CMA:Pulmonary and Systemic Effects of Deployment Related Particulate Matter Exposures

CMA：与部署相关的颗粒物暴露对肺部和全身的影响

• 批准号: 10383650
• 负责人: Farrah Kheradmand
• 金额: --
• 依托单位: MINNEAPOLIS VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10383650
• 关键词: Adaptive Immune System; Airborne Particulate Matter; Asia; Asthma; Autoantigens; Biochemical; Bioinformatics; Biological Markers; Biometry; Biophysics; Boston; Caliber; Cells; Chronic; Clinical; Cluster Analysis; Complement; Coughing; Data; Desmosine; Development; Diffusion; Disease; Dyspnea; Eosinophilia; Exhalation; Exposure to; Fibrinogen; Funding; Future; Gases; Goals; Health; Hypersensitivity; IgE; Immune; Immune response; Immunity; Immunologic Markers; Immunology; Industrialization; Inflammasome; Inflammatory; Lung; Lung diseases; Measurement; Measures; Military Personnel; Nitric Oxide; Participant; Particulate Matter; Patients; Phenotype; Physiological; Pulmonary Function Test/Forced Expiratory Volume 1; Pulmonary Inflammation; Pulmonary function tests; Quantitative Evaluations; Recording of previous events; Reporting; Respiratory Signs and Symptoms; Risk; Secretory Cell; Services; Site; Smoke; Smoking History; Southeastern Asia; Sphingolipids; Spirometry; Structure; Structure of parenchyma of lung; Symptoms; Technology; Testing; Veterans; Wheezing; X-Ray Computed Tomography; airway inflammation; airway obstruction; base; biomarker discovery; burn pit; clinical application; cohort; cooperative study; cytokine; design; disorder subtype; dust storms; eosinophilic inflammation; fine particles; former smoker; imaging biomarker; immune activation; injured airway; lung injury; metabolomics; monocyte; multiple omics; non-smoker; parent project; pollutant; pulmonary function; recruit; respiratory; response; secretory protein; soluble RAGE; sound; systemic inflammatory response; treatment strategy

Military personnel deployed to Southeast Asia (SA) report increased respiratory symptoms. Unique to SA deployment is a history of exposure to high levels of airborne particulate matter ≤ 2.5 µm in diameter (PM2.5) consisting of seasonal dust storms, burn-pit smoke, and unregulated industrial and vehicular pollutants. Objective findings among returning Veterans are limited, therefore, the VA Cooperative Study #595 Service and Health Among Deployed Veterans (SHADE) was funded to assess satellite confirmed exposure history during land-based deployments to SA, in nearly 5000 at risk Veterans in six centers. The overall aim of SHADE (Parent Project) is to associate PM2.5 exposure with spirometrically assessed pulmonary function, and asthma history. Because SHADE offers a unique opportunity to identify early deployment-related lung findings related to PM exposure, we propose to use this cohort to identify biophysical and clinical impact of PM exposure through three inter-related Aims. To accomplish our goals we will recruit 280 SHADE participants with (50%) and without (50%) respiratory symptoms (chronic cough, wheeze, or dyspnea) who are non- or former-smokers with <10 pack year history of smoking from four participating SHADE sites (Minneapolis, Houston, Boston and Seattle). This study will provide evidence for the systemic effects of exposure with linkage to respiratory symptoms and reduced pulmonary function. This proposal is one of three coordinated projects to systematically examine pulmonary and systemic effects of exposure during deployment. Specifically, this project will use state-of-the-art technology and expertise (biomarker discovery, multi-omic analysis, immunology and bioinformatics) to provide a comprehensive assessment of systemic inflammatory and airway related biomarkers in deployment-related PM2.5 exposure. Further, our proposed approach using systemic and immune based biomarkers contributes to the overall rationale for our Collaborative Merit Applications. We will test the hypothesis that increased systemic biomarkers of airway and pulmonary injury and/or immune cell activation status will distinguish previously deployed veterans with and without respiratory symptoms and associate with greater deployment related PM2.5 exposures. Specifically, we will examine the association between systemic biomarkers of airway injury with activation of the innate and acquired immune system to respiratory symptoms, lung function parameters, and PM2.5 exposures. In this collaborative proposal all four sites will study the same 280 patients that in addition to biomarker studies will have lung structure evaluation by quantitative CT imaging (Boston VA project) and additional physiologic characterization using diffusion capacity and exhaled nitric oxide to evaluate eosinophilic airway inflammation (Seattle VA project). Using well-designed biostatistical approaches, we will test our hypothesis that greater exposure to PM2.5 results in specific airway and lung parenchymal endotypes that could be distinguished by functional, structural, and biochemical mechanisms. Our three coordinated proposals will complement CSP #595 by comprehensively characterizing early deployment-related lung findings related to PM2.5 exposure that may in the future be used to assess disease. The resultant exposure-related disease types identified provide new clinical applications for the recognition, management, and future treatment strategies for Veterans with deployment-related lung disease.

