Department of Clinical Laboratory, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, Guangdong, China.
Guangzhou Laboratory, Guangzhou International Bio Island, XingDaoHuanBei Road, Guangzhou, 510005, Guangdong Province, China.
Respir Res. 2024 Jan 19;25(1):46. doi: 10.1186/s12931-023-02661-6.
Numerous studies have documented significant alterations in the bodily fluids of Chronic Obstructive Pulmonary Disease (COPD) patients. However, existing literature lacks causal inference due to residual confounding and reverse causality.
Summary-level data for COPD were obtained from two national biobanks: the UK Biobank, comprising 1,605 cases and 461,328 controls, and FinnGen, with 6,915 cases and 186,723 controls. We also validated our findings using clinical data from 2,690 COPD patients and 3,357 healthy controls from the First Affiliated Hospital of Guangzhou Medical University. A total of 44 bodily fluid biomarkers were selected as candidate risk factors. Mendelian randomization (MR) and meta-analyses were used to evaluate the causal effects of these bodily fluids on COPD and lung function (FEV1/FVC).
Mendelian randomization (MR) and meta-analyses, by integrating data from the UK Biobank and FinnGen cohort, found that 3 bodily fluids indicators (HDLC, EOS, and TP) were causally associated with the risk of COPD, two (EOS and TP) of which is consistent with our observational findings. Moreover, we noticed EOS and TP were causally associated with the risk of lung function (FEV1/FVC).
The MR findings and clinical data highlight the independent and significant roles of EOS and TP in the development of COPD and lung function (FEV1/FVC), which might provide a deeper insight into COPD risk factors and supply potential preventative strategies.
大量研究已经证明慢性阻塞性肺疾病（COPD）患者的体液发生了显著改变。然而，由于残余混杂和反向因果关系，现有文献缺乏因果推断。
从两个国家生物库（英国生物库，包含 1605 例病例和 461328 例对照；FinnGen，包含 6915 例病例和 186723 例对照）获得 COPD 的汇总水平数据。我们还使用来自广州医科大学第一附属医院的 2690 例 COPD 患者和 3357 例健康对照的临床数据验证了我们的发现。共选择了 44 种体液生物标志物作为候选风险因素。孟德尔随机化（MR）和荟萃分析用于评估这些体液对 COPD 和肺功能（FEV1/FVC）的因果影响。
MR 和荟萃分析，通过整合英国生物库和 FinnGen 队列的数据，发现 3 种体液指标（HDLC、EOS 和 TP）与 COPD 的风险有因果关系，其中 2 种（EOS 和 TP）与我们的观察性发现一致。此外，我们注意到 EOS 和 TP 与肺功能（FEV1/FVC）的风险有因果关系。
MR 发现和临床数据突出了 EOS 和 TP 在 COPD 和肺功能（FEV1/FVC）发展中的独立和重要作用，这可能为 COPD 风险因素提供更深入的了解，并提供潜在的预防策略。
