Airway-Occluding Mucus Plugs and Mortality in Patients With Chronic Obstructive Pulmonary Disease

Abstract

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.

Mucus Plugs and Mortality in Patients With COPD

“…Moreover, the comorbidity counts were positively associated with scores on the St George’s Respiratory Questionnaire and COPD exacerbations . In this study, the adjusted hazard ratio of mucus plugs and mortality was less than 1.20. Although mucus plugs may reflect disease severity or influence the natural course of COPD, the observed effect size was likely overestimated without accounting for these other chronic medical conditions.…”

“…Expiratory gas trapping is independently associated with decreased forced expiratory volume in the first second of expiration (FEV 1 ), increased dyspnea score, decreased 6-minute walk distance, and a decline of FEV 1 over time . However, in this study, gas trapping was not included as a covariate.…”

“…To the Editor We have some concerns about the recent study that found a positive association between mucus plugs obstructing medium to large airways on chest computed tomographic (CT) scans and all-cause mortality, even after adjusting for clinical covariates.…”

Kommentar zu „Schleimpfropfen erhöhen Mortalität bei COPD“

“…Für die Forschung müssen die Ergebnisse zunächst Ansporn zu einer Reihe weiterer Analysen sein. Außer COPDGene [1] und SPIROMICS [2] haben auch andere Konsortiennicht zuletzt auch das deutsche Konsortium COSYCONET -Thorax-CTs entweder als im Rahmen der Studienprotokolle geforderten Untersuchungen oder als routinemäßig durchgeführte CTs gesammelt. Hier sollte versucht werden, die jetzt vorliegenden Analysen zu reproduzieren und zu erweitern.…”

“…Dabei muss auch der Frage der Korrelation und Überlappung zwischen den klinischen Symptomen der chronischen Bronchitis und dem CT nochmals nachgegangen werden, was in der vorliegenden Arbeit gemacht wurde (Vorhandensein ja/ nein), aber möglicherweise in noch größerer Genauigkeit möglich ist. Das ist wichtig, weil über 50 % der Patienten mit Mucus-Plugs klinisch keine chronische Bronchitis aufweisen [1,2] und beide Merkmale daher nicht einfach austauschbar sind.…”