be rechecked every 2 years.
Selective screening of children who are at risk for high cholesterol and heart disease or familial hypercholesterolemia, which is genetically elevated cholesterol. Risk factors include having parents with total cholesterol levels greater than 240, or having a parent or grandparent who had symptomatic heart disease at age 55 or younger.
Patients already being treated for high cholesterol should be checked every 2 - 6 months.

Lifestyle Changes

Although most studies that prove that lowering cholesterol saves lives are done using drug therapy, the absolute mandate for improving cholesterol levels is to first make changes in lifestyle (both diet and exercise). Even when drugs are used, healthy diet and physical activity are critical companions.

Although there are many major dietary approaches for protecting health, experts generally agree on the following recommendations for heart protection:·

Choose fiber-rich food (whole grains, legumes, nuts) as the main source of carbohydrates, along with a high intake of fresh fruits and vegetables. Walnuts in particular have cholesterol-lowering properties and are a good source of antioxidants and alpha-linolenic acid.
Avoid saturated fats (found mostly in animal products) and trans fatty acids (found in hydrogenated fats and many commercial products and fast foods). Choose unsaturated fats (particularly omega-3 fatty acids found in vegetable and fish oils).
In selecting proteins, choose soy protein, poultry, and fish over meat. A 2006 study found that soy does not help improve cholesterol. However, experts still recommend it as a heart healthy food choice.
Controlling weight, quitting smoking, and exercising are essential companions of any diet program.

After embarking on any heart healthy diet, it generally takes an average of 3 - 6 months before any noticeable reduction in cholesterol occurs. However, some people see improved levels in as few as 4 weeks. An intensive program may be necessary to achieve significant improvements in cholesterol levels and to reduce heart risk factors.

Therapeutic Lifestyle Changes (TLC) from the National Cholesterol Education Program. Guidelines from the National Cholesterol Education Program include these recommendations for preventing and managing high cholesterol levels in adults:

Choose five or more servings of fresh fruits and vegetables and six or more servings of whole grains, legumes. Soluble fiber is preferred (from cereal grains, beans, peas, legumes, and many fruits and vegetables).
Fats can be up to 35% of daily calories, but no more than 7% should be from saturated fat. (People with high triglycerides, low HDL, or both may need a higher fat intake.) Choose fats containing unsaturated fatty acids (from vegetables, fish, legumes, and nuts). Choose margarines containing sterols or stanols (Benecol, Take Control). Avoid trans fatty acids found in commercial baked products.
Protein choices should be fat-free and low-fat milk products, fish, legumes, skinless poultry, and lean meats.
Limit dietary cholesterol intake to less than 200 mg per day.
Maintain healthy body weight and a healthy level of physical fitness.

Mediterranean Diet. The Mediterranean diet is rich in heart-healthy fiber and nutrients, including omega-3 fatty acids and antioxidants. The diet consists of fruits, vegetables, and unsaturated “good” fats, particularly olive oil. Olive oil has been associated with lower blood pressure, a lower risk for heart disease, and possible benefits for people with type 2 diabetes. Olive oil also contains polyphenol, which are phytochemicals that may help boost HDL levels.

A 2006 study that compared several types of Mediterranean diets to a low-fat diet found that Mediterranean diets were better at lowering blood pressure, cholesterol levels, and blood sugar levels after only 3 months. And, in research presented at the 2007 American College of Cardiology annual conference, the Mediterranean diet proved just as good as the American Heart Association low-fat diet for preventing recurrence of heart attack, stroke, or other heart events.

There are several variations to the Mediterranean diet but general recommendations include:

Limit red meats.
Drink one or two glasses of wine each day if alcohol is enjoyable and there are no reasons to restrict its use.
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.
Eat plenty of fresh fruits and vegetables, nuts, legumes, beans, and whole grains.
Season with garlic, onions, and herbs. Unfortunately, garlic does not appear to help lower cholesterol, but it may have other heart benefits. [See Herbs and Supplements in this section.]

Low-Carbohydrate Diets. The Atkins, South Beach, The Zone, and other diet restrict carbohydrate intake include. A 2006 review of low-carbohydrate diets found that they did help weight loss in the short term. However, while these diets appeared to lower triglyceride and raise HDL (“good”) cholesterol levels, they also raised overall and LDL (“bad”) cholesterol levels.

In contrast, a 2007 Journal of the American Medical Association study that compared four different low-carbohydrate and low-fat diet plans (Atkins, Zone, Ornish, and LEARN) found that the Atkins diet was best at raising HDL levels and reducing triglyciderides. In terms of LDL reduction, the low-fat Ornish diet produced the best improvements while the Atkins diet had no effect on LDL. The Atkins diet did result in better moderate weight loss (an average of 10 pounds over the course of a year versus 4 - 6 pounds for the other diet plans), which in itself may have accounted for the improved heart risk factors.

Glycemic Index. Low-carb diets -- such as South Beach, The Zone, and Sugar Busters -- rely on a concept called the "glycemic index," or GI, which ranks foods by how fast and how high they cause blood sugar levels to rise. Foods on the lowest end of the index take longer to digest. Slow digestion wards off hunger pains. It also helps stabilize insulin levels. Foods high on the glycemic index include bread, white potatoes, and pasta while low-glycemic foods include whole grains, fruit, lentils, and soybeans. (These low-glycemic foods are also important components of low-fat diet plans.) A 2006 study indicated that a high-protein, low-glycemic index diet can help produce better reductions in total and LDL cholesterol than a high-protein, high-glycemic index diet. Reducing glycemic load may also help to promote weight loss, especially for women.

Low Fat Diets. Dietary guidelines recommend keeping total fat intake to 20 - 30% of total daily calories, with saturated fat less than 10% of calories. Low-fat diets generally restrict fat intake to 20% or less of total daily calories. The Ornish program, which is recommended for some heart disease patients, limits fats even more drastically. It aims at reducing saturated fats as much as possible, restricting total fat to 10%, and increasing carbohydrates to 75% of calories. In 2006, the largest study to date on low-fat diets found that they did not help prevent heart disease or cancer. Women in the study reduced their fat consumption to 24 - 29% of total daily calories. Some critics say that the study did not do enough to distinguish between good types of fats (monounsaturated omega-3 polyunsaturated) and bad fats (saturated and trans fats).

The DASH Diet. The DASH diet (Dietary Approaches to Stop Hypertension) is proven to help lower blood pressure. Results are sometimes seen within a few weeks. Restricting sodium improves results. The diet appears to have antioxidant effects and may help lower LDL cholesterol levels, although beneficial HDL levels also decline. This diet is not only rich in important nutrients and fiber but also includes foods that contain far more electrolytes, potassium (4,700 mg/day), calcium (1,250 mg/day), and magnesium (500 mg/day) than are found in the average American diet.

A diet that is effective in lowering blood pressure is called Dietary Approaches to Stop Hypertension (DASH).

The DASH diet recommends:

Limit salt intake to no more than 2,300 mg a day (a maximum intake of 1,500 mg a day is an even better goal).
Reduce saturated fat to no more than 6% of daily calories and total fat to 27% of daily calories. (But, include dairy products that are non- or low-fat. Low-fat dairy products appear to be especially beneficial for lowering systolic blood pressure).
When choosing fats, select monounsaturated oils, such as olive or canola oils.
Choose whole grains over white flour or pasta products.
Choose fresh fruits and vegetables every day. Many of these foods are rich in potassium, fiber, or both which may help lower blood pressure.
Include nuts, seeds, or legumes (dried beans or peas) daily.
Choose modest amounts of protein (no more than 18% of total daily calories). Fish, skinless poultry, and soy products are the best protein sources.
Other daily nutrient goals in the DASH diet include limiting carbohydrates to 55% of daily calories and dietary cholesterol to 150 mg. Patients should try to get at least 30 g of daily fiber.

Slight changes to the DASH diet might help lower blood pressure even more, as well as improve cholesterol and lipid levels. Researchers reporting in the Journal of the American Medical Association and at the 2005 American Heart Association meeting said that replacing some carbohydrates in the DASH diet with more protein (from mostly plant sources) or monounsaturated fats may help reduce heart disease risk factors.

Calorie Restriction. Calorie restriction has been the cornerstone of weight-loss programs. Restricting calories in such cases also appears to have beneficial effects on cholesterol levels, including reducing LDL and triglycerides and increasing HDL levels. At this point, reducing calories and increasing exercise is still the best method for maintaining weight loss and preventing serious conditions, notably diabetes. A 2006 study reported that a low-calorie, but nutritionally balanced diet can help prevent an aging-associated change in heart function. Patients in the small study took in 1,400 - 2,000 calories a day for an average of 6 years.

The standard dietary recommendations for losing weight are the following:

As a rough rule of thumb, one pound of fat equals about 3,500 calories, so one could lose a pound a week by reducing daily caloric intake by about 500 calories a day. Naturally, the more severe the daily calorie restriction, the faster the weight loss.
To determine the daily calorie requirements for specific individuals, multiply the number of pounds of ideal weight by 12 - 15 calories. The number of calories per pound depends on gender, age, and activity levels. For instance, a 50-year-old moderately active woman who wants to maintain a weight of 135 pounds might require only 12 calories per pound (1,620 calories a day). A 25-year-old female athlete who wants to maintain the same weight might require 25 calories per pound 2,025 (calories a day).

Fat intake should be no more than 30% of total calories. Most fats should be in the form of monounsaturated fats (such as olive oil). Saturated fats (found in animal products) should be avoided.

Inactivity is one of the four major risk factors for coronary artery disease, on par with smoking, unhealthy cholesterol, and high blood pressure. In fact, studies suggest that people who change their diet in order to control cholesterol only achieve a lower risk for heart disease when they also follow a regular aerobic exercise program.

People who maintain an active lifestyle have a 45% lower risk of developing heart disease than sedentary people. Even moderate exercise reduces the risk of heart attack. One study of women found that just 1 hour of walking a week was associated with a lower risk for heart disease. The effects were similar even in women at high risk for developing heart disease.
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.
Burning at least 250 calories a day (the equivalent of about 45 minutes of brisk walking or 25 minutes of jogging) seems to offer the greatest protection against coronary artery disease, most likely because it raises HDL ("good cholesterol") levels. Moderate exercise has little effect on HDL.
Aerobic exercise helps to open up blood vessels and, in combination with a healthy diet, may improve blood-clotting factors.
Resistance (weight) training offers a complementary benefit to aerobics by reducing LDL ("bad cholesterol") levels.
Exercises that train and strengthen the chest muscles may prove to be very important for patients with angina.

Cigarette smoking lowers HDL and is directly responsible for approximately 20% of all deaths from heart disease. The importance of breaking this habit cannot be emphasized enough. Once a person quits smoking, HDL cholesterol levels rise within weeks or months to levels that are equal to their nonsmoking peers. Passive smoking also reduces HDL levels in people exposed to cigarette smoke.

A number of studies have found heart protection from moderate intake of alcohol (one or two glasses a day). Moderate amounts of alcohol help raise HDL levels. Although red wine is most often cited for healthful properties, any type of alcoholic beverage appears to have similar benefit. Pregnant women, anyone who cannot drink moderately, and people with liver disease should not drink at all.

The following natural remedies are of interest for cholesterol control:

Garlic. Contrary to popular belief, garlic does not significantly reduce cholesterol, according to a 2007 Archives of Internal Medicine study. Researchers tested raw garlic and two types of garlic supplements in 192 patients with moderately high LDL levels. None of the forms of garlic had any effect on LDL levels. However, the researchers note that garlic may still help people with very high LDL levels and it may contain other heart-protective properties.

Policosonol. Policosanol is a nutritional supplement derived from sugar cane that has been promoted as having lipid-lowering benefits. In a randomized, placebo-controlled trial published in 2007 in the Archives of Internal Medicine, policosanol was no better than placebo in reducing LDL levels.

Treatment

In 2004, the National Cholesterol Education Program issued its latest recommendations for cholesterol control and management. These guidelines increase the number of Americans who should be taking LDL-lowering medication.

Starting Medications. Even modest lowering of high cholesterol levels, whether through drug therapy or lifestyle changes, reduces the risk of disability and death from heart disease. Most experts now focus on lowering LDL ("bad") cholesterol. Reducing LDL levels is particularly critical for patients with diabetes.

The doctor will start or consider medication when:

LDL cholesterol is 190 mg/dL or higher.
LDL cholesterol is 160 mg/dL or higher AND patient has one risk factor for heart disease.
LDL cholesterol is 130 mg/dL or higher AND patient has either diabetes or two other risk factors for heart disease.
LDL cholesterol is 100 mg/dL or higher AND patient has heart disease. (If patient has diabetes, even without heart disease, medication may be considered for an LDL cholesterol of 100 mg/dL.)
LDL cholesterol is greater than 70 mg/dL AND patient has had a recent heart attack or has known heart disease along with diabetes, current cigarette smoking, poorly controlled high blood pressure, or the metabolic syndrome (high triglycerides, low HDL, and obesity).

