• Alejandro A Diaz, José L Orejas, Scott Grumley, Hrudaya P Nath, Wei Wang, Wojciech R Dolliver, Andrew Yen, Seth J Kligerman, Kathleen Jacobs, Padma P Manapragada, Mostafa Abozeed, Muhammad Usman Aziz, Mohd Zahid, Asmaa N Ahmed, Nina L Terry, Ruben San José Estépar, Victor Kim, Barry J Make, MeiLan K Han, Sushilkumar Sonavane, George R Washko, Michael Cho, and San José EstéparRaúlRHarvard Medical School, Boston, Massachusetts.Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts..
• Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
• JAMA. 2023 Jun 6; 329 (21): 183218391832-1839.

ImportanceAirway mucus plugs are common in patients with chronic obstructive pulmonary disease (COPD); however, the association of airway mucus plugging and mortality in patients with COPD is unknown.ObjectiveTo determine whether airway mucus plugs identified on chest computed tomography (CT) were associated with increased all-cause mortality.Design, Setting, And ParticipantsObservational retrospective analysis of prospectively collected data of patients with a diagnosis of COPD in the Genetic Epidemiology of COPD cohort. Participants were non-Hispanic Black or White individuals, aged 45 to 80 years, who smoked at least 10 pack-years. Participants were enrolled at 21 centers across the US between November 2007 and April 2011 and were followed up through August 31, 2022.ExposuresMucus plugs that completely occluded airways on chest CT scans, identified in medium- to large-sized airways (ie, approximately 2- to 10-mm lumen diameter) and categorized as affecting 0, 1 to 2, or 3 or more lung segments.Main Outcomes And MeasuresThe primary outcome was all-cause mortality, assessed with proportional hazard regression analysis. Models were adjusted for age, sex, race and ethnicity, body mass index, pack-years smoked, current smoking status, forced expiratory volume in the first second of expiration, and CT measures of emphysema and airway disease.ResultsAmong the 4483 participants with COPD, 4363 were included in the primary analysis (median age, 63 years [IQR, 57-70 years]; 44% were women). A total of 2585 (59.3%), 953 (21.8%), and 825 (18.9%) participants had mucus plugs in 0, 1 to 2, and 3 or more lung segments, respectively. During a median 9.5-year follow-up, 1769 participants (40.6%) died. The mortality rates were 34.0% (95% CI, 32.2%-35.8%), 46.7% (95% CI, 43.5%-49.9%), and 54.1% (95% CI, 50.7%-57.4%) in participants who had mucus plugs in 0, 1 to 2, and 3 or more lung segments, respectively. The presence of mucus plugs in 1 to 2 vs 0 and 3 or more vs 0 lung segments was associated with an adjusted hazard ratio of death of 1.15 (95% CI, 1.02-1.29) and 1.24 (95% CI, 1.10-1.41), respectively.Conclusions And RelevanceIn participants with COPD, the presence of mucus plugs that obstructed medium- to large-sized airways was associated with higher all-cause mortality compared with patients without mucus plugging on chest CT scans.

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