Originally created 07/23/98

Study: Drugs effective in exercise-induced asthma



People whose asthma kicks up when they exercise often have trouble finding the right type of treatment. But two new studies could help doctors more effectively control this common respiratory problem.

Among the researchers' findings was that a common long-term inhalant may lose its effectiveness over time and may need to be supplemented with other medications for people who have exercise-induced asthma.

An estimated 15 million Americans have asthma, the chronic lung condition that causes wheezing, chest tightness, coughing and other breathing problems. Asthma can be treated with medication. But public health officials are concerned because incidence continues to climb worldwide.

Asthma cases have more than doubled since 1980, according to the federal Centers for Disease Control and Prevention. No one understands exactly why, but it may be due to better detection and an increased awareness of symptoms.

When the condition is not diagnosed or not properly treated, it can be debilitating and even deadly. An estimated 5,000 people die each year from asthma attacks.

But when they receive regular treatment, people with asthma often can lead active, normal lives. Olympic gold medal winners Jackie Joyner-Kersee and Tom Dolan are two of the elite athletes who have competed successfully despite having asthma.

Exercise-induced asthma is just one type of the disease and is also know as mild or intermittent asthma. It is seldom life-threatening. About 10 to 15 percent of people with asthma first experience symptoms either during exercise or shortly after physical activity. Some people who have the symptoms when exercising never have any other asthma problems, but nearly everyone who has been diagnosed with asthma gets bouts of exercise-induced asthma when they work out, particularly if they exercise in cold weather.

Exercise-induced asthma seems to be related to the heat and water loss that occurs during physical activity. As breathing increases during workouts, each breath replaces hot, moist air normally found in the lungs with cooler drier air. This change triggers chest tightness and spasms in the lungs of people with asthma.

Doctors often prescribe a drug called albuterol to treat such an asthma attack. But it is effective for only two to three hours, not long enough, for example, to provide protection for a child who might be playing at recess and then going to an after-school sports practice.

In that case, doctors often turn to a long-acting drug called salmeterol, sold under the trade name Serevent. Like albuterol, salmeterol is inhaled. It acts directly on the bronchioles in the lungs to prevent their narrowing during bouts of exercise-induced asthma. The advantage of salmeterol is that its protection lasts for up to 12 hours.

What researchers wanted to do know, however, is whether daily use of salmeterol might erode its long-term effectiveness. Researchers, led by E.R. McFadden Jr. of the University Hospitals of Cleveland, studied 20 people with exercise-induced asthma. Participants were randomly assigned to two groups. One received twice-daily doses of salmeterol for a month. The other received a placebo. There was a one-week break and then the two groups were switched for another month.

The study, which was published in last week's issue of the New England Journal of Medicine, found that salmeterol protected well against exercise-induced asthma. But the study also showed that the length of time salmeterol was effective declined significantly during treatment.

"Nobody anticipated that," said John Hansen-Flaschen, co-author of an editorial that accompanies the paper and chief of the pulmonary and critical care division at the University of Pennsylvania School of Medicine in Philadelphia.

When the study began, the drug helped prevent bouts of exercise-induced asthma both at 30 minutes after administration and nine hours later in 95 percent of participants. But after twice-daily use for a month, its length of effectiveness declined significantly. By then, only 45 percent of participants still had protection nine hours after taking the drug.

"What this study shows is that with regular use, you lose the ability of this drug to protect against exercise-induced asthma," said Homer Boushey, director of the asthma clinical research center at the University of California at San Francisco.

The findings are likely to change the way doctors prescribe the drug, according to asthma experts. "It wouldn't surprise me if you just used salmeterol on the days when you know you are going to exercise and need protection," said Martha White, director of research at the Institute for Asthma and Allergy at Washington Hospital Center.

In other cases, the findings suggest that it may be necessary for doctors to prescribe a second dose of salmeterol half an hour before exercising. "Doctors are going to need to be aware that they either need to pretreat by giving salmeterol later in the day or add one of the shorter-acting drugs, such as albuterol," White said. "This may cause people to be a little more selective in using salmeterol."

Another option is to use a different kind of drug called montelukast. Given by chewable pill, this medication controls asthma by neutralizing chemicals that are released by white blood cells during an asthma attack.

In a separate study that also appeared last week in the New England Journal, researchers from Merck & Co. -- maker of montelukast -- reported that the drug provided "significant protection against exercise-induced asthma over a 12-week period."

The study involved 110 people. Participants ranged in age from 15 to 45 years. Half received montelukast at bedtime for 12 weeks; half received a placebo or sugar pill. There was a two-week break in the study and then the two groups were reversed.

After 12 weeks on montelukast, which is sold under the trade name Singulair, the study found that participants showed better lung function, were more likely to rate their asthma as being under better control and were less likely to require so-called "rescue" therapy with other drugs during or after exercise.

"Both studies are very worthwhile," said Hansen-Flaschen.

But there are still important unanswered questions. Most people with asthma take other medications, including inhaled glucocorticoids, more commonly known as steroids, such as the drug flunisolide. "The biggest issue with the montelukast study is how this drug compares to inhaled glucocorticoids for control of day-inday-out exercise-induced asthma," Hansen-Flaschen said.

Both studies also involved only people with mild, intermittent asthma. "It would be useful to know how these drugs worked for moderate and severe disease," he said.

The thinking is that they may be beneficial, he said, "but we don't know that to be true."



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