血清总胆红素与慢性阻塞性肺疾病之间的关联：一项横断面研究和双向孟德尔随机化分析的结果
Association Between Serum Total Bilirubin and COPD: Results from a Cross-Sectional Study and a Bidirectional Mendelian Randomization Analysis.
作者信息
Dai Cuiqiong, Wang Zihui, Yang Huajing, Xiao Shan, Xu Jianwu, Deng Zhishan, Wu Fan, Wen Xiang, Zheng Youlan, Lu Lifei, Zhao Ningning, Huang Peiyu, Zhou Yumin, Ran Pixin
机构信息
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, People's Republic of China.
Guangzhou Laboratory, Bio-Island, Guangzhou, People's Republic of China.
出版信息
Clin Epidemiol. 2022 Mar 10;14:289-298. doi: 10.2147/CLEP.S353389. eCollection 2022.
BACKGROUND
The potential protective role of serum total bilirubin (TB) for chronic obstructive pulmonary disease (COPD) is controversial. We aimed to investigate whether serum TB could prevent airflow limitation (reduce the risk of COPD) and whether these associations were causal or reversely causal.
METHODS
We conducted a multi-center and cross-sectional study including 3069 participants. Logistic regression model (LRM) with restricted cubic spline (RCS) and priori defined quintile categories were used to assess the associations of TB with COPD. Besides, ordinary least squares (OLS) regression model with RCS curves were applied to assess the dose-response relationship between serum TB and airflow limitation (FEV/FVC). To verify the causal direction between TB and COPD, a bidirectional Mendelian randomization analysis was carried out with GWAS data from European ancestry.
RESULTS
In the cross-sectional study, the relationship between levels of TB and COPD risk was U shaped (P=0.001), and the low and high concentrations of TB apparently increasing the risk of COPD (OR 1.40, 95% CI 1.07 to 1.82 for less than 9 μmol/L; OR 1.36, 95% CI 1.06 to 1.76 for 9.01-1 0.88 μmol/L; OR 1.50, 95% CI 1.16 to 1.95 for more than 13 μmol/L). There was a significant non-linear relationship between TB and FEV/FVC (non-linear p=0.004). Furthermore, results of bidirectional Mendelian randomization analysis (OR 1.000; 95% CI 0.983 to 1.017 for MR and OR 0.998; 95% CI 0.976 to 1.020 for reversal MR) did not support the causal effects between serum TB and FEV/FVC after controlling the effect of potential confounders and revised causality.
CONCLUSION
Our study reveals that there was non-linear does-response pattern between serum TB and COPD. However, there was little evidence for the linear causal associations of serum TB with airflow limitation. The relationship of TB with COPD needs further study and careful interpretation.
背景
血清总胆红素（TB）对慢性阻塞性肺疾病（COPD）的潜在保护作用存在争议。我们旨在研究血清TB是否能预防气流受限（降低COPD风险），以及这些关联是因果关系还是反向因果关系。
方法
我们进行了一项多中心横断面研究，纳入3069名参与者。使用带有受限立方样条（RCS）的逻辑回归模型（LRM）和预先定义的五分位数类别来评估TB与COPD的关联。此外，应用带有RCS曲线的普通最小二乘法（OLS）回归模型来评估血清TB与气流受限（FEV/FVC）之间的剂量反应关系。为了验证TB与COPD之间的因果方向，利用欧洲血统的全基因组关联研究（GWAS）数据进行了双向孟德尔随机化分析。
结果
在横断面研究中，TB水平与COPD风险之间的关系呈U形（P = 0.001），低浓度和高浓度的TB明显增加COPD风险（TB浓度低于9 μmol/L时，OR = 1.40，95%CI为1.07至1.82；9.01 - 10.88 μmol/L时，OR = 1.36，95%CI为1.06至1.76；高于13 μmol/L时，OR = 1.50，95%CI为1.16至1.95）。TB与FEV/FVC之间存在显著的非线性关系（非线性p = 0.004）。此外，双向孟德尔随机化分析结果（MR的OR = 1.000；95%CI为0.983至1.017，反向MR的OR = 0.998；95%CI为0.976至1.020）在控制潜在混杂因素的影响并修正因果关系后，不支持血清TB与FEV/FVC之间的因果效应。
结论
我们的研究表明血清TB与COPD之间存在非线性剂量反应模式。然而，几乎没有证据表明血清TB与气流受限存在线性因果关联。TB与COPD的关系需要进一步研究和谨慎解读。
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