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J Appl Physiol (1985). 2017 Nov 1;123(5):1188-1194. doi: 10.1152/japplphysiol.00640.2016. Epub 2017 Aug 10.

Peripheral ventilation heterogeneity determines the extent of bronchoconstriction in asthma.

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Woolcock Institute of Medical Research, The University of Sydney, Australia.
Department of Respiratory Medicine, Royal North Shore Hospital, St. Leonards Australia.
Department of Nuclear Medicine, Royal North Shore Hospital, St. Leonards Australia; and.
Department of Respiratory Research, George Institute of Global Health, Australia.
Woolcock Institute of Medical Research, The University of Sydney, Australia;
NHMRC Centre of Excellence in Severe Asthma, The University of Sydney, Australia.


In asthma, bronchoconstriction causes topographically heterogeneous airway narrowing, as measured by three-dimensional ventilation imaging. Computation modeling suggests that peripheral airway dysfunction is a potential determinant of acute airway narrowing measured by imaging. We hypothesized that the development of low-ventilation regions measured topographically by three-dimensional imaging after bronchoconstriction is predicted by peripheral airway function. Fourteen asthmatic subjects underwent ventilation single-photon-emission computed tomography/computed tomography scan imaging before and after methacholine challenge. One-liter breaths of Technegas were inhaled from functional residual capacity in upright posture before supine scanning. The lung regions with the lowest ventilation (Ventlow) were calculated using a thresholding method and expressed as a percentage of total ventilation (Venttotal). 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. Forced expiratory volume in 1 s (FEV1) was 87.6 ± 15.8% predicted, and seven subjects had airway hyperresponsiveness. Ventlow at baseline was unrelated to spirometry or multiple-breath nitrogen washout indices. Methacholine challenge decreased FEV1 by 23 ± 5% of baseline while Ventlow increased from 21.5 ± 2.3%Venttotal to 26.3 ± 6.7%Venttotal (P = 0.03). The change in Ventlow was predicted by baseline Sacin (rs  = 0.60, P = 0.03) and by LCI (rs  = 0.70, P = 0.006) but not by Scond (rs  = 0.30, P = 0.30). The development of low-ventilation lung units in three-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.NEW & NOTEWORTHY Using ventilation SPECT/CT imaging in asthmatics, we show induced bronchoconstriction leads to the development of areas of low ventilation. Furthermore, the relative volume of the low-ventilation regions was predicted by ventilation heterogeneity in diffusion-dependent acinar airways. This suggests that the pattern of regional airway narrowing in asthma is determined by acinar airway function.


airway hyperresponsiveness; asthma; peripheral airways; single-photon-emission computed tomography; ventilation heterogeneity

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