In the midst of the first U.S. asthma epidemic, a team led by researchers at the University of California, San Francisco and Harvard Medical School is launching a national study to find out how best to treat the most common form of the disease and how much damage it causes. The study will compare different drug treatments for mild, persistent asthma and determine whether the condition is likely to lead to irreversible scarring and blockage of airways much as chronic cigarette smoking does.
The study funded by the National Heart, Lung and Blood Institute (NHLBI) comes at a time when opinion is divided as to how to treat the less severe forms of asthma that affect about 80 percent of the nation's 15 million asthma sufferers. Strong but indirect evidence recently convinced a national panel of experts to recommend daily drug treatments for people who experience asthma symptoms at least twice a week (a hallmark of the "mild, persistent" condition). Daily medication for this group would cost $2 billion annually.
Some physicians believe, however, that medication is not needed daily, but only when asthma symptoms erupt. The new investigation compares the two treatment regimes and also compares the two most widely used types of asthma drugs.
Concern about medication to control asthma stems in part from evidence that chronic asthma leads to irreversible obstructive lung disease, leaving the airways as damaged as if the person had been a life-long smoker. A few recent studies have shown that treatment with inhaled steroids protects against this airway obstruction among those with early-stage asthma, and some researchers think that daily medication will provide similar protection for people with long-term mild, but persistent asthma.
"Some researchers think that airway damage from asthma occurs mainly during the bursts of symptoms, but others think the damage is more or less continuous," explained Homer Boushey, M.D., UCSF professor of medicine and co- leader of the national study with Elliot Israel, M.D., of Harvard Medical School and the Brigham and Women's Hospital in Boston.
"This is our best opportunity to determine not just how to provide relief to people with mild, persistent asthma, but also to determine how best to protect them from airway scarring that can lead to disabling complications."
The new study will also track how different treatments affect the severity of asthma attacks, number of non-urgent and emergency visits, amount of work loss, quality of life and cost of care.
"As with many diseases, successfully treating asthma requires listening to patients and also educating them," says Theresa Ward, RN, coordinator of the portion of the study to be carried out at the Asthma Clinical Research Center, part of UCSF Medical Center. "We need to determine not only the effectiveness of different treatments, but also which ones people are most likely to follow." All patients enrolled in the study will be taught how to recognize symptoms of worsening asthma and how to treat themselves with short courses of therapy. In the past, Ward says, many patients have found that simply learning how to take care of themselves made a big difference in their ability to live with their asthma after studies ended.
Corticosteroids inhaled as an aerosol spray are the most commonly prescribed long-term asthma treatment and are considered the most effective. Steroids ease harmful inflammatory conditions in the airways of asthmatics by targeting the immune cells that trigger the exaggerated asthma response to allergens or viral respiratory infections.
Many with asthma are prescribed continual steroid treatment, but only about 30 percent of patients renew their prescriptions even once, Boushey notes. Many people aren't convinced they need to take the drugs when their symptoms have subsided, and many remain uncomfortable taking steroids even though most research has found the drugs safe at the relatively low doses used for long-term asthma treatment. (Boushey cautions that a recent study uncovered evidence that long-term treatment with moderate dosages -- higher than those usually needed for mild asthma -- slightly increased the risk of osteoporosis and cataracts.)
In 1997, about the time that the national panel recommended daily drug treatment for mild, persistent asthma, a new type of drug came on the market. Called anti-leukotrienes or leukotriene modifiers, these drugs target a class of molecules made by inflammatory cells in the airways. The drug appears to be less effective than inhaled steroids, but it can be taken in pill form and offers an alternative for those with mild asthma concerned about taking steroids, Boushey notes.
In the six-city study now getting under way, 234 people with mild, persistent asthma will take daily doses of either inhalant steroids, anti-leukotriene drugs or a placebo for 18 months. All participants will also have clearly labeled inhalant steroid sprays for short periods when asthma symptoms flare up. In this way, the study not only compares the two drugs against each other and a placebo, but also tests intermittent versus continual medications, since those in the placebo group end up taking medication only during flare-ups.
"In essence, this trial compares the way patients and their physicians really seem to be treating mild asthma -- with short courses of inhaled corticosteroids when symptoms become troublesome -- and the way that experts recommend it should be treated: with fairly long-term, regular use of the steroids or leukotriene antagonists," points out John Fahy, co-investigator in the study and UCSF associate professor of medicine. "The big question is whether the experts are right. If long-term regular treatment does prevent irreversible loss of lung function from airway scarring and narrowing, then the study will determine if both types of drugs can provide this protection."
The study, known as IMPACT, for Improving Asthma Control Trial, is being carried out at six hospital research centers selected by NIH in 1993 to form the Asthma Clinical Research Network for "well-designed clinical trials and rapid evaluation of new treatments."
In addition to UCSF and Harvard's Brigham and Women's Hospital, the Network includes the National Jewish Medical and Research Center in Denver, the Harlem Lung Center in New York City, Jefferson Medical College in Philadelphia, and University of Wisconsin in Madison. Data coordination will be done at the M.S. Hershey Medical Center, Hershey, Pennsylvania.
The research is funded by the National Heart, Lung and Blood Institute of the National Institutes of Health. Medications will be donated by Astra-Zeneca Pharmaceuticals in Wayne, Pennsylvania.
For more information, contact the Asthma Clinical Research Network's Website, http://www.acrn.org. For information on the UCSF arm of the study, contact the UCSF Asthma Clinical Research Center's Recruitment line at 415-502-4849, or by e-mail at asthma@itsa.ucsf.edu