Popular Asthma Drug Not Effective Alone, Study Shows

May 22, 2001
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A drug widely prescribed as the sole treatment for asthma is incapable by itself of preventing asthma attacks or controlling the airway inflammation thought to lead to deteriorated lung function and gradual worsening of asthma, according to a study published in the May issue of the Journal of the American Medical Association (JAMA).

While the popular drug, known as a long-acting beta agonist, provides effective and satisfying relief of asthma symptoms, it doesn't attack the inflammation nearly always present in the airways of people with asthma, the study found. "Most asthma experts have concluded that long-acting beta agonists alone do not provide enough protection," said Dr. Stephen Lazarus, a pulmonologist at UCSF Medical Center and leader of the national study. "This is the first clear-cut clinical study confirming this impression." The most effective treatment is a combination of the beta agonist and an inhaled steroid or other anti-inflammatory drug.

"People with mild to moderate persistent asthma -- and that is about 75 percent of asthma patients -- need medication that addresses the underlying inflammation if they are to keep their asthma under control," Lazarus said.

The federally funded study of people with mild to moderate asthma compared progress on either a long-acting beta agonist or an inhaled corticosteroid. Researchers found that most patients were satisfied with how the beta agonist controlled their symptoms, but they suffered more asthma attacks and had more airway inflammation than patients using the inhaled corticosteroid.

The 28-week study of 164 asthma patients was carried out at the six university hospitals across the country, including UCSF Medical Center, that make up the Asthma Clinical Research Network. The network is funded by the National Heart, Lung and Blood Institute of the National Institutes of Health.

Patients with mild to moderate asthma -- symptoms more than three times a week -- were treated for six weeks with the inhaled corticosteroid triamcinolone to control asthma and then split into three groups: those who continued this treatment for 16 more weeks; those who switched to the long-term beta agonist salmeterol; and a group who received only a placebo. Throughout the study patients kept daily diaries of asthma symptoms and quality of life, and were assessed every two to four weeks for lung function and airway inflammation.

Although the long-acting beta agonist was effective at improving symptoms of asthma, it was no more effective than placebo at preventing asthma attacks.

Beta agonists are popular because they dilate constricted bronchial airways, providing relief from wheezing and shortness of breath. Inhaled steroids, on the other hand, don't act as quickly, but they reduce inflammation. Because their effects are not obvious over the short term, patients often use inhaled steroids inconsistently or stop them completely. Some patients and physicians also remain concerned about the safety of using inhaled steroids, even in low doses.

"Inhaled steroids are widely underutilized," Lazarus said. "In low doses they are safe, and they are the most proven method of attacking the inflammation that is asthma's greatest long-term danger."

Lazarus is co-author of a companion article in the May issue of JAMA that found once asthma was brought under control with inhaled steroids and long-acting beta agonists, most patients with more severe asthma could cut their steroid dosage in half with no ill effects. But if steroids were dropped completely, the asthma could not be adequately controlled.

Taken together, the two studies clarify and underscore the importance of an effective anti-inflammatory drug such as the inhaled corticosteroids in treating asthma, Lazarus said. Newer non-steroid drugs have also been approved to control airway inflammation. So-called leukotriene receptor antagonists, such as montelukast and zafirlukast, are an alternative to inhaled steroids for some patients.

In addition, he said, "In the near future we likely will have medicines that allow us to stop the allergic inflammatory cascade before it starts." A monoclonal antibody directed against another antibody, IgE -- a kind of anti-missile missile -- is currently undergoing clinical trials, Lazarus said.

The authors have research funding and other affiliations with a number of pharmaceutical companies, noted at the end of the JAMA article. The study was funded by the National Heart, Lung and Blood Institute.