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

Background Airway remodeling in COPD is due to luminal narrowing and/or loss of airways. Existing CT metrics of airway disease reflect only components of these processes. Rationale With progressive airway narrowing, the ratio of the airway luminal surface area to volume (SA/V) should increase, and with predominant airway loss, SA/V should decrease. Methods We analyzed the airway trees of 4,325 subjects with COPD GOLD stages 0-4 and 73 non-smokers enrolled in the multicenter COPDGene cohort. Surface area and volume measurements were estimated for the sub-tracheal airway tree to derive SA/V. We performed multivariable regression analyses to test associations between SA/V and lung function, six-minute walk distance, SGRQ, change in FEV1, and mortality, adjusting for demographics, total airway count, airway wall thickness, and emphysema. Based on change in SA/V over 5-years, we categorized subjects into predominant airway narrowing [positive ∆(SA/V)>0] and predominant airway loss [negative ∆(SA/V)<0], and compared survival between the two groups. Results Airway SA/V was independently associated with FEV1/FVC (β=0.12,95%CI 0.09 to 0.14;p<0.001) and FEV1 %predicted (β=20.10,95%CI 15.13 to 25.08;p<0.001). Airway SA/V (per 100 cm2/ml) was also independently associated with six-minute walk distance, respiratory-quality of life, and with lung function decline. Compared with subjects with predominant airway narrowing (n=2914, 66.3%), those with predominant airway loss (n=1484, 33.7%) had worse survival (adjusted HR for all-cause mortality = 1.58, 95%CI 1.18 to 2.13;p=0.002). Conclusion CT-based airway SA/V is an imaging biomarker of airway remodeling and provides differential information on predominant airway narrowing and loss in COPD. SA/V is associated with respiratory morbidity, lung function decline, and survival.