Bronchoprotective effect of vilanterol against methacholine-induced bronchoconstriction in mild asthmatics: A randomized three-way crossover study.

Abstract

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).

• Authors: Grace L M Westbury, Christianne M Blais, Beth E Davis, Donald W Cockcroft
• Journal: Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (Ann Allergy Asthma Immunol) Vol. 121 Issue 3 Pg. 328-332 (09 2018) ISSN: 1534-4436 [Electronic] United States
• PMID: 30017826 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: Copyright © 2018 Elsevier Ltd. All rights reserved.

Chemical References

• Adrenergic beta-2 Receptor Agonists
• Androstadienes
• Benzyl Alcohols
• Bronchodilator Agents
• Chlorobenzenes
• vilanterol
• Methacholine Chloride
• fluticasone furoate

Topics

• Adrenergic beta-2 Receptor Agonists (therapeutic use)
• Androstadienes (therapeutic use)
• Asthma (drug therapy)
• Benzyl Alcohols (therapeutic use)
• Bronchoconstriction (drug effects)
• Bronchodilator Agents (therapeutic use)
• Chlorobenzenes (therapeutic use)
• Cross-Over Studies
• Female
• Forced Expiratory Volume (drug effects)
• Humans
• Male
• Methacholine Chloride (toxicity)