[A prospective cohort and Mendelian randomization study of association of snoring and adiposity with chronic obstructive pulmonary disease].

内容摘要

Objective: To investigate the causal association between snoring and chronic obstructive pulmonary disease (COPD), and the role of obesity in their relationship. Methods: Based on the individual-level data from the United Kingdom Biobank prospective cohort, a Cox proportional hazards regression model was carried out to estimate the association between snoring at baseline survey and the risk for COPD (n=254 757, 3 438 COPD cases). Multivariable logistic regression analysis was conducted to assess the association between COPD and the probability of snoring (n=22 096, 3 481 snorers). Univariable Mendelian randomization (MR), multivariate MR (MVMR) analyses were conducted on causal association of snoring and obesity [BMI, waist circumference adjusted for BMI (WCadjBMI)], and COPD. Results: Snoring at baseline survey was positively associated with the risk for COPD in the prospective cohort analysis (HR=1.20, 95%CI: 1.12-1.29). With applying MR approach, genetically predicted one-fold increased probability of snoring was associated with 77% (inverse-variance weighted: OR=1.77, 95%CI: 1.04-3.00) higher risk for COPD. After adjustment for obesity, snoring at baseline survey was not statistically associated with the risk for COPD (HR=1.07, 95%CI: 1.00-1.14, P=0.067). No significant association was observed between COPD at baseline survey and the probability of snoring (OR=0.91, 95%CI: 0.81-1.02). No causal association between snoring and COPD was observed in the MVMR analysis. Conclusions: The prospective cohort and MR analysis showed consistent evidence that obesity contributed to the association between snoring and COPD. Management of obesity, especially the general obesity, might be an important strategy for the prevention of COPD. 目的： 探讨打鼾与慢性阻塞性肺疾病（COPD）的因果关联，以及肥胖在该关联中的作用。 方法： 基于英国生物银行的前瞻性队列个体数据，采用Cox比例风险回归模型分析基线打鼾与COPD发病风险的关联（n=254 757，随访期间3 438名研究对象新发COPD）；并采用多因素logistic回归模型分析COPD与打鼾发生概率之间可能的关联（n=22 096，3 481名研究对象在基线至第二次重复调查期间新发打鼾）。采用单变量孟德尔随机化（MR）、多变量MR（MVMR）探讨打鼾、肥胖［BMI、经BMI校正的腰围（WCadjBMI）］与COPD的因果关联。 结果： 前瞻性队列分析中，基线打鼾与COPD发病风险呈正相关（HR=1.20，95%CI：1.12~1.29）。MR分析中，遗传预测的打鼾发生概率每升高1倍，COPD发病风险升高77%（逆方差加权法：OR=1.77，95%CI：1.04~3.00）。调整肥胖后，基线打鼾与COPD发病风险无统计学关联（HR=1.07，95%CI：1.00~1.14，P=0.067），基线患COPD与打鼾发生概率之间无统计学关联（OR=0.91，95%CI：0.81~1.02）。MVMR分析中未观察到打鼾与COPD的因果关联。 结论： 前瞻性队列与MR研究一致表明，肥胖因素作用于打鼾与COPD之间的关联。进行肥胖管理，特别是全身性肥胖管理，可能有助于预防COPD发病。.