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加重。独有的