The cumulative effect of methacholine on large and small airways when deep inspirations are avoided

• Published in: Respirology (Carlton, Vic.) Vol. 28; no. 3; pp. 226 - 235
• Main Authors: Henry, Cyndi, Boucher, Magali, Boulay, Marie‐Ève, Côté, Andréanne, Boulet, Louis‐Philippe, Bossé, Ynuk
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.03.2023; Wiley Subscription Services, Inc
• Subjects: Airway Resistance - physiology; airway responsiveness; Asthma; Asthma - diagnosis; Bronchial Provocation Tests; deep inspiration; Forced Expiratory Volume; Humans; hyperinflation; Lung Volume Measurements; Methacholine; Methacholine Chloride - pharmacology; oscillometry; Respiratory function; respiratory function tests; respiratory structure and function; Respiratory System; Respiratory tract; airway responsiveness; deep inspiration; respiratory function tests; respiratory structure and function; hyperinflation; asthma; oscillometry; methacholine
• ISSN: 1323-7799; 1440-1843; 1440-1843
• DOI: 10.1111/resp.14387

Background and Objective The effect of serial incremental concentrations of methacholine is only slightly cumulative when assessed by spirometry. This limited cumulative effect may be attributed to the bronchodilator effect of deep inspirations that are required between concentrations to measure lung function. Using oscillometry, the response to methacholine can be measured without deep inspirations. Conveniently, oscillometry can also dissociate the contribution of large versus small airways. Herein, oscillometry was used to assess the cumulative effect of methacholine in the absence of deep inspirations on large and small airways. Methods Healthy and asthmatic volunteers underwent a multiple‐concentration methacholine challenge on visit 1 and a single‐concentration challenge on visit 2 using the highest concentration of visit 1. The maximal response was compared between visits to assess the cumulative effect of methacholine. The lung volume was also measured after the final concentration to assess hyperinflation. Results In both healthy and asthmatic subjects, increases in resistance at 19 Hz (Rrs19), reflecting large airway narrowing, did not differ between the multiple‐ and the single‐concentration challenge. However, increases in resistance at 5 Hz (Rrs5) minus Rrs19, reflecting small airway narrowing, were 117 and 270% greater in the multiple‐ than the single‐concentration challenge in healthy (p = 0.006) and asthmatic (p < 0.0001) subjects, respectively. Hyperinflation occurred with both challenges and was greater in the multiple‐ than the single‐concentration challenge in both groups. Conclusion Without deep inspirations, the effect of methacholine is cumulative on small airways but not on large airways. Lung hyperinflation and derecruitment may partially explain these different responses. The limited cumulative effect of serial doses of methacholine may be due to intercalated deep inspirations when the airway response is assessed by spirometry. In this study, oscillometry was used to avoid deep inspirations. The findings suggested that the effect of methacholine is cumulative on small but not large airways. See related Editorial