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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.

Author information

1
Woolcock Institute of Medical Research, The University of Sydney, Australia.
2
Department of Respiratory Medicine, Royal North Shore Hospital, St. Leonards Australia.
3
Department of Nuclear Medicine, Royal North Shore Hospital, St. Leonards Australia; and.
4
Department of Respiratory Research, George Institute of Global Health, Australia.
5
Woolcock Institute of Medical Research, The University of Sydney, Australia; ggk@woolcock.org.au.
6
NHMRC Centre of Excellence in Severe Asthma, The University of Sydney, Australia.

Abstract

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.

KEYWORDS:

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

PMID:
28798203
DOI:
10.1152/japplphysiol.00640.2016
[Indexed for MEDLINE]
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