Lung function and systemic inflammation associated with short-term air pollution exposure in chronic obstructive pulmonary disease patients in Beijing, China
- 作者列表："Nannan Gao","Wenshuai Xu","Jiadong Ji","Yanli Yang","Shao-Ting Wang","Jun Wang","Xiang Chen","Shuzhen Meng","Xinlun Tian","Kai-Feng Xu
Abstract Background Exposure to air pollution is associated with chronic obstructive pulmonary disease (COPD). However, findings on the effects of air pollution on lung function and systemic inflammation in Chinese COPD patients are inconsistent and scarce. This study aims to evaluate the effects of ambient air pollution on lung function parameters and serum cytokine levels in a COPD cohort in Beijing, China. Methods We enrolled COPD participants on a rolling basis from December 2015 to September 2017 in Beijing, China. Follow-ups were performed every 3 months for each participant. Serum levels of 20 cytokines were detected every 6 months. Hourly ambient pollutant levels over the same periods were obtained from 35 monitoring stations across Beijing. Geocoded residential addresses of the participants were used to estimate daily mean pollution exposures. A linear mixed-effect model was applied to explore the effects of air pollutants on health in the first-year of follow-up. Results A total of 84 COPD patients were enrolled at baseline. Of those, 75 COPD patients completed the first-year of follow-up. We found adverse cumulative effects of particulate matter less than 2.5 μm in aerodynamic diameter (PM2.5), nitrogen dioxide (NO2), sulfur dioxide (SO2) and carbon monoxide (CO) on the forced vital capacity % predicted (FVC % pred) in patients with COPD. Further analyses illustrated that among COPD patients, air pollution exposure was associated with reduced levels of serum eotaxin, interleukin 4 (IL-4) and IL-13 and was correlated with increased serum IL-2, IL-12, IL-17A, interferon γ (IFNγ), monocyte displacing protein 1 (MCP-1) and soluble CD40 ligand (sCD40L). Conclusion Acute exposures to PM2.5, NO2, SO2 and CO were associated with a reduction in FVC % pred in COPD patients. Furthermore, short-term exposure to air pollutants increased systemic inflammation in COPD patients; this may be attributed to increased Th1 and Th17 cytokines and decreased Th2 cytokines.
文摘背景暴露于空气污染与慢性阻塞性肺疾病 (COPD) 相关。然而，中国 COPD 患者中空气污染对肺功能和全身炎症影响的研究结果不一致，也很少。本研究旨在评估中国北京 COPD 队列中环境空气污染对肺功能参数和血清细胞因子水平的影响。方法我们在 2015年12月至 2017年9月在中国北京滚动招募了 COPD 参与者。对每位参与者每 3 个月进行一次随访。每 6 个月检测 20 种细胞因子的血清水平。从北京各地的 35 个监测站获得了同一时期每小时的环境污染物水平。使用参与者的地理编码住宅地址估计每日平均污染暴露。应用线性混合效应模型探讨了随访第一年空气污染物对健康的影响。结果基线时共入组 84 例 COPD 患者。其中，75 例 COPD 患者完成了第一年的随访。我们发现空气动力学直径 (PM2.5) 、二氧化氮 (NO2) 、二氧化硫 (SO2) 和一氧化碳 (CO) 中小于 2.5 μ m 的颗粒物的不利累积效应对 COPD 患者用力肺活量 % 预测 (FVC % pred)。进一步分析表明，在 COPD 患者中，空气污染暴露与血清 eotaxin 、白细胞介素 4 (IL-4) 和 IL-13 水平降低相关，与血清 IL-2 、 IL-12 、 IL-17A 、干扰素 γ (ifn γ) 、单核细胞置换蛋白 1 (MCP-1) 和可溶性 CD40 配体 (sCD40L)。结论 COPD 患者急性 PM2.5 、 NO2 、 SO2 和 CO 暴露与 FVC % pred 降低有关。此外，短期暴露于空气污染物会增加 COPD 患者的全身炎症; 这可能归因于 Th1 和 Th17 细胞因子增加和 Th2 细胞因子降低。
METHODS::Translation of genomic alterations to protein changes in chronic obstructive pulmonary disease (COPD) is largely unexplored. Using integrated proteomic and RNA sequencing analysis of COPD and control lung tissues, we identified a protein signature in COPD characterised by extracellular matrix changes and a potential regulatory role for SUMO2. Furthermore, we identified 61 differentially expressed novel, non-reference, peptides in COPD compared with control lungs. This included two peptides encoding for a new splice variant of SORBS1, of which the transcript usage was higher in COPD compared with control lungs. These explorative findings and integrative proteogenomic approach open new avenues to further unravel the pathology of COPD.