The inverse agonist propranolol confers no corticosteroid sparing activity in mild to moderate persistent asthma

The murine asthma model shows that switching off airway beta-2 receptors with an inverse agonist may confer anti-inflammatory effects as well as corticosteroid-sparing activity. We assessed for any corticosteroid-sparing effects of propranolol, an inverse agonist, added to low dose inhaled corticosteroid (ICS) versus higher dose ICS. A randomized, double-blind, placebo-controlled, crossover trial in mild-moderate persistent asthmatics was performed. After a run-in (2weeks) on hydrofluoroalkane-beclometasone dipropionate (HFA-BDP) 100μg/day, patients received randomised treatments (4weeks) with propranolol 80mg/day plus HFA-BDP 100μg/day; versus placebo plus HFA-BDP 400μg/day. Propranolol was up-titrated to 80mg/day over initial 2weeks. Tiotropium was co-administered until 5days before each histamine challenge (the primary outcome). 16 patients completed, mean age 38yr; FEV1 86.4%; histamine PC20 1.39mg/ml; ICS dose 406μg/day. Histamine PC20 was unchanged by adding propranolol to HFA-BDP100 compared to baseline (HFA-BDP100): 0.17 doubling dilution (dd) difference (95%CI -0.58-0.92), but there was a significant improvement with HFA-BDP400 compared to both baseline 1.05dd (95%CI 0.43-1.66), P=0.02; and propranolol + HFA-BDP100:0.88dd (95%CI 0.45-1.30), P=0.006. Significant improvements were also observed with HFA-BDP400 for exhaled nitric oxide, blood eosinophils, serum eosinophilic cationic protein and asthma quality of life questionnaire symp...
Source: Clinical Science - Category: Biomedical Science Authors: Source Type: research