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

Introduction

Chronic obstructive pulmonary disease (COPD) is a major contributor to global mortality, with death tolls rising from 2.2 million (6th leading cause) in 1990 to 3.5 million (4th) in 2021.^1–3 Global Burden of Disease projections indicate COPD will become the third leading cause of death by 2050,⁴ annual COPD deaths may exceed 7 million by 2060—surpassing combined diabetes and asthma mortality.⁵ This trajectory impedes progress toward United Nations Sustainable Development Goal (SDG) 3.4, which targets a one-third reduction in premature non-communicable disease mortality by 2030.⁶ Economically, COPD mortality accounts for 68.3% of the disease’s total burden, costing $49.1 billion annually in lost productivity.⁷

As an unambiguous endpoint reflecting disease severity and healthcare system efficacy, mortality data provide a critical benchmark for assessing health system performance and optimizing resource allocation to high-risk populations. Reinforcing this, the World Health Organization (WHO) designates COPD mortality surveillance as Essential Indicator E119 for SDG 3.4—explicitly aligning with its mandate for a 30% reduction in non-communicable disease mortality by 2030.⁸ Given COPD’s established preventability and treatability, identifying modifiable risk factors underlying COPD-attributable mortality is an urgent public health priority. Indeed, a complex interplay of factors significantly influences the risk of death in individuals with COPD. Major determinants include: disease severity;⁹ history of acute exacerbations;¹⁰ comorbidities (such as cardiovascular disease, lung cancer, and metabolic syndrome);¹¹ and demographic/lifestyle factors (including smoking, low body mass index, older age, and low socioeconomic status).¹² Understanding how these factors modulate not just overall survival, but also specific causes of death, is crucial for risk stratification and targeted interventions. Therefore, synthesizing evidence on both all-cause and cause-specific mortality by these variables is essential.

Epidemiological research into mortality associated with COPD has been increasing; however, existing studies have predominantly examined the impact of single factors on all-cause mortality exclusively.^13–15 Although a meta-analysis has examined all-cause mortality in patients with mild COPD,¹⁶ a critical gap persists: to our knowledge, no study has concurrently synthesized evidence on both all-cause and major cause-specific mortalities within a unified analytical framework. This limitation precludes a holistic understanding of COPD mortality patterns. To address this gap, our meta-analysis provides an integrated synthesis of existing evidence on all-cause and cause-specific mortality in COPD patients, with specific focus on quantifying differential effects of key factors across these outcomes via subgroup and meta-regression analyses.

Methods

The protocol for this systematic review has been prospectively registered in the international Prospective Register of Systematic Reviews (CRD420251103371) (https://www.crd.york.ac.uk/PROSPERO/view/CRD420251103371), and the entire study was conducted in strict accordance with the PRISMA 2020 statement¹⁷ (Preferred Reporting Items for Systematic Reviews and Meta-Analyses).

Search Strategy

A systematic literature search was conducted in PubMed, Embase, the Cochrane Library, and Web of Science for studies on COPD mortality, with language restricted in English. The search encompassed records from database inception to 10 April 2025. To ensure comprehensive identification of relevant literature, we manually screened the reference lists of included articles. The search strategy utilized a combination of Medical Subject Headings terms and free-text keywords, including “COPD” “mortality” and related synonyms. The detailed search strategy is provided in Supplementary Table 1.

Eligibility Criteria

Studies were included based on the following predefined criteria: (1) study populations comprised individuals with clinically confirmed COPD; (2) control groups consisted of non-COPD individuals; (3) study design was restricted to cohort studies; (4) primary outcomes included mortality, with studies required to report multivariable-adjusted hazard ratios (HRs) or relative risks (RRs) and corresponding 95% confidence intervals (CIs) relative to reference groups.

Exclusion Criteria

Studies were excluded according to the following criteria: (1) conference abstracts, comments, and reviews; (2) studies with incomplete data reporting or lacking outcomes of interest; (3) duplicate publications; (4) For studies utilizing the same dataset by identical authors, only the publication with the longest follow-up duration or the largest sample size was retained.

Study Selection and Data Extraction

Two independent reviewers (GX Z and L W) conducted initial screening by evaluating titles and abstracts of identified records. Following independent cross-checking of screening decisions, potentially eligible studies were provisionally selected. Any disagreements unresolved after discussion were adjudicated by a third reviewer (ZZ F). The full-text articles of provisionally included studies were subsequently obtained and independently assessed by both reviewers against predefined eligibility criteria. Final inclusion was restricted to studies meeting all inclusion requirements.

