Airway closure in response to treatment with methacholine is common in patients with asthma, particularly in those who are older and obese, according to a study published in Respirology.

Using studies conducted by the American Lung Association-Airways Clinical Research Centers, investigators analyzed methacholine challenge data from a large group of de-identified participants with asthma (n=936) to determine the degree and determinants of airway closure in response to methacholine. Per the American Thoracic Society/European Respiratory Society guidelines, the methacholine challenge study protocols use the dosimeter method, and spirometric methods included exhalation for ≥6 seconds and development of a 1-second plateau in exhaled volume over time.

Data collected included the individual changes in forced expiratory volume in 1 second (FEV₁) and forced vital capacity (FVC) at the maximum concentration of methacholine and calculated the closing index as %ΔFVC/%ΔFEV₁. The closing index was also calculated using the %ΔFVC at the provocative concentration of methacholine causing a 20% decrease in FEV₁, which was done to assess the degree of airway closure standardized for the same level of change in FEV₁.

A higher closing index was associated with female sex, older age, obesity, later onset of asthma, and use of inhaled corticosteroid/long-acting beta-agonist (ICS/LABA) in univariate analysis. After controlling for race, sex, and study, multivariable linear regression revealed that higher closing index was associated with older age in 10-year increments (P <.005) and obesity (P <.001). Age at asthma onset and baseline use of ICS/LABA were dropped due to lack of significance.

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Limitations of this study included its retrospective, cross-sectional design because of the potential variability between studies. In addition, measurement of residual volume/total lung capacity was not performed in order to directly link the closing index with airway closure.

This study is the first to demonstrate that airway closure occurs in response to methacholine, and greater airway closure is associated with older age and obesity, in a large cohort of patients with asthma participating in clinical trials. Based on these findings, the authors suggested that in patients with a high closing index, “therapies directed at airway closure may be important.”


Kaminsky DA, Chapman DG, Holbrook JT, et al. Older age and obesity are associated with increased airway closure in response to methacholine in patients with asthma [published online March 5, 2019]. Respirology. doi:10.1111/resp.13496