2/1 - Mongolian Center for Environmental & Occupational Health - Mongolia

摘要 近几十年来，蒙古经历了重大的经济和环境变化，并遭受了 来自严重的空气污染。乌兰巴托(UB)和达克汗市(DC)的环境颗粒物含量最高 世界上最大的颗粒物(PM)浓度，经常出现病毒性呼吸道疾病的流行。这个 PM暴露与心肺疾病死亡率和发病率之间的关系已经有了很好的记录， 2019年，全球已有667万人因空气污染而过早死亡。最近，关注 关于PM污染和呼吸道病毒感染之间的关联的研究有所增加。因此，这个<English>U01</English>提案， 作为蒙古国地质健康中心项目的一部分，重点研究 PM暴露和呼吸道病毒感染之间的关系。U01项目包括一项主要研究和两项试验 开始中心活动的研究。主要项目旨在测试PM暴露会削弱这一假设 对呼吸道病毒感染的免疫防御。它有三个相互关联的具体目标。目标1是 用时间序列分析描述PM暴露与呼吸道病毒感染的关系 每周流感样疾病(ILI)发生率与UB和DC内和跨DC的PM水平相关，调整 潜在的混杂因素和共同污染物。作为一项空气污染控制措施，UB开始实施 2019年5月，加工煤使用量下降，而DC继续使用原煤。将这一政策干预嵌套到 时间序列分析加强了PM-ILI关联的因果推断 随着时间的推移而变化。目标2是检查个人PM暴露的免疫学和病毒反应 分别在UB和DC的居民中进行的两项平行小组研究。每个小组由100-120名无烟者组成 在3年的随访期内每半年进行一次测量的成年人。ILI计数与免疫学 生物标志物将与个人PM暴露相关。目标3是定义PM暴露的直接影响 对上皮完整性和免疫信号以及随后对抗病毒反应的影响。这将是 通过与目标2直接相关的细胞培养研究(作为细胞捐赠者)实现。两名飞行员 这些研究建立在目标2主要研究的基础上，旨在探索PM对肺结核和骨骼的影响 分别是矿物质流失。这些研究的动机是结核病和骨质疏松症的高患病率。 在蒙古，越来越多的证据表明PM或PM中的重金属是危险因素。这份U01提案 是一个跨学科的研究项目，涉及流行病学、毒理学、环境学和 职业健康、接触科学、生物统计学、病毒学、免疫学、环境工程、 呼吸医学和传染病，来自蒙古、杜克大学和杜克大学的多个机构 昆山大学。U01研究旨在成为吸引U2R研究员的初始主要平台 (受训者)和学院(导师)的研究和培训。 1

ABSTRACT In recent decades, Mongolia has experienced major economic and environmental changes, and suffered from severe air pollution. Ulaanbaatar (UB) and Darkhan City (DC) have some of the highest ambient particulate matter (PM) concentrations in the world and frequently suffer epidemics of viral respiratory diseases. The associations between PM exposure and cardiorespiratory mortality and morbidity have been well documented, with an established 6.67 million premature deaths globally attributed to air pollution in 2019. Recently, attention has increased regarding the association of PM pollution and respiratory viral infection. Hence, this U01 proposal, as part of the Mongolian GEOHealth Hub program, focuses on studying the relationships and interactions between PM exposure and respiratory viral infections. The U01 project consists of a main study and two pilot studies to begin Center activities. The main project is designed to test the hypothesis that PM exposure weakens the immune defense against respiratory viral infection. It has three interconnected specific aims. Aim 1 is to characterize the relationship between PM exposure and respiratory viral infection through a time-series analysis of weekly influenza-like illness (ILI) rates in association with PM levels within and across UB and DC, adjusting for potential confounders and co-pollutants. As an air pollution control measure, UB started the implementation of processed coal use in May, 2019, whereas DC continues to use raw coal. Nesting this policy intervention into the time-series analysis strengthens the causal inference of the PM-ILI association derived from natural variabilities over time. Aim 2 is to examine immunologic and viral responses to personal PM exposure through two parallel panel studies in residents of UB and DC, respectively. Each panel consists of 100-120 nonsmoking adults who will be measured semiannually during a 3-year follow-up period. ILI counts and immunologic biomarkers will be associated with personal PM exposures. Aim 3 is to define the direct effects of PM exposure on epithelial integrity and immune signaling and the subsequent impact on anti-viral responses. This will be achieved through cell culture studies that are directly linked to Aim 2 subjects (as cell donors). The two pilot studies, built upon the Aim 2 main study, aim to explore the effects of PM on pulmonary tuberculosis and bone mineral loss, respectively. These studies are motivated by high prevalence of both tuberculosis and osteoporosis in Mongolia and by emerging evidence suggesting PM or heavy metals in PM as risk factors. This U01 proposal is an interdisciplinary research project involving researchers in epidemiology, toxicology, environmental and occupational health, exposure science, biostatistics, virology, immunology, environmental engineering, respiratory medicine, and infectious disease from multiple institutions in Mongolia, Duke University, and Duke Kunshan University. The U01 research is designed to be the initial main platform for engaging U2R Fellows (trainees) and Faculty (mentors) in research and training. 1