部署到东南亚的军事人员报告呼吸道症状增加。独有 SA部署是暴露于高水平的直径≤ 2.5 µm的空气颗粒物的历史 （PM2.5）包括季节性沙尘暴，燃烧坑烟雾和不受管制的工业和车辆污染物。 返回退伍军人的客观结果是有限的，因此，VA合作研究#595服务 已部署退伍军人健康中心（SHADE）获得资助，评估卫星确认的接触史 在陆基部署到SA期间，在六个中心的近5000名处于危险中的退伍军人中。的总体目标 SHADE（母项目）将PM2.5暴露与肺功能评估相关联， 哮喘病史因为SHADE提供了一个独特的机会来识别早期部署相关的肺部发现 与PM暴露相关，我们建议使用该队列来确定PM的生物物理和临床影响 通过三个相互关联的目标。为了实现我们的目标，我们将招募280名SHADE参与者 有（50%）和无（50%）呼吸道症状（慢性咳嗽、喘息或呼吸困难）的非或 来自四个参与的SHADE地点的吸烟史<10包年的前吸烟者（明尼阿波利斯， 休斯顿、波士顿和西雅图）。本研究将为暴露的全身效应提供证据， 与呼吸道症状和肺功能下降有关。 该提案是三个协调项目之一，以系统地检查肺和全身 部署期间暴露的影响。具体而言，该项目将使用最先进的技术， 专业知识（生物标志物发现，多组学分析，免疫学和生物信息学）， 部署相关的全身炎症和气道相关生物标志物的综合评估 PM2.5暴露。此外，我们提出的使用基于全身和免疫的生物标志物的方法有助于 我们的协作绩效应用程序的总体原理。我们将检验一个假设， 气道和肺损伤和/或免疫细胞活化状态的全身性生物标志物将 区分以前部署的退伍军人有和没有呼吸道症状，并与 更多与部署相关的PM2.5暴露。具体来说，我们将研究系统性 气道损伤的生物标志物，伴随先天性和获得性免疫系统对呼吸道症状的激活， 肺功能参数和PM2.5暴露。 在这项合作提案中，所有四个研究中心将研究相同的280名患者，除了生物标志物外， 研究将通过定量CT成像（Boston VA项目）进行肺结构评价， 使用弥散容量和呼出一氧化氮评估嗜酸性气道的生理特征 炎症（西雅图VA项目）。使用设计良好的生物统计方法，我们将测试我们的假设 更多地暴露于PM2.5会导致特定的气道和肺实质内型， 以功能、结构和生化机制区分。我们的三项协调建议将 通过全面表征与以下相关的早期展开相关肺部发现来补充CSP #595 PM2.5暴露在未来可能被用来评估疾病。由此产生的与糖尿病相关的疾病类型 确定了为识别，管理和未来的治疗策略提供新的临床应用， 退伍军人与部署相关的肺部疾病。