Computed Tomography-based Airway Surface Area-to-Volume Ratio for Phenotyping Airway Remodeling in Chronic Obstructive Pulmonary Disease

Rationale: Airway remodeling in chronic obstructive pulmonary disease (COPD) is due to luminal narrowing and/or loss of airways. Existing computed tomographic metrics of airway disease reflect only components of these processes. With progressive airway narrowing, the ratio of the airway luminal surface area to volume (SA/V) should increase, and with predominant airway loss, SAN should decrease. Objectives: To phenotype airway remodeling in COPD. Methods: We analyzed the airway trees of 4,325 subjects with COPD Global Initiative for Chronic Obstructive Lung Disease stages 0 to 4 and 73 nonsmokers enrolled in the multicenter COPDGene (Genetic Epidemiology of COPD) cohort. Surface area and volume measurements were estimated for the subtracheal airway tree to derive SA/V. We performed multivariable regression analyses to test associations between SA/V and lung function, 6-minute-walk distance, St. George's Respiratory Questionnaire, change in FEV1, and mortality, adjusting for demographics, total airway count, airway wall thickness, and emphysema. On the basis of the change in SA/V over 5 years, we categorized subjects into predominant airway narrowing [positive Delta(SA/V) more than 0] and predominant airway loss [negative Delta(SA/V) less than 0] and compared survival between the two groups. Measurements and Main Results: Airway SA/V was independently associated with FEV1/FVC (beta = 0.12; 95% confidence interval [CI], 0.09-0.14; P< 0.001) and FEV1 % predicted (beta = 20.10; 95% CI, 15.13-25.08; P< 0.001). Airway SA/V was also independently associated with 6-minute-walk distance, respiratory quality of life, and lung function decline. Compared with subjects with predominant airway narrowing (n = 2,914; 66.3%), those with predominant airway loss (n = 1,484; 33.7%) had worse survival (adjusted hazard ratio for all-cause mortality = 1.58; 95% CI, 1.18-2.13; P=0.002). Conclusions: Computed tomography-based airway SA/V is an imaging biomarker of airway remodeling and provides differential information on predominant airway narrowing and loss in COPD. SAN is associated with respiratory morbidity, lung function decline, and survival.