Carla R Copeland, Hrudaya Nath, Nina L J Terry, Carla G Wilson, Young-Il Kim, David A Lynch, Sandeep Bodduluri, J Michael Wells, Mark T Dransfield, Alejandro A Díaz, George R Washko, Marilyn G Foreman, Surya P Bhatt

Expiratory central airway collapse (ECAC) is associated with respiratory morbidity independent of underlying lung disease. However, not all smokers develop ECAC and the etiology of ECAC in adult smokers is unclear. Paraseptal emphysema in the paratracheal location, by untethering airway walls, may predispose smokers to developing ECAC. To evaluate whether paratracheal paraseptal emphysema (paratracheal PSE) is associated with ECAC. We analyzed paired inspiratory and expiratory computed tomography scans from participants enrolled in a multicenter study (COPDGene) of smokers aged 45-80 years. ECAC was defined as >50% reduction in cross sectional area of the trachea during expiration. In a nested case-control design, participants with and without ECAC were included in a 1:2 fashion, and inspiratory scans were further analyzed using the Fleischner Society criteria for presence of centrilobular emphysema, paraseptal emphysema, airway wall thickening, and paratracheal PSE (maximal diameter > 0.5 cm). 1320 patients were included, 440 with and 880 without ECAC. Those with ECAC were older, had higher BMI, and were less likely to be male or current smokers. Paratracheal PSE was more frequent in those with ECAC than controls (16.6% vs. 11.8%; p=0.016), and after adjustment for age, race, sex, body-mass-index, smoking pack-years, and FEV1, paratracheal PSE was independently associated with ECAC (adjusted OR 1.53, 95%CI 1.18 to 1.98; p=0.001). Further, increasing size of paratracheal PSE (maximal diameter of at least 1 cm and 1.5 cm) was associated with greater odds of ECAC (adjusted OR 1.63, 95%CI 1.18 to 2.25; p=0.003 and 1.77, 95%CI 1.19 to 2.64; p=0.005, respectively). Paraseptal emphysema adjacent to the trachea is associated with ECAC. The identification of this risk factor on inspiratory scans should prompt further evaluation for ECAC. Clinical trial registered with ClinicalTrials.gov (NCT00608764).