慢性阻塞性肺病、支气管扩张和中性粒细胞炎症:考虑气道炎症、感染和吸烟的影响

A. Gülsen
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摘要

背景:支气管扩张与慢性阻塞性肺疾病(COPD)之间的因果关系仍不清楚。本研究旨在探讨二者之间的潜在因果关系,特别关注气道炎症、感染和吸烟在慢性阻塞性肺病发病中的媒介作用。研究方法我们进行了双样本孟德尔随机化(MR)分析,以评估(1)支气管扩张对慢性阻塞性肺病、性别、吸烟状况、感染、嗜酸性粒细胞和中性粒细胞计数的因果影响,以及慢性阻塞性肺病对支气管扩张的因果影响;(2)吸烟状况、感染和中性粒细胞计数对慢性阻塞性肺病的因果效应;以及(3)吸烟状况、感染和中性粒细胞计数可能在多大程度上介导支气管扩张对慢性阻塞性肺病发展的影响。研究结果慢性阻塞性肺病与较高的支气管扩张风险相关(OR 1.28 [95% CI 1.05, 1.56])。支气管扩张与较高的慢性阻塞性肺病风险(OR 1.08 [95% CI 1.04, 1.13])、较高的中性粒细胞水平(OR 1.01 [95% CI 1.00, 1.01])、较高的呼吸道感染风险(OR 1.04 [95% CI 1.02, 1.06])和较低的吸烟风险相关。在进行敏感性分析并考虑不同的水平褶积模型后,中性粒细胞增多、呼吸道感染和吸烟与慢性阻塞性肺病风险升高之间的因果关系依然存在,OR 值分别为 1.17、1.69 和 95.13。对中性粒细胞、呼吸道感染和吸烟进行遗传调整后,支气管扩张与慢性阻塞性肺病的效应分别为 0.99、0.85 和 122.79。结论慢性阻塞性肺病和支气管扩张互为因果。中性粒细胞计数和呼吸道感染的增加似乎在很大程度上介导了支气管扩张对慢性阻塞性肺病的影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
COPD, Bronchiektasen und neutrophile Inflammation: Den Einfluss von Atemwegsentzündungen, Infektionen und Rauchen bedenken
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.
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