Dynamic property of central airway walls assessed by computed tomography: correlation with asthma pathophysiology

Objective A subset of asthmatics suffers from frequent exacerbations. Various features of airway remodeling and the resultant elastic property of airway walls may play pathophysiological roles in these exacerbations. The aim of the study was to examine the collapsibility of airways and sputum biomarkers associated with airway remodeling with different frequencies of exacerbations.Methods We studied 29 moderate-to-severe asthmatics classified by the number of exacerbations in the previous year as, ≤1: stable, n = 18; ≥2: difficult, n = 11, and 11 healthy controls (HC). Absolute wall area (Awa) and luminal area (Ai) of a segmental bronchus were measured by computed tomography at full-inspiration (FI) and full-expiration (FE). We examined the %change of Ai (a measure of airway collapsibility) and Awa (a possible measure of vascular/water contents in the airway wall) from FI to FE. Sputum biomarkers associated with fibrosis [TGF-β1 and matrix metalloproteinase (MMP)-9 / tissue inhibitors of metalloproteinase (TIMP)-1 molar ratio] and those associated with angiogenesis/edema [vascular endothelial growth factor (VEGF) and vascular permeability index (sputum/serum ratio of albumin levels)] were examined.Results Airway collapsibility was greater in difficult asthmatics than in stable asthmatics and HC. Sputum TGF-β1 levels were higher and MMP-9/TIMP-1 molar ratios were lower in stable asthmatics than in HC. Sputum VEGF levels and vascular permeability index were higher in difficult asthmatics than in HC.Conclusions Collapsibility of thickened airway walls may determine their susceptibility to exacerbations. This may depend on the balance between fibrosis and angiogenesis/edema in the airways.