Data extraction was performed using a customized Microsoft Excel spreadsheet. The extracted information encompassed: (1) basic study characteristics: title, first author, publication year, and country of conduct; (2) participant characteristics: source population, sample size, diagnostic criteria, and mortality verification methods; (3) outcome indicators of interest: effect estimates with corresponding 95% CI for all relevant endpoints; (4) adjusted covariates in statistical models; (5) follow-up duration.

Quality Assessment

Two reviewers independently assessed risk of bias in the included cohort studies using the Newcastle-Ottawa Scale (NOS)¹⁸ – an 8-item tool evaluating three domains: (1) participant selection, (2) group comparability, and (3) outcome assessment. Studies were scored on a 9-star system and categorized as low quality (0–3 stars), moderate quality (4–6 stars), or high quality (7–9 stars).

Statistical Analysis

Statistical analyses were performed using Stata 15.0 (Stata Corp, College Station, TX). Pooled HRs with 95% CI were calculated. In all analyses, the hazard ratio represents the mortality risk in a specific group of COPD patients compared to the corresponding group of non-COPD individuals who share the same characteristics (eg, same sex, smoking status, or comorbidity status). Heterogeneity was assessed using χ²-tests and quantified by I² statistics, with thresholds of 25%, 50%, and 75% indicating low, moderate, and high heterogeneity, respectively. A fixed-effects model was applied when heterogeneity was nonsignificant (I² < 50%, P ≥ 0.1). Otherwise, a random-effects model was employed. Subgroup analyses were conducted to explore sources of substantial heterogeneity or assess covariate effects. Sensitivity analyses examined robustness through sequential exclusion of individual studies. Publication bias was evaluated by funnel plot symmetry and Egger’s linear regression test for outcomes with ≥10 studies. If detected, the trim-and-fill method was employed for bias correction. Statistical significance was defined as P < 0.05.

Results

Identification of Studies

The initial search identified 45,766 records from four databases: PubMed (n = 20,128), Cochrane Library (n = 3,931), Embase (n = 8,918), and Web of Science (n = 12,789). After removal of 16,119 duplicates, 29,647 records underwent title/abstract screening, excluding 29,599 irrelevant studies. Full-text assessment of 48 articles led to the exclusion of 21 studies, yielding 27 eligible cohort studies.^19–45 The literature selection process is detailed in Figure 1.

Figure 1 Flowchart of literature screening.

Study Characteristics

This systematic review incorporated 27 cohort studies covering 286,314 participants. Eleven studies enrolled fewer than 1,000 participants, while 16 studies included ≥ 1,000 individuals. COPD diagnosis was primarily based on spirometry (22 studies), supplemented by International Classification of Diseases codes (4 studies) and registry records (1 study). The studies originated from 13 countries, with the United States, United Kingdom, and Denmark contributing the largest proportion. Geographically, 13 studies were from Europe, 9 from the Americas, and 5 from the Western Pacific. Two studies were from upper-middle-income countries (UMICs) and 25 from high-income countries (HICs). Follow-up duration ranged from 4 to 29 years, with 14 studies reporting <10 years and 13 studies reporting ≥10 years. Notably, only one study had a minimum follow-up of 4 years; all others follow-up durations of ≥ 5 years. Overall, the basic characteristics of included studies are summarized in Table 1. Adjusted confounding factors in the included literature in Supplementary Table 2.

Table 1 Basic Characteristics of the Included Studies

Of the 27 included studies reporting mortality risk in COPD, 13 provided data on overall COPD mortality without distinction by GOLD grade.^{19,22–24,27,30–32,35–37,39,40} Other studies reported risk data for specific GOLD grades, as follows: GOLD 1 (13 studies),^{20,21,25–28,33,34,38,41,43–45} GOLD 2 (7 studies),^{20,21,26,27,33,34,41} GOLD 3 (5 studies),^{20,27,33,34,41} and GOLD 4 (3 studies).^20,27,34 In addition, several studies presented combined risk estimates for adjacent GOLD grades, including GOLD 2–3 (2 studies),^25,38 GOLD 2–4 (4 studies),^28,43–45 and GOLD 3–4 (2 studies).^21,26 Regarding smoking status, the numbers of current, former, and never-smokers among COPD and non-COPD individuals were reported in 20,^{19,20,23–25,27–30,32–38,41,43–45} 18,^{19,23–25,27–30,32–37,41,43–45} and 17^{19,22,24,27–30,32–37,41,43–45} studies, respectively. Pooled analysis indicated that in the COPD group, there were 19,925 current smokers, 17,022 former smokers, and 24,386 never-smokers. In the non-COPD group, the corresponding numbers were 208,704, 115,751, and 644,016, respectively.

