Microbial Dysbiosis Among Veterans Following Deployment-Related Airborne Exposures

退伍军人在与部署相关的空气暴露后出现微生物失调

• 批准号: 10426050
• 负责人: ALEXA A PRAGMAN
• 金额: --
• 依托单位: MINNEAPOLIS VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-10-01 至 2025-09-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10426050
• 关键词: Acute; Affect; Afghanistan; Airborne Particulate Matter; Ancillary Study; Area; Asthma; Autoimmunity; Award; Biological Models; Boston; Case/Control Studies; Chronic; Chronic Disease; Chronic Obstructive Pulmonary Disease; Classification; Cohort Studies; Collaborations; Communicable Diseases; Communities; Coughing; Country; Data; Disease; Doctor of Medicine; Doctor of Philosophy; Epithelium; Exposure to; Feces; Funding; Guidelines; Health; Immune Tolerance; Immune response; Immunity; Industrialization; Inflammation; Inflammation Mediators; Inflammatory; Iraq; K-Series Research Career Programs; Link; Literature; Lung; Lung diseases; Measures; Mediating; Mediator; Medical History; Military Personnel; Minnesota; Oral; Organ; Participant; Particulate Matter; Pathway interactions; Persons; Phenotype; Physicians; Pollution; Population; Prevention; Primary Prevention; Publications; Publishing; Pulmonary Inflammation; Reporting; Research; Resources; Respiratory Disease; Respiratory Signs and Symptoms; Risk; Risk Factors; Rodent Model; Sampling; Schedule; Seasons; Secondary Prevention; Services; Shortness of Breath; Site; Smoke; Sputum; Structure of parenchyma of lung; Symptoms; Tissues; United States Environmental Protection Agency; Universities; Veterans; Wheezing; Work; airway inflammation; beta diversity; burn pit; cooperative study; dust storms; dysbiosis; fine particles; gut microbiota; high risk; high risk population; human microbiota; human model; immune activation; inflammatory marker; lung health; lung microbiota; microbial; microbiota; microorganism; military veteran; patient oriented; pollutant; professor; prospective; pulmonary function; pulmonary symptom; recruit; research and development; respiratory; respiratory microbiota; saliva sample; stool sample; systemic inflammatory response

This is an application for a Merit Award to Dr. Alexa A. Pragman, M.D., Ph.D., a Staff Physician in Infectious Disease at the Minneapolis VA and an Assistant Professor at the University of Minnesota. Dr. Pragman’s current work on the chronic obstructive pulmonary disease lung microbiota is funded by a 5-year Career Development Award-2 from the VA Office of Research and Development. Dr. Pragman has established a record of accomplishments and publications related to her patient-oriented work on the lung microbiota in chronic inflammatory pulmonary diseases. This Merit Award will provide the resources necessary to study the effects of fine particle airborne pollution on the lung microbiota of veterans following deployment to southwest Asia (Iraq, Afghanistan, or neighboring countries). Following deployment to southwest Asia, veterans are disproportionately affected by chronic lung problems including coughing, wheezing, and shortness of breath. While deployed, these veterans were exposed to excessive concentrations of airborne particulate matter of ≤2.5 μm in size (PM2.5) as a result of seasonal dust storms, burn pit smoke, and industrial pollution. PM2.5 exposure causes acute and chronic respiratory problems, and may lead to diseases such as asthma and chronic obstructive pulmonary disease. PM2.5 exposure has been linked to airway and gut microbiota dysbiosis in humans and rodent models, suggesting that dysbiosis is a potential mediator for the inflammation, symptoms, and lung tissue destruction that continue long after excessive PM2.5 exposure has stopped. Dysbiosis is defined as an imbalance or maladaptation in the community of micro-organisms inhabiting a particular site. In this Merit Award application, Dr. Pragman proposes a prospective case-control study to assess the relationships between PM2.5 exposure, microbiota dysbiosis, and inflammation. This will be accomplished in collaboration with VA Cooperative Study #595, Service and Health Among Deployed Veterans (SHADE), which aims to understand the association between PM2.5 exposures during deployment and subsequent respiratory symptoms. Dr. Pragman’s study will recruit 140 SHADE participants with chronic lung symptoms (coughing, shortness of breath, or wheezing) and 140 SHADE participants without chronic lung symptoms. All subjects will provide saliva and stool samples for microbiota analyses on an annual basis for 3 years. Sputum samples for microbiota analysis will also be obtained from a subset of subjects on the same schedule. We will assess microbiota dysbiosis and tissue-specific and systemic markers of inflammation. Our analysis will take into account PM2.5 exposure levels (obtained from the SHADE study), tissue or site-specific effects, and incorporate other risk factors for microbial dysbiosis. In Aim 1, Dr. Pragman will determine associations between deployment-related PM2.5 exposure and site-specific dysbiosis. In Aim 2, Dr. Pragman will determine associations between site-specific dysbiosis and respiratory symptoms. In Aim 3, Dr. Pragman will determine site-specific associations between dysbiosis and inflammation. Our overall objective is to establish microbial dysbiosis as a mediator between PM2.5 exposure and respiratory symptoms. Our central hypothesis is that deployed veterans’ PM2.5 exposures place them at increased risk for dysbiosis, which in turn increases risk of developing chronic respiratory symptoms and disease. These findings may identify veterans at high risk for developing lung disease, and may identify a new treatment target—the microbiota—for primary and secondary prevention of lung disease in this high-risk veteran population.

