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

Rationale Unblinded studies have shown improvements in airway hyper-responsiveness (AHR) with chronic nadolol in steroid naïve asthmatics. Objective To assess the effects of chronic non-selective beta-blockade as add on to inhaled corticosteroids (ICS) in asthmatics. Methods A double-blind randomised placebo controlled crossover trial of propranolol in mild-to-moderate asthmatics receiving ICS was performed. Participants underwent a six to eight week dose titration of propranolol or placebo as tolerated to a maximum of 80mg per day. Tiotropium was given for the first four to six weeks of each treatment period. Measurements 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). Main Results 18 patients completed: mean (SEM); age 36 (4), FEV1% 93 (2), ICS ug/day 440 (66). No significant difference was observed in methacholine or histamine challenge following exposure to propranolol versus placebo. For methacholine challenge the doubling dilution difference (DDD) was 0·04 (95%CI -0·56 - 0·63), p=0·89. Albuterol recovery at 20mins post histamine challenge was partially attenuated by propranolol vs placebo, FEV1% mean difference: 5.28 (95%CI 2.54-8.01), p=0.001. Post chronic beta-blockade there was a small worsening in FEV1 % predicted of 2·4% (95%CI -0·1 - 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 non-selective beta-blockade in asthma, showing no significant effect of propranolol compared to placebo on either methacholine or histamine AHR and no change in ACQ or AQLQ. Clinical trial registration information available at www.clinicaltrials.gov, i.d. NCT01074853Read More: http://www.atsjournals.org/doi/abs/10.1164/rccm.201212-2206OC?prevSearch=%3Cb%3EFull+Text%3C%2Fb%3E%3A+lipworth&searchHistoryKey