Peripheral Ventilation Heterogeneity Determines the Extent of Bronchoconstriction in Asthma

In asthma, bronchoconstriction causes topographically heterogeneous airway narrowing, as measured by 3-dimensional ventilation imaging. Computation modelling suggests that peripheral airway dysfunction is a potential determinant of acute airway narrowing measured by imaging. We hypothesised that the development of low ventilation regions measured topographically by 3-dimensional imaging after bronchoconstriction is predicted by peripheral airway function. Fourteen (14) asthmatic subjects underwent ventilation Single Photon Emission Computed Tomography/CT (VSPECT/CT) before and after methacholine challenge. 1L breaths of Technegas were inhaled from FRC, in upright posture before supine scanning. The lung regions with the lowest ventilation (Vent_low) were calculated using a thresholding method, and expressed as a percentage of total ventilation (Vent_total). Multiple breath nitrogen washout was used to measure diffusion dependent and convection dependent ventilation heterogeneity (Sacin and Scond, respectively) and Lung Clearance Index (LCI), before and after challenge. FEV1 was 87.6 ±15.8 % predicted and 7 subjects had airway hyperresponsiveness. Vent_low at baseline was unrelated to spirometry or MBNW indices. Methacholine challenge decreased FEV1 by 23 ±5% of baseline while Ventlow increased from 21.5 ±2.3 %Vent_total to 26.3 ±6.7 %Vent_total (p=0.03). The change in Vent_low was predicted by baseline Sacin (r_s = 0.60, p=0.03) and by LCI (r_s = 0.70, p=0.006) but not by Scond (r_s = 0.30, p=0.30). The development of low-ventilation lung units in 3-dimensional ventilation imaging is predicted by ventilation heterogeneity in diffusion-dependent airways. This relationship suggests that acinar ventilation heterogeneity in asthma may be of mechanistic importance in terms of bronchoconstriction and airway narrowing.

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