Airway Constriction Pattern Is a Central Component of Asthma Severity

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Abstract
Measurements of lung resistance and elastance (RL and EL) from 0.1 to 8 Hz reflect both the mean level and pattern of lung constriction. The goal of this study was to establish a relation between a deep inspiration (DI) and the heterogeneity of constriction in healthy versus asthmatic subjects. Constriction pattern was assessed from measurements of the RL and EL from 0.1 to 8 Hz in seven healthy subjects and in 12 asthmatics. These data were acquired before and after a DI and before and after a standard methacholine challenge versus a modified challenge in which a DI is prohibited. Generally, avoidance of a DI increased responsiveness. In healthy subjects and in those with mild-to-moderate baseline asthma a bronchial challenge, especially during self-inhibited DI, produced a heterogenous pattern of constriction inclusive of randomly distributed airway closures or near closures. Nevertheless, such subjects were able to reopen their airways via a DI. In contrast, in subjects with severe baseline asthma, there is a more extreme heterogeneous constriction pattern with random airway closures even at baseline. Further, there is no residual bronchodilatory effect of a DI either before or after bronchial challenge. We conjecture that inflammation and wall-remodeling facilitate a dangerous degree of heterogeneous constriction inclusive of airway closures or near closures, and contribute to the prevention of a DI from having a residual bronchodilatory effect.