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: 10553621
• 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 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10553621
• 关键词: Adaptive Immune System; Airborne Particulate Matter; Asia; Asthma; Autoantigens; Biochemical; Bioinformatics; Biological Markers; Biometry; Biophysics; Boston; Cells; Chronic; Clinical; Cluster Analysis; Complement; Coughing; Data; Desmosine; Development; Diameter; Diffusion; Disease; Dyspnea; Early identification; Eosinophilia; Exhalation; Exposure to; Fibrinogen; Funding; Future; Gases; Goals; Health; Hypersensitivity; IgE; Immune; Immune response; Immunity; Immunologic Markers; Immunology; Industrialization; Inflammasome; Inflammatory; Innate Immune System; Lung; Lung diseases; Measurement; Measures; Military Personnel; Nitric Oxide; Participant; Particulate Matter; Patients; Phenotype; Physiological; Predisposition; Pulmonary Function Test/Forced Expiratory Volume 1; Pulmonary Inflammation; Pulmonary function tests; Quantitative Evaluations; Recording of previous events; Reporting; Respiratory Signs and Symptoms; Risk; Seasons; 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; biomarker discovery; burn pit; clinical application; cohort; cooperative study; cytokine; design; disorder subtype; dust storms; eosinophilic inflammation; former smoker; immune activation; injured airway; lung injury; metabolomics; meter; monocyte; multiple omics; 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(SA)的军事人员报告称，呼吸道症状增加。独一无二 SA部署是暴露于高水平空气悬浮颗粒物≤2.5um直径的历史 (PM2.5)由季节性沙尘暴、燃烧坑烟雾以及未受管制的工业和车辆污染物组成。 在退伍军人中的客观发现是有限的，因此，退伍军人研究合作研究#595服务 已部署退伍军人的健康和健康(SHADE)得到资助，以评估卫星确认的接触史 在陆上部署到SA期间，在六个中心的近5000名面临风险的退伍军人中。的总体目标 Shade(Parent Project)是将PM2.5暴露与肺活量评估的肺功能联系起来，以及 哮喘史。因为Shape提供了一个独特的机会来识别早期部署相关的肺部表现 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进行曝光。为了实现我们的目标，我们将招募280名阴影参与者。 有(50%)和没有(50%)呼吸道症状(慢性咳嗽、喘息或呼吸困难)的非或 有10年吸烟史的前吸烟者来自四个参与的遮阳点(明尼阿波利斯， 休斯顿、波士顿和西雅图)。这项研究将为接触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。 这项建议是三个协调的项目之一，系统地检查肺和全身 部署期间暴露的影响。具体地说，这个项目将使用最先进的技术和 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)，以提供 部署相关全身炎症和呼吸道相关生物标记物的综合评估 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 我们的Collaborative Merit应用程序的总体原理。我们将检验增加的假设 呼吸道和肺损伤和/或免疫细胞激活状态的系统生物标志物 区分以前部署的有和没有呼吸道症状的退伍军人，并将 更多与部署相关的PM2.5暴露。具体地说，我们将研究系统性和系统性之间的关联 呼吸道损伤的生物标志物与呼吸道症状的先天和获得性免疫系统的激活， 肺功能参数和PM2.5暴露。 在这项合作提案中，除了生物标记物，所有四个站点都将研究相同的280名患者 研究将通过定量CT成像来评估肺结构(波士顿VA项目)和其他 用扩散能力和呼出一氧化氮评价嗜酸性气道的生理学特征 炎症(西雅图退伍军人事务部项目)。使用精心设计的生物统计学方法，我们将检验我们的假设 更大的PM2.5暴露会导致特定的呼吸道和肺实质内型， 以功能、结构和生化机制为特点的。我们的三个协调一致的建议将 通过全面描述与早期部署相关的肺部表现来补充CSP#595 未来可能被用来评估疾病的PM2.5暴露。由此产生的与暴露相关的疾病类型 为识别、管理和未来的治疗策略提供了新的临床应用 患有与部署相关的肺病的退伍军人。

项目成果

Challenges in initiating a lung cancer screening program: Experiences from two VA medical centers.

启动肺癌筛查计划的挑战：两个退伍军人管理局医疗中心的经验。

• DOI: 10.1053/j.seminoncol.2022.06.006
• 发表时间: 2022
• 期刊: Seminars in oncology
• 影响因子: 4
• 作者: Bujarski,Stephen;Flowers,Robert;Alkhunaizi,Mansour;Cuvi,Dave;Sathya,Sneha;Melcher,Jennifer;Kheradmand,Farrah;Holt,Gregory
• 通讯作者: Holt,Gregory

Risk Factors of Pneumonia in Primary Antibody Deficiency Patients Receiving Immunoglobulin Therapy: Data from the US Immunodeficiency Network (USIDNET).

接受免疫球蛋白治疗的原发性抗体缺乏患者肺炎的危险因素：来自美国免疫缺陷网络 (USIDNET) 的数据。

• DOI: 10.1007/s10875-022-01317-2
• 发表时间: 2022
• 期刊: Journal of clinical immunology
• 影响因子: 9.1
• 作者: Syed,MahaN;Kutac,Carleigh;Miller,JenniferM;Marsh,Rebecca;Sullivan,KathleenE;Cunningham-Rundles,Charlotte;Fuleihan,RamsayL;Kheradmand,Farrah;Hajjar,Joud
• 通讯作者: Hajjar,Joud