Older age and obesity are associated with increased airway closure in response to methacholine in patients with asthma.

Document Type


Publication Date


Publication Title

Respirology (Carlton, Vic.)


airway closure; airway hyperresponsiveness; asthma; methacholine; obesity


BACKGROUND AND OBJECTIVE: The reduction of forced expiratory volume in 1 s (FEV

METHODS: We used the methacholine challenge data from participants in five studies of the ALA-ACRC to determine the closing index, defined as the contribution of airway closure to the decrease in FEV

RESULTS: There were a total of 936 participants with asthma, among whom the median closing index was 0.67 relative to that of a published healthy population of 0.54. A higher closing index was associated with increased age (10-year increments) (0.04, 95% CI = 0.02, 0.05, P < 0.005) and obesity (0.07, 95% CI = 0.03, 0.10, P < 0.001). There was no association between the closing index and asthma control.

CONCLUSION: Our findings confirm that airway closure in response to methacholine occurs in a large, diverse population of asthmatic participants, and that increased airway closure is associated with older age and obesity. These findings suggest that therapies targeting airway closure may be important in patients with a high closing index.


Pulmonary Medicine