Quality Assessment

Methodological quality appraisal was conducted using the NOS. All 27 cohort studies satisfied criteria for comparability of cohorts and explicitly defined follow-up duration, thereby achieving total NOS scores ≥ 7. These results demonstrate high methodological quality across included studies (Supplementary Table 3).

Meta-Analysis of All-Cause Mortality Risk

All-Cause Mortality Risk in Overall COPD

Thirteen studies^{19,22–24,27,30–32,35–37,39,40} involving overall COPD cohorts (n = 255,923) reported all-cause mortality data. The pooled analysis revealed a significantly elevated all-cause mortality risk in COPD patients compared with non-COPD (HR, 1.80; 95% CI: 1.40–2.30) (Figure 2). Subgroup analyses stratified by geographic region, country, follow-up duration, income level, and sample size indicated statistically significant differences across all subgroups (P < 0.05) (Figure 3). Leave-one-out sensitivity analysis confirmed the robustness of pooled estimates (Supplementary Figure 1).

Figure 2 Forest plot of mortality risk of overall COPD compared with non-COPD individuals.

Figure 3 Pooled forest plot of mortality risk of overall COPD by subgroup analysis.

All-Cause Mortality Risk of COPD in Different Severity Grades

Quantitative analysis demonstrated that patients with COPD had significantly higher all-cause mortality across all GOLD stages compared to non-COPD individuals (all P < 0.001), with a progressively increasing risk corresponding to disease severity. The HRs were as follows: GOLD 1 (HR, 1.32; 95% CI:1.19–1.47),^{20,21,25–28,33,34,38,41,43–45} GOLD 2 (HR, 1.62; 1.45–1.81),^{20,21,26,27,33,34,41} GOLD 3 (HR, 2.18; 1.59–2.99),^{20,27,33,34,41} and GOLD 4 (HR, 2.94; 1.78–4.85).^20,27,34 Furthermore, analyses of combined severity groups also showed consistently elevated risks: GOLD 2–3 (HR, 2.79; 1.86–4.18),^25,38 GOLD 2–4 (HR, 1.73; 1.61–1.85),^28,43–45 and GOLD 3–4 (HR, 3.23; 2.11–4.93)^21,26 (Table 2). Forest plots are provided in Supplementary Figures 2–8.

Table 2 All-Cause Mortality Risk of COPD in Different Severity Grades

Stratified analysis by geographic region and GOLD stage further indicated a consistent severity-risk gradient across all regions and countries, except for GOLD 1 patients in the Western Pacific region, where the association was not statistically significant (P > 0.05) (Table 2). Sensitivity analysis restricted to GOLD 1 cohorts with ≥10 included studies confirmed the robustness of these findings (Supplementary Figure 9).

All-Cause Mortality Risk of COPD in Different Smoking Status

Pooled analyses of all-cause mortality risk stratified by smoking status and GOLD classification demonstrated a consistent graded elevation in mortality risk with increasing COPD severity across all smoking strata: among never-smokers, individuals with COPD exhibited higher mortality compared to never-smokers without COPD in the overall COPD group (HR, 1.41; 95% CI: 1.27–1.56),^27,29,37 GOLD 1 (HR, 1.14; 95% CI: 1.02–1.28),^27,33,45 GOLD 2 (HR, 1.36; 95% CI: 1.25–1.47),^27,33 and GOLD 3 (HR, 1.82; 95% CI: 1.66–2.00);^27,33 among former smokers, COPD individuals had higher mortality than former smokers without COPD, with corresponding HRs of 1.37 (95% CI: 1.30–1.45) for overall COPD,^27,37 1.10 (95% CI: 0.98–1.22) for GOLD 1,^27,33,45 1.56 (95% CI: 1.43–1.69) for GOLD 2,^27,33 and 2.41 (95% CI: 1.26–4.60) for GOLD 3;^27,33 among current smokers, COPD individuals showed higher mortality compared to current smokers without COPD, with HRs of 1.48 (95% CI: 1.25–1.76) for overall COPD,^27,29,37 1.26 (95% CI: 1.10–1.43) for GOLD 1,^27,33,45 1.61 (95% CI: 1.41–1.84) for GOLD 2,^27,33 and 2.39 (95% CI: 1.52–3.78).^27,33 (Figure 4).

