The role of Neutrophil counts, infections and Smoking in mediating the Effect of Bronchiectasis on Chronic Obstructive Pulmonary Disease: a mendelian randomization study
Abstract Background The causality of the relationship between bronchiectasis and chronic obstructive pulmonary disease (COPD) remains unclear. This study aims to investigate the potential causal relationship between them, with a specific focus on the role of airway inflammation, infections, smoking...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-03-01
|
| Series: | BMC Pulmonary Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12890-024-02962-6 |
| _version_ | 1827310388873527296 |
|---|---|
| author | Lei Gu Wei Liu Jian-an Huang Lujian Zhu Xiaowen Hu Jian Yue Jing Lin |
| author_facet | Lei Gu Wei Liu Jian-an Huang Lujian Zhu Xiaowen Hu Jian Yue Jing Lin |
| author_sort | Lei Gu |
| collection | DOAJ |
| description | Abstract Background The causality of the relationship between bronchiectasis and chronic obstructive pulmonary disease (COPD) remains unclear. This study aims to investigate the potential causal relationship between them, with a specific focus on the role of airway inflammation, infections, smoking as the mediators in the development of COPD. Methods We conducted a two-sample Mendelian randomization (MR) analysis to assess: (1) the causal impact of bronchiectasis on COPD, sex, smoking status, infections, eosinophil and neutrophil counts, as well as the causal impact of COPD on bronchiectasis; (2) the causal effect of smoking status, infections and neutrophil counts on COPD; and (3) the extent to which the smoking status, infections and neutrophil counts might mediate any influence of bronchiectasis on the development of COPD. Results COPD was associated with a higher risk of bronchiectasis (OR 1.28 [95% CI 1.05, 1.56]). Bronchiectasis was associated with a higher risk of COPD (OR 1.08 [95% CI 1.04, 1.13]), higher levels of neutrophil (OR 1.01 [95% CI 1.00, 1.01]), higher risk of respiratory infections (OR 1.04 [95% CI 1.02, 1.06]) and lower risk of smoking. The causal associations of higher neutrophil cells, respiratory infections and smoking with higher COPD risk remained after performing sensitivity analyses that considered different models of horizontal pleiotropy, with OR 1.17, 1.69 and 95.13, respectively. The bronchiectasis–COPD effect was 0.99, 0.85 and 122.79 with genetic adjustment for neutrophils, respiratory infections and smoking. Conclusion COPD and bronchiectasis are mutually causal. And increased neutrophil cell count and respiratory infections appears to mediate much of the effect of bronchiectasis on COPD. |
| first_indexed | 2024-04-24T19:58:59Z |
| format | Article |
| id | doaj.art-312dcb1f079947d9b5d12e790541c834 |
| institution | Directory Open Access Journal |
| issn | 1471-2466 |
| language | English |
| last_indexed | 2024-04-24T19:58:59Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Pulmonary Medicine |
| spelling | doaj.art-312dcb1f079947d9b5d12e790541c8342024-03-24T12:09:21ZengBMCBMC Pulmonary Medicine1471-24662024-03-012411910.1186/s12890-024-02962-6The role of Neutrophil counts, infections and Smoking in mediating the Effect of Bronchiectasis on Chronic Obstructive Pulmonary Disease: a mendelian randomization studyLei Gu0Wei Liu1Jian-an Huang2Lujian Zhu3Xiaowen Hu4Jian Yue5Jing Lin6Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow UniversityDepartment of Respiratory and Critical Care Medicine, The 900th Hospital of Joint Logistic Support Force, People’s Liberation Army, Fujian Medical UniversityDepartment of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow UniversityDepartment of Infectious Diseases, Affiliated Jinhua Hospital, Zhejiang University School of MedicineDepartment of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, HefeiThe People’s Hospital of GaozhouDepartment of Infectious Diseases, The First Affiliated Hospital of Soochow UniversityAbstract Background The causality of the relationship between bronchiectasis and chronic obstructive pulmonary disease (COPD) remains unclear. This study aims to investigate the potential causal relationship between them, with a specific focus on the role of airway inflammation, infections, smoking as the mediators in the development of COPD. Methods We conducted a two-sample Mendelian randomization (MR) analysis to assess: (1) the causal impact of bronchiectasis on COPD, sex, smoking status, infections, eosinophil and neutrophil counts, as well as the causal impact of COPD on bronchiectasis; (2) the causal effect of smoking status, infections and neutrophil counts on COPD; and (3) the extent to which the smoking status, infections and neutrophil counts might mediate any influence of bronchiectasis on the development of COPD. Results COPD was associated with a higher risk of bronchiectasis (OR 1.28 [95% CI 1.05, 