Regular versus as-needed short-acting inhaled beta-agonist therapy for chronic obstructive pulmonary disease

Regular short-acting inhaled beta -agonist therapy is of uncertain benefit in patients with chronic obstructive pulmonary disease (COPD). We conducted a randomized, concealed, double-blind, placebo-controlled crossover trial in two periods, each of 3-mo duration, involving 53 patients with a smoking history of > 20 pack-years, an FEV1 of < 70% predicted, and an FV1/VC rati o of < 0.7 after inhalation of 200 mug albuterol. All patients received reg ular ipratropium bromide at 20 mug per puff in 2 puffs four times daily, be clomethasone at 250 mug per puff or equivalent corticosteroid in 2 puffs tw ice daily, and open-label inhaled albuterol as needed. Interventional thera py consisted of regular inhaled albuterol (100 mug per puff, in 2 puffs fou r times daily) versus placebo. Patients used twice as much active albuterol in the regular use period (mean: 8.07 puffs of coded and 4.68 puffs of ope n-label medication; total: 12.75 puffs daily) than during the as-needed per iod (mean: 6.34 puffs of open-label albuterol daily). Despite greater beta -agonist use, patients showed similar results during treatment and control periods for all outcomes. Differences between active and placebo periods we re: FEV1: -0.04 L (95% confidence interval [CI]: -0.09 to 0.01 L); slow vit al capacity: 0.04 L (95% CI: -0.12 to 0.20 L); 6-min walk test distance: -3 .1 m (95% CI: -16.8 to 10.5 m); and Chronic: Respiratory Questionnaire scor es for dyspnea: 0.02 (95% CI: -0.13 to 0.16); fatigue: -0.02 (95% CI: -0.25 to 0.20); mastery: 0.01 (95% CI: -0.20 to 0.24); and emotional function: 0 .02 (95% CI: -0.20 to 0.24). We found that in patients with COPD, use of re gular short-acting inhaled P-agonists resulted in twice as much p-agonist u se without physiologic or clinical benefit as did use on an as needed basis .