Risk factors for heart disease 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)

Recent studies have found that aggressive lipid lowering with high-dose statin therapy is more beneficial than standard statin therapy in patients with existing heart disease. The Pravastatin or Atorvastatin Evaluation and Infection Trial (PROVE-IT) and the Reversal of Atherosclerosis with Aggressive Lipid-Lowering trial (REVERSAL) compared the benefits of standard statin therapy (pravastatin, 40 mg) with intensive statin therapy (atorvastatin, 80 mg) in treating patients with heart disease.

Results from PROVE-IT demonstrated that for high-risk patients, intensive statin therapy is more effective than standard therapy in lowering LDL cholesterol and C-reactive protein (CRP) levels, and that CRP levels predict risk even when LDL cholesterol has been lowered substantially. The REVERSAL data suggest that intensive statin therapy produces greater reductions in LDL and CRP levels, and that the more that statins can lower LDL, the more effective they are in reducing the progression of atherosclerosis.

An important 2006 study found that aggressive treatment with rosuvastatin (Crestor):

Helped lower LDL to below guideline levels
Moderately increased HDL levels
Reduced fatty plaque in the arteries

Experts hoped that these results suggested that statin therapy might have the potential to reverse coronary atherosclerosis. 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 and to explore whether other statins have a similar positive effect on coronary artery disease. Rosuvastatin lowers LDL more than other statins, but it also carries greater risks for more serious side effects (see Adverse Effects section). Many experts believe that the more that LDL is reduced through statin therapy, the greater the reduction in risk for heart disease, heart attack, and stroke.

It is important to emphasize that cholesterol-lowering medications are used along with healthy lifestyle habits, not in place of them.

Choosing the Correct Lipid-Lowering Medication. Experts now recommend that drug treatments be tailored for raising or lowering specific lipids, depending on the patient's blood lipid picture:

Statins are now the standard drugs for most people who require LDL-lowering therapy. Bile-acid binding resins or niacin may be considered. If LDL goals are not achieved, combinations of a statin with a bile-acid resin or niacin should be considered.
Fibrates or niacin are beneficial for people who need to lower triglycerides and increase HDL.

Considerations for Children and Adolescents. In 2007, the American Heart Association (AHA) issued a scientific statement addressing the use of cholesterol drugs in children and adolescents. The AHA recommends that for children who are overweight or obese, lifestyle modifications (diet, exercise) are preferred over drug therapy and should be the first step in lowering cholesterol.

For children and adolescents who have high-risk cholesterol imbalances -- and have a family history of high cholesterol, heart attack, stroke, and diabetes -- the AHA now recommends statins as the first-line drug therapy.

Considerations for People with Diabetes. At this time, statins are recommended as the best drugs for improving cholesterol and lipid levels in people with diabetes. Studies suggest that they can reduce the risk for adverse heart events in people with diabetes, even if their cholesterol levels are normal or if their diabetes is mild. Furthermore, in one study, a statin was shown to reduce the risk of developing diabetes by 30% in people with high cholesterol. Fibrates may also be useful for people with type 2 diabetes. Niacin (nicotinic acid) has the best effect on the cholesterol profile of people with diabetes but it also increases blood sugar levels. One well-controlled study, however, found that people with diabetes who used niacin had little trouble with glucose control, and some experts believe it now may be used as an alternative to or in combination with statins.


	Effect on High LDL	Effect on Low HDL	Effect on High Triglycerides	Effect on Lp(a)
Statins	Decrease (18 - 55%)	Modest increase (5 - 15%)	Decrease (7 - 30%)	No change
Nicotinic acid (Niacin)	Modest decrease (5 - 25%) In combination with statins, may convert more dangerous LDL type to less dangerous.	Increase (15 - 35%) Drugs of choice for improving HDL levels	Decrease (20 - 50%) Drug of choice for lowering triglycerides	Decrease
Fibrates	Effect varies, but in general has little effect or modest decrease (5 - 20%)	Modest increase (6 - 20%)	Decrease (20 - 50%)	No change
Bile acid-binding resins	Decrease (15 - 30%)	Very modest increase (3 - 5%)	No change	No change

Statins are the most effective drugs for the treatment of high cholesterol, and may even prove important drugs for many people at risk for heart disease who have normal cholesterol levels. Statins inhibit the liver enzyme HMG-CoA reductase, which is used in the manufacturing of cholesterol. These drugs effectively reduce the risk of major coronary events, including first and second heart attacks, in both adult women and men of any age with unhealthy cholesterol levels. Experts estimate a 25 - 30% reduction in mortality rates when patients take statins after a heart attack. (Some believe the decrease may even be greater.) These drugs may also help improve the outcome in patients with heart disease who have had angioplasty.

Important studies have reported lower rates of heart attack, stroke, and mortality rates from all causes in statin users who were at high risk for heart disease, even if they had normal or low cholesterol levels. Benefits were similar in these people regardless of gender, age, or the presence of specific heart risk factors, such as diabetes or peripheral artery disease.

Brands. Statins are currently categorized into four groups:

So-called natural statins, including lovastatin (Mevacor, generics), pravastatin (Pravachol), and simvastatin (Zocor, generics). These are the most studied statins and have proven effectiveness and good safety record.
Synthetic statins include fluvastatin (Lescol) and atorvastatin (Lipitor). Studies using atorvastatin suggest they may reduce LDL more effectively than natural statins. In 2007, Lipitor was approved for additional indications to reduce the risk of heart attacks, strokes, certain types of heart surgery, hospitalization for heart failure, and chest pain in patients with heart disease. Lipitor is also approved for children.
The newer statins include rosuvastatin (Crestor), which was approved in 2003. Trial results have suggested that rosuvastatin is more effective in improving lipid profiles than atorvastatin, simvastatin, or pravastatin. However, like all statin drugs, rosuvastatin can cause serious side effects (see the Adverse Effects section in this report). The risks may be higher for Asian patients; this population should be started on the lowest rosuvastatin dose (5 mg).
Fixed-dose combination statins, which combine two drugs in one pill, first appeared on the market in 2004. Ezetimibe/simvastatin (Vytorin) combines two cholesterol medications that work in different ways. Simvastatin blocks cholesterol production in the liver, while ezetimibe (a non-statin cholesterol medication) blocks cholesterol absorption in the digestive tract. A 2005 study found that Vytorin was more effective than atorvastatin in lowering LDL and increasing HDL levels. Amlodipine/atorvastatin (Caduet) is a dual-therapy medication that combines the antihypertensive calcium channel blocker amlodipine with atorvastatin. It is used to treat simultaneously high blood pressure and high cholesterol.

Statins are generally administered once a day, typically in the evening because most cholesterol synthesis occurs between midnight and 3 a.m. (Atorvastatin and rosuvastatin, however, can be taken in the morning.) Statins are often prescribed along with other cholesterol-lowering drugs such as bile acid-binding resins, nicotinic acid (niacin), and fibrates.

Beneficial Effects on the Heart and Circulation.

Statins are particularly effective for lowering LDL levels. They also reduce triglycerides, apparently in direct proportion to their LDL-lowering effects. Statins also raise HDL levels, but to a lesser extent than other anti-cholesterol drugs. (The newer statins appear to produce more significant increases in HDL.) Evidence now strongly suggests that statins may offer other health benefits beyond lowering cholesterol:

Statins may improve the function of the endothelium (the lining of blood vessels), thereby improving blood flow. (This benefit apparently does not extend to people with diabetes.)
Statins appear to reduce inflammation in the arteries, which is now believed to be a major factor in blood vessel injury.
Some evidence suggests that statins may help prevent blood clotting, a major factor in heart attacks.

Beneficial Effects Outside the Heart. Studies also suggest that the benefits of statins go beyond the heart. At this time, nearly all studies on the following conditions have used natural statins:

Stroke. Statins may reduce the risk for ischemic stroke in high-risk patients with a wide range of cholesterol and lipid levels. (Ischemic strokes occur from blockage in the blood vessels that lead to the brain.) In 2003, statin therapy was shown to reduce both fatal and non-fatal stroke in patients with hypertension and at least three additional cardiovascular risk factors. A 2004 study of stroke patients found that those who were receiving statin therapy at the time of their stroke had more favorable long-term outcomes than patients who were not on statin therapy, suggesting that statin therapy may provide additional benefits to patients who develop stroke.
Diabetes. Statins may have a number of effects that are helpful for patients with diabetes, and may even prevent diabetes in some people with high cholesterol. Statins, however, do not appear to have any effect on blood vessel inflexibility in diabetes, which is an important risk factor for heart disease in these patients. A major 2003 study found that statin therapy helped prevent cardiovascular events including coronary death, heart attack, stroke, and the need for revascularization therapy in patients with diabetes, even in those who did not have high cholesterol levels or established coronary disease.
High Blood Pressure. In an important 2002 study, patients with high blood pressure but normal hMG-CoA reductase or slightly high cholesterol levels had fewer heart attacks and strokes when they took the statin atorvastatin. The study was stopped so all subjects could take statins. An earlier study showed similar benefits with the statin simvastatin.
Alzheimer's Disease. A number of studies have reported a significantly lower risk for Alzheimer's disease in people who take specific statins. Some evidence suggests they may even improve mental function in people without unhealthy cholesterol levels. Statins showing the greatest promise include lovastatin (Mevacor), pravastatin (Pravachol), and atorvastatin (Lipitor.) These statins appear to reduce levels of beta-amyloid. Other statins have not been associated with a lower risk for Alzheimer's. In fact, some researchers are concerned that certain statins that cross the blood-brain barrier may actually worsen Alzheimer's in people who already have it.
Kidney Disease. Statins may prove to protect against heart disease development in patients with mild kidney disorders. According to a 2004 study, statins may also help slow the progression of existing kidney disease.
Eye Disease. Studies are investigating whether statins can help prevent macular degeneration, an age-related eye disease that can lead to blindness. Research is still preliminary, and results have been mixed.

Macular degeneration is a disease of the retina that affects the macula in the back of the eye. The macula is important for clear central vision, allowing an individual to see fine details. There are two types of macular degeneration, dry and wet. Dry macular degeneration is more common and is characterized by the thinning of the retina and drusen, small white deposits that form within the retina. The dry form of macular degeneration is usually mild. Wet macular degeneration can happen more quickly and be more serious. It occurs when vessels under the retinal layer hemorrhage and cause the retinal cells to die, creating blind spots or distorted vision in the central vision. The disease becomes increasingly common among people in each succeeding decade over 50.

Adverse Effects. The statins tend to be better tolerated than other cholesterol-lowering drugs. In many studies the side effects reported were nearly the same as those taking placebo. Side effects may include gastrointestinal discomfort, headaches, skin rashes, muscle aches, sexual dysfunction, drowsiness, dizziness, nausea, constipation, and peripheral neuropathy (numbness or tingling in the hands and feet).

The primary safety concern with statins has involved an uncommon condition called myopathy, which can cause muscle damage and in some cases, muscle and joint pain. A specific myopathy, called rhabdomyolysis, can lead to kidney failure. Reports of rhabdomyolysis prompted the recall of cerivastatin (Baycol) in 2001. The risk for myopathy/rhabdomyolysis is highest at higher doses and in older people (over 65 years), those with hyperthyroidism, and those with renal insufficiency (kidney disease). Both statins and fibrates carry a risk for myopathy. The combination of the two drugs increases this side effect. Some people who use a statin-fibrate combination withdraw from the regimen because of muscle discomfort.

In 2005, the FDA issued a public health advisory for rosuvastatin (Crestor), noting that this drug, like other statins, increased the risk for myopathy and rhabdomyolysis. The risks were greatest at the highest dose level (40 mg). The FDA advises that patients should not start therapy at this dose. In addition, the FDA reported the results of a post-marketing study that found that people of Asian heritage had twice the blood levels of the drug as Caucasians who had taken the same dose. Because of this difference in drug metabolism, the FDA advises that Asian Americans should start treatment at the lowest rosuvastatin dose (5 mg). In general, all statin therapy should start at a lower dose and be raised incrementally until healthy cholesterol levels are maintained. Patients should immediately tell their doctor about any unusual muscle discomfort or weakness, fever, nausea or vomiting, or darkening of urine color.

Statins can also affect the liver, particularly at higher doses, so patients should have periodic liver function tests. Statins should not be taken by anyone with liver problems or by women during pregnancy or breast-feeding. Similarly, high statin doses increase the risk for kidney failure, particularly for patients with other existing risk factors (diabetes, hypertension, atherosclerosis, history of heart failure).

Interactions with Drugs and Food. Statins may have some adverse interactions with other drugs, including other cholesterol-lowering medications. Among the drugs that increase the risk for adverse effects are cyclosporine, macrolide antibiotics, and certain antifungals. Patients should tell their doctors about any other medications they are taking. Grapefruit juice and Seville oranges may increase statin potency.

Brands. Nicotinic acid is the active compound found in niacin, or vitamin B3. It is the first choice for patients with low HDL levels. Brands include Niacor, Nicolar, and Slo-Niacin. An extended-release form (Niaspan), administered at bedtime, may have fewer side effects, including headaches and flushing, than rapidly-acting niacin drugs. Although niacin is available over the counter, the active form used for cholesterol is given in much higher doses and is available only by prescription. It is important to take this medication under a doctor's direction in order to ensure its safety and effectiveness.

