Mucus Plugs as Precursors to Exacerbation and Lung Function Decline in COPD Patients

Background: Mucus plugs identified through chest computed tomography (CT) scans have emerged as potential prognostic factors in chronic obstructive pulmonary disease (COPD). This 5-year longitudinal study investigated their impact on exacerbations and FEV₁ decline.

Methods: COPD patients with baseline chest CT and spirometric assessments were categorized based on mucus plug presence. Propensity-score matching yielded balanced groups. Exacerbation rates, time to exacerbation events, hazard ratio (HR) for exacerbations, and annual rates of FEV₁ decline were evaluated. Sensitivity analysis was performed with stratification according to mucus plug scores of 0, 1-2, and ≥3.

Results: Among 623 eligible patients, the mucus plug group was 44.3%. Through 1:1 propensity-score matching, each group was comprised of 187 individuals with balanced covariates. The mucus plug group showed higher rates of moderate-to-severe (0.51/year vs. 0.58/year, P=0.035), severe exacerbations (0.21/year vs. 0.24/year, P=0.032), and non-eosinophilic exacerbations (0.45/year vs. 0.52/year, P=0.008). Mucus plugs were associated with increased hazard of moderate-to-severe (adjusted HR=1.502 [95% CI 1.116-2.020]), severe (adjusted HR=2.106 [95% CI, 1.429-3.103]), and non-eosinophilic exacerbations (adjusted HR=1.551 [95% CI, 1.132-2.125]). Annual FEV₁ decline was accelerated in the mucus plug group (β-coefficient=-62 [95% CI, -120 to -5], P=0.035). Sensitivity analysis showed higher risk of exacerbations and accelerated FEV₁ decline in mucus plug score ≥3 compared to score 0.

Conclusions: Mucus plugs are associated with increased risks of exacerbations, particularly non-eosinophilic, and accelerated FEV₁ declines over 5 years. Our study identified the potential prognostic value of mucus plugs on future exacerbation risks and lung function decline trajectories.