Effects of Air Pollution on Childhood Tuberculosis in Viet Nam

 描述（由申请人提供） 空气污染和结核病（TB）是全球范围内的公共卫生威胁，全球三分之一的人感染了结核病，近90%的全球人口生活在污染超过世界卫生组织规定的安全标准的地区。越南儿童暴露于二手烟、烹饪烟雾和交通排放物的水平令人担忧，但人们对这些污染物对儿童结核病的影响知之甚少。因此，我们建议研究空气污染物对越南儿童结核病的临床和免疫影响。我们的总体假设是，空气污染暴露将与结核病感染的风险增加和对结核分枝杆菌（Mtb）的免疫反应改变有关。为了验证这一假设，我们将首先开发和验证一份问卷和空气污染模型，以准确预测越南有结核病风险的儿童的空气污染暴露（目标1）。I目标2，为了评估空气污染暴露作为结核病感染的风险因素，我们将首先招募90名家庭接触者（最近接触过涂阳结核病家庭成员的儿童）参加一项横断面研究，测量连续个人PM2.5暴露和尿液可替宁水平作为预测因素，并检测结核病感染（结核菌素皮肤试验）作为我们的主要指标。 结果。然后，我们将在前瞻性队列研究中随访基线时无结核感染的患者，使用考克斯回归分析中的结核感染时间作为我们的纵向结局。在目标3中，目标2中确定的结核感染儿童将入组额外的交叉研究 通过流式细胞术评估PM2.5和尿可替宁对产生IFN-γ的Mtb特异性CD 4+和CD 8+细胞频率的影响。我已经组建了一个由国际知名科学家组成的导师和科学顾问团队来解决这一至关重要的假设，并将利用Nahid博士和Nhung博士（导师）广泛的CDC和NIH资助的研究基础设施，并在2019年之前提供资金来开展这项研究。我还制定了一个全面的培训计划，通过该计划，我将在三个领域完善我的专业知识：空气污染测量和分析;免疫学理论和实验室经验;先进的研究设计，生物统计学和结核病研究方法。我们设计了一种研究策略，通过该策略，我们可以通过3个不同但相关的目标中的生物学相关免疫机制来证实观察结果。我们的预期发现将通过激励这一领域的进一步研究和指导公共卫生政策来影响公共卫生，以最好地保护我们的儿童免受空气中毒素的有害影响。重要的是，K23的研究和培训将为我提供成功应用R 01的必要工具，并推动我在空气污染健康影响研究方面的职业生涯。

 DESCRIPTION (provided by applicant) Air pollution and tuberculosis (TB) are public health threats of global proportion, with one-third f people worldwide infected with TB and nearly 90% of the global population living in areas where pollution exceeds safe standards set by the World Health Organization. Children in Viet Nam are exposed to concerning levels of secondhand smoke, cooking smoke, and traffic emissions, yet little is known about the effects of these pollutants on childhood TB. We therefore propose to study the clinical and immunologic effects of air pollutants on childhood TB in Viet Nam. Our overall hypothesis is that air pollution exposures will be associated with increased risk for TB infection and altered immunologic responses to Mycobacterium tuberculosis (Mtb). To test this hypothesis, we will first develop and validate a questionnaire and air pollution models that accurately predict air pollution exposures in children at risk for TB living in Viet Nam (Aim 1). I Aim 2, to evaluate air pollution exposures as risk factors for TB infection, we will first enroll 90 household contacts (children recently exposed to a household member with smear positive TB) into a cross-sectional study, measuring continuous personal PM2.5 exposures and urine cotinine levels as predictors and testing for TB infection (tuberculin skin testing) as our primary outcome. We will then follow those without TB infection at baseline in a prospective cohort study, using time to TB infection in Cox regression analysis as our longitudinal outcome. In Aim 3, those children with TB infection identified from Aim 2 will be enrolled into an additional cross sectional study to evaluate the effects of PM2.5 and urine cotinine on frequencies of IFN-¿ producing Mtb-specific CD4+ and CD8+ cells by flow cytometry. I have assembled a Mentor and Scientific Advisory Team of internationally acclaimed scientists to address this critically important hypothesis, and will leverage Drs. Nahid and Nhung's (Mentors) extensive CDC- and NIH-funded research infrastructure with funding through 2019 to carry out this research. I have also developed a comprehensive training plan through which I will refine my expertise in three areas: air pollution measurement and analysis; immunology theory and lab experience; and advanced study design, biostatistics, and TB research methodology. We have designed a research strategy by which we can substantiate observational findings through biologically relevant immunologic mechanisms in 3 distinct but related Aims. Our expected findings will impact public health through motivating further research in this area and guiding public health policy to best protect our children from the harmful effects of airborne toxins. Importantly, this K23 research and training will provide me with essential tools for a successful R01 application and to advance my career in air pollution health effects research.