Benefits. When used in high doses, it has the following benefits:

Raises HDL levels higher than other anti-cholesterol drugs
Reducing triglyceride levels very effectively
Lowers LDL-cholesterol and lipoprotein(a)
Costs less than other anti-cholesterol drugs

Combinations with other drugs, particularly statins, may add significant benefits.

Side Effects. Many patients do not like the side effects of the rapidly-absorbed form of nicotinic acid. About a quarter of patients who use rapid-acting forms of nicotinic acid stop taking them. The most common side effects are flushing of the face and neck, itching, headache, blurred vision, and dizziness. They usually occur between 5 minutes to hours after taking the drug and can last for minutes to, uncommonly, hours. The body does eventually become tolerant to these effects, and they generally subside.

The following may reduce flushing and itching:

Starting with low doses taken at mealtime and gradually working up to the prescribed dose.
Taking low-dose aspirin about 30 minutes before taking nicotinic acid. This may help prevent flushing.
Avoiding hot drinks.
Choosing an extended release form. (Even with this form, it is wise to gradually increase the bedtime dose over time and take a low-dose aspirin a half-hour beforehand.)

Stomach problems are common. Other side effects include dry skin and mucous membranes and darkening of the skin.

About 30% of patients who take niacin experience elevated levels in blood glucose, which can be a problem for people with diabetes. Niacin's effects on HDL and triglycerides, however, are especially suited for the lipid imbalances that are common in diabetes. And, some studies report that people with diabetes who use niacin have little trouble with blood sugar control.

Potentially Serious Complications. About 3 - 5% of people taking nicotinic acid develop liver problems, which disappear after the medication is discontinued. The extended form (Niaspan) appears to be safe for the liver, but people with chronic liver disease should not use any form of nicotinic acid. People with gout should also avoid nicotinic acid because it elevates uric acid.

Bile-acid binding resins work, as their name suggests, by binding to bile in the digestive tract. This reduces cholesterol in the following way:

Bile is made in the liver and is used as one of the body's primary manufacturing components.

Click the icon to see an image of the gallbladder.

Once the resins bind to bile in the digestive tract, the bile is excreted in feces.
As the resins eliminate bile from the body, the liver takes more cholesterol from the bloodstream in order to produce more bile.
As cholesterol is taken out of the bloodstream, LDL levels drop.

When used in combination with dietary control, LDL levels are reduced by 15 - 20%. Combinations with nicotinic acid are even more effective, with reductions of 40 - 60% observed.

Brands. The bile-acid binding resins and similar drugs include cholestyramine (Questran, Questran Light). They are commonly used in a powder that is dissolved in liquid. Colesevelam (Welchol) is available in tablet form.

Side Effects. None of these drugs poses major risks. Most, however, cause constipation, heartburn, gas, and other gastrointestinal problems, side effects that many people cannot tolerate. One study found that only half the standard dose of colestipol was needed when psyllium, (a soluble fiber supplement found in Metamucil, Fiberall, and Perdiem), was added to the drink. In addition, bloating and constipation were reduced. Colesevelam, a newer resin, appears to have significantly fewer of these side effects.

Bile-acting drugs may contribute to calcium loss and therefore increase the risk for osteoporosis. Over time, deficiencies of vitamins A, D, E, and K may occur, and vitamin supplements may be necessary.

Rarely, toxic effects on the liver have been reported. Patients with liver disorders should be monitored.

Drug Interactions. Bile-acid binding resins may also interfere with other medications, including digoxin (Lanoxin), warfarin, beta-blocker drugs, and a number of medications used to treat low blood sugar. In order to prevent drug interactions, other drugs should be taken 1 hour before or 4 - 6 hours after taking the bile acid-binding resins.

Brands. Fibrates (sometimes called fibric acid derivatives) break down the particles that make triglycerides. Gemfibrozil is the standard fibrate. It is usually taken twice a day, 30 minutes before breakfast and before the evening meal. Newer fibrates, including fenofibrate (Lofibra, Tricor, Triglide), may be more effective in lowering cholesterol than gemfibrozil.

Benefits. Most fibrates have been shown to lower the risk of heart attack. In a 2001 study, men with both low HDL and LDL levels had a slightly lower risk of stroke after taking gemfibrozil. Fibric acid derivatives, or fibrates, have the following effects on cholesterol, lipids, and other factors:

They are good choices for many patients who need to lower triglyceride levels and increase HDL but who cannot take drugs ordinarily used for these purposes, such as nicotinic acid. In one study gemfibrozil, the standard fibrate, reduced the risk for adverse heart events by 22%.
Fibrates can produce modest reductions in LDL levels, although not as effectively as statins or other drugs. LDL may actually increase in patients with very high triglycerides who take these drugs. (The newer fibrates are much more effective in lowering LDL than gemfibrozil.)
A study on bezafibrate suggested it might have anti-inflammatory effects in patients with high triglyceride levels. Inflammation in the blood vessels is now recognized as a major contributor to the process leading to heart disease. However, according to a 2004 study, patients with diabetes or impaired fasting glucose levels were less likely to benefit from bezafibrate.
A study on fenofibrate further suggested that it reduced certain clotting factors (another risk factor for heart disease) and also uric acid (a risk factor for gout). Another study, published in 2004, demonstrated that like bezafibrate, fenofibrate has significant anti-inflammatory properties in patients with high triglyceride levels.

Concerns. Fibrates do not appear to reduce mortality rates. In one study, people who took gemfibrozil had higher rates of death from other causes, including cancer. Some evidence suggests that fibrates may affect receptors involved in cancer development. However, a number of studies have found no higher incidence of cancer.

Side Effects. Side effects may include gastrointestinal discomfort, aching muscles, sensitivity to sunlight, and skin rashes. Fibrates have been known to cause gallstones, so people with gallbladder problems should not use these drugs.

Click the icon to see an image of gallstones in the gallbladder.

The drugs may cause abnormal heart rhythms and can affect the liver and kidney.

Drug Interactions. Fibrates interact with a number of drugs and substances including warfarin, some oral drugs used for diabetes, certain antibiotics, and grapefruit juice.

Ezetimibe (Zetia) blocks absorption of cholesterol that comes from food. Ezetimibe is usually prescribed alone or in combination with a statin. In 2004, the FDA approved Vytorin, which combines ezetimbe and the statin simvastatin into a single pill.

In 2006, the FDA approved the use of ezetimbe in combination with fenofibrate (Tricor) for reduction of total cholesterol and LDL in patients with mixed hyperglycemia (high LDL levels, high triglycerides, low HDL levels) whose cholesterol has not been adequately controlled through diet alone. Fenofibrate is a cholesterol drug that is used along with diet to reduce LDL and triglycerides.

CETP Inhibitors. Cholesteryl ester transfer protein (CETP) inhibitors, such as the experimental drug torcetrapib, are a new drug class that is being investigated for its effect on raising HDL ("good" cholesterol) levels while lowering LDL ("bad") cholesterol levels. Torcetrapib was the most widely studied of these drugs. However, in December 2006, the drug’s manufacturer abruptly stopped late-stage clinical trials after discovering that torcetrapib significantly increased blood pressure and risk of death.

Several studies published in 2007 in the New England Journal of Medicine revealed that while torcetrapib does greatly boost HDL levels (by 61% in one study) and lower LDL, it has no effect on arterial plaque. Scientists are trying to understand why this drug did not work. One theory is that torcetrapib may have increased the quantity of HDL, but not the quality. It is still not clear whether the failure of trocetrapib is specific to this drug or the entire CETP drug class. Given the current findings, it is also unclear whether research will continue on other CETP drugs.

Selective Estrogen-Receptor Modulators(SERMs). Selective estrogen-receptor modulators (SERMs) 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. They include tamoxifen (Nolvadex), raloxifene (Evista), and droloxifene. Any beneficial effects of the SERMs on cholesterol and the heart are still unclear. SERMs pose a risk for deep vein blood clots, which may have implications for people with heart problems. Longer studies are needed on possible risks and benefits.

Recombinant ApoA-I Milano. ApoA-I Milano is a type of HDL protein that is found in people with very low levels of HDL. A 2003 study showed that treating patients with a synthetic form of HDL, derived from ApoA-I Milano, caused a significant regression of atherosclerosis. Ongoing trials will evaluate whether this drug can prevent cardiovascular events such as heart attack or death.

Plasmapheresis and Familial Hypercholesterolemia. Plasmapheresis is a blood-filtering procedure that is used to dramatically reduce triglycerides and may also be used to remove LDL. The procedure may be beneficial for patients with severe hereditary forms of high cholesterol who do not respond to other therapies. Studies suggest, for example, that plasmapheresis is particularly useful for patients with familial hypercholesterolemia. The process takes about 3 hours. If not performed regularly, its benefits last only about 2 weeks. People using this procedure are still advised to maintain a healthy diet and continue to take any prescribed medications to control cholesterol.

Resources

www.nhlbi.nih.gov/about/ncep -- National Cholesterol Education Program
www.nhlbi.nih.gov -- National Heart, Lung, and Blood Institute
www.acc.org -- American College of Cardiology
www.americanheart.org -- American Heart Association
www.eatright.org -- American Dietetic Association

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Gardner CD, Lawson LD, Block E, Chatterjee LM, Kiazand A, Balise RR, et al. Effect of raw garlic vs commercial garlic supplements on plasma lipid concentrations in adults with moderate hypercholesterolemia: a randomized clinical trial. Arch Intern Med. 2007 Feb 26;167(4):346-53.

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McCrindle BW, Urbina EM, Dennison BA, Jacobson MS, Steinberger J, Rocchini AP, et al. Drug therapy of high-risk lipid abnormalities in children and adolescents. A scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee, Council of Cardiovascular Disease in the Young, With the Council on Cardiovascular Nursing. Circulation. 2007 Mar 21; [Epub ahead of print]

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Nissen SE, Tardif JC, Nicholls SJ, Revkin JH, Shear CL, Duggan WT, et al. Effect of torcetrapib on the progression of coronary atherosclerosis. N Engl J Med. 2007 Mar 26; [Epub ahead of print]

Review Date:
7/23/2007
Reviewed By:
Alan Greene, MD, FAAP, Chief Medical Officer, A.D.A.M., Inc.; and Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

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Non-small cell lung cancer

FitSugar — Wed, 08 Oct 2008 17:35:06 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Risk Factors
Lifestyle Changes
Diagnostic Tests
Staging Systems
Surgical Procedures
Radiation Treatments
Treatment Options by Stages...
Chemotherapy Treatments
Investigative Agents
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Research News:

About 3,000 nonsmokers die each year of lung cancer resulting from exposure to secondhand smoke, according to a 2006 Surgeon General report.
Advexin, a genetic therapy that contains the p53 tumor-suppressor gene, is showing promise. A 2006 study in Japan found that out of 13 patients with advanced NSCLC receiving Advexin, 10 had stabilized. Advexin is in Phase II clinical trials for NSCLC.
Studies are finding that NSCLC tumors in people who never smoked have a much higher rate of epithelial growth-factor receptor (EGFR) mutations. EGFR helps new blood vessels grow to feed tumors. This discovery may help tailor future treatments to specific patient populations. It also helps explain why some newer treatments seem effective mostly in patients who never smoked.

Treatment News:

Video-assisted thoracic surgery (VATS) is a new, less-invasive surgical technique that uses a thin tube containing a miniature camera and surgical instruments. Though the procedure is not appropriate in all cases, it offers significant advantages, especially in older or frail patients, in the treatment of early stage non-small cell lung cancer (NSCLC).
Bevacizumab, a monoclonal antibody, was approved in October 2006 as a first-line treatment (in combination with carboplatin and paclitaxel) for inoperable, locally advanced, metastatic, or recurrent non-squamous, non-small cell lung cancer.
Gefitinib (Iressa), a drug that targets EGFR, proved disappointing in final clinical trials. However, erlotinib (Tarceva), a drug that targets a different part of the EGFR molecule, has shown benefits. Erlotinib is now approved as a second-line chemotherapy to treat patients with locally advanced or metastatic NSCLC after a previous course of chemotherapy failed.

Introduction

Although lung cancer accounts for only 13% of all cancers, it is among the most lethal, accounting for over 28% of all cancer deaths. It is more deadly than colon, breast, and prostate cancers combined. An estimated 160,390 people will die from lung cancer in 2007. Death rates have been declining in men over the past decade, and they have now stabilized in women.

The lungs are two spongy organs surrounded by a thin moist membrane called the pleura. Each lung is composed of smooth, shiny lobes: the right lung has three lobes, and the left has two. About 90% of the lung is filled with air; only 10% is solid tissue.

Air is carried from the trachea (the windpipe) into the lung through flexible airways called bronchi.
Like the branches of a tree, the bronchi in turn divide into over a million smaller airways called bronchioles.
The bronchioles lead to grape-like clusters of microscopic sacs called alveoli.
In each adult lung, there are about 300 million of these tiny alveoli. A thin membrane makes up the alveoli sacs. Oxygen and carbon dioxide pass through this membrane to and from capillaries.
Capillaries, the smallest of our blood vessels, carry blood throughout the body.

The major features of the lungs include the bronchi, the bronchioles, and the alveoli. The alveoli are the microscopic blood vessel-lined sacks in which oxygen and carbon dioxide gas are exchanged.

