Association Between Airway Mucus Plugs and Risk of Moderate-to-Severe Exacerbations in Patients With COPD

Airway mucus plugs are frequently identified on computed tomography (CT) scans of patients with chronic obstructive pulmonary disease (COPD) and are associated with worse airflow obstruction and higher mortality. However, the association between airway mucus plugs and the risk of acute exacerbation of COPD (AECOPD) has not been extensively studied. Are airway mucus plugs associated with the risk of future moderate-to-severe AECOPD? In this prospective cohort study, we identified airway mucus plugs on CT scans of COPD patients. Mucus plugs were scored from 0 to 18 based on the number of pulmonary segments affected and categorized into three groups (0, 1-3, and ≥4). Patients were followed for two years. Negative binomial regression and Cox regression were used to model the association between airway mucus plugs and moderate-to-severe AECOPD, adjusting for potential confounders. Among the 194 COPD patients, 22%, 35%, and 43% had mucus plugs in 0, 1-3, and ≥4 pulmonary segments, respectively. During the following year, 30% of patients experienced at least one moderate-to-severe AECOPD, with the incidence 12%, 25%, and 44% for patients with 0, 1-3, and ≥4 pulmonary segments with mucus plugs, respectively. In negative binomial regression, each 1-point increase in airway mucus plug score was associated with an 8.3% higher risk of moderate-to-severe exacerbations(RR[95% CI], 1.08[1.01-1.16], p=0.028). In multivariate Cox regression, mucus plugs in ≥4 versus 0 and ≥4 versus 1-3 pulmonary segments were associated with hazard ratios of moderate-to-severe exacerbation of 5.02(95% CI, 1.84-13.75, p=0.002) and 2.32(95% CI, 1.25-4.33, p=0.008), respectively. Consistent results were observed in the subset of patients completing the two-year follow-up (n=150). In COPD patients, airway mucus plugs are associated with increased future risk of subsequent moderate-to-severe AECOPD. Registered with the International Clinical Trials Registry (NCT03240315, 2017-07-3).