Figure 4 Pooled forest plot of mortality risk in COPD compared with non-COPD stratified by smoking status.

All-Cause Mortality Risk of COPD in Different Diseases

Two studies conducted a quantitative analysis of all-cause mortality risk by subgroup in patients with COPD comorbid with respiratory disease (overall COPD,^23,35 GOLD,^28,34 and GOLD 2–4^28,43). The pooled results showed that among individuals with respiratory diseases, COPD patients had the following all-cause mortality risks compared to non-COPD patients: an overall HR of 3.64 (95% CI: 3.10–4.27) for COPD, 1.71 (95% CI: 1.03–2.82) for GOLD 1, and 2.70 (95% CI: 0.37–19.81) for GOLD 2–4. A significant association between respiratory diseases and all-cause mortality was observed in the overall COPD and GOLD 1 groups (both P < 0.05), but not in the GOLD 2–4 group (P = 0.329) (Table 3).

Table 3 All-Cause Mortality Risk of COPD in Different Diseases

Aggregated quantitative synthesis from three studies on overall COPD,^35–37 five on GOLD 1,^{21,28,34,43,44} two on GOLD 2,^21,34 and three on GOLD 2–4^28,43,44 demonstrated that COPD patients with comorbid cardiovascular disease had a higher mortality risk compared with non-COPD individuals with cardiovascular disease: overall COPD (HR, 1.29; 95% CI: 1.10–1.50), GOLD 1 (HR, 1.18; 95% CI: 0.98–1.43), GOLD 2 (HR, 1.75; 95% CI: 1.01–3.05) and GOLD 2–4 (HR, 2.14; 95% CI: 1.59–2.87), with statistical significance (P < 0.05) observed in all groups except GOLD stage 1 (Table 3).

The risk of cancer-attributable all-cause mortality was evaluated in several studies comparing COPD patients to non-COPD individuals with cancer. The analysis involved: two studies for the overall COPD population,^35,42 four for GOLD 1,^21,34,42,43 three for GOLD 2,^21,34,42 and two for GOLD 3 studies.^34,42 Fixed-effect meta-analyses revealed a statistically significant increase in risk for overall COPD (HR, 1.69; 95% CI: 1.37–2.10), GOLD 2 (HR, 1.75; 95% CI: 1.45–2.12), and GOLD 3 (HR, 1.85; 95% CI: 1.28–2.68). The risk increase for GOLD 1 was not statistically significant (HR, 1.23; 95% CI: 0.99–1.52). Additionally, a separate analysis of four studies on lung cancer-specific mortality also showed a significantly elevated risk (HR, 2.57; 95% CI: 2.04–3.24), as presented in Table 3.

Two studies^37,40 evaluated the association of all-cause mortality between patients with COPD and non-COPD individuals among populations with diabetes. The pooled analysis revealed on statistically significant difference in risk (HR, 1.43; 95% CI: 0.52–3.94). Additionally, a study²⁵ comprising two prospective cohorts further analyzed cause-specific mortality stratified by GOLD severity in COPD patients compared to non-COPD individuals. The results demonstrated significantly elevated mortality risks due to both circulatory diseases and other causes across all COPD severity groups (P < 0.05) (Table 3). Specifically, the HRs for circulatory disease mortality were 1.90 (95% CI: 1.51–2.39) in the GOLD 1 group and 2.35 (95% CI: 1.84–2.99) in the GOLD 2–3 group. Meanwhile, the corresponding HRs for mortality from other causes were 2.18 (95% CI: 1.62–2.94) in the GOLD 1 group and 3.53 (95% CI: 1.70–7.31) in the GOLD 2–3 group.

Three studies^31,37,40 evaluated the risk of mortality between COPD patients and non-COPD individuals in the absence of comorbidities. The results demonstrated a significantly elevated risk of death among COPD patients, with a pooled HR of 3.03 (95% CI: 2.30–3.98). Furthermore, two studies^31,40 assessed the difference in mortality risk between COPD and non-COPD subjects when both groups had pre-existing comorbidities. The results showed that HR was 3.06 (95% CI: 2.74–3.41) in individuals with one comorbidity, and 2.08 (95% CI: 1.90–2.29) in those with four or more comorbidities (Table 3).