Lung cancer develops when genetic mutations (changes) occur in a normal cell within the lung. As a result, the cell becomes abnormal in shape and behavior, and reproduces endlessly. The abnormal cells form a tumor that, if not surgically removed, invades neighboring blood vessels and lymph nodes and spreads to nearby sites. Eventually, the cancer can spread (metastasize) to locations throughout the body.

The two major categories of lung cancer are small cell lung cancer and non-small cell lung cancer. Most lung cancers are non-small cell cancer, the subject of this report. Less common cancers of the lung are known as carcinoids, cylindromas, and certain sarcomas (cancer in soft tissues).

Some experts believe all primary lung cancers come from a single common malignant (cancerous) stem cell that, as it copies itself, can develop into any one of these cancer types in different individuals.

In addition, cancers in the lung may have spread from other primary sites, such as the breast, thyroid, or colon. In these cases, doctors name the cancer after its original location; for example, "breast cancer with lung metastases."

Non-small cell lung cancers are categorized into three types: squamous cell carcinoma (also called epidermoid carcinoma), adenocarcinoma, and large cell carcinoma. These separate types are grouped together because, in early stages before the cancers have spread, they all can be treated surgically.

Squamous Cell Carcinoma. Squamous cells are formed from reserve cells, which are round cells that replace injured or damaged cells in the lining (the epithelium) of the bronchi, the major airways. Tumors formed from squamous cells are usually found in the center of the lung, either in a major lobe or in one of the main airway branches. They may grow to large sizes and form cavities in the lungs.

Click the icon to see an image of squamous cell carcinoma.

When squamous cell cancer metastasizes, it may travel to the bone, adrenal glands, liver, small intestine, and brain.

Squamous cell carcinoma is nearly always caused by smoking and used to be the most common cancer. It still makes up 25 - 40% of all lung cancers.

Adenocarcinoma. Adenocarcinomas usually arise from the mucus-producing cells in the lung. About two-thirds of adenocarcinomas develop in the outer regions of the lung, while one-third develop in the center of the lung. In 1965, 12% of lung cancers were adenocarcinomas. They are now estimated to account for 30 - 50% of all lung cancers and are the most common lung cancers in many countries. They are also the most common lung cancers in women. In fact, a 2000 European study showed that nearly 34% of the women with lung cancer under investigation had adenocarcinoma, compared to 26.4% who had squamous cell carcinoma, and 22.3% with small cell lung cancer. Adenocarcinoma is also increasing dramatically in men. Until recently, adenocarcinoma was only weakly linked to smoking. Experts now suggest, however, that the dramatic increase in recent decades in this lung cancer type may be due to low-tar, filtered cigarettes. People who smoke them draw tiny particles deeper into the lungs, thereby possibly increasing the risk for adenocarcinoma.

The course of this cancer varies widely. Most often, it develops slowly and causes few or no symptoms until it is far advanced. In some cases, however, it can be extremely aggressive and rapidly fatal. In 50% of cases in which this cancer spreads, it spreads only to the brain. Other common locations it spreads to include the other lung, the liver, the adrenal glands, and bone.

Click the icon to see an image of adenocarcinoma.

Bronchoalveolar Lung Cancer. Bronchoalveolar lung cancer is actually a subtype of adenocarcinoma. It develops as a layer of column-like cells on the lung and spreads through the airways, causing great volumes of sputum. This cancer also is increasing in incidence.

Large Cell Carcinoma. Large cell carcinoma, which makes up about 10 - 20% of lung cancers, includes cancers that cannot be identified under the microscope as squamous cell cancers or adenocarcinomas.

Click the icon to see an image of large cell carcinoma.

Small cell lung cancer may, like squamous cells, be derived from reserve cells or other cells in the epithelium. It causes 15 - 25% of all lung cancers; without chemotherapy, it is very aggressive and usually rapidly fatal. It requires a different treatment approach from non-small cell lung cancer, so it is not discussed in this report.

Click the icon to see an image of small cell carcinoma.

Causes

Cigarette Smoke. Smoking causes 87% of lung cancer deaths, accounting for 30% of all cancer deaths. Cigarettes, nicotine, or both may contribute to lung cancer in one or more of the following ways:

In general, chronic exposure to nicotine may cause an acceleration of coronary artery disease, peptic ulcer disease, reproductive disturbances, esophageal reflux, hypertension, fetal illnesses and death, and delayed wound healing.

The smoke is the most dangerous component of the cigarette. Chemicals formed during smoking trigger genetic mutations that lead to cancer. When people inhale cigarette smoke, they bring into their lungs tar that includes over 4,000 chemicals, some of which are carcinogenic (cancer-causing). Other inhaled chemicals in cigarette smoke that may increase the risk for cancer include cyanide, benzene, formaldehyde, methanol (wood alcohol), acetylene (the fuel used in torches), and ammonia. Smoke also contains nitrogen oxide and carbon monoxide, both of which are harmful gases.
Nicotine itself may be a hazard. A 2000 laboratory study suggested that the human body might be converting inhaled nicotine into a chemical called aminoketone, which has been linked to the formation of tobacco-related lung cancer. A 2001 study reported that nicotine triggered new blood vessel growth, which could, in theory, promote growth of any existing tumors. A study published in 2005 found that nicotine was responsible for disabling a gene that induces the death of cancer cells in lung tumors. Whether or not these studies apply to long-term use of nicotine replacement products (such as patches), or to cigarette smoking, is still unclear. The studies should certainly not discourage people from using nicotine replacement methods for quitting. However, these studies may indicate that people should not use these devices on a long-term basis.

Radon. Radon is a gas produced naturally by the breakdown of uranium. It is often present in the soil and in water and can seep into any dwelling. Radon may be responsible for between 10% and 14% of lung cancer deaths, making it, after smoking, the second leading cause of this cancer.

Other Contributors. Toxic particles leading to precancerous changes in the lung are also found in marijuana. In one study, 53.8% of cigarette smokers, 66.7% of marijuana smokers, and all of those subjects who smoked both substances showed evidence of precancerous changes in the lungs.

There is considerable debate over the lung cancer risk posed by depleted uranium used in military weapons (such as in the Gulf and Balkan conflicts). A 2001 study estimated that it would cause an additional 8 deaths from lung cancer out of every 10,000 people or soldiers who were highly exposed to this substance. The study was based on a mathematical model, however, and the issue is not settled.

Other lung carcinogens include asbestos, arsenic, certain petrochemicals (materials made from crude oil or natural gas), and other airborne (carried through the air) byproducts of various mining and manufacturing processes.

Click the icon to see an image of the tobacco plant.

Genetic mutations that cause cancer generally occur in two types of genes:

Tumor-suppressor genes, which prevent cells from endlessly copying themselves
Proto-oncogenes, which encourage cells to keep making copies of themselves [when a proto-oncogene changes (becomes mutated), it is then called an oncogene]

Damage to either type of gene can cause a mutation that results in an uncontrolled division of cells. This uncontrolled division forms tumors.

It is unlikely that a single specific abnormality causes all lung cancer. It probably takes a variety of mutations to start the devastating chain of events leading to cancer. The following mutations are among those under investigation:

BPDE-caused mutations: The chemical BPDE, a byproduct of tobacco smoke, is involved with a number of genetic mutations, including those to an oncogene called K-ras and to three tumor-suppressor genes known as p53, PPP2R1B, and p16. When normal, the tumor-suppressor genes are involved in cell repair and healthy copying of the cell. When they are damaged or blocked, out of control cell production can occur, leading to cancer. About 10% of the population may carry a gene that protects against lung cancer, by reducing levels of BPDE.
Chemotherapy resistance genes: Tumors that contain the p53 mutation may also be more resistant to chemotherapy.
Rb Mutations: Another important contributor to lung cancer is a genetically defective protein called retinoblastoma (Rb), which is associated with very aggressive tumors. Low levels of the normal Rb gene may sometimes predict aggressive cancer, especially in patients with small cell lung cancer.
Mutations to the FHIT gene: Another potentially important mutation may be an abnormality in the FHIT gene. This mutation causes the cells lining the lung to become more vulnerable to the effects of tobacco smoke and other carcinogens.

Symptoms

Lung cancer is unlikely to produce symptoms until the disease is advanced. When symptoms develop, they may result from the lung tumor itself, from its effects on tissues outside the lung, or from the spread of malignant cells to other organs.

Early symptoms may include the following:

Frequent bouts of pneumonia, or pneumonia that does not clear up in a normal period of time
Coughing (particularly coughing up blood)
Weight loss
Fever
Shortness of breath
Chest pain

Later-stage symptoms include the following:

Shortness of breath: This common symptom is the result of cancer that has spread in the lung and the pleura, the membrane covering the lung.
Superior vena cava syndrome: In some cases, tumor growth or spreading of the cancer presses against the superior vena cava, a large vein that returns blood from the upper part of the body to the heart. When this happens, a condition called superior vena cava syndrome may occur, leading to obvious swelling in the arms and face.
Trouble swallowing: The esophagus is the pipe that takes food from the mouth to the stomach. The cancer may spread to or press against the esophagus, interfering with swallowing and nutrition.
Hoarseness: Cancer can damage the nerves that control the voice box, causing hoarseness.
Pancoast syndrome: Damage to the brachial plexus, a group of nerves branching from the neck, can cause pain, weakness, or numbness in the arm or hand (Pancoast syndrome).
Bronchoalveolar lung cancer may produce very large amounts of mucus.
Hypercalcemia: Some lung cancers produce substances that remove calcium from bone and release it into the bloodstream, causing a condition called hypercalcemia. Patients with this disorder can experience nausea, vomiting, constipation, weakness, and fatigue.

Other lung cancers (usually small cell cancer) cause the body to retain water, lowering the blood's sodium levels. This condition, called hyponatremia, can produce confusion, weakness, and even seizures.

Risk Factors

Before cigarettes became popular in the beginning of the 20th century, lung cancer was rare. In 2007, lung cancer is expected to strike up to 213,380 Americans, and about 160,390 are expected to die from it.The disease usually occurs in people over 50 years old. Men have a significantly greater incidence of lung cancer compared to women. On the encouraging side, the rate of lung cancer in men has been declining significantly over the past decade. While lung cancer rates have been increasing dramatically in women (by 600% from 1950 to 2000), they now appear to be stabilizing.

Smoking appears to be the primary risk factor in 85 - 90% of lung cancers. About 15% of all people who smoke develop lung cancer. The risk depends on the duration of the addiction and the number of pack years. (One pack year equals the number of packs of cigarettes smoked per day, multiplied by the number of years that the person has smoked.) Genetic damage in the lung occurs in nearly all chronic smokers, even if cancer has not developed.

An elevated risk for lung cancer can persist for more than 20 years after quitting smoking, although the risk drops significantly even in the first year after quitting. And, there are benefits to quitting smoking even for people who are well into middle age.


Quitting Age	Percentage
30	2%
40	3%
50	6%
60	10%

Second-Hand Smoke. The Environmental Protection Agency has classified second-hand smoke as a carcinogen (cancer-causing chemical). Exposure to second-hand tobacco smoke increases the risk of lung cancer in the nonsmoker by about 20 - 30%. A 2006 Surgeon General report found that about 3,000 nonsmokers die each year of lung cancer resulting from exposure to secondhand smoke.

There may be some ethnic differences in lung cancer risk. For example, African-Americans face a risk that is two to four times higher than that in Caucasians, regardless of smoking status. It is not clear what factors are responsible for this higher risk. Some African-Americans appear to have a genetic vulnerability to the harmful chemicals in cigarette smoke.

In China, an estimated one third of all young male smokers will eventually die because of tobacco-related illnesses. Their risk for lung cancer, however, is much less than it is for chronic lung disease, the opposite of the Western trend. A 2001 study reported that the lower rate of lung cancer among Chinese people might be due to a slow rate of clearing nicotine, which results in smoking fewer cigarettes.

People with High Exposure to Radon. Studies have shown that radon raises the risk of lung cancer in underground miners by 40%. It is unclear whether the results of these studies would apply to people exposed to radon in their homes One study suggests that people with intense or prolonged exposure to radon in their homes do indeed face the same risk as miners exposed to similar levels of radon. A cumulative long-term exposure to radon and smoking also increases the danger. Most people move an average of 10 or 11 times over their lifetime, so the risk of developing lung cancer through radon exposure is very low in most individuals, even for those who lived for awhile in areas with high radon levels. People with homes that have high radon levels and those who sleep or spend many hours to days in basements with detectable but moderate levels should consider taking protective measures.

Workers Highly Exposed to Carcinogens. An estimated 9,000 - 10,000 men and 900 - 1,900 women develop lung cancer each year because of occupational exposure to carcinogens. More than half of these cases are attributable to past exposure to asbestos, which has long been known to be a risk factor for mesothelioma (cancer of the pleura, the lining around the lung) and can increase the risk of lung cancer in smokers. With better protective measures, these rates are expected to fall in the future.

