Airway smooth muscle force adaptation on the methacholine response in asthmatic patients

A sustained contraction of the airway smooth muscle increases its contractile capacity through a time-dependent process called force adaptation and concordantly increases the response to methacholine in healthy subjects. Whether this occurs in asthma remains to be investigated. The present study aimed at evaluating force adaptation on the methacholine response in asthmatic patients. Thirty-four very mild to mild asthmatic patients underwent a methacholine challenge on two separate visits. Although the same cumulative concentration was administered on both visits, one challenge was preceded by force adaptation induced by inhaling low concentrations of methacholine at 5-min intervals. On each visit, respiratory mechanics were monitored before and throughout the methacholine challenge by oscillometry, and the degree of inflammation was assessed by measuring the fraction of exhaled nitric oxide. The results demonstrate that the final response to methacholine was greater in the challenge with than without force adaptation. For example, whereas the average change in respiratory system reactance caused by the methacholine challenge without force adaptation was 55.4 ± 67.9%, it amounted to 118.1 ± 150.7% with force adaptation (P = 0.0069). Interestingly, force adaptation on the methacholine response was weakly but negatively correlated with the degree of inflammation. In fact, when patients were split into two groups, one with the least inflammation and one with the most inflammation, force adaptation potentiated the methacholine response in the former but not in the latter. We conclude that although force adaptation potentiates the response to methacholine in asthmatic patients, this effect is mainly driven by patients with very little inflammation.NEW & NOTEWORTHY A sustained contraction of the airway smooth muscle (ASM) increases its contractility through force adaptation, but whether this alters the methacholine response in asthma is unknown. Asthmatic patients underwent two methacholine challenges with identical cumulative concentration but one including a period of ASM preactivation. The preactivation enhanced the response in patients with little inflammation but not in more inflamed patients. This suggests that force adaptation increases the methacholine response only in patients with low inflammation.