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

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.

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.

In both healthy and asthmatic subjects, increases in resistance at 19 Hz (R_rs19 ), reflecting large airway narrowing, did not differ between the multiple- and the single-concentration challenge. However, increases in resistance at 5 Hz (R_rs5 ) minus R_rs19 , 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.

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.