Zinc as a protective factor against COPD: Insights from observational and Mendelian randomization analyses

Chronic obstructive pulmonary disease (COPD) remains a major global health burden, with limited effective preventative strategies. Zinc, a key micronutrient, plays critical roles in immune regulation, anti-inflammatory processes, and maintaining epithelial integrity, yet its relationship with COPD and related infections remains poorly understood. This study utilized data from the National Health and Nutrition Examination Survey and Mendelian randomization (MR) analyses. Serum zinc levels were assessed in 67,502 participants, with COPD diagnosed based on forced expiratory volume in 1 second/forced vital capacity <0.70 or physician reports. Weighted logistic regression and restricted cubic spline analyses explored nonlinear associations between zinc exposure and COPD risk. Stratified analyses examined the role of age, race, and smoking status as modifiers. MR analyses were conducted to assess causality, with sensitivity tests ensuring robustness. Higher zinc levels were associated with reduced COPD risk, showing significant nonlinear dose-response patterns (P-overall < .001; P-nonlinear = .030). Stratified analyses revealed stronger protective effects in individuals aged ≤ 65 years (odds ratio [OR] = 0.963, P = .003), Non-Hispanic Whites (OR = 0.965, P = .051), and smokers (OR = 0.965, P = .023). MR analysis confirmed Zinc's causal protective role in reducing COPD-related infections (OR = 0.979, P = .042), independent of confounders. This study provides robust evidence supporting zinc as a protective factor against COPD and related infections, emphasizing its potential as a therapeutic target for prevention and management. Future studies should explore optimal zinc supplementation strategies and gene-environment interactions to maximize its clinical benefits.