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

2/1 - 蒙古环境中心

• 批准号: 10448171
• 负责人: Davaalkham - Dambadarjaa
• 金额: $ 28.91万
• 依托单位: MONGOLIAN NATIONAL UNIV/MEDICAL SCIENCES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-13 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10448171
• 关键词: Address; Adult; Affect; Air; Air Pollution; Anti-Inflammatory Agents; Antiviral Response; Attention; Back; Bacterial Infections; Biological Markers; Biometry; COVID-19 impact; COVID-19 pandemic; Caliber; Cell Culture Techniques; Cell model; Cells; Cessation of life; Cities; Coal; Communicable Diseases; Data; Disease; Economics; Environmental Engineering technology; Environmental Health; Epidemic; Epidemiology; Epithelial; Exposure to; Government; Heating; Heavy Metals; High Prevalence; Human; Immune; Immune response; Immune signaling; Immunologic Markers; Immunologics; Immunology; Impairment; Incidence; Infection; Inflammatory; Inflammatory Response; Influenza; Institution; Interdisciplinary Study; Interferon Type I; Intervention; Laboratories; Length; Ligands; Link; Liquid substance; Literature; Longitudinal trends; Measures; Medical; Medicine; Minerals; Mongolia; Morbidity - disease rate; Nose; Observational Study; Occupational Health; Osteoporosis; Oxidative Stress; Ozone; Participant; Particulate; Particulate Matter; Pilot Projects; Policies; Pollution; Population; Predisposition; Process; Protocols documentation; Public Health; Publishing; Pulmonary Inflammation; Pulmonary Tuberculosis; Research; Research Design; Research Personnel; Research Project Grants; Research Training; Respiratory Disease; Risk; Risk Factors; Role; Science; Severities; Source; Statistical Models; Study Subject; Study models; TLR3 gene; TLR7 gene; Temperature; Testing; Time; Time Series Analysis; Toxicology; Traction; Tuberculosis; Universities; Variant; Viral; Viral Respiratory Tract Infection; Virus; Virus Diseases; Visit; Work; air pollution control; airway epithelium; bone; coarse particles; cytokine; design; environmental change; epidemiology study; experience; experimental study; faculty mentor; fine particles; flu; follow-up; improved; insight; interdisciplinary approach; member; mortality; non-smoking; pollutant; premature; programs; respiratory; response; systemic inflammatory response; virology

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

抽象的 近几十年来，蒙古国经历了重大的经济和环境变化，遭受了巨大的损失。 来自严重的空气污染。乌兰巴托 (UB) 和达尔汗市 (DC) 的环境颗粒物含量最高 世界范围内PM2.5浓度最高，经常遭受病毒性呼吸道疾病的流行。这 PM 暴露与心肺死亡率和发病率之间的关联已得到充分记录， 2019 年，全球因空气污染导致 667 万人过早死亡。近期，关注 PM 污染与呼吸道病毒感染之间的关联性有所增加。因此，这个U01提案， 作为蒙古 GEOHealth 中心计划的一部分，重点研究关系和相互作用 PM 暴露与呼吸道病毒感染之间的关系。 U01项目由一项主要研究和两项试点组成 研究开始中心活动。主要项目旨在检验 PM 暴露减弱的假设 针对呼吸道病毒感染的免疫防御。它具有三个相互关联的具体目标。目标 1 是 通过时间序列分析描述 PM 暴露与呼吸道病毒感染之间的关系 每周流感样疾病 (ILI) 率与 UB 和 DC 内部及之间的 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 月加工煤的使用量减少，而 DC 继续使用原煤。将这一政策干预嵌套到 时间序列分析强化了源自自然的 PM-ILI 关联的因果推断 随时间的变化。目标 2 是通过以下方式检查对个人 PM 暴露的免疫和病毒反应 分别针对 UB 和 DC 居民进行的两项平行小组研究。每个小组由 100-120 个禁止吸烟的人组成 在 3 年随访期间每半年进行一次测量的成年人。 ILI 计数和免疫学 生物标志物将与个人PM暴露相关。目标 3 是确定 PM 暴露的直接影响 对上皮完整性和免疫信号传导以及随后对抗病毒反应的影响。这将是 通过与目标 2 受试者（作为细胞供体）直接相关的细胞培养研究来实现。两名飞行员 研究以 Aim 2 主要研究为基础，旨在探讨 PM 对肺结核和骨骼的影响 分别是矿物质损失。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，新出现的证据表明 PM 或 PM 中的重金属是风险因素。这个U01提案 是一个跨学科研究项目，涉及流行病学、毒理学、环境学和环境学等领域的研究人员 职业健康、暴露科学、生物统计学、病毒学、免疫学、环境工程、 蒙古、杜克大学、杜克大学多个机构的呼吸内科、传染病科 昆山大学. U01 研究旨在成为吸引 U2R 研究员的最初主要平台 （学员）和教师（导师）进行研究和培训。 1