Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine of Fujian Province, The Second Affiliated Hospital of Fujian Medical University, No.950, Donghai Street, Fengze District, Quanzhou, Fujian Province, China.
Department of Pulmonary and Critical Care Medicine, School of Medicine, Zhongshan Hospital of Xiamen University, Xiamen University, Xiamen, Fujian, China.
BMC Pulm Med. 2024 Aug 26;24(1):409. doi: 10.1186/s12890-024-03228-x.
This study aimed to elucidate the causal relationship between Obstructive Sleep Apnea (OSA) and Chronic Respiratory Diseases (CRDs), employing Mendelian Randomization (MR) to overcome limitations inherent in observational studies.
Utilizing a two-sample MR approach, this study analyzed genetic variants as instrumental variables to investigate the causal link between OSA and various CRDs, including chronic obstructive pulmonary disease (COPD), asthma, bronchiectasis, and idiopathic pulmonary fibrosis (IPF). Data were sourced from the FinnGen Consortium (OSA, n = 375,657) and UK Biobank, focusing on genome-wide associations between single-nucleotide polymorphisms (SNPs) and the diseases. Instrumental variables were selected based on strict criteria, and analyses included a random-effects inverse-variance weighted method supplemented by several sensitivity analyses.
The study suggests a protective effect of OSA against COPD (OR = 0.819, 95% CI 0.722-0.929, P-value = 0.002), which becomes non-significant after adjusting for BMI, indicating a potential mediating role of BMI in the OSA-COPD nexus. No significant causal links were found between OSA and other CRDs (asthma, IPF, bronchiectasis) or between COPD, asthma, and OSA.
Our findings reveal a BMI-mediated protective effect of OSA on COPD, with no causal connections identified between OSA and other CRDs. These results emphasize the complex relationship between OSA, BMI, and COPD, guiding future clinical strategies and research directions, particularly in light of the study's genetic analysis limitations.
本研究旨在运用孟德尔随机化（MR）克服观察性研究固有的局限性，阐明阻塞性睡眠呼吸暂停（OSA）与慢性呼吸系统疾病（CRD）之间的因果关系。
本研究采用两样本 MR 方法，利用遗传变异作为工具变量分析 OSA 与各种 CRD（包括慢性阻塞性肺疾病（COPD）、哮喘、支气管扩张和特发性肺纤维化（IPF））之间的因果关系。数据来源于芬兰人群基因组研究（OSA，n=375657）和英国生物库，重点关注单核苷酸多态性（SNP）与疾病之间的全基因组关联。根据严格标准选择工具变量，并采用随机效应逆方差加权法进行分析，同时进行了几项敏感性分析。
本研究表明 OSA 对 COPD 具有保护作用（OR=0.819，95%CI 0.722-0.929，P 值=0.002），但在调整 BMI 后，该结果变得不显著，表明 BMI 在 OSA-COPD 关联中可能发挥中介作用。OSA 与其他 CRD（哮喘、IPF、支气管扩张）或 COPD、哮喘与 OSA 之间均未发现显著的因果关系。
本研究结果揭示了 OSA 通过 BMI 对 COPD 具有保护作用，且 OSA 与其他 CRD 之间不存在因果关系。这些结果强调了 OSA、BMI 和 COPD 之间的复杂关系，为未来的临床策略和研究方向提供了指导，特别是考虑到研究的遗传分析局限性。