Other chemicals that put workers at risk for lung cancer include:

Arsenic (insecticide and herbicide sprayers, tanners, oil refinery workers)
Chloromethyl methyl ether (workers exposed to certain polymers, water repellents, or products using chloride and formaldehyde)
Chromium compounds (workers using certain alloys, paints, pigments, and preservatives)
Depleted uranium (soldiers exposed to weapons during battlefield conditions)
Crystalline silica

By contrast, agricultural workers seem to have a lower lung cancer rate, despite their possible occupational exposures to risky chemicals. While this rate has traditionally been attributed to good health habits, including low tobacco use, a 2000 study suggests that agricultural workers' exposure to endotoxin may be responsible. Endotoxin is a component of common bacteria found in soil and animals and may have cancer-preventing effects on the immune system.

Exposure to Smoke from Grills. Grilling and high-heat frying emit chemicals called heterocyclic amines, which are known to be carcinogenic. A 2000 study of Chinese women found that smokers who stir-fried meat daily and inhaled cooking fumes had a higher risk of lung cancer than did those who stir-fried meat less frequently. No higher risk was found among nonsmokers.

Air Pollution. Although any risk from air pollution is very small, it nevertheless may be a contributor to those lung cancers not obviously related to smoking. Some studies, including a major analysis of vital statistics in 2002, have found an association between increased risk for lung cancer and long-term exposure to very small particulates, especially sulfates, present in polluted air. The risk, if any, is very small.

A family history of lung cancer may play a role in increasing susceptibility to this disease. In one study, people who had parents or siblings with respiratory tract cancers had a 30% higher risk for lung cancer, compared to people without a family history. Women with mothers or sisters with lung cancer had triple the risk. A higher risk occurred in both smokers and nonsmokers. There was no association between a history of other cancers and lung cancer. Both genetic factors and secondhand smoke appeared to contribute to the danger in these individuals.

Smokers with emphysema or chronic inflammatory lung diseases, such as asthma, are at increased risk for lung cancer. Both smokers and nonsmokers whose lungs are scarred from recurrent lung diseases, such as pneumonia or tuberculosis, are also at increased risk, particularly for bronchoalveolar lung cancer.

Lifestyle Changes

Quitting improves lung function almost immediately. Some evidence suggests that the benefits for the lungs are even more significant for women who quit than for men. It should be noted, however, that it can take 20 years or longer, particularly in heavy smokers, for the lungs to be restored to a fully healthy condition in which the risk for lung cancer is as low as for nonsmokers. Quitting is extremely difficult. No one should be discouraged if they relapse. Everyone should keep trying to quit. With continued efforts, many people succeed.

The many methods of quitting smoking include counseling and support groups, nicotine patches, gums and sprays, and incremental reduction.

At this time perhaps the most effective method for quitting is a combination of the following:

Nicotine replacement products that reduce withdrawal symptoms and cravings.
The antidepressants bupropion (Zyban) or nortriptyline (Pamelor, Aventyl), which reduce emotional effects and cravings associated with withdrawal, and improve abstinence rates.
Professional counseling or support organizations that may be effective, in addition to the medication, in helping people maintain abstinence.

[See In-Depth Report #41: Smoking.]

While people are in the process of quitting (and afterwards), they should maintain as healthy a lifestyle as possible.

Phytochemicals. Some data suggest that diets rich in fresh fruits and vegetables may be protective against lung cancer in both smokers and non-smokers. Some studies have reported protection from specific plant chemicals (phytochemicals), such as the following:

Isothiocyanates. These chemicals are found in cruciferous vegetables (broccoli, cauliflower, and Brussels sprouts). They may help block the effects of carcinogens in smoke, suppress tumor growth, and inhibit growth-promoting steroid hormones.
Flavonoids. Major sources are apples, grapefruit, onions, red wine, and tea. In one study on flavonoids, apple eaters had the lowest cancer risk, 68% less than those who ate fruit infrequently. In another, those who ate relatively more onions, apples, and white grapefruit had less than half the lung cancer risk as people who ate relatively small amounts of these foods. Flavonoids are also found in soybeans, berries, broccoli, carrots, citrus fruits, eggplant, peppers, squash, and tomatoes. Specific flavonoids in dark chocolate may be protective against lung cancer (but not other cancers).
Lycopene. Lycopene is found in tomatoes, which have been associated with a lower risk for lung cancer. Cooking the tomatoes appears to increase the potency of lycopene.
Cryptoxanthin. Some studies suggest that eating foods rich in cryptoxanthin, a yellow-orange pigment, reduces the risk for lung cancer. Foods with high amounts of cryptoxanthin include pumpkin, corn, papaya, red bell peppers, tangerines, oranges, and peaches. More research is needed in this area, however.
Isoflavones. Isoflavones, found in soy beans and flax seed, behave like estrogen in some ways and not in others. Some evidence suggests the genistein (a type of isoflavone) in soy may have properties that are protective against lung cancer.

Click the icon to see an image of phytochemicals.

Note: Studies on these chemicals are not consistent. It is unlikely that individual phytochemicals offer protection, but rather that the benefits come from a collection of vitamins and plant chemicals contained in fruits and vegetables. Fruit, especially, appears to be protective.

Fats and Oils. Some studies have indicated that diets high in animal fats increase the risk for lung cancer. Others have suggested some protection from cod liver oil, which contains omega-3 fatty acids (found in fatty fish), omega-6 fatty acids (found in flax and in soybean and canola oils), and monounsaturated oils (found in olive and canola oils). Of interest was a 2002 study reporting that women who had a high intake of cheese had a lower risk of lung cancer. Despite these intriguing pieces of information, the ability of these substances to protect against lung cancer remains controversial, and discontinuation of smoking remains the best advice.

Click the icon to see an image of fats and oils.

Vitamin Supplements. Even with a healthful diet, smoking reduces the levels of a number of vitamins, importantly vitamin C. There is no evidence, however, to support any protection from antioxidant supplements, including vitamins E, A, or beta carotene.

In fact, evidence is now suggesting that high doses of vitamin C, vitamin E, and beta carotene supplements may have harmful effects. A 2000 study, for example, reported a higher risk for cancer in male smokers who took multivitamins plus A, C, or E. The strongest studies to date on negative effects of antioxidant supplements have reported an increase in lung cancer and overall mortality rates among smokers who took beta carotene supplements. In determining reasons for this disturbing effect, one animal study suggested that beta carotene increased enzymes in the lungs that actually promote cancerous changes. In other words, antioxidants may actually be harmful in people who already harbor cancer cells. This is particularly important information for smokers, who may carry precancerous or cancerous cells for years prior to developing the disease. The best way of achieving healthy levels of important nutrients is from healthy foods.

Click the icon to see the benefits of vitamin A.

Click the icon to see dietary sources of vitamin A.

Trace Element Supplements. Trace elements may be important in cancer risk and prevention.

Selenium appears to inhibit cell production and may have other anti-cancer properties. A few studies have reported some protection with selenium. However, a major 2002 analysis supports previous work, indicating that taking selenium helps only people who are deficient to begin with.

Click the icon to see the benefits of selenium.

Zinc may prove to be more important than selenium. Some research suggests that zinc may help protect smokers by blocking cadmium. Smokers have higher levels of cadmium in their body, and there may be a link between cadmium and a higher risk for lung cancer. Some laboratory studies have indicated that zinc might help protect against tumor progression. There is no evidence that taking zinc supplements will reduce the risk for lung cancer, however.

A 2003 study reported a lower risk in lung cancer in men and women who were physically active. Both moderate and intensive exercises were associated with protection.

People concerned about radon in their home or area can purchase a test approved by the Environmental Protection Agency. Methods for removing radon include installing a soil suction system. It should be noted, however, that home prevention measures rarely reduce radon levels to zero. Simply sleeping by an open window reduces the risk.

Nonsteroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors (coxibs) both block cyclooxygenase (COX) enzymes. NSAIDs block COX-1 and 2, and coxibs selectively block COX-2. Evidence now strongly suggests that the COX-2 enzyme plays a role in blood vessel growth (angiogenesis) that can feed lung cancers.

NSAIDs. NSAIDs include aspirin, ibuprofen (Advil), and naproxen (Aleve, Naprosyn, Naprelan, Anaprox). These agents inhibit COX-2, but they also target another COX enzyme. Studies are now reporting an association between regular use of aspirin or other NSAIDs and a reduced risk for non-small cell lung cancer.

COX-2 Inhibitors. The COX-2 inhibitors are more recent forms of NSAIDs. Currently, only celecoxib (Celebrex) is still on the market. Rofecoxib (Vioxx) and valdecoxib (Bextra) were withdrawn from the market due to their high risk of causing strokes and heart attacks. Because they target the COX-2 enzyme specifically, researchers are focusing on these drugs for a possible role in treating lung cancer and preventing recurrence.

Diagnostic Tests

Chest X-Rays. In a small percentage of cases, a routine chest x-ray reveals the first signs of lung cancer. Usually, however, symptoms of existing lung cancer, such as coughing, chest pain, and blood in the sputum, will lead to a chest x-ray. If non-small cell lung cancer is present, chest x-rays may show lesions (damaged or abnormal tissue) in the center of the lung, cavities formed by squamous cell carcinoma, or lace-like pattern of cells spreading through the lungs. By the time lung cancer is diagnosed by chest x-rays, however, it has often spread so far that it cannot be surgically cured. Four major studies found no survival benefits in early detection from chest x-rays and sputum screening. Regular screening for lung cancer using x-rays is therefore not currently recommended.

Computed Tomography. Computed tomography (CT), particularly the specific technique called low-dose spiral (or helical) CT, is more effective than x-rays for detecting cancer in patients with suspected lung cancer. It is the standard imaging procedure for determining if and where the cancer has spread (metastasized). Surgeons also use CT scans to evaluate patients before lung surgery.

CT stands for computerized tomography. In this procedure, a thin x-ray beam is rotated around the area of the body to be visualized. Using very complicated mathematical processes called algorithms, the computer is able to generate a 3-D image of a section through the body. CT scans are very detailed.

The use of helical CT for early screening is still controversial. Studies of CT scans in smokers suggest that early screening will detect about 2% of lung cancers, most of these in early stages. In the studies, 62 - 82% of the patients with stage 1A cancer (when the tumor has not spread yet) were still alive at 5 years. Neither study, however, was controlled (compared with other groups, such as non-smokers). The survival figures were likely to be higher than in actual practice.

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

Evidence regarding the survival benefits of early detection is not clear. Many experts are highly opposed to widespread screening for lung cancer. Some evidence, for example, suggests that lung cancer cells in non-small cell lung cancer are often very aggressive at microscopic levels (before a tumor is formed). If this were true, the cancer would be highly likely to have already spread, long before it was visible with CT scans. Moreover, some studies have found no association between tumor size at the time of diagnosis and survival times. On the other hand, some suspicious areas detected by CT scans may actually be innocent, and these patients might be more likely to die from aggressive treatments than from the disorder itself.

It should also be noted that about 98% of suspicious areas seen on CT scans turn out to be benign. Even after rescreening, many scans will show suspicious areas that turn out to be harmless but will require invasive and expensive biopsies. Additional experience with CT scans, however, may allow experts to better determine which abnormalities are likely to be benign.

High-risk individuals who are still interested in early screening with CT scans should ask their doctor about available clinical trials.

Computed tomography is the standard imaging procedure for determining if and where the cancer has spread (metastasized). Other imaging tests, however, may be useful for staging and tracking lung cancers (staging means finding out how advanced the cancer is).

Positron Emission Tomography. Positron emission tomography (PET), specifically a technique known as FDG/PET, is the most accurate noninvasive test for detecting early lung cancer. It is also the best imaging technique for staging lung cancers, not only those located in the lungs, but also those that have spread, particularly into the space between the two lungs (the mediastinum). With this imaging test, the patient is first injected with a specially formulated liquid sugar (called FDG), and then viewed with a machine that records energy given off by tumor cells.

PET is expensive and not widely available. However, its supporters suggest that it may prevent many unnecessary surgeries by identifying patients whose cancer has advanced past the stage at which surgery is helpful. There is some evidence that FDG/PET scan can detect a metabolic (processing) response to treatments that may help predict the outlook for the patient.

Scintigraphy. Scintigraphy is an imaging procedure in which patients are administered low-level radioactive agents that bind to cancer cells, which then can be tracked by special cameras to reveal the cancer cells' location and intensity. Agents selected are those that can best bind successfully with specific tumor types. For example, a 2001 study of the binding agent 111In-DOTA-LAN demonstrated excellent results in identifying non-small cell lung tumors. This study further suggests the possibility of using such highly-targeted binding agents as lung cancer treatments.

Magnetic Resonance Imaging. Magnetic resonance imaging (MRI), an imaging procedure that uses radio wave energy, is frequently used instead of CT scanning to locate brain and bone metastases that can be associated with lung cancer.

Biopsies of lung tissue are needed to confirm lung cancer. This requires invasive procedures that may vary from simple needle aspiration to chest surgery.

Needle Aspiration. Sometimes, a biopsy specimen is obtained by inserting a needle between the ribs, and then guiding it with the use of computed tomography scans, ultrasound, or fluoroscopy (a device allowing an x-ray view). Specific techniques include transbronchial or transthoracic needle aspiration (TBNA or TTNA) or endoscopic ultrasound-guided needle aspiration (EUS-NA). Their use depends on how much of the area can be observed with less invasive imaging methods. There is a 5 -10% risk for bleeding or collapsed lung with needle aspiration.

