Abstract
Background: Pneumoconiosis is associated with chronic pulmonary and systemic complications, yet its relationship with pleural empyema remains insufficiently defined. This study evaluated the risk of pleural empyema among individuals with pneumoconiosis using a nationwide population-based cohort. Methods: Using Taiwan's National Health Insurance database, we identified 14,441 patients with newly diagnosed pneumoconiosis and 57,764 matched controls by age, sex, and index year. Pleural empyema was ascertained using ICD-based definitions. Cox proportional hazards models, stratified and cluster-adjusted to account for matched design, were used to estimate hazard ratios (HRs). Competing-risk models, propensity score matching, E-value estimation, and mediation analysis were performed to evaluate robustness and residual confounding. Results: During follow-up, the incidence of pleural empyema was significantly higher in the pneumoconiosis cohort than in controls (2.33 vs. 1.02 per 1000 person-years). Pneumoconiosis was associated with an increased risk of pleural empyema (adjusted HR = 1.79, 95% CI: 1.47-2.18), consistent across subgroup analyses and competing-risk models. The strongest associations were observed among younger individuals and those without comorbidities. Sensitivity analyses, including 1:1 propensity score matching, yielded similar effect estimates. The E-value suggested that only a strong unmeasured confounder could fully explain the observed association. Conclusions: Patients with pneumoconiosis face a substantially elevated risk of developing pleural empyema, independent of demographic factors, comorbidities, corticosteroid use, and healthcare utilization. Intensified monitoring for pleural complications in pneumoconiosis patients who develop respiratory infections may lead to earlier diagnosis and a reduction in the negative outcomes associated with pleural empyema.