Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Institute of Respiratory Medicine, School of Medicine, Tongji University, Shanghai, China.
Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Respir Res. 2024 Nov 20;25(1):413. doi: 10.1186/s12931-024-03034-3.
Previous studies have demonstrated that asthma is closely associated with bronchiectasis, however, the causal relationship between asthma and bronchiectasis has not been investigated in depth. Therefore, this study aims to explore the causal relationship and to identify potential factors that mediate between these two diseases.
All the necessary summarized information were obtained from publicly available genome-wide association study (GWAS). Two-sample Mendelian randomization (two-sample MR) was employed to explore the causal relationship between asthma and bronchiectasis, with an additional dataset used for validation. Heterogeneity and pleiotropy analyses were utilized to verify the robustness of the results. Subsequently, mediation MR analyses were performed to identify potential mediating factors. Lastly, a retrospective observational study was conducted to validate the findings.
Preliminary inverse-variance weighted (IVW) results indicated there was a causal effect of asthma on bronchiectasis (odds ratio [OR] = 1.228, 95% confidence interval [CI]: 1.077-1.400, P = 0.002). Repetition validation yielded a consistent result. Mediation MR analysis demonstrated that the presence of nasal polyps (OR = 1.063, 95% CI: 1.015-1.113, mediation ratio = 30.492%, P = 0.009), acute sinusitis (OR = 1.062, 95% CI: 1.009-1.118, mediation ratio = 30.157%, P = 0.018), chronic sinusitis (OR = 1.085, 95% CI: 1.024-1.150, mediation ratio = 40.677%, P = 0.005), and peripheral eosinophil counts (OR = 1.013, 95% CI: 1.000-1.026, mediation ratio = 6.514%, P = 0.042) served as significant mediators in the occurrence and development of bronchiectasis induced by asthma. Furthermore, a retrospective observational study observed that bronchiectasis patients with asthma had a higher prevalence of sinusitis (5.043% vs 2.971%, P < 0.001), nasal polyps (0.536% vs 0.152%, P < 0.001), and rhinitis (13.197% vs 1.860%, P < 0.001). The ratio (1.950 (0.500, 5.600) vs 1.500 (0.500, 2.600), P = 0.006) and counts (0.125 (0.040, 0.363) vs 0.090 (0.030, 0.160), P < 0.001) of peripheral blood eosinophils were also elevated in bronchiectasis patients with asthma.
The MR analysis uncovered a notable genetic association between asthma and bronchiectasis, which was partially mediated by sinusitis, nasal polyps, and eosinophils. A subsequent retrospective study provided further evidence by demonstrating that bronchiectasis patients with asthma had a higher prevalence of sinusitis, nasal polyps, an elevated proportion of eosinophils, and higher eosinophil counts.
先前的研究表明哮喘与支气管扩张密切相关，但哮喘与支气管扩张之间的因果关系尚未深入研究。因此，本研究旨在探讨两者之间的因果关系，并确定潜在的中介因素。
所有必要的汇总信息均从公开的全基因组关联研究（GWAS）中获得。采用两样本孟德尔随机化（two-sample MR）方法探讨哮喘与支气管扩张之间的因果关系，并使用额外的数据集进行验证。采用异质性和多效性分析来验证结果的稳健性。随后，进行中介 MR 分析以确定潜在的中介因素。最后，进行了一项回顾性观察性研究来验证研究结果。
初步的逆方差加权（IVW）结果表明，哮喘对支气管扩张有因果影响（比值比 [OR] = 1.228，95%置信区间 [CI]：1.077-1.400，P = 0.002）。重复验证得出了一致的结果。中介 MR 分析表明，鼻息肉（OR = 1.063，95%CI：1.015-1.113，中介比例 = 30.492%，P = 0.009）、急性鼻窦炎（OR = 1.062，95%CI：1.009-1.118，中介比例 = 30.157%，P = 0.018）、慢性鼻窦炎（OR = 1.085，95%CI：1.024-1.150，中介比例 = 40.677%，P = 0.005）和外周血嗜酸性粒细胞计数（OR = 1.013，95%CI：1.000-1.026，中介比例 = 6.514%，P = 0.042）是哮喘引起支气管扩张发生和发展的显著中介因素。此外，一项回顾性观察性研究发现，患有哮喘的支气管扩张患者鼻窦炎（5.043% 比 2.971%，P < 0.001）、鼻息肉（0.536% 比 0.152%，P < 0.001）和鼻炎（13.197% 比 1.860%，P < 0.001）的患病率更高。比值（1.950（0.500，5.600）比 1.500（0.500，2.600），P = 0.006）和外周血嗜酸性粒细胞计数（0.125（0.040，0.363）比 0.090（0.030，0.160），P < 0.001）也在哮喘合并支气管扩张患者中升高。
MR 分析揭示了哮喘与支气管扩张之间存在显著的遗传关联，部分是由鼻窦炎、鼻息肉和嗜酸性粒细胞介导的。随后的回顾性研究进一步提供了证据，表明患有哮喘的支气管扩张患者鼻窦炎、鼻息肉的患病率更高，嗜酸性粒细胞比例和计数更高。
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