Does increased baseline ventilation heterogeneity following chest wall strapping predispose to airway hyperresponsiveness?

Baseline ventilation heterogeneity is associated with airway hyperresponsiveness (AHR) in asthma; however, it is unknown whether increased baseline ventilation heterogeneity leads to AHR or both are independent effects of similar disease pathophysiology. Reducing functional residual capacity (FRC) in healthy subjects increases baseline ventilation heterogeneity and airway responsiveness, but the relationship between the two is unclear. The aim was to determine whether an increase in baseline ventilation heterogeneity due to a reduction in FRC correlated with the increase in response to methacholine. In 13 healthy male subjects, ventilation heterogeneity was measured by multiple-breath N(2) washout before a cumulative high-dose (0.79-200 μmol) methacholine challenge. On a separate day, the protocol was performed with chest wall strapping (CWS) to reduce FRC. Indexes of ventilation heterogeneity in the convection-dependent (Scond) and diffusion-convection-dependent (Sacin) airways were calculated from the multiple-breath N(2) washout. CWS decreased FRC by 15.6 ± 2.7% (P < 0.0001). CWS increased the percent fall in forced expiratory volume in 1 s during bronchial challenge (P = 0.006), and the magnitude of this effect was independently determined by the effect of CWS on Sacin and FRC (r(adj)(2) = 0.55, P = 0.02). This suggests that changes in baseline ventilation heterogeneity in healthy subjects are sufficient to increase airway responsiveness, independent of the presence of disease pathology.