Chronic obstructive pulmonary disease (COPD) affects 14 million Americans annually and is the fourth leading cause of death in adults in the United States. Treatment typically consists of therapy with bronchodilators, which improves symptoms and ultimately enhances the patient's quality of life. Both beta₂ agonists and anticholinergic agents are used as initial therapy because they improve lung function and reduce breathlessness. Most studies have reviewed the effectiveness of short-acting beta₂ agonists. However, little is known about the effectiveness of longer acting beta₂ agonists, such as salmeterol, which has a 12-hour duration of action. Mahler and colleagues compared the safety and effectiveness of salmeterol with that of ipratropium and placebo in patients with COPD.

Patients were eligible for the multicenter, randomized, double-blinded, placebo-controlled trial if they had a 10-pack–year history of smoking and met the American Thoracic Society's definition of COPD. Before randomization, patients were evaluated for responsiveness to beta₂ agonists and anticholinergic agents. During the baseline period, pulmonary function studies, history of dyspnea and other symptoms, six-minute walking distance and quality-of-life data were obtained. Patients in the treatment groups received either salmeterol, in a dosage of 42 mg twice daily, or ipratropium, in a dosage of 36 mg four times daily. Patients in the control group received two puffs of a placebo four times daily. Patients were allowed to use a short-acting beta₂ agonist for any acute episodes of shortness of breath. Pulmonary function, the severity of dyspnea, six-minute walking distance and quality-of-life data were measured multiple times during the 12-week trial. The incidence of adverse events was measured every two weeks.

Patients in the salmeterol group had significantly improved pulmonary function, greater improvement in nighttime symptoms and overall better quality-of-life ratings than patients in the other groups. However, there was no improvement in the six-minute walking distance with either agent compared with placebo. Both salmeterol and ipratropium improved dyspnea ratings over time and reduced the use of short-acting beta₂ agonists. The incidence of adverse reactions was similar across groups.

The authors conclude that salmeterol improved pulmonary function and provided better symptom control compared with ipratropium and placebo. Both treatment drugs reduced symptoms and decreased the need for short-acting beta₂ agonists for breakthrough symptoms. Salmeterol appears to be safe and effective, and therefore should be considered first-line therapy for the long-term treatment of COPD.