这是一份向传染病科主治医师 Alexa A. Pragman 博士申请优异奖的申请 明尼阿波利斯退伍军人管理局的疾病和明尼苏达大学的助理教授。普拉格曼博士的 当前关于慢性阻塞性肺疾病肺微生物群的工作由 5 年职业资助 VA 研究与开发办公室颁发的 2 号开发奖。普拉格曼博士建立了 与她以患者为中心的肺部微生物群工作相关的成就和出版物的记录 慢性炎症性肺部疾病。该优异奖将提供研究所需的资源 细颗粒空气污染对部署到西南地区的退伍军人肺部微生物群的影响 亚洲（伊拉克、阿富汗或邻国）。 部署到西南亚后，退伍军人不成比例地受到慢性肺部疾病的影响 包括咳嗽、喘息和呼吸短促。这些退伍军人在部署期间暴露在 由于季节性灰尘导致空气中 ≤2.5 μm 的颗粒物 (PM2.5) 浓度过高 风暴、燃烧坑烟雾和工业污染。 PM2.5暴露导致急性和慢性呼吸道疾病 问题，并可能导致哮喘和慢性阻塞性肺病等疾病。 PM2.5 在人类和啮齿动物模型中，暴露与气道和肠道微生物群失调有关，这表明 生态失调是持续存在的炎症、症状和肺组织破坏的潜在介质 在过度的 PM2.5 暴露停止很久之后。生态失调被定义为生态系统的不平衡或适应不良。 居住在特定地点的微生物群落。 在这份优异奖申请中，普拉格曼博士提出了一项前瞻性病例对照研究来评估 PM2.5 暴露、微生物群失调和炎症之间的关系。这将在 与退伍军人管理局合作研究#595，部署退伍军人的服务和健康 (SHADE) 合作，该研究 旨在了解部署期间 PM2.5 暴露与随后的呼吸系统之间的关联 症状。 Pragman 博士的研究将招募 140 名患有慢性肺部症状（咳嗽、 呼吸急促或喘息）和 140 名 SHADE 参与者没有慢性肺部症状。所有科目都会 三年内每年提供唾液和粪便样本用于微生物群分析。痰样本 微生物群分析也将从同一时间表的一部分受试者中获得。我们将评估 微生物群失调以及炎症的组织特异性和系统性标志物。我们的分析将考虑 考虑 PM2.5 暴露水平（从 SHADE 研究中获得）、组织或特定部位的影响，并纳入 微生物失调的其他危险因素。在目标 1 中，Pragman 博士将确定之间的关联 部署相关的 PM2.5 暴露和特定地点的生态失调。在目标 2 中，Pragman 博士将确定 特定部位生态失调与呼吸道症状之间的关联。在目标 3 中，Pragman 博士将确定 生态失调和炎症之间的位点特异性关联。我们的总体目标是建立微生物 生态失调作为 PM2.5 暴露与呼吸道症状之间的中介。我们的中心假设是 部署的退伍军人暴露于 PM2.5 使他们面临更高的生态失调风险，进而增加了 出现慢性呼吸道症状和疾病。这些发现可能会确定退伍军人面临高风险 发展肺部疾病，并可能为原发性和继发性肺部疾病确定新的治疗目标——微生物群 预防这一高危退伍军人群体的肺部疾病。