Thoracoscopy. Thoracoscopy is usually very effective for diagnosing cancer in the outer areas of the lungs, or those involving the pleura (membrane surrounding the lungs). This is a surgical procedure that uses a fiber-optic tube to view the area:

The procedure requires general anesthesia.
The surgeon passes surgical instruments and a fiber-optic tube through a small incision in the chest. The tube has a camera in it, which allows the surgeon to look at the lungs on a video screen.

Bronchoscopy. To locate cancer that develops in the central areas and major airways of the lung (usually squamous or small cell cancer), bronchoscopy is typically performed. The procedure is done as follows:

The patient is given a local anesthetic, supplementary oxygen, and sedatives.
The doctor inserts a bronchoscope, a hollow flexible tube often containing a fiber-optic light source, into the lower respiratory tract through the nose or mouth.
The tube acts like a telescope into the body, allowing the doctor to see the windpipe and major airways. In a procedure called fluorescence bronchoscopy, the doctor injects the patient with a drug that makes cancer tissue appear red when exposed to laser light from the bronchoscope.
The surgeon removes specimens for biopsy, ideally combining techniques to include cutting tissue, brushings, and a washing process called bronchoalveolar lavage (BAL). BAL involves injecting saline through the bronchoscope into the lung and then immediately suctioning the fluid back through the hollow tube of the bronchoscope; the fluid is then analyzed in the laboratory. Both brushing and washing procedures may be very valuable additions.

Advances in this procedure, such as laser-induced fluorescence endoscopic bronchoscopy, may improve early detection of cancer.

Bronchoscopy is usually very safe, but complications can occur; they include allergic reactions to the sedatives or anesthetics, asthma attacks in susceptible patients, and bleeding. Fever may follow the procedure.

Click the icon to see an image of bronchoscopy procedure.

Click the icon to see an image of a bronchoscope.

Mediastinoscopy. Mediastinoscopy uses a tube inserted between the lungs to locate the appropriate areas for biopsy. It is performed if the physician suspects that cancer has spread to nearby lymph nodes but has not yet metastasized.

Sputum Analysis for Presence of Cancer Cells. Some experts are now recommending an analysis of coughed-up sputum as a useful and cost-effective measure for identifying cancer cells, particularly those located in central areas of the lung. However, although sputum analysis appears to be as accurate as any other screening test currently conducted, it may miss cancers such as adenocarcinoma, which form in mucus-producing cells typically in the outer portion of the lungs. If a sputum analysis does not show cancer cells, but other signs of lung cancer are present, including blood in the sputum and suspicious areas on x-rays, other tests are performed.

Biomarkers. Biologic markers, called biomarkers, are high levels of substances that are released by tumors and indicate the presence of specific cancers. Biomarkers can be found in sputum, blood, and tissue samples. They can include enzymes, hormones, amino-acid compounds, antigens (identified by antibodies that specifically target them), growth factors, and other chemicals. Some biomarkers may prove to reveal the presence of cancer cells before they are evident on CT scans or other imaging tests. For example, genetic mutations, notably K-ras and p53, can now be detected in cells found in sputum, or cells taken during bronchoscopy. Such mutations occur only with cancerous changes and may enable early detection. Other markers that prove to be important for predicting aggressive cancers are high levels of matrix metalloproteinase (MMP9) and vascular endothelial growth factor (VEGF), which are compounds involved with angiogenesis (the process in which blood vessels serving the tumor develop).

As part of the doctor's initial examination, patients may have a pulmonary function test to evaluate lung health and capacity. In addition, since the heart and lungs are often involved in complications following lung cancer surgery, the doctor may be especially interested in taking a complete history of those systems in patients who might need surgery.

Staging Systems

Tests to Determine Cancer Stage. After diagnosing non-small cell lung cancer, the doctor makes treatment choices by determining the cancer's stage (how large the tumor is and how far the cancer has spread). To stage the cancer and determine other aspects of the disease, a number of tests are conducted:

The cancer cells are examined microscopically for size, shape, and other configurations.
Computer tomography (CT), magnetic resonance imaging (MRI), or both, are used to scan the lung and perhaps other locations, such as the liver, upper abdomen, and brain, to determine the extent of the disease.

Physical Examination. A detailed physical examination of the whole body is very important to identify or rule out the spread of cancer to other areas, and to determine the general condition of the patient. For example, questions about dizziness or headaches can help the doctor determine if the cancer has spread to the brain, while bone or joint pain might suggest that the cancer has spread to the bone. The doctor will also look for head and neck symptoms that might reveal the presence of other tumors. Also, according to a 2000 review, the patient's weight loss and ability to function are two very important factors for predicting survival following treatment. Patients who are mobile and have lost less than 10% of their pre-treatment weight tend to have better survival rates.

In lung cancer, the stage of the disease at the time of diagnosis is a major factor in determining how to treat the cancer, and how long the patient can expect to live. In general, survival is longest for patients with very early-stage disease and shortest for patients with very advanced disease that has spread to several regions of the body. Staging is based on the results of physical and surgical examinations, and laboratory and imaging tests, including biopsies.

To determine the stage, medical professionals first categorize each tumor by size and by how far it has extended. This identification method is called the TNM system.

The TNM categories then determine the stage (numbered 0 to IV), indicating how advanced the cancer is.

TNM stands for Tumor, regional lymph Nodes, and Metastasis (cancer spread beyond the original tumor).

T refers to the size and extension of the tumor itself. In TX and T0, the tumor is indicated by cancer cells in sputum or lung samples but cannot be seen. Tis: Carcinoma in situ. The cells are cancerous, but the tumor does not show evidence of spreading. In T1, the tumor is 3 cm or less in size, is still contained in the lung or the membrane covering the lung, and has not reached the main airway.

In T2, the tumor has one or more of the following features:

It is greater than 3 cm
It involves the main airway
It is 2 cm or more away from the ridge (the carina) at the lowest part of the windpipe
It has invaded the pleura
It is associated with collapsed lung tissue (atelectasis) or swelling that blocks part (but not all) of the lung

In T3, a tumor of any size has directly invaded any of the following:

Chest wall
Diaphragm
The membrane covering organs and structures in the chest
The outer wall of the membrane around the heart (pericardium)

In addition, one or more of the following conditions are present:

The tumor is in the main airway, less than 2 cm away from the carina, but is not in the trachea (windpipe).
The tumor is associated with a collapsed lung or swelling that blocks the entire lung.

In T4, the tumor has invaded any of the following:

The area between the lungs (mediastinum)
The heart
The great vessels (the blood vessels that carry blood from the heart)
Carina, trachea, or esophagus
Main portion of the spine

In addition, one or both of the following occurs: separate tumors are present in the same lobe; the tumor is accompanied by an increased amount of fluid between the pleural membrane and the lung.

N followed by a number from 0 to 3 refers to whether the cancer has reached regional (in the area of tumor) lymph nodes. In stage N0, the regional lymph nodes are still cancer-free.

In N1, the cancer has spread to the nearest lymph nodes around the airways, to the hilum (a central zone in the lung where blood and lymph vessels enter), or both. The tumor has extended directly into lymph nodes within the lung. In N2, the cancer has spread to lymph nodes in the middle of the chest that are still next to the affected lung, to the nodes below the carina, or to both regions.

In N3 the cancer has spread to lymph nodes in the middle of the chest that are next to the opposite lung, to the hilum in the opposite lung, to lymph nodes in nearby or opposite muscle tissue, or to lymph nodes above the collar bone.

M Stages refer to metastasis. In M0, metastasis has not occurred.

In M1 distant metastasis has occurred. This includes the presence of a separate tumor in a different lobe.

Staging factors are used to help determine treatment and outlook. The following suggest a more aggressive disease:

The presence of respiratory symptoms
A tumor larger than 3 cm
High numbers of blood vessels in the tumor

Researchers are always looking for more accurate ways to determine a treatment and outlook for lung cancer. For example, some research involves specific biomarkers and related blood vessel development within tumors. These markers might eventually help determine how aggressive a cancer is likely to be, and what the best treatment approach is.

If the cancer is still localized, surgery can produce 5-year survival rates of up to 75% in stage I patients and up to 50% in stage II patients. Unfortunately, very few patients are diagnosed at such early stages. In locally advanced stages, the standard treatment is concurrent radiation and chemotherapy. However, even with this approach average survival times are less than 2 years. Even if an initial tumor has been surgically removed or irradiated, cancer recurrence rates are very high. The risk for recurrence is lower in smokers who quit after treatment.

On an encouraging note, advances in therapies for later stage lung cancer are now offering some hope for improving survival. Still at this time, the mortality rate for lung cancer is still extremely high, and reports of improved response or survival rates using drugs or combinations of therapies do not mean cures. Ultimately, the patient must weigh a diminished quality of life using aggressive treatments against a chance for a modestly prolonged life.

Surgical Procedures

Surgery is performed in the following circumstances:

The surgical removal of an entire lobe or parts of a lung is the primary treatment for eligible patients in early stages of cancer. Recurrence is high after surgery, although the new tumor is often operable.
Some patients with stage IIIA cancer may also benefit from surgery. The intent at this stage is to extend survival time, rather than cure the disease.
Surgery is not out of the question in rare cases of metastasis when the cancer appears in a single operable location, such as the brain.

Unfortunately, lung surgery may be too risky for patients with other lung diseases or serious medical conditions, and because lung cancers tend to occur in smokers over 50, such health problems are likely to be present. Long-term survival rates appear to be better in patients treated at hospitals that perform large numbers of lung cancer surgeries, and when surgeries are performed by thoracic surgeons, who specialize in chest procedures.

The type of surgery depends on the amount of lung or other tissue that needs to be removed.

Wedge Resection or Segmentectomy. Wedge resection and segmentectomy remove only a small part of the lung; consequently, they preserve almost normal breathing function after the operation.

Lobectomy. Removal of one of the lobes of the lung is called lobectomy. The patient's lung function must be adequate before undergoing this procedure. The operation carries an overall mortality rate of 3 - 5%, with older patients having the highest risk.

Click the icon to see an illustrated series detailing surgery to remove diseased lobes of the lung.

Pneumonectomy. Pneumonectomy removes the entire lung. The procedure itself carries a mortality rate of 5 - 8%, with the oldest patients having the greatest risk. In such patients, recurrence almost always occurs.

Surgical advances are allowing a wider range of options, including minimal surgeries for early cancers and surgeries that relieve cancer symptoms in late stages of the disease.

Thoracoscopy. Thoracoscopy, also known as video-assisted thoracic surgery (VATS), is a less-invasive technique that employs a thin tube containing a miniature camera and surgical instruments. It requires much smaller incisions than open surgery and speeds recovery to the point that patients are up within hours. Though the procedure is not appropriate in all cases, it offers significant advantages, especially in older or frail patients. The death and complication rates following VATS are lower than those following conventional surgeries. Pain is reduced, and patients are released from the hospital quicker. Several studies found that the 5-year survival and recurrence rates in patients with stage I NSCLC treated with VATS were comparable to those in patients treated with traditional open chest surgeries.

Laser Surgery. Laser surgeries allow removal of minimal amounts of lung tissue and are proving useful for improving symptoms in stage II and IIIA patients. They may also be beneficial in treating cancers that have spread to the throat, obstructing it.

Photodynamic Therapy. Photodynamic therapy uses bronchoscopy and special laser light beams combined with a light-sensitive drug, called porfimer sodium (Photofrin), to kill cancer cells. The most common side effect is sun sensitivity. Serious side effects include bleeding in the lungs. Photodynamic therapy may be considered for patients in early-stage disease who are not candidates for other surgical procedures. It may also be used to reduce symptoms in late-stage disease.

Cryosurgery. Cryosurgery uses a probe chilled to below freezing to destroy the tumor cells on contact and is being investigated in combination with radiation therapy. It may also be an alternative in early stage cancer for patients who cannot have surgery.

Electric Cauterization. Electric cauterization, the use of electricity to produce heat that destroys tissue, is also under investigation as a treatment for early-stage disease.

Back Surgery. Spinal cord compression is a common cause of pain in patients with advanced lung cancer. Because such patients can live for a year or longer, some research indicates that back surgery followed by radiation therapy can significantly improve the quality of life for many of these patients.

Radiation Treatments

In addition to surgery, radiation is the other primary treatment for early-stage lung cancer. Doctors are also studying the benefits of radiation treatment in advanced lung cancer.

Radical Radiation in Early-Stage Cancer. Radical radiation is used as the sole procedure in stage I and some stage II patients who have adequate lung function but, for medical or other reasons, cannot be treated with surgery. In these cases, the 5-year survival rate is about 20%, and the cancer is likely to recur. Survival rates may be higher or lower, depending on the tumor size. In general, treatment with radiation therapy alone shows less benefit with larger tumors. A 2002 analysis suggested that the use of radiotherapy after surgery in patients whose tumors had been completely removed might be associated with reduced survival rates. Nevertheless, a recent study confirmed earlier results that show that radiation therapy by itself is as effective as surgery in patients who are unable or unwilling to have surgery for early stage non-small cell lung cancer.

