All-Cause and Cause-Specific Mortality in Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

Background: Chronic obstructive pulmonary disease (COPD) is a major global cause of death, imposing substantial socioeconomic and healthcare burdens. This meta-analysis synthesizes evidence on all-cause and cause-specific mortality risks in COPD populations to identify high-risk subgroups and guide precision management strategies. Methods: We searched PubMed, Embase, Web of Science, and Cochrane Library for cohort studies reporting death risks in COPD from database inception to April 10, 2025. Study screening, data extraction, and quality assessment were independently performed by two investigators. Meta-analyses pooled risks for all-cause and cause-specific mortality. Sensitivity analyses tested robustness; publication bias was assessed via funnel plots and Egger's test. Results: Twenty-seven studies covering 286,314 showed COPD patients had significantly higher all-cause mortality versus non-COPD individuals (HR, 1.80; 95% CI: 1.40-2.30). Mortality risk exhibited a graded increase with COPD severity compared to non-COPD individuals: mild (HR, 1.32; 95% CI: 1.19-1.47), moderate (HR, 1.62; 95% CI: 1.45-1.81), severe (HR, 2.18; 95% CI: 1.59-2.99), and very severe (HR, 2.94; 95% CI: 1.78-4.85). When stratified by smoking status, COPD patients had consistently higher mortality than their non-COPD counterparts within each subgroup: never-smokers (HR, 1.41; 95% CI: 1.27-1.56), former smokers (HR, 1.37; 95% CI: 1.30-1.45), and current smokers (HR, 1.48; 95% CI: 1.25-1.76). The presence of comorbidities further amplified mortality risks in COPD patients versus non-COPD individuals, particularly in those with respiratory diseases (HR, 3.64; 95% CI: 3.10-4.27), cardiovascular diseases (HR, 1.29; 95% CI: 1.10-1.50), and all-cancers (HR, 1.69; 95% CI: 1.37-2.10), especially lung cancer (HR, 2.57; 95% CI: 2.04-3.24). Conclusion: COPD patients have significantly higher death risks than non-COPD individuals, worsening with disease severity. Independent determinants of COPD-attributable mortality risk comprise smoking, coexisting respiratory diseases, cardiovascular diseases, and cancer (particularly lung cancer). These findings provide an evidence-based foundation for developing targeted intervention strategies to mitigate COPD-related mortality.