Airway Mucus Plugs on Chest Computed Tomography Are Associated with Exacerbations in Chronic Obstructive Pulmonary Disease

Abstract

Rationale: 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. Objective: To examine associations between mucus plugs on chest computed tomography (CT) and future moderate-to-severe AEs in two independent cohorts with spirometrically-confirmed COPD. Methods: Mucus plugs were visually identified on baseline chest computed tomography scans from smokers with Global Initiative for Chronic Obstructive Lung Disease grade 2-4 COPD enrolled in two multicenter cohort studies: ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) and COPDGene (Genetic Epidemiology of COPD). Associations between ordinal mucus plug score categories (0, 1-2, and ≥3) and prospectively ascertained AEs, defined as worsening respiratory symptoms requiring systemic steroids and/or antibiotics (moderate to severe) and/or emergency room visit or hospitalization (severe), were assessed using multivariable-adjusted zero-inflated Poisson regression; subjects were exacerbation-free at enrollment. Measurements and Main Results: Among 3,250 participants in COPDGene (mean age ± SD, 63.7 ± 8.4 yr; FEV₁, 50.6 ± 17.8% predicted; 45.1% female) and 1,716 participants in ECLIPSE (age, 63.3 ± 7.1 yr; 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], 1.07 [95% CI, 1.05-1.09] and 1.15 [1.1-1.2] in COPDGene; aRR, 1.06 [95% CI, 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 [95% CI, 1.01-1.08] and 1.09 [1.02-1.18] in COPDGene; aRR, 1.17 [95% CI, 1.07-1.27] and 1.37 [1.15-1.62] in ECLIPSE, respectively). Conclusions: Computed tomography-detected mucus plugs are associated with an increased risk for future COPD AEs.