Combined Treatments for Improving Survival in Advanced Cancer. Radiation is also being investigated in various combinations with chemotherapy, surgery, or both. At this time, concurrent radiation treatment plus platinum-based chemotherapy may extend survival times in advanced lung cancer. Other combinations are showing promise.

Palliative Radiation. Doctors use palliative radiation to shrink tumors and reduce pain and symptoms. Palliative radiation is appropriate for patients with advanced disease and poor lung functions, or in those with metastasized cancer. In up to 85% of patients with advanced disease, palliative radiation therapy helps relieve pain, shortness of breath, the superior vena cava syndrome, coughing up blood, and symptoms caused by brain metastases. Radiation, in these cases, is not generally used with the intention of reducing mortality rates, although it may increase survival in some patients, such as those with excellent lung function whose tumors are small.

Delaying radiation therapy until symptoms develop does not appear to reduce survival times or impair quality of life compared to starting it right away, in patients with minimal or no symptoms.

Radiation Therapy in Metastasis to the Brain. Radiation is the primary treatment when cancer has spread to the brain unless the cancer is small enough to be treated surgically. When radiation is used, a technique called stereotactic radiosurgery may be used to deliver powerful, highly targeted radiation to specific areas in the brain. Some trials are investigating using radiation to the head to prevent metastasis to the brain.

The goal of radiation treatment is to administer doses as high as possible to kill as many cancer cells as possible, without destroying surrounding healthy tissues or causing a dangerous reaction. Doctors may try different procedures for the same patient. The exact radiation procedure depends on the site of the cancer or how far it has spread:

External-Beam Radiation. External-beam radiation therapy focuses a beam of radiation directly on the tumor. It is generally used for metastasized cancer.
Brachytherapy. Brachytherapy involved the implantation of radioactive seeds through thin tubes directly into the cancer sites. Brachytherapy may be used for lung cancers that have spread to the throat and caused obstruction. High-dose-rate brachytherapy may also have some value for patients with inoperable tumors in the central region of the lung.

Hyperfractionated radiotherapy gives smaller than standard doses a number of times a day (usually two or three). This allows doctors to use a higher cumulative dose over the whole course of treatment. It is not as useful as therapy by itself, but should be combined with chemotherapy to have any survival benefits.

Hyperfractionated Accelerated Radiotherapy. Continuous hyperfractionated accelerated radiotherapy (CHART) administers multiple doses per day but uses standard doses. This allows the total dose of radiation to be administered over a shorter time period than the standard 6 weeks. CHART is proving to extend survival rates of patients with localized cancer over that of standard radiotherapy or non-accelerated hyperfractionated radiation. It can cause severe swallowing problems. A modification in which treatment is suspended for 2 days out of 7 may help reduce this effect.

Three-dimensional (3-D) conformal radiotherapy delivers external-beam radiation designed to closely match the specific targeted organs or tissues. This allows significantly higher doses to attack the cancer while reducing the risk to healthy cells. In a 2003 report, 3-year survival rates in stage IIIA patients were nearly 60%, and nearly half the patients experienced no side effects.

Stereotactic body radiotherapy, an advance on conformal radiation, uses a body frame and an abdominal press to immobilize the patient's body and limit breath movement. This allows a more accurate delivery of high-energy radiation. The technique is still investigational.

Radiation can have significant side effects when used as part of intensive treatments, such as hyperfractionated radiotherapy or radiotherapy in combination with chemotherapy. Among the most serious problems is severe inflammation in the esophagus (esophagitis) or the lungs (pneumonitis). Infection is also a danger.

The use of targeted approaches, such as conformal radiotherapy, may help reduce these complications. Investigators are also studying drugs, notably amifostine, which appear to help reduce throat and lung inflammation caused by radiation, without reducing its cancer-fighting effects.

Treatment Options by Stages

In the occult stage (TX, N0, M0), cancer cells are found in a sample of a patient's coughed-up sputum, but no cancer cells have yet been detected in the lung.

Treatment Options. Surgical removal of the tumor, if one can be located, allows identification of its stage and often results in cure.

Stage 0 or carcinoma in situ (Tis, N0, M0) are noninvasive cancers and only a few layers of cancer cells are detected within one local area. The cancer has not grown through to the top lining in the lung and can be surgically removed. There is a high risk for development of a second tumor, however.

Treatment Options:

Surgery, often a limited procedure, where only part of a lobe is removed from the lung.
In patients who cannot be treated surgically, consider photodynamic therapy, cryotherapy, or brachytherapy.

In stage I, the cancer has reached higher layers of the lung but has not spread into the lymph nodes or beyond the lung.

General Treatment Options. The primary treatment is surgery, such as lobectomy (removal of a whole lobe), if possible. Patients with poor lung function should undergo partial lobectomy, if possible. Radiation treatments may be appropriate and beneficial for patients who cannot have surgery. It is not clear if early-stage lung cancer patients, who have radiation or chemotherapy in addition to surgery, have higher survival rates. A 2002 analysis suggested that the use of radiotherapy after surgery in patients whose tumors had been completely removed might be associated with reduced survival rates. An analysis of studies using chemotherapy in addition to surgery or radiotherapy, however, indicated benefits in survival. The overall 5-year survival rates for early stage-cancer are in the range of 30 - 50%. Patients should consider clinical trials for prevention of recurring (returning) cancer after the initial treatment. The risk for recurrence is highest in patients who continue to smoke.

Stage IA (T1, N0, M0). The 5-year survival rates for stage IA patients after successful treatment can be as high as 80%. Treatment options are:
- Lobectomy or sometimes pneumonectomy (removal of one lung)
- Wedge or segment removal, particularly in patients with poor lung function who cannot withstand lobectomy
- Radiation in selected patients whose condition is inoperable (for example, frail patients with T1 tumors); 5-year survival rates can be equal to those with surgery, between 32 - 60%
- Clinical trials of adjuvant chemotherapy following surgery

Stage 1B (T2, N0, M0). Stage IB survival rates after treatment can be better than 60%. Treatment options are:
- Lobectomy or sometimes pneumonectomy; wedge or segment removal, particularly patients with poor lung function
- Clinical trials of chemotherapy following surgery
- Clinical trials of chemotherapy before surgery (induction therapy; studies are promising)
- Clinical trials for radiation treatments in selected patients whose condition is inoperable
- Clinical trials of chemotherapy before, after, or during radiation treatments

In stage II the cancer cells have spread to nearby lymph nodes.

General Treatment Options. Surgery, usually removal of a lobe (lobectomy) or one lung (pneumonectomy), is the treatment of choice. Five-year survival rates associated with stage II surgery can vary. A 2000 review of existing research places the numbers as high as 40 - 50%, but notes that they can drop to 25% and below if the cancer has spread beyond the immediate lymph nodes.

Patients whose cancer is inoperable may consider radiation treatments. In patients who can complete treatment, 5-year survival rates average 20 - 30%, with higher rates for stage IIA. Patients should consider clinical trials for prevention of recurring cancer after primary treatment. To date, however, supplementing surgical treatment with radiation or chemotherapy does not appear to prolong survival rates.

Stage IIA (T1, N1, M0). Survival rates can be as high as 60%. Treatment options are:
- Surgery
- Radiation
- Clinical trials of chemotherapy following surgery
- Clinical trials of chemotherapy before, after, or during radiation treatments
- Clinical trials of chemotherapy to reduce tumor size before surgery (induction therapy)
Stage IIB (T2, N1, M0) or (T3, N0, M0). Survival rates can be over 40%. Treatment options are:
- Surgery
- Radiation
- Clinical trials of chemotherapy following surgery
- Clinical trials of chemotherapy before surgery (induction therapy)
- Clinical trials of chemotherapy before, after, or given at the same time as radiation treatments

In stage III, the cancer cells have spread beyond the lung to the chest wall, diaphragm, or further lymph nodes, such as those in the neck.

General Treatment Options. Generally, the treatment of choice for stage III tumors is radiation and sometimes surgery, chemotherapy, or combinations of all three.

Combination approaches may be significantly more effective than single treatments. For example, of particular interest is a treatment approach that starts with chemotherapy and radiation, given at the same time, followed by surgery. In one study, 5-year survival in stage III patients treated this way was nearly 50%.

Stage IIIA (T1, N2, M0) or (T2, N2, M0) or (T3, N1, M0) or (T3, N2, M0).
- Surgery, if the tumor and affected lymph nodes can be completely removed. Consider platinum-based chemotherapy or radiation therapy after surgery.
- Radiation treatment plus platinum-based chemotherapy, given at the same time, is an option for those in otherwise good health. This regimen should be followed by surgery, if possible.
- Consider clinical trials using advanced radiation techniques, including continuous hyperfractionated accelerated radiation, or 3-D conformal radiation.
- Consider other clinical trials, including those of various combination treatments, preventive radiation therapy to the brain, and new second-line drugs.
Stage IIIB (Any T, N3, M0) or (T4, Any N, M0). Some patients may consider surgery if there is no lymph node involvement (T4, N0), and tumor can be removed. Surgery is not an option for other patients with stage IIIB cancer. Treatment options are:
- Radiation alone, usually for symptom control; it may improve survival in certain patients, such as those with lymph node involvement above the collar bone
- Chemotherapy alone
- Concurrent (given at the same time) cisplatin-based chemotherapy plus radiation, sometimes followed by surgery if possible
- Clinical trials using induction chemotherapy alone to shrink tumors, which may then be treated with surgery or radiation
- Clinical trials using advanced radiation techniques, including continuous hyperfractionated accelerated radiation, or 3-D conformal radiation
- Other clinical trials, including those of various combination treatments, preventive radiation therapy to the brain, and new second-line drugs

In stage IV (any T, any N, M1), the cancer has spread (metastasized) to other parts of the body.

Treatment Options are:

Combination of two- or three-drug chemotherapies that include platinum-based drugs and newer agents; the best patient candidates are those in otherwise good health, who have a limited number of distant metastasized sites. Chemotherapy is not recommended for patients who are too ill
External-beam radiation for symptom relief
Paclitaxel or gemcitabine as a single medication
Other clinical trials
If metastasized cancer involves only one or two areas in the brain, it may respond to surgery followed by radiation to the brain

Recurring or additional new tumors occur, usually in the lung again, in half of treated patients. Research shows that a single tumor in the lung is more often a new tumor that, in many cases, may be operable.

Treatment Options are:

Radiation for symptom control
Chemotherapy with or without bevacisumab (Avastin)
If the cancer spread to only one site in the brain, it may respond to surgery, followed by whole-brain radiation. Extended disease-free survival is possible. If the brain tumor is not operable, it is treated with radiation. Even if cancer returns in the brain (in 50% of cases), treating it again is possible in many patients, if the disease has not spread elsewhere
Laser therapy or interstitial radiation for tumors inside the airways
Stereotactic radiosurgery (in a few selected patients)

Chemotherapy Treatments

Chemotherapy is the use of drugs given by mouth or by injection to destroy cancer cells that may have spread beyond the tumor. Until recently, there has been some doubt about the effectiveness of chemotherapy for lung cancer. A major 2002 analysis of 52 trials supported its use, particularly with platinum-based regimens, and with the use of supportive care.

Chemotherapy in early stages: Chemotherapy is proving to be beneficial in many patients as an additional (adjuvant) treatment with surgery or radiation.
Chemotherapy in advanced disease: Chemotherapy may be used as first-line treatment in patients with inoperable or metastasized lung cancer. It is typically used in late stages to reduce symptoms and, in some cases, extend survival. Since 2006, the combination of bevacizumab (Avastin, a monoclonal antibody) and platinum-based chemotherapy is also a first line treatment choice for such patients, if the cancer is the non-squamous type

Powerful platinum compounds, either cisplatin (Platinol) or carboplatin (Paraplatin), are the basis for most chemotherapy regimens. Two-drug combinations, with one drug being a platinum-based agent, are currently the preferred regimens. Reasonable combinations include paclitaxel (Taxol) and carboplatin or cisplatin. This regimen can also include gemcitabine, docetaxel, or vinblastine or its derivative (vindesine or vinorelbine). There does not seem to be any significant differences in effectiveness among them. Gemcitabine and vinorelbine combination might be a good option for patients who cannot tolerate platinum compounds. Chemotherapy for lung cancer may have reached its peak. Still, investigative chemotherapeutic drugs may yet improve response. Many experts are pinning their hope on agents called biologic response modifiers, such as gefitinib (Iressa) or LY900003 (Affinitak). To date, however, they have not achieved better results than standard platinum-based chemotherapies. Gefitinib (Iressa), a second-line therapy for non-small cell lung cancer (NSCLC), is now available only for a limited group of patients. These patients have benefited from gefitinib in the past, or they are enrolled in a clinical study with the drug. While this medicine initially showed great promise in clinical trials, results from a newer study failed to show that it prolonged survival in advanced lung cancer patients who failed other treatments.

If you are currently taking gefitinib, do not stop taking it without talking to your doctor.

Erlotinib (Tarceva) is in the same medication class as gefitinib. It is approved for patients with locally advanced or metastatic NSCLC, who have failed one type of chemotherapy treatment in the past (it is a second-line treatment). Unlike gefitinib, erlotinib shows survival and progression-free benefits compared to placebo. However, it should not be combined with platinum-based chemotherapy.

