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: 9774557
• 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 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9774557
• 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; Dust; Dyspnea; Eosinophilia; Exhalation; Exposure to; Fibrinogen; Funding; Future; Gases; Goals; Health; Hypersensitivity; IgE; Immune; Immune response; Immunity; Immunologic Markers; Immunology; Industrialization; Inflammasome; Inflammation; Inflammatory; Injury; Lung; Lung diseases; Measurement; Measures; Military Personnel; Nitric Oxide; Participant; Particulate Matter; Patients; Phenotype; Physiological; Pulmonary Function Test/Forced Expiratory Volume 1; Pulmonary function tests; Quantitative Evaluations; Recording of previous events; Reporting; Respiratory Signs and Symptoms; Respiratory physiology; Risk; Secretory Cell; Services; Site; Smoke; Smoker; 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; clinical application; cohort; cooperative study; cytokine; design; disorder subtype; eosinophilic inflammation; imaging biomarker; immune activation; injured airway; metabolomics; monocyte; multiple omics; parent project; pollutant; pulmonary function; recruit; respiratory; response; secretory protein; soluble RAGE; sound; structured data; 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（SA）的军事人员报告增加了呼吸道症状。独特 SA部署是暴露于高水平的特殊物质≤2.5µm直径的历史 （PM2.5）由季节性的沙尘暴，燃烧的烟雾以及不受管制的工业和车辆污染物组成。 返回退伍军人之间的客观发现是有限的，因此，VA合作研究＃595服务 部署的退伍军人（阴影）中的健康资金用于评估卫星确认的暴露历史 在向SA的陆基部署期间，六个中心的近5000名处于危险的退伍军人中。总体目的 阴影（父项目）是将PM2.5与精神法评估的肺功能相关联，并且 哮喘历史。因为Shade提供了一个独特的机会来识别早期部署相关的肺发现 与PM暴露有关，我们建议使用此队列来识别PM的生物物理和临床影响 通过三个相互关联的目标暴露。为了实现我们的目标，我们将招募280个阴影参与者 没有（50％）和没有（50％）呼吸道症状（慢性咳嗽，喘息或呼吸困难） 从四个参与的阴影站点吸烟的前吸烟史（明尼阿波利斯， 休斯顿，波士顿和西雅图）。这项研究将提供证据证明与 与呼吸道症状的联系和肺功能降低。 该提案是系统检查肺和全身的三个协调项目之一 部署过程中暴露的影响。特别是，该项目将使用最先进的技术和 专业知识（生物标志物发现，多摩管分析，免疫学和生物信息学） 全面评估与部署相关的系统性炎症和气道相关的生物标志物 PM2.5暴露。此外，我们使用基于系统和免疫的生物标志物的拟议方法有助于 我们协作功绩申请的总体原理。我们将测试增加的假设 气道和肺部损伤和/或免疫细胞激活状态的全身生物标志物将 具有和没有呼吸症状的以前部署的退伍军人独特 与部署相关的PM2.5暴露更大。具体而言，我们将研究系统性之间的关联 气道损伤的生物标志物，激活先天和获得的免疫系统呼吸道症状， 肺功能参数和PM2.5暴露。 在此协作提案中，所有四个站点都将研究除生物标志物外的280名患者 研究将通过定量CT成像（波士顿VA项目）和其他 使用扩散能力和呼出的一氧化氮来评估嗜酸性气道的生理表征 炎症（西雅图VA项目）。使用精心设计的生物统计方法，我们将检验我们的假设 更大的暴露于PM2.5会导致特定的气道和肺实质内型可能是 通过功能，结构和生化机制区分。我们的三个协调提议将 通过全面表征与早期部署相关的肺发现，补充CSP＃595 PM2.5将来可能会用于评估疾病。由此产生的与暴露有关的疾病类型 确定为识别，管理和未来治疗策略提供新的临床应用 与部署相关的肺部疾病的退伍军人。