Airway Mucus Plugs on Chest Computed Tomography Are Associated with Exacerbations in COPD

• Published in: American journal of respiratory and critical care medicine
• Main Authors: Wan, Emily, Yen, Andrew A, Elalami, Rim, Grumley, Scott, Nath, Hrudaya P, Wang, Wei, Brouha, Sharon, Manapragada, Padma P, Abozeed, Mostafa, Aziz, Muhammad Usman, Zahid, Mohd, Ahmed, Asmaa N, Terry, Nina L, Nardelli, Pietro, Ross, James C, Kim, Victor, Sonavane, Sushilkumar, Kligerman, Seth J, Vestbo, Jørgen, Agusti, Alvar, Kim, Kangjin, San José Estépar, Raul, Silverman, Edwin K, Cho, Michael H, Diaz, Alejandro A
• Format: Journal Article
• Language: English
• Published: United States 29.10.2024
• Subjects: Mucus plugs; Chest computed tomography; COPD exacerbations; COPD
• ISSN: 1073-449X; 1535-4970; 1535-4970
• DOI: 10.1164/rccm.202403-0632OC

Rationale/Objective: Acute exacerbations (AEs) of chronic obstructive pulmonary disease (COPD) are associated with significant morbidity and mortality. Whether mucus plugs are associated with prospective exacerbations has not been examined extensively. Mucus plugs were visually-identified on baseline chest computed tomography (CT) scans from smokers with Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 2-4 COPD enrolled in two multicenter cohort studies: Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) and COPDGene. Associations between ordinal mucus plug score categories (0/1-2/≥3) and prospectively-ascertained AEs, defined as worsening respiratory symptoms requiring systemic steroids and/or antibiotics (moderate-to-severe) and/or ER/hospitalization (severe), were assessed using multivariable-adjusted zero-inflated Poisson regression; subjects were exacerbation-free at enrollment. Among 3,250 participants in COPDGene (mean±SD age 63.7±8.4 years, FEV1 50.6%±17.8% predicted, 45.1% female) and 1,716 participants in ECLIPSE (age 63.3±7.1 years, FEV1 48.3%±15.8% predicted, 36.2% female), 44.4% and 46.0% had mucus plugs, respectively. The incidence rates of AEs were 61.0 (COPDGene) and 125.7 (ECLIPSE) per 100 person-years. Relative to those without mucus plugs, the presence of 1-2 and ≥3 mucus plugs was associated with increased risk (adjusted rate ratio, aRR [95%CI]=1.07[1.05-1.09] and 1.15[1.1-1.2] in COPDGene; aRR=1.06[1.02-1.09] and 1.12[1.04-1.2] in ECLIPSE, respectively) for prospective moderate-to-severe AEs. The presence of 1-2 and ≥3 mucus plugs was also associated with increased risk for severe AEs during follow-up (aRR=1.05[1.01-1.08] and 1.09[1.02-1.18] in COPDGene; aRR=1.17[1.07-1.27] and 1.37[1.15-1.62] in ECLIPSE, respectively). CT-based mucus plugs are associated with an increased risk for future COPD AEs.