• Miranda Kirby, Naoya Tanabe, Wan C Tan, Guohai Zhou, Ma'en Obeidat, Cameron J Hague, Jonathon Leipsic, Jean Bourbeau, Don D Sin, James C Hogg, Harvey O Coxson, CanCOLD Collaborative Research Group, Canadian Respiratory Research Network, and CanCOLD Collaborative Research Group, the Canadian Respiratory Research Network.
• 1 The University of British Columbia Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada.
• Am. J. Respir. Crit. Care Med. 2018 Jan 1; 197 (1): 56-65.

RationaleStudies of excised lungs show that significant airway attrition in the "quiet" zone occurs early in chronic obstructive pulmonary disease (COPD).ObjectivesTo determine if the total number of airways quantified in vivo using computed tomography (CT) reflects early airway-related disease changes and is associated with lung function decline independent of emphysema in COPD.MethodsParticipants in the multicenter, population-based, longitudinal CanCOLD (Canadian Chronic Obstructive Lung Disease) study underwent inspiratory/expiratory CT at visit 1; spirometry was performed at four visits over 6 years. Emphysema was quantified as the CT inspiratory low-attenuation areas below -950 Hounsfield units. CT total airway count (TAC) was measured as well as airway inner diameter and wall area using anatomically equivalent airways.Measurements And Main ResultsParticipants included never-smokers (n = 286), smokers with normal spirometry at risk for COPD (n = 298), Global Initiative for Chronic Obstructive Lung Disease (GOLD) I COPD (n = 361), and GOLD II COPD (n = 239). TAC was significantly reduced by 19% in both GOLD I and GOLD II compared with never-smokers (P < 0.0001) and by 17% in both GOLD I and GOLD II compared with at-risk participants (P < 0.0001) after adjusting for low-attenuation areas below -950 Hounsfield units. Further analysis revealed parent airways with missing daughter branches had reduced inner diameters (P < 0.0001) and thinner walls (P < 0.0001) compared with those without missing daughter branches. Among all CT measures, TAC had the greatest influence on FEV1 (P < 0.0001), FEV1/FVC (P < 0.0001), and bronchodilator responsiveness (P < 0.0001). TAC was independently associated with lung function decline (FEV1, P = 0.02; FEV1/FVC, P = 0.01).ConclusionsTAC may reflect the airway-related disease changes that accumulate in the "quiet" zone in early/mild COPD, indicating that TAC acquired with commercially available software across various CT platforms may be a biomarker to predict accelerated COPD progression.

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