Association of asthma and bronchiectasis: Mendelian randomization analyses and observational study

Abstract Background 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...

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Main Authors: Rui Fan, Hao Qian, Jia-Yan Xu, Jia-Yi Wang, Yue Su, Jia-Wei Yang, Fang Jiang, Wei-Jun Cao, Jin-Fu Xu
Format: Article
Language:English
Published: BMC 2024-11-01
Series:Respiratory Research
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Online Access:https://doi.org/10.1186/s12931-024-03034-3
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author Rui Fan
Hao Qian
Jia-Yan Xu
Jia-Yi Wang
Yue Su
Jia-Wei Yang
Fang Jiang
Wei-Jun Cao
Jin-Fu Xu
author_facet Rui Fan
Hao Qian
Jia-Yan Xu
Jia-Yi Wang
Yue Su
Jia-Wei Yang
Fang Jiang
Wei-Jun Cao
Jin-Fu Xu
author_sort Rui Fan
collection DOAJ
description Abstract Background 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. Method 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. Result 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. Conclusion 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.
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spelling doaj-art-b2fd15238cdd4eb48e403e62748dfcd82025-08-20T02:22:30ZengBMCRespiratory Research1465-993X2024-11-0125111110.1186/s12931-024-03034-3Association of asthma and bronchiectasis: Mendelian randomization analyses and observational studyRui Fan0Hao Qian1Jia-Yan Xu2Jia-Yi Wang3Yue Su4Jia-Wei Yang5Fang Jiang6Wei-Jun Cao7Jin-Fu Xu8Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Institute of Respiratory Medicine, School of Medicine, Tongji UniversityDepartment of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Institute of Respiratory Medicine, School of Medicine, Tongji UniversityDepartment of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Institute of Respiratory Medicine, School of Medicine, Tongji UniversityDepartment of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Institute of Respiratory Medicine, School of Medicine, Tongji UniversityDepartment of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Institute of Respiratory Medicine, School of Medicine, Tongji UniversityDepartment of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Institute of Respiratory Medicine, School of Medicine, Tongji UniversityDepartment of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong KongDepartment of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Institute of Respiratory Medicine, School of Medicine, Tongji UniversityDepartment of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Institute of Respiratory Medicine, School of Medicine, Tongji UniversityAbstract Background 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. Method 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. Result 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. Conclusion 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.https://doi.org/10.1186/s12931-024-03034-3AsthmaBronchiectasisMendelian randomizationSinusitisNasal polypEosinophil
spellingShingle Rui Fan
Hao Qian
Jia-Yan Xu
Jia-Yi Wang
Yue Su
Jia-Wei Yang
Fang Jiang
Wei-Jun Cao
Jin-Fu Xu
Association of asthma and bronchiectasis: Mendelian randomization analyses and observational study
Respiratory Research
Asthma
Bronchiectasis
Mendelian randomization
Sinusitis
Nasal polyp
Eosinophil
title Association of asthma and bronchiectasis: Mendelian randomization analyses and observational study
title_full Association of asthma and bronchiectasis: Mendelian randomization analyses and observational study
title_fullStr Association of asthma and bronchiectasis: Mendelian randomization analyses and observational study
title_full_unstemmed Association of asthma and bronchiectasis: Mendelian randomization analyses and observational study
title_short Association of asthma and bronchiectasis: Mendelian randomization analyses and observational study
title_sort association of asthma and bronchiectasis mendelian randomization analyses and observational study
topic Asthma
Bronchiectasis
Mendelian randomization
Sinusitis
Nasal polyp
Eosinophil
url https://doi.org/10.1186/s12931-024-03034-3
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