All-Cause Mortality Risk of COPD in Different Sex

A sex-stratified meta-analysis of all-cause mortality in patients with COPD revealed divergent risk profiles: male patients with COPD exhibited a significantly elevated mortality risk compared with non-COPD males for overall COPD (HR, 1.38; 95% CI: 1.33–1.44)^27,32,37 and GOLD 1 (HR, 1.17; 95% CI: 1.06–1.29).^27,45 In contrast, female patients with COPD showed a significantly higher mortality risk than non-COPD females in unstratified cohorts (HR, 1.32; 95% CI: 1.25–1.40),^27,37 but no statistically significant increase was observed for GOLD 1 stage (HR, 1.09; 95% CI: 0.97–1.22; P = 0.172)^27,45 (Table 4).

Table 4 All-Cause Mortality Risk of COPD in Different Sex

Publication Bias

Egger’s regression test detected significant publication bias in overall COPD mortality studies (t = −2.45, P = 0.032). Trim-and-fill adjustment yielded a recalibrated pooled HR of 1.80 (95% CI: 1.41–2.30), which demonstrated striking concordance with the pre–adjustment estimate (HR, 1.80; 95% CI: 1.40–2.30), confirming analytical robustness. For GOLD 1 cohorts, Egger’s test indicated no significant bias (P = 0.219). Publication bias analyses were omitted for others due to insufficient studies (n < 10), with detailed results provided in Supplementary Figures 10 and 11.

Discussion

This systematic meta-analysis, integrating data from 27 cohort studies encompassing 286,314 COPD patients, provides the first comprehensive assessment of all-cause mortality risk in this population. Results demonstrated a significantly increased all-cause mortality risk among COPD patients versus non-COPD individuals (HR,1.80; 95% CI: 1.40–2.30). Crucially, this risk association persisted consistently across all COPD severity strata, comorbidities (respiratory, cardiovascular, and cancers), smoking behavior categories (never-smokers, former smokers, current smokers), and both genders. Risk-stratified analyses further revealed a progressive mortality risk escalation with advancing disease severity. Collectively, these findings robustly confirm COPD’s pervasive adverse impact on all-cause mortality, providing critical evidence for prognostic assessment and clinical management optimization.

COPD presents a critical global public health challenge, necessitating precise mortality risk assessment to optimize clinical management and improve prognosis.^46–48 This study confirms significantly elevated all-cause mortality in COPD patients versus non-COPD controls, a pattern persisting across diverse geographical regions, income levels, and countries, due to core pathophysiological mechanisms of COPD-progressive airflow limitation and systemic inflammation.⁴⁹ Notably, higher COPD-attributed mortality estimates in HICs compared to UMICs likely reflect systemic limitations in many UMICs, such as constrained healthcare infrastructure and inadequate disease awareness, which elevate underdiagnosis rates and cause significant under-ascertainment of COPD as an underlying cause of death.⁵⁰ Furthermore, Europe demonstrates higher COPD-attributed mortality risk than the Americas and Western Pacific regions, attributable to its older population structure, prolonged history of widespread smoking prevalence, and crucially, more advanced healthcare systems with robust mortality surveillance mechanisms that enhance detection and accurate certification of COPD as a contributing or underlying cause of death.

Precise stratification of mortality risk across distinct COPD severity levels is critical for accurate prognostic assessment, optimized healthcare resource allocation, and individualized management strategies. Our analysis demonstrates a graded increase in mortality risk with progressive disease severity, consistent with established evidence.^51–53 Crucially, supporting histopathological evidence⁵⁴ reveals detectable microscopic alterations in lung tissue even at early stages (GOLD 1–2), prior to overt emphysematous destruction. These include early elastin fibers loss within alveolar attachments and progressive luminal narrowing in terminal bronchioles–pathological changes that correlate with advancing disease severity. This dual pathology, characterized by small airway remodeling and diminished parenchymal elastic recoil, underlies the heightened incidence of complications such as hypoxemia and chronic respiratory failure in severe airflow limitation. Consequently, this pathophysiological progression translates into a significantly elevated mortality risk.

