Lin Shan, Lai Dingfeng, He Wanmei, Zhan Qingyuan
Department of Respiratory and Critical Care Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China.
Department of Medical Intensive Care Unit, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.
Heliyon. 2025 Jan 18;11(2):e42100. doi: 10.1016/j.heliyon.2025.e42100. eCollection 2025 Jan 30.
BACKGROUND: Numerous observational studies have posited that gastroesophageal reflux disease (GERD) might amplify the risk of chronic airway conditions such as chronic obstructive pulmonary disease (COPD) and asthma. Yet, a definitive causal link remains to be established. To this end, we utilized a two-sample Mendelian randomization approach (MR) to investigate the potential causal dynamics between GERD and these chronic obstructive respiratory diseases. METHODS: Using a two-sample bidirectional MR, we explored the causal influence of GERD on the risks of developing COPD and asthma, drawing on aggregated genome-wide association study data from European cohorts. RESULTS: Our analysis elucidated a notable causal relationship, with individuals genetically inclined towards GERD exhibiting a significantly elevated propensity to develop COPD (odds ratio [OR] = 1.520, 95 % confidence interval [CI] 1.376-1.680, P = 2.173 × 10) and asthma (OR = 1.420, 95 % CI 1.340-1.504, P = 1.269 × 10). The absence of heterogeneity and pleiotropy was confirmed through the Cochran Q test, funnel plots, MR-Egger intercept test, and MR-PRESSO. Directional causality was further substantiated by Steiger testing. Conversely, reverse MR analyses did not identify a significant causal pathway between COPD or asthma and GERD onset. CONCLUSION: This investigation substantiates a robust positive correlation between GERD and increased risks for COPD and asthma, laying a foundational basis for incorporating GERD management into preventive and therapeutic strategies for these chronic obstructive respiratory diseases.
背景:大量观察性研究认为,胃食管反流病(GERD)可能会增加慢性气道疾病的风险,如慢性阻塞性肺疾病(COPD)和哮喘。然而,尚未确定明确的因果关系。为此,我们采用双样本孟德尔随机化方法(MR)来研究GERD与这些慢性阻塞性呼吸道疾病之间的潜在因果动态关系。 方法:利用双样本双向MR,我们借鉴欧洲队列的全基因组关联研究汇总数据,探讨GERD对患COPD和哮喘风险的因果影响。 结果:我们的分析阐明了一种显著的因果关系,遗传上易患GERD的个体患COPD(优势比[OR]=1.520,95%置信区间[CI]1.376-1.680,P=2.173×10)和哮喘(OR=1.420,95%CI 1.340-1.504,P=1.269×10)的倾向显著增加。通过Cochran Q检验、漏斗图、MR-Egger截距检验和MR-PRESSO证实了不存在异质性和多效性。Steiger检验进一步证实了方向性因果关系。相反,反向MR分析未发现COPD或哮喘与GERD发病之间存在显著的因果途径。 结论:本研究证实了GERD与COPD和哮喘风险增加之间存在强有力的正相关,为将GERD管理纳入这些慢性阻塞性呼吸道疾病的预防和治疗策略奠定了基础。
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