Airway Tapering in Chronic Obstructive Pulmonary Disease

Background Luminal narrowing is a hallmark feature of airway remodeling in COPD, but current measures focus on airway wall remodeling. 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 multicenter 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 (SGRQ), modified Medical Research Council (mMRC) dyspnea score, 6-minute walk distance (6 MWD), FEV 1 change, exacerbations, and all-cause mortality after adjusting for demographics, %CT emphysema, and total airway count. Results The T-Slope decreased with increasing COPD severity: 2.69 (0.70) in nonsmokers and 2.33 (0.70), 2.11 (0.65), 1.78 (0.58), 1.60 (0.53), and 1.57 (0.52) in GOLD stages 0 through 4 respectively (Jonckheere-Terpstra p=0.04). On multivariable analyses, the T-Slope was independently associated with FEV 1 (β=0.13 L, 95% CI 0.10 to 0.15, p<0.001), 6MWD (β=15.0 m, 95%CI 10.8 to 19.2, p<0.001), change in FEV 1 (β=−4.50 ml·year −1 , 95% CI −7.32 to −1.67; p=0.001), exacerbations (IRR=0.78, 95% CI 0.73 to 0.83, p<0.001), and mortality (HR=0.79, 95% CI 0.72 to 0.86, p<0.001). Conclusion T-Slope is a measure of airway luminal remodeling and is associated with respiratory morbidity and mortality.