Effect of Air Pollution on the Immune Response to Respiratory Viral Infection in Adults

空气污染对成人呼吸道病毒感染免疫反应的影响

• 批准号: 10312136
• 负责人: Daniel Patrick Croft
• 金额: $ 23.97万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-07 至 2025-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10312136
• 关键词: Acute; Adaptive Immune System; Admission activity; Adult; Air; Air Pollutants; Air Pollution; Area; Asthma; Caliber; Carbon Black; Carbon Monoxide; Cause of Death; Cessation of life; Chronic; Chronic Obstructive Pulmonary Disease; Chronic lung disease; Clinical; Clinical Research; Coughing; Counseling; Crossover Design; Data; Development; Diagnosis; Diagnostic; Doctor of Philosophy; Down-Regulation; Dyspnea; Elderly; Enrollment; Environmental Epidemiology; Epidemiology; Ethnic Origin; Exposure to; Funding; Future; Gene Expression; Gene Expression Profiling; Genes; Genetic Transcription; Hospitalization; Human Metapneumovirus; Immune; Immune Response Genes; Immune response; Immune system; Infection; Influenza; Inhalation; Innate Immune Response; Innate Immune System; Interferons; Lead; Leadership; Learning; Link; Lower Respiratory Tract Infection; Measurement; Mentored Patient-Oriented Research Career Development Award; Mentors; Microbiology; Modeling; Modification; Morbidity - disease rate; NF-kappa B; Natural Immunity; New York; Nitrogen Dioxide; Outcome; Ozone; Particulate; Pathway interactions; Patients; Peripheral; Physicians; Policies; Pollution; Population; Predisposition; Prospective Studies; Pulmonary Heart Disease; RNA; Race; Research; Research Personnel; Resources; Respiratory Signs and Symptoms; Respiratory Tract Infections; Respiratory syncytial virus; Risk; Risk Factors; Site; Source; Structure; Sulfate; Sulfur Dioxide; Testing; Toxin; Universities; Up-Regulation; Viral Respiratory Tract Infection; Vulnerable Populations; Whole Blood; adjudicate; adjudication; air quality regulation; ambient air pollution; base; epidemiology study; fighting; fine particles; gene network; hospitalization rates; improved; innate immune pathways; land use; mortality; novel; particle; patient population; peripheral blood; pollutant; prospective; residence; respiratory health; response; risk minimization; secondary analysis; sex; skills; study population; transcriptome sequencing; transcriptomics; ultrafine particle; virology; wood smoke

This proposed Mentored Patient-Oriented Research Career Development Award will support Dr. Croft's advancement as a physician-researcher studying the effects of air pollution on the immune response to respiratory viral infection (RVI). Specifically, Dr. Croft's proposed study provides an opportunity for mentored development in advanced environmental epidemiology approaches, exposure assessment, immune system transcriptomics, and research team management. RVIs are a serious cause of morbidity and mortality in adults. PM2.5 and combustion related air pollution (black carbon: a marker of traffic pollution) have been linked to an increased rate of hospitalizations for RVI. However, the immune mechanisms by which air pollution may enhance susceptibility to severe RVIs (i.e. requiring hospitalization) in adults remains unclear. Dr. Croft's overarching hypothesis is that short-term exposure to ambient air pollution increases the risk of a severe documented respiratory viral infection in adults, by disrupting key gene pathways (e.g. NF-κB and IFN-γ) within the innate immune response. To test this hypothesis, Dr. Croft will enroll patients hospitalized with rigorously adjudicated, microbiologically proven RVI from an active R01 study on improved diagnostics for respiratory infection. In this population of patients with RVI, he will then lead analyses to explore whether short-term increases in multiple air pollutant and source-specific pollutant concentrations are associated with an increased rate of hospitalization for specific RVIs (e.g. influenza or respiratory syncytial virus). In the same population of patients, he will determine whether these pollutant exposures are associated with activation or suppression of key innate immune pathways. Specifically, using a population of patients with clinically adjudicated diagnoses of RVI, his study will use a case-crossover design to estimate the rate of RVI hospitalizations associated with acute increases in the concentration of particulate and gaseous pollutants in the prior 28 days (Aim 1). Patients with confirmed infection will undergo RNA transcriptional profiling of peripheral blood, allowing Dr. Croft to also examine the association between the same short-term increases in pollutant concentrations and gene expression within the innate immune system (Aim 2). In both aims, we will determine whether this response may be sex-specific, race or ethnicity specific or unique in patients with COPD or asthma. This study may immediately benefit the clinical counseling of patients with exposure to air pollution and may also help guide future air quality policies to minimize the risk to populations vulnerable to RVI. Finally, the study results will provide valuable data upon which to base a future prospective study of the effects of air pollution on respiratory infection and innate immunity. His mentors include experts in environmental epidemiology (David Rich, ScD), virology (Ann Falsey, MD) and transcriptomics (Thomas Mariani, PhD). Dr. Croft's highly productive mentor team, including multiple content specific mentors, will help support his development into an independent investigator pursuing clinical research on the respiratory health effects of inhaled toxins.

这项建议的指导以患者为导向的研究职业发展奖将支持克罗夫特博士的 作为一名研究空气污染对免疫反应影响的医生， 呼吸道病毒感染（RVI）。具体来说，克罗夫特博士提出的研究提供了一个机会， 发展先进的环境流行病学方法、接触评估、免疫系统 转录组学和研究团队管理。RVIs是一个严重的发病率和死亡率的原因， 成年人了PM2.5和燃烧相关的空气污染（黑碳：交通污染的标志）已经联系起来 RVI住院率的增加。然而，空气污染的免疫机制可能 增加成人对严重RVIs（即需要住院治疗）的易感性仍不清楚。克罗夫特医生 总体假设是，短期暴露于环境空气污染会增加严重的 记录的成人呼吸道病毒感染，通过破坏关键基因通路（如NF-κB和IFN-γ）， 先天免疫反应为了验证这一假设，克罗夫特博士将招募住院的患者， 通过一项关于改善呼吸道疾病诊断的R 01研究，裁定并经微生物学证实的RVI 感染在这些RVI患者中，他将进行分析，以探讨是否存在短期的 多种空气污染物和特定污染源浓度的增加与 因特定RVI（如流感或呼吸道合胞病毒）而住院的比率。试者群体的 患者，他将确定这些污染物暴露是否与激活或抑制相关， 关键的先天免疫途径。具体而言，使用具有临床裁定诊断的患者人群 他的研究将使用病例交叉设计来估计与RVI相关的RVI住院率。 在过去28天内，颗粒物和气体污染物的浓度急剧增加（目标1）。患者 确认感染的患者将接受外周血RNA转录谱分析，这使得克罗夫特博士也可以 研究污染物浓度的短期增加与基因之间的关系， 在先天免疫系统内的表达（Aim 2）。在这两个目标中，我们将确定这种反应是否 在COPD或哮喘患者中可能具有性别特异性、人种或种族特异性或独特性。这项研究可能 立即有益于暴露于空气污染的患者的临床咨询，也可能有助于指导 未来的空气质量政策，以尽量减少对易受RVI影响的人群的风险。最后，研究结果将 提供有价值的数据，作为未来空气污染对呼吸系统影响的前瞻性研究的基础。 感染和先天免疫。他的导师包括环境流行病学专家（大卫里奇，ScD）， 病毒学（Ann Falsey，MD）和转录组学（托马斯马里亚尼，PhD）。克罗夫特博士的高产导师 团队，包括多个具体内容的导师，将帮助支持他的发展成为一个独立的 从事吸入毒素对呼吸系统健康影响的临床研究的调查员。