Introduction and Objectives Chronic propranolol does not improve airway hyper-responsiveness (AHR) in persistent asthmatics taking medium dose inhaled corticosteroid (ICS), 440µg/day¹. We wished to assess for any putative corticosteroid-sparing effect of propranolol added to low dose ICS versus higher dose ICS, on histamine AHR.

Methods We conducted a randomised double-blind placebo-controlled crossover trial in mild-moderate persistent asthmatics. Patients were run-in for 2 weeks on hydrofluoroalkane-beclometasone dipropionate (HFA-BDP) 100µg/day. Patients were then randomised to either: propranolol 80mg/day plus HFA-BDP 100µg/day; or placebo plus HFA-BDP 400µg/day, each for 4 weeks. Propranolol was up-titrated to 80mg/day for the second 2 weeks of treatment. Patients received tiotropium 18µg/day during run-in and both treatments, which was subsequently discontinued 5 days prior to histamine challenge (primary outcome).

Results 16 patients completed, mean: age 38yr; FEV₁ 86.4%; Histamine PC₂₀ 1.39mg/ml; ICS 406µg/day. Histamine PC₂₀ remained unchanged 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 0.88dd (95%CI 0.45–1.30), P = 0.006 (Figure 1a). Significant improvements from baseline were observed with HFA-BDP400 for exhaled nitric oxide, blood eosinophils (Figure 1b) and Asthma Quality of Life Questionnaire (AQLQ) symptom score (Figure 1c), but not with propranolol. Salbutamol recovery time post-challenge was partially blunted by propranolol (median prolongation 5min compared to both baseline and HFA-BDP400, P = 0.002). Domiciliary evening FEV₁ also fell with propranolol (mean reduction from baseline 0.22L [95%CI 0.10–0.34L], P = 0.012) while Asthma Control Questionnaire (ACQ) showed no significant changes with either treatment compared to baseline.

Conclusions In mild-moderate persistent asthmatics, propranolol produced no additive effects on top of low dose ICS, while further significant improvements in AHR and inflammation were seen with a higher dose of ICS. Propranolol attenuated salbutamol recovery and reduced evening FEV₁, but not ACQ or AQLQ.

References

1. Short PM, Williamson PA, Anderson WJ, Lipworth BJ. Randomised placebo- controlled trial to evaluate chronic dosing effects of propranolol in asthma. Am J Respir Crit Care Med 2013;187:1308–1314.

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Abstract P162 Figure 1 (A)

Histamine provocative concentration causing 20% fall in FEV1. Geometric means with 95% confidence intervals (Cl). (B) Blood eosinophil count. Means with 95% Cl. (C.) Asthma Quality of Life Questionnaire (AQLQ) symptom component score. Means with 95% CI. HFA = hydrofluoroalkane beclometasone dipropionate. Base = post run-in baseline measurements. HFA100 = 100µg/day. HFA400 = 400µg/day. Prop = Propranolol 80mg/day.