title: Randomized placebo-controlled trial to evaluate chronic dosing effects of propranolol in asthma.
abstract: BACKGROUND
  Unblinded studies have shown improvements in airway hyperresponsiveness with chronic nadolol in steroid-naive patients with asthma.
  
  
  OBJECTIVE
  To assess the effects of chronic nonselective β-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.
  
  
  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) μg/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 β-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 β-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. Clinical trial registered with www.clinicaltrials.gov (NCT01074853).
authors.affiliation: Asthma and Allergy Research Group, Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee, United Kingdom.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Short
authors.forename: Peter A
authors.initials: PA
authors.lastname: Williamson
authors.forename: William J
authors.initials: WJ
authors.lastname: Anderson
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Lipworth
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D001249:Asthma / Q000188:drug therapy*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011433:Propranolol / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D000319:Adrenergic beta-Antagonists; D011433:Propranolol