Liu Banghui, Yuan Jinhe, Huan Lu, Peng Li
Outpatient Department, Renji Hospital, School of Medicine, Chongqing University, Chongqing, China.
Department of Respiratory and Critical Care Medicine, Renji Hospital, School of Medicine, Chongqing University, Chongqing, China.
Medicine (Baltimore). 2025 Aug 8;104(32):e43340. doi: 10.1097/MD.0000000000043340.
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.
慢性阻塞性肺疾病（COPD）仍然是一个重大的全球健康负担，有效的预防策略有限。锌作为一种关键的微量营养素，在免疫调节、抗炎过程和维持上皮完整性方面发挥着关键作用，但其与COPD及相关感染的关系仍知之甚少。本研究利用了来自美国国家健康与营养检查调查的数据和孟德尔随机化（MR）分析。对67502名参与者的血清锌水平进行了评估，根据1秒用力呼气量/用力肺活量<0.70或医生报告诊断COPD。加权逻辑回归和受限立方样条分析探讨了锌暴露与COPD风险之间的非线性关联。分层分析检查了年龄、种族和吸烟状况作为调节因素的作用。进行MR分析以评估因果关系，并进行敏感性测试以确保稳健性。较高的锌水平与降低COPD风险相关，呈现出显著的非线性剂量反应模式（P总体<0.001；P非线性=0.030）。分层分析显示，在年龄≤65岁的个体（优势比[OR]=0.963，P=0.003）、非西班牙裔白人（OR=0.965，P=0.051）和吸烟者（OR=0.965，P=0.023）中，保护作用更强。MR分析证实了锌在减少COPD相关感染方面的因果保护作用（OR=0.979，P=0.042），独立于混杂因素。本研究提供了有力证据，支持锌作为预防COPD及相关感染的保护因素，强调了其作为预防和管理治疗靶点的潜力。未来的研究应探索最佳的锌补充策略以及基因-环境相互作用，以最大限度地提高其临床益处。
