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Bronchoprotective effect of vilanterol against methacholine-induced bronchoconstriction in mild asthmatics: A
Grace L M Westbury1, Christianne M Blais2, Beth E Davis2
1Department of Physiology, Division of Respirology, Critical Care and Sleep Medicine, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Background:
Ultra-long-acting β2 agonists (uLABA) are relatively new anti-asthma medications of which there are three different formulations currently available: olodaterol, indacaterol, and vilanterol. The first 2 formulations have been shown to exert bronchoprotective effects; they are able to prevent airway smooth muscle contraction on exposure to constricting stimuli. However, studies have found that these 2 drugs produce different degrees and durations of bronchoprotection against methacholine.
Objective:
The objective of this study was to investigate the degree of bronchoprotection provided by vilanterol against methacholine-induced bronchoconstriction.
Methods:
Fourteen patients with mild-to-moderate asthma (8 male; baseline percent predicted forced expiratory volume in 1 second [FEV1] > 65%; provocative concentration of methacholine causing a 20% reduction in FEV1 [PC20] ≤ 8 mg/mL) completed this randomized, double-blind, 3-way crossover study. Methacholine challenges were performed before treatment administration (placebo, 100 μg fluticasone furoate, or 25 μg vilanterol + 100 μg fluticasone furoate) and at 0.5 and 24 hours posttreatment. Each treatment arm was separated by a minimum 7-day washout period. A combination therapy of vilanterol+fluticasone furoate was used, because vilanterol is not available as a monotherapy.
Results:
Significant bronchoprotection was evident after the combination treatment at both 0.5 and 24 hours with doubling dose shifts in methacholine PC20 of 2.0 (P = .0004) and 1.6 (P = .0001), respectively. Clinically significant bronchodilation was only recorded at 24 hours after combination treatment (P < .05).
Conclusion:
These findings suggest that vilanterol (in combination with fluticasone furoate) provides significant bronchoprotection against methacholine-induced bronchoconstriction for at least 24 hours in patients with mild-to-moderate asthma.
Clinical Trial Registration:
clinicaltrials.gov (NCT03315000).
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