Airway tapering in COPD

Background Luminal narrowing is a hallmark feature of airway remodelling in COPD, but current measures focus on airway wall remodelling. Quantification of the natural increase in cumulative cross-sectional area along the length of the human airway tree can facilitate assessment of airway narrowing. Methods We analysed the airway trees of 7641 subjects enrolled in the multicentre COPDGene cohort. Airway luminal tapering was assessed by estimating the slope of the change in cumulative cross-sectional area along the length of the airway tree over successive generations (T-Slope). We performed multivariable regression analyses to test the associations between T-Slope and lung function, St George's Respiratory Questionnaire score, modified Medical Research Council dyspnoea score, 6-min walk distance (6MWD), forced expiratory volume in 1 s (FEV 1 ) change, exacerbations and all-cause mortality after adjusting for demographics, emphysema measured as the percentage of voxels with density <−950 HU on inspiratory computed tomography scans (%CT emphysema) and total airway count. Results The mean± sd T-Slope decreased with increasing COPD severity: 2.69±0.70 mm −1 in non-smokers and 2.33±0.70, 2.11±0.65, 1.78±0.58, 1.60±0.53 and 1.57±0.52 mm −1 in GOLD stages 0 through 4, respectively (Jonckheere–Terpstra p=0.04). On multivariable analyses, T-Slope was independently associated with FEV 1 (β=0.13 (95% CI 0.10–0.15) L; p<0.001), 6MWD (β=15.0 (95% CI 10.8–19.2) m; p<0.001), change in FEV 1 (β= −4.50 (95% CI −7.32– −1.67) mL·year −1 ; p=0.001), exacerbations (incidence risk ratio 0.78 (95% CI 0.73–0.83); p<0.001) and mortality (hazard ratio 0.79 (95% CI 0.72–0.86); p<0.001). Conclusion T-Slope is a measure of airway luminal remodelling and is associated with respiratory morbidity and mortality.