Tobacco smoking constitutes the principal modifiable risk factor for COPD,^55,56 with cohort evidence consistently demonstrating elevated all-cause mortality risk in smokers versus never-smokers across all disease severity strata–reflecting a positive correlation between smoking intensity and both COPD incidence and mortality.^57,58. Notably, the mortality risk in never-smokers with COPD was also significantly higher compared to non-COPD individuals. Although potential inconsistencies in the diagnosis of COPD among never-smokers cannot be fully excluded, the fact that most included studies adopted pulmonary function testing as the core diagnostic criterion ensures the overall reliability of this subgroup analysis. Pathogenetically, smoking mediates damage through interrelated mechanisms:^59–61 at the airway level, smoke constituents stimulate mucus hypersecretion and impair ciliary function, compromising mucociliary clearance; at the functional level, smoke exposure induces bronchospasm and persistent airflow limitation; and at the molecular level, smoke triggers immune cell infiltration and disrupts the protease-antiprotease balance, accelerating parenchymal destruction. Smoking cessation represents the single most potent primary preventive and secondary interventional measure. Robust evidence confirms that quitting smoking not only reduces disease incidence but also significantly attenuates mortality risk among individuals with established COPD.^62,63

COPD disproportionately affects older adults, with its hallmark persistent pulmonary and systemic inflammation significantly elevating comorbidity risk.^64,65 Meta-analysis⁶⁶ evidence corroborated that cardiovascular and cancer comorbidities substantially increase long-term mortality risk in COPD patients, aligning with the present findings. Pathogenetically, COPD is characterized as a systemic inflammatory condition; pulmonary inflammation triggers systemic responses via inflammatory mediator release, subsequently impairing cardiovascular, metabolic, and other physiological systems.^67,68 This multisystem dysfunction drives diverse comorbidities, ultimately accelerating functional decline, quality of life deterioration, and worsened prognosis.^69,70 Notably, COPD-associated mortality risk is elevated in both genders. While females typically exhibit lower cumulative tobacco exposure than males, inhalation of poorly ventilated cooking fumes represents a significant gender-specific risk factor for COPD-related mortality among women.

To our knowledge, as the first comprehensive meta-analysis quantifying COPD-attributable mortality, this study demonstrates these core strengths: First, by restricting inclusion to cohort studies, it capitalizes on prospective designs to enhance causal inference validity while mitigating selection bias. Second, incorporated studies further exhibit rigorous methodology with extended follow-up durations (96% ≥ 5 years), ensuring robust survival estimates through sufficient endpoint accrual. Third, all extracted HRs were consistently multivariable-adjusted, substantially reducing confounding effects on pooled estimates. Fourth, beyond providing all-cause mortality risk stratified by COPD severity, we systematically evaluated the effects of smoking status and comorbidity burden, thereby establishing a multidimensional evidence base to inform personalized prognosis and targeted interventions.

Notwithstanding the above strengths, this study has several limitations. First, the geographic representation of included studies is suboptimal: 93% originated from HICs, with merely two from UMICs and none from low-income nations; this imbalance may substantially underestimate the global COPD mortality burden due to unaccounted epidemiological heterogeneity. Second, insufficient cohort numbers restricted multidimensional risk exploration, preventing rigorous assessment of determinants such as e-cigarette exposure, body mass index, and age. Furthermore, the assessment of comorbidities was limited to broad categories. Due to this constraint in the available data, a pooled analysis of the impact of specific individual diseases on COPD mortality was not feasible. Third, Due to the limited number of available studies, we were unable to conduct further investigations to explore the sources of substantial heterogeneity for some outcomes with high heterogeneity. Fourth, heterogeneity in adjusted confounders across studies impedes sensitivity analyses of critical variables, potentially compromising the precision of effect size estimates. Last but not least, heterogeneity may exist in the definition of “never-smokers,” particularly regarding the consideration and extent of secondhand smoke exposure. The lack of such standardization could lead to inconsistencies in case identification and may compromise the accuracy of risk estimates associated with COPD in never-smokers. Consequently, future research should develop prospective cohorts spanning multilingual and diverse socioeconomic contexts, standardizing covariate collection to enhance global generalizability and precision of COPD mortality risk prediction.

Conclusion

This study provides the first systematic evidence demonstrating significantly elevated all-cause mortality risk in COPD patients compared with non-COPD cohorts. Tobacco exposure, coexisting cardiovascular disorders, other respiratory diseases, and malignancies (notably lung cancer) were identified as major modifiable risk factors. A progressive mortality risk gradient was strongly associated with advancing disease severity, necessitating intensified comprehensive management across all stages. Crucially, the excessive mortality risk exhibited a sex-independent pattern. Given this risk profile, public health strategies should prioritize COPD risk reduction through early identification and coordinated management of high-risk cohorts to alleviate disease burden. Collectively, these findings provide an evidence-based foundation for optimizing clinical interventions and informing health policy development.