1.56]). Bronchiectasis was associated with a higher risk of COPD (OR 1.08 [95% CI 1.04, 1.13]), higher levels of neutrophil (OR 1.01 [95% CI 1.00, 1.01]), higher risk of respiratory infections (OR 1.04 [95% CI 1.02, 1.06]) and lower risk of smoking. The causal associations of higher neutrophil cells, respiratory infections and smoking with higher COPD risk remained after performing sensitivity analyses that considered different models of horizontal pleiotropy, with OR 1.17, 1.69 and 95.13, respectively. The bronchiectasis–COPD effect was 0.99, 0.85 and 122.79 with genetic adjustment for neutrophils, respiratory infections and smoking. Conclusion COPD and bronchiectasis are mutually causal. And increased neutrophil cell count and respiratory infections appears to mediate much of the effect of bronchiectasis on COPD.https://doi.org/10.1186/s12890-024-02962-6BronchiectasisChronic obstructive Pulmonary DiseaseNeutrophilRespiratory infectionsSmokingMendelian randomization |
| spellingShingle | Lei Gu Wei Liu Jian-an Huang Lujian Zhu Xiaowen Hu Jian Yue Jing Lin The role of Neutrophil counts, infections and Smoking in mediating the Effect of Bronchiectasis on Chronic Obstructive Pulmonary Disease: a mendelian randomization study BMC Pulmonary Medicine Bronchiectasis Chronic obstructive Pulmonary Disease Neutrophil Respiratory infections Smoking Mendelian randomization |
| title | The role of Neutrophil counts, infections and Smoking in mediating the Effect of Bronchiectasis on Chronic Obstructive Pulmonary Disease: a mendelian randomization study |
| title_full | The role of Neutrophil counts, infections and Smoking in mediating the Effect of Bronchiectasis on Chronic Obstructive Pulmonary Disease: a mendelian randomization study |
| title_fullStr | The role of Neutrophil counts, infections and Smoking in mediating the Effect of Bronchiectasis on Chronic Obstructive Pulmonary Disease: a mendelian randomization study |
| title_full_unstemmed | The role of Neutrophil counts, infections and Smoking in mediating the Effect of Bronchiectasis on Chronic Obstructive Pulmonary Disease: a mendelian randomization study |
| title_short | The role of Neutrophil counts, infections and Smoking in mediating the Effect of Bronchiectasis on Chronic Obstructive Pulmonary Disease: a mendelian randomization study |
| title_sort | role of neutrophil counts infections and smoking in mediating the effect of bronchiectasis on chronic obstructive pulmonary disease a mendelian randomization study |
| topic | Bronchiectasis Chronic obstructive Pulmonary Disease Neutrophil Respiratory infections Smoking Mendelian randomization |
| url | https://doi.org/10.1186/s12890-024-02962-6 |
| work_keys_str_mv | AT leigu theroleofneutrophilcountsinfectionsandsmokinginmediatingtheeffectofbronchiectasisonchronicobstructivepulmonarydiseaseamendelianrandomizationstudy AT weiliu theroleofneutrophilcountsinfectionsandsmokinginmediatingtheeffectofbronchiectasisonchronicobstructivepulmonarydiseaseamendelianrandomizationstudy AT jiananhuang theroleofneutrophilcountsinfectionsandsmokinginmediatingtheeffectofbronchiectasisonchronicobstructivepulmonarydiseaseamendelianrandomizationstudy AT lujianzhu theroleofneutrophilcountsinfectionsandsmokinginmediatingtheeffectofbronchiectasisonchronicobstructivepulmonarydiseaseamendelianrandomizationstudy AT xiaowenhu theroleofneutrophilcountsinfectionsandsmokinginmediatingtheeffectofbronchiectasisonchronicobstructivepulmonarydiseaseamendelianrandomizationstudy AT jianyue theroleofneutrophilcountsinfectionsandsmokinginmediatingtheeffectofbronchiectasisonchronicobstructivepulmonarydiseaseamendelianrandomizationstudy AT jinglin theroleofneutrophilcountsinfectionsandsmokinginmediatingtheeffectofbronchiectasisonchronicobstructivepulmonarydiseaseamendelianrandomizationstudy AT leigu roleofneutrophilcountsinfectionsandsmokinginmediatingtheeffectofbronchiectasisonchronicobstructivepulmonarydiseaseamendelianrandomizationstudy AT weiliu roleofneutrophilcountsinfectionsandsmokinginmediatingtheeffectofbronchiectasisonchronicobstructivepulmonarydiseaseamendelianrandomizationstudy AT jiananhuang roleofneutrophilcountsinfectionsandsmokinginmediatingtheeffectofbronchiectasisonchronicobstructivepulmonarydiseaseamendelianrandomizationstudy AT lujianzhu roleofneutrophilcountsinfectionsandsmokinginmediatingtheeffectofbronchiectasisonchronicobstructivepulmonarydiseaseamendelianrandomizationstudy AT xiaowenhu roleofneutrophilcountsinfectionsandsmokinginmediatingtheeffectofbronchiectasisonchronicobstructivepulmonarydiseaseamendelianrandomizationstudy AT jianyue roleofneutrophilcountsinfectionsandsmokinginmediatingtheeffectofbronchiectasisonchronicobstructivepulmonarydiseaseamendelianrandomizationstudy AT jinglin roleofneutrophilcountsinfectionsandsmokinginmediatingtheeffectofbronchiectasisonchronicobstructivepulmonarydiseaseamendelianrandomizationstudy |