American Thoracic Society
American Thoracic Society: May 18-23, 2007, San Francisco, California
Bronchodilators for Chronic Obstructive Pulmonary Disease
Presenter: Bartolome R. Celli, MD, Professor of Medicine, Tufts University, Boston, Massachusetts
The importance of treating hyperinflation emerged as a strong theme in several presentations on pharmacotherapy for chronic obstructive pulmonary disease (COPD) at the meeting. As a speaker at a symposium, Dr. Celli asked this question: Why do bronchodilators reduce exacerbations of COPD?
Although it is well known that steroids reduce inflammation, he suggested that bronchodilators help prevent exacerbations of COPD by countering the hyperinflation that ensues when disease progression, over years and decades, leads to a loss of lung elastic recoil, air trapping, and static hyperinflation. As a result, the patient breathes at a higher lung volume. During an exacerbation, triggering of systemic inflammation stimulates a syndrome somewhat similar to exercise in the laboratory.
“The only difference, Dr. Celli said, “is that the patient can’t get off the bike. But I believe that it is possible that if we can influence hyperinflation, you may be able to decrease the threshold level at which patients perceive shortness of breath.” canadian pharmacy generic viagra
Presenter: James Donahue, MD, Chief of Pulmonology and Critical Care Medicine, University of North Carolina, Chapel Hill
A 12-month trial compared once-daily bronchodilation plus arformoterol (Brovana, Sepracor) 50 mcg, administered via nebulization to 528 patients, with twice-daily dosing of the bronchodilator salmeterol (Serevent Diskus, GlaxoSmith-Kline) 42 mcg, given by a metered dose inhaler to 265 patients. He emphasized the potential value of longer-acting broncho-dilation with a 24-hour agent.
“We’ve begun to think that the hyperinflation seen in COPD is actually inflammatory. So it’s better to keep the airway open the whole time, because long-term bronchodilation deflates the lung.”
Patients included in the study were 35 years of age and older with confirmed COPD. Endpoints were adverse events and changes in 1-second forced expiratory volume (FEV1). The arformoterol dose was 1.7 times greater than the approved twice-daily dose.
The mean FEV1 at baseline was 38.9% with arformoterol and 37% with salmeterol. At one year, the overall frequency of adverse events was similar for arformoterol and salmeterol, as was the frequency of serious adverse events (12.7% for arformoterol and 12.5% for salmeterol), and for respiratory serious adverse events (5.5% and 5.7%, respectively).
COPD exacerbations did not increase in frequency over 12 months. Stable decreases in the use of a rescue medication, albuterol, occurred in both groups at these approximate rates: with arformoterol, 1.1 days per week, 1 puff per day; with sal-meterol, 0.9 days per week, 0.9 puffs per day.
The peak percent change in FEV1 from a visit that included predosing with arformoterol over four hours was slightly better but not to a clinically significant degree, Dr. Donohue said. Three patients receiving arformoterol and two patients receiving salmeterol died.
Dr. Donahue concluded that the safety of nebulizer arfor-moterol 50 mcg once daily was similar to that of salmeterol 42 mcg twice a day. Long-acting bronchodilators were not associated with a loss of COPD control over 12 months, as indicated by stability in the need for rescue medication and by the frequency of COPD exacerbations.
“With all the concerns about beta-agonist safety, this study is reassuring,” he said in an interview. “This higher dose would work once a day, no question,” he added.