Randomized Placebo-controlled Trial to Evaluate Chronic Dosing Effects of Propranolol in Asthma

Rationale: Unblinded studies have shown improvements in airway hyperresponsiveness with chronic nadolol in steroid-naive patients with asthma. Objectives: To assess the effects of chronic nonselective beta-blockade as add-on to inhaled corticosteroids (ICS) in patients with asthma. Methods: A double-blind randomized placebo-controlled crossover trial of propranolol in patients with mild-to-moderate asthma receiving ICS was performed. Participants underwent a 6- to 8-week dose titration of propranolol or placebo as tolerated to a maximum of 80 mg per day. Tiotropium was given for the first 4 to 6 weeks of each treatment period. Measurements and Main Results: Primary outcome was methacholine challenge. Secondary outcomes included histamine challenge, pulmonary function, mini-asthma quality of life questionnaire (mini-AQLQ), and asthma control questionnaire (ACQ). Eighteen patients completed (mean [SEM]): age, 36 (4) yr; FEV1%, 93 (2); ICS, 440 (66) mu g/d. No significant difference was observed in methacholine or histamine challenge after exposure to propranolol versus placebo. For methacholine challenge, the doubling dilution difference was 0.04 (95% confidence interval [CI], -0.56 to 0.63), P=0.89. Albuterol recovery at 20 minutes after histamine challenge was partially attenuated by propranolol versus placebo: FEV1% mean difference, 5.28 (95% CI, 2.54-8.01), P = 0.001. After chronic beta-blockade there was a small worsening in FEV1% predicted of 2.4% (95% CI, -0.1 to 4.8), P = 0.055. No difference was found for ACQ or mini-AQLQ. Conclusions: This is the first placebo-controlled study to assess the effects of chronic nonselective beta-blockade in asthma, showing no significant effect of propranolol compared with placebo on either methacholine or histamine airway hyperresponsiveness and no change in ACQ or AQLQ.