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暴露于环境空气污染物作为原发性干燥综合征的一个风险因素。

Exposure to environmental air pollutants as a risk factor for primary Sjögren's syndrome.

机构信息

Department of Pediatrics, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States.

出版信息

Front Immunol. 2023 Feb 14;13:1044462. doi: 10.3389/fimmu.2022.1044462. eCollection 2022.

Abstract

BACKGROUND

Environmental etiology of primary Sjögren's syndrome (pSS), an autoimmune disease, has been proposed. This study determined whether the exposure to air pollutants was an independent risk factor for pSS.

METHODS

Participants were enrolled from a population-based cohort registry. Daily average concentrations of air pollutants from 2000 to 2011 were divided into 4 quartiles. Adjusted hazard ratios (aHRs) of pSS for exposure to air pollutants were estimated in a Cox proportional regression model adjusting for age, sex, socioeconomic status, and residential areas. A subgroup analysis stratified by sex was conducted to validate the findings. Windows of susceptibility indicated years of exposure which contributed the most to the observed association. Ingenuity Pathway Analysis was used to identify underlying pathways of air pollutant-associated pSS pathogenesis, using Z-score visualization.

RESULTS

Two hundred patients among 177,307 participants developed pSS, with a mean age of 53.1 years at acumulative incidence of 0.11% from 2000 to 2011. Exposure to carbon monoxide (CO), nitric oxide (NO), and methane (CH4) was associated with a higher risk of pSS. Compared to those exposed to the lowest concentration level, the aHRs for pSS were 2.04 (95%CI=1.29-3.25), 1.86 (95%CI=1.22-2.85), and 2.21 (95%CI=1.47-3.31) for those exposed to high levels of CO, NO, and CH4, respectively. The findings persisted in the subgroup analysis, in which females exposed to high levels of CO, NO, and CH4 and males exposed to high levels of CO were associated with significantly great risk of pSS. The cumulative effect of air pollution on pSS was time-dependent. The underlying cellular mechanisms involved chronic inflammatory pathways including the interleukin-6 signaling pathway.

CONCLUSION

Exposure to CO, NO, and CH4 was associated with a high risk of pSS, which was biologically plausible.

摘要

背景

原发性干燥综合征(pSS)是一种自身免疫性疾病,其发病的环境病因学已被提出。本研究旨在确定空气污染物暴露是否是 pSS 的独立危险因素。

方法

参与者从基于人群的队列登记处招募。2000 年至 2011 年期间,将空气污染物的日平均浓度分为四组。在 Cox 比例风险回归模型中,调整年龄、性别、社会经济地位和居住区域后,估计 pSS 暴露于空气污染物的调整后风险比(aHR)。进行了按性别分层的亚组分析以验证研究结果。敏感性窗口表明,暴露于空气污染物的年份对观察到的关联贡献最大。采用 Z 分数可视化的方法,使用通路分析工具(Ingenuity Pathway Analysis,IPA)来确定与空气污染物相关的 pSS 发病机制的潜在途径。

结果

在 177307 名参与者中,有 200 名患者发展为 pSS,累积发病率为 0.11%,从 2000 年至 2011 年平均年龄为 53.1 岁。接触一氧化碳(CO)、一氧化氮(NO)和甲烷(CH4)与 pSS 的风险增加相关。与暴露于最低浓度水平的人相比,暴露于高水平 CO、NO 和 CH4 的 pSS 的 aHR 分别为 2.04(95%CI=1.29-3.25)、1.86(95%CI=1.22-2.85)和 2.21(95%CI=1.47-3.31)。在按性别分层的亚组分析中,女性暴露于高水平 CO、NO 和 CH4以及男性暴露于高水平 CO 与 pSS 的风险显著增加相关。空气污染对 pSS 的累积效应具有时间依赖性。涉及慢性炎症途径的潜在细胞机制包括白细胞介素 6 信号通路。

结论

接触 CO、NO 和 CH4 与 pSS 的高风险相关,这在生物学上是合理的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a79b/9972220/0ff31930ba45/fimmu-13-1044462-g001.jpg

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