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Associations of Mucus Plug With Prognosis in COPD: A Systematic Review and Meta-Analysis
Jiaqi Pu1, Shijia Hong1, Jian-Qing He1
1Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China; State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
Background:
Radiologically defined mucus plugs in COPD have not been systematically evaluated for prognosis, constraining their use in clinical risk stratification.
Research Question:
In adults with COPD, is the burden of radiologically defined mucus plugs associated with increased risks of mortality, exacerbations, lung function decline, and impaired quality of life?
Study Design And Methods:
A systematic review and meta-analysis (PROSPERO: CRD [removed]) was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science were comprehensively searched from inception to November 11, 2025. Observational studies involving adults with COPD that reported data on mortality, exacerbations, lung function, or quality of life were included. Pooled hazard ratios (HRs) were generated by using random-effects meta-analysis. Prespecified subgroup analyses were stratified according to plug severity (low-grade [score 1-2] vs high-grade [score ≥ 3]) and exacerbation type.
Results:
Seven studies involving 15,702 patients were included. Compared with patients without mucus plugs, those with low-grade plugs had a 14% higher risk of all-cause mortality (HR, 1.14; 95% CI, 1.03-1.26), which further increased to 48% in the high-grade group, although this estimate did not reach statistical significance (HR, 1.48; 95% CI, 0.86-2.54; P = .16). Similarly, the risk of exacerbations exhibited a graded increase, for both moderate to severe (low-grade: HR, 1.07 [95% CI, 1.05-1.09]; high-grade: HR, 1.15 [95% CI, 1.08-1.23]) and severe (low-grade: HR, 1.11 [95% CI, 1.00-1.22]; high-grade: HR, 1.41 [95% CI, 1.04-1.91]) events. Narrative synthesis confirmed associations with worse lung function and quality of life.
Interpretation:
This first meta-analysis found a consistent graded association between CT-defined mucus plug burden and poor clinical outcomes in COPD, supporting its role as a clinically relevant prognostic marker for risk stratification. These findings support integrating CT-based plug assessment into clinical practice for risk stratification and highlight the need for targeted mucus-directed therapies.
Clinical Trial Registration:
PROSPERO; No.: CRD [removed]; URL: https://www.crd.york.ac.uk/prospero.
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