Chemotherapy treatments are usually performed in an outpatient setting and in regular cycles for several months. How many chemotherapy cycles to administer in late-stage cancers, the timing of those cycles, and the sequences of the drugs are still matters of investigation. For instance, research suggests that a three- or four-course cycle may achieve the same survival times and better quality of life than the standard of six or more course cycles. Changing even one day in a drug sequence can sometimes significantly affect outcome. Such fine-tuning of chemotherapy regimens is likely to have the most effect on patients with advanced-stage disease, which requires more tailored treatment than early-stage disease.

Treatment for lung cancer depends on the type of cancer and the stage of the disease. Chemotherapy is a form of treatment for lung cancer that may cure, shrink, or keep the cancer from spreading.

Side effects of chemotherapy treatments are common, and they are more severe with higher doses. Side effects increase over the course of treatment. Some trials suggest that they can be reduced by giving the drugs for shorter durations, without loss of cancer-killing effects. Common side effects include the following:

Diarrhea
Temporary hair loss
Weight loss
Fatigue
Depression
Nausea and vomiting: Drugs known as serotonin antagonists, especially ondansetron (Zofran), can relieve these two side effects. Serotonin antagonists work well in nearly all patients given moderate drugs, and in most patients who take drugs that are more powerful. In one study, a combination of dexamethasone (a steroid) with ondansetron, taken within 24 hours of chemotherapy, achieved either a major or complete reduction in nausea and vomiting.
Anemia: Anemia, an abnormally low number of red blood cells, is common in lung cancer. Treatments include transfusions or injections of erythropoietin, an agent that causes more red blood cell production. Erythropoietin is available as epoetin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp), which requires fewer injections. These agents improve well-being and quality of life. Trials are in progress to determine if they may have survival benefits as well.

These side effects are nearly always temporary. Most patients are able to continue with normal activities for all but perhaps 1 or 2 days per month.

Serious complications of chemotherapy can also occur and may vary depending on the specific drugs. They include the following:

Increased chance for infection from suppression of the immune system.
Severe drops in white blood cells (neutropenia): Certain chemotherapy drugs, such as taxanes, pose a higher risk for this complication than other drugs. White blood cell count can improve with the addition of a type of drug called granulocyte colony-stimulating factor (filgrastim and lenograstim).
Liver and kidney damage: Amifostine (Ethyol) reduces the risk for kidney damage in patients taking repeated regimens of cisplatin-based therapy. It is also a radioprotector; that is, it helps prevent severe effects in the esophagus from radiotherapy, with or without chemotherapy.
Abnormal blood clotting (thrombocytopenia).
Allergic reaction, particularly to platinum-based agents: A simple skin test is under investigation that may identify people with a potential allergic response.

Second-line chemotherapy is used for patients whose cancers have recurred after first-line chemotherapy. Some experts believe that the longer survival rates for advanced lung cancer seen for the past 5 years may be due to these drugs. Because platinum-based agents are most often used first, they are not beneficial for second-line therapy. The following are commonly used second-line agents.

Docetaxel (Taxotere). Docetaxel is the drug of choice at this time for cancers that do not respond to initial chemotherapy. Studies have reported that it achieves longer survival times than supportive care alone. It is usually given every 21 days. This regimen causes more side effects than pemetrexed, the newer major second-line drug. Weekly doses of docetaxel are effective and less toxic than the 3-week schedule. It is not clear if survival rates are comparable to those of pemetrexed with that schedule, however.

Pemetrexed (Alimta). Pemetrexed, known as an anti-folate, is another promising new agent for second-line therapy and possibly for first-line treatment as well. The drug targets a number of enzymes that play a role in how cancer cells increase. Some research suggests that it is as effective as docetaxel. Pemetrexed does have some serious toxic effects, but they can be significantly reduced with folic acid and vitamin B12 supplements. It is then less toxic than docetaxel, when docetaxel is given every 21 days, but not when it is given weekly.

Gefitinib (Iressa) and Other Tyrosine Kinase Inhibitors. Much research is focusing on drugs that block small molecules involved with the growth of blood vessels that feed the tumor (a process called angiogenesis). Compounds called growth factors, which may be important in cancer cell production, control the growth of these new blood vessels. Researchers, then, are interested in medications that literally turn off these growth factors or their receptors, such as epidermal growth factor receptor (EGFR). In so doing, the agents may be able to cut off cancer's lifeblood. Gefitinib and erlotinib are angiogenesis inhibitors that target receptors of an epidermal growth factor called tyrosine kinase. Interestingly, studies are finding that NSCLC tumors in people who have never smoked have a much higher rate of EGFR mutations. This helps to explain why gefitinib and erlotinib are more effective in treating NSCLC in people who have never smoked.

Gefitinib (Iressa) was approved in 2003 as a second-line therapy for non-small cell lung cancer. Many patients report significant improvement in symptoms and quality of life, and the drug initially showed great promise. In one study, gefitinib reduced tumor size by 50% in about 10% of the patients. However, recent large-scale clinical trial results have failed to confirm any survival advantage for most patients. At this time, gefitinib is available only for patients who have benefited from it in the past.
Erlotinib (Tarceva) was approved as a single agent second-line therapy in November 2004. Study results show that the drug prolonged survival by several more months than placebo (6.7 versus 4.7 months). Erlotinib is administered orally and has very low toxicity (rash and diarrhea are common).

Chemotherapy Following Surgery (Adjuvant Chemotherapy). Chemotherapy is being evaluated in combination with surgery, radiation therapy, or both. Fairly strong evidence is now supporting the use of platinum-based chemotherapy as adjuvant treatment after surgery in patients with lung cancers in stages Ib-IIIa, with some research indicating a 5% improvement in five-year survival rates. Not all studies confirm survival benefits, however, and trials are ongoing.

Chemotherapy before Surgery (Induction Chemotherapy). Some researchers are testing induction chemotherapy, which is used to shrink potentially operable tumors before surgery. Studies have been mixed in reporting any survival benefits in patients with advanced lung cancer.

Combined and Multi-Modal Therapy. In stage III cancers, investigators are researching very intensive treatments that use two or more combinations of chemotherapy, radiation, and surgery.

For example, radiation plus chemotherapy may be helpful in patients whose tumors are surgically removable.

In inoperable lung cancer, combining radiation with chemotherapy is proving to extend the time to recurrence, the overall duration of survival, or both, compared to radiation alone. Evidence also suggests that giving radiation treatments at the same time as chemotherapy (instead of in separate cycles) improves 5-year survival rates, compared to a sequential approach (separate cycles following each other). Chemotherapy and radiation treatments given at the same time are more toxic, however.

Other approaches use even more intensive multi-modal therapy. For example, some trials use radiation therapy with chemotherapy, followed by surgery. Patients are then sometimes given additional chemotherapy or radiation. In other promising regimens, patents are given concurrent radiation and chemotherapy followed by chemotherapy alone. Such approaches are very toxic but appear to improve survival in selected patients.

Severe inflammation in the esophagus is the most common severe side effect of the radiation and chemotherapy combination. There is also a very high risk of serious infections, including pneumonia, herpes zoster, and cytomegalovirus. Long-term antibiotic therapy may be needed.

Although patients over 70 may suffer more from toxic effects than younger patients, studies now suggest that they can achieve survival rates with combined treatments that are equal to those in younger patients.

There are many painkilling medications available. Research shows that aggressive pain relief can help patients manage cancer treatment symptoms (in addition to pain) better. For example, a 2001 study suggested that reducing pain in elderly cancer patients markedly lowered their fatigue levels, and improved other symptoms as well.

Opioids are the most potent painkillers. The correct use of these strong medications is very important for reaching acceptable pain relief, and preventing a toxic response. For example, the long-lasting version of oxycodone (OxyContin) must be swallowed whole; chewing, inhaling, or injecting it can create a deadly overdose.

Investigative Agents

According to a 2001 article, of the nearly 500 cancer drugs currently in development, 58 of them (about 13%) are aimed at fighting lung cancer. Only the number of breast cancer drugs exceeded that percentage. Unfortunately, none to date have shown any real benefit in terms of patient survival. However, some drugs are showing promise, and at this time, these agents are the best hope for improving lung cancer survival rates.

Monoclonal antibodies (MAbs) are genetically designed immune factors. MAbs mark foreign compounds called antigens for attack by the immune system. Trastuzumab (Herceptin) and cetuximab (Erbitux) are MAbs under investigation for lung cancer. Bevacizumab (Avastin) was approved in October 2006 as a first-line treatment (in combination with carboplatin and paclitaxel) for inoperable, locally advanced, metastatic, or recurrent non-squamous, non-small cell lung cancer.

All three of these MAbs block epidermal growth factor. These agents are of particular interest for patients who have cancers that produce too much of the protein called HER2. These agents show great promise in combination with chemotherapies and newer drugs, such as the tyrosine kinase inhibitors. For example, the disease-free survival time in patients with advanced NSCLC is longer when adding bevacizumab to platinum-based chemotherapy.

Antisense oligonucleotides are drugs being used to block molecules that result in too many cells that cause cancers. LY900003 (Affinitak), for example, targets an enzyme called PKC-alpha, which promotes tumor growth. Early studies with Affinitak showed some promising results. However, a 2003 study found no difference in survival when patients received Affinitak in combination with platinum-based chemotherapy, compared to patients receiving chemotherapy alone.

Genasense (G3139, oblimersen) blocks Bcl-2. Bcl-2 is a protein that is expressed in abnormally high amounts in some cancers. This antisense drug is also under investigation.

Advexin, a genetic therapy that contains the p53 tumor-suppressor gene, is showing promise. In one early study, 60% of patients experienced partial or total tumor shrinkage when the agent was used in combination with radiation therapy. A 2006 study in Japan found that out of 13 patients with advanced NSCLC receiving Advexin, 10 had stabilized. Three of the stabilized patients remained stable for over 9 months. One patient had a partial response to Advexin. The only side effect of the multiple doses given was a passing fever that disappeared within 24 hours. Advexin is in Phase II clinical trials for NSCLC.

Vaccines use inactivated genetic materials from cancer cells, such as defective p53 or ras genes, to cause a highly targeted immune response to attack the cancer.

Retinoids are vitamin A-like antioxidant chemicals that help repair cell damage and appear to support growth of lung cells. A number of retinoid-like agents (retinal palmitate, TAC-101, 23-cis-retinoic acid, N-acetyl-cysteine) are being studied for the treatment or prevention of lung cancer.

Resources

www.cancer.gov -- National Cancer Institute
www.cancer.org -- American Cancer Society
www.cancercare.org -- Cancer Care
www.lungusa.org -- The American Lung Association
www.asco.org -- American Society of Clinical Oncology
www.alcase.org -- Alliance for Lung Cancer
www.lungcancer.org -- Joint project of Cancer Care and the Oncology Nursing Society
www.nccn.org -- National Comprehensive Cancer Network
www.lungcanceronline.org -- Lung cancer information
www.epa.gov/iaq/radon -- National radon information
www.clinicaltrials.gov -- Find clinical trials
www.cancer.gov/clinicaltrials -- Find clinical trials

References

Abeloff MD, Armitage JO, Niederhuber JE, Kastan MB, McKena WG. Clinical Oncology. 3rd ed. Orlando, Fl: Churchill Livingstone; 2004:1690-1701.

American Cancer Society. Cancer Facts and Figures 2006. Atlanta, Ga: American Cancer Society; 2006.

American Cancer Society. Cancer Facts and Figures 2007. Atlanta, Ga.: American Cancer Society; 2007:34.

Janne PA. Non-small Cell Lung Cancer in Never-smokers: A Biologically and Clinically Distinct Type of Lung Cancer. In: ASCO 2007 Educational Book. Meeting of the American Society of Clinical Oncology, Chicago, Ill.: June 1-5, 2007.

Kagawa S, Fujiwara T, Saijo Y, et al. A multicenter phase I study of adenoviral p53 (ADVEXIN) in Japanese patients with advanced non-small cell lung cancer. Journal of Clinical Oncology. 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 2564.

Mehra R, Moore BA, Crothers K, Tetrault J, Fiellin DA. The association between marijuana smoking and lung cancer: a systematic review. Arch Intern Med. 2006 Jul 10;166(13):1359-67.

National Cancer Institute. Lung Cancer Home Page. Bethesda, Md.: U.S. National Institutes of Health. Available online.

National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer. Version 1.2007. Available online.

Tarceva [Package Insert]. Melville, NY: OSI Pharmaceuticals; 2005.

U.S. Department of Health and Human Services. The Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon General. Atlanta, Georgia: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Coordinating Center for Health Promotion, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2006.

U.S. Food and Drug Administration, Center for Drug Evaluation and Research. List of Approved Oncology Drugs with Approved Indications. In: Oncology Tools. Available online.

U.S. Preventive Services Task Force. Lung cancer screening. Ann Int Med. 2004;140:738-739.

Xin M, Deng X. Nicotine Inactivation of the Proapoptotic Function of Bax through Phosphorylation. J Biol Chem. 2005 Mar 18;280(11):10781-9.

Review Date:
8/3/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

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