Association between serum uric acid levels and COPD: a meta-analysis and mendelian randomization study.
TL;DR
Observational evidence indicated elevated SUA in COPD, especially during exacerbations, while genetically predicted higher SUA showed a modest protective effect, which suggests a complex, dual role of uric acid.
Abstract
Objective
Chronic obstructive pulmonary disease (COPD) poses a major global health burden, but its relationship with serum uric acid (SUA) remains controversial. This study combined meta-analysis and Mendelian randomization (MR) to evaluate the observational association and potential causal relationship between SUA and COPD.
Methods
We systematically searched PubMed, Embase, Web of Science, CNKI, and Wanfang Data for observational studies comparing SUA levels between COPD patients and healthy controls published up to December 2025. Meta-analysis was performed using a random-effects model to calculate mean differences (MD) and 95% confidence intervals (CI), followed by subgroup analyses. This meta-analysis has been registered with PROSPERO under the registration number CRD420251234511. Two-sample bidirectional MR analysis was conducted using publicly available GWAS summary data, with inverse variance weighting (IVW) as the primary method, supplemented by weighted median, MR-Egger regression, and sensitivity analyses.
Results
The meta-analysis included 22 studies, comprising a total of 3739 COPD patients and 2778 healthy controls. Results showed that SUA levels were significantly higher in stable COPD patients compared to healthy controls (MD: 1.19 mg/dL, 95% CI: 0.83-1.55, P < 0.00001). Patients with acute exacerbation of COPD (AECOPD) exhibited even higher uric acid levels (MD: 1.30 mg/dL, 95% CI: 0.36-2.24, P < 0.00001), and SUA levels were significantly higher in severe COPD patients compared to those with mild-to-moderate COPD (MD: 1.18 mg/dL, 95% CI: 0.76-1.60, P = 0.02). Bidirectional MR analysis revealed that genetically predicted higher SUA levels were causally associated with reduced COPD risk (IVW: OR: 0.883, 95% CI: 0.811-0.961, P = 0.004). Reverse MR analysis found no significant causal effect of COPD on uric acid levels (P > 0.05). Sensitivity analyses supported the robustness of the MR findings.
Conclusion
Observational evidence indicated elevated SUA in COPD, especially during exacerbations, while genetically predicted higher SUA showed a modest protective effect. These findings suggest a complex, dual role of uric acid. However, observational associations may be confounded by reverse causality, and the MR estimates-derived from East Asian populations-are method-sensitive. Current evidence does not yet support altering uric acid management in COPD, and further prospective and interventional studies across diverse populations are warranted.