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）的军事人员报告呼吸道症状增加。独特于 SA 部署是指曾接触过大量直径≤ 2.5 µm 的空气颗粒物 (PM2.5) 包括季节性沙尘暴、燃烧坑烟雾以及不受管制的工业和车辆污染物。 返回退伍军人的客观发现有限，因此，VA 合作研究 #595 服务 部署退伍军人健康 (SHADE) 获得资助来评估卫星确认的暴露历史 在南澳陆基部署期间，六个中心的近 5000 名退伍军人处于危险之中。总体目标是 SHADE（父项目）将 PM2.5 暴露与肺活量测定评估的肺功能联系起来，并且 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检查结果 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进行曝光。为了实现我们的目标，我们将招募 280 名 SHADE 参与者 有 (50%) 和没有 (50%) 呼吸道症状（慢性咳嗽、喘息或呼吸困难）的人 来自四个参与 SHADE 站点（明尼阿波利斯、明尼阿波利斯、 休斯顿、波士顿和西雅图）。这项研究将为暴露于以下物质的系统性影响提供证据： 与呼吸道症状和肺功能下降有关。 该提案是系统检查肺部和全身系统的三个协调项目之一 部署期间暴露的影响。具体来说，该项目将采用最先进的技术和 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）提供 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系统和免疫的生物标志物的方法有助于 我们合作优秀申请的总体理由。我们将检验增加的假设 气道和肺损伤和/或免疫细胞激活状态的全身生物标志物将 区分先前部署的有或没有呼吸道症状的退伍军人，并与 更大的部署相关 PM2.5 暴露。具体来说，我们将检查系统性之间的关联 气道损伤的生物标志物，激活先天和后天免疫系统对呼吸道症状的影响， 肺功能参数和 PM2.5 暴露。 在这项合作提案中，除了生物标志物之外，所有四个中心都将研究相同的 280 名患者 研究将通过定量 CT 成像（波士顿 VA 项目）和其他方法评估肺结构 使用扩散能力和呼出一氧化氮的生理特征来评估嗜酸性粒细胞气道 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 更多地接触 PM2.5 会导致特定的气道和肺实质内型，这可能是 根据功能、结构和生化机制进行区分。我们的三项协调提案将 通过全面描述与早期部署相关的肺部发现来补充 CSP #595 PM2.5 暴露未来可能用于评估疾病。由此产生的与暴露相关的疾病类型 确定的结果为识别、管理和未来治疗策略提供了新的临床应用 患有与服役相关的肺部疾病的退伍军人。