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: 10553639
• 负责人: Vincent S Fan
• 金额: --
• 依托单位: VA PUGET SOUND HEALTHCARE SYSTEM
• 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/10553639
• 关键词: Address; Afghanistan; Air; Air Pollution; Airway Resistance; Alveolus; Asia; Biochemical; Biological Markers; Blood; Boston; Breath Tests; Bronchiolitis; Carbon Monoxide; Case Series; Clinical; Clinical Research; Cluster Analysis; Complement; Coughing; Country; Data; Deposition; Development; Diameter; Diffusion; Disease; Dyspnea; Enrollment; Epidemiology; Exposure to; Functional Residual Capacity; Funding; Future; Gases; Goals; Health; Healthcare Systems; Heterogeneity; Human Resources; IgE; Immune response; Impairment; Industrialization; Iraq; Location; Lung; Lung CAT Scan; Lung diseases; Measurement; Measures; Mechanics; Military Personnel; Nitrogen; Obstructive Lung Diseases; Oscillometry; Oxygen; Parents; Participant; Particulate Matter; Peripheral; Physiological; Physiology; Population; Pulmonary Emphysema; Pulmonary Function Test/Forced Expiratory Volume 1; Questionnaires; Records; Reporting; Research; Respiratory Disease; Respiratory Signs and Symptoms; Services; Shortness of Breath; Site; Smoke; Smoker; Smoking History; Solid; Source; Spirometry; Structural defect; Symptoms; Testing; Thick; Time; Veterans; Wheezing; X-Ray Computed Tomography; airway obstruction; associated symptom; burn pit; chronic respiratory disease; cooperative study; disorder subtype; dust storms; eosinophilic inflammation; epidemiology study; experience; fine particles; former smoker; health assessment; immune activation; indexing; injured airway; interstitial; lung injury; lung volume; meter; never smoker; particle; programs; pulmonary function; recruit; respiratory health; small airways disease; sound; ventilation; wasting

Over 2.7 million military personnel were deployed to Afghanistan, Iraq, and other countries in Southwest Asia and exposed to high levels of particulate matter ≤2.5 µm in diameter (PM2.5, particles small enough to deposit in the small airways and alveoli) from frequent dust storms, burn-pit smoke (waste burning), and poorly regulated industrial and vehicular sources. Previous studies have reported that deployed personnel have experienced symptoms consistent with chronic respiratory disease. However, objective evidence of exposure- related health effects is limited. To address this concern, VA Cooperative Study #595 “Service and Health Among Deployed Veterans (SHADE)” is being conducted to examine the hypothesis that greater cumulative exposure to PM2.5 while deployed is associated with lower lung function assessed by spirometry. A key strength of SHADE is an exposure assessment approach that will use historical satellite and regional visibility records to reconstruct deployment-related PM2.5 in 5000 Veterans assessed at 6 centers. A limitation of spirometry is that it is insensitive to early lung disease. This proposal is one of three collaborative projects to systematically examine the pulmonary consequences of exposure during deployment. We will conduct additional assessments in a subset of 280 SHADE participants at four sites (Seattle, Boston, Minneapolis, and Houston) both with and without respiratory symptoms (cough, wheeze, dyspnea) as assessed on the CSP #595 respiratory health questionnaire, and with little smoking history (former smokers with <10 pack years or never smokers). Our hypothesis is that exposure to PM2.5 during deployment to Southwest Asia and Afghanistan is associated with early and often undiagnosed pulmonary diseases. In the VA Puget Sound proposal, we will complete 3 additional lung physiology measurements to assess for abnormalities in gas exchange and in small airways function that could indicate early lung disease. We will measure the diffusing capacity for carbon monoxide (DLCO), a breath test that indirectly measures oxygen transfer from air to blood, and is a marker of gas exchange abnormality and lung injury. We will also measure two clinical tests that examine small airways function: (1) impulse oscillometry which uses forced oscillations to measure small airways resistance (R5-R20), and (2) nitrogen multiple breath washout test to determine the lung clearance index, a measure of ventilation heterogeneity. The MBW test also provides the functional residual capacity, a measure of lung volumes not available with spirometry alone. We will examine whether these clinical tests are associated with respiratory symptoms and air pollution during deployment (PM2.5). In addition to the physiologic tests in this proposal, as part of the overall collaborative proposal, participants will also have: (a) structural assessment of the lung by CT scan (project led by Dr. Garshick at the Boston VA) and (b) assessment of systemic biomarkers and immune cell activation (project led by Dr. Wendt at the Minneapolis VA, and Dr. Kheradmand at the Houston VA). Using the CT data from the Boston VA project, this proposal will examine the relationship between DLCO, R5-R20, and LCI with CT structural abnormalities such as emphysema and gas-trapping. In the collaborative analysis, we will test the hypothesis that greater exposure to deployment-related 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. By identifying different exposure-related disease types, this research will help in the recognition and treatment of Veterans with deployment-related lung disease.

超过270万军事人员被部署到阿富汗，伊拉克和西南亚的其他国家 并暴露于高水平的颗粒物物质≤2.5µm直径（PM2.5，颗粒小到足以沉积的颗粒 在小型气道和肺泡中），经常发生沙尘暴，燃烧的烟雾（废物燃烧）和不良 受管制的工业和车辆来源。先前的研究报告说，部署的人员有 经历了与慢性呼吸系统疾病一致的症状。但是，暴露的客观证据 - 相关的健康效果是有限的。为了解决这个问题，VA合作研究＃595“服务与健康 在部署的退伍军人（阴影）中，正在进行以下假设：累积性更大 部署时暴露于PM2.5与通过肺活量测定法评估的较低肺功能有关。钥匙 阴影的强度是一种曝光评估方法，它将使用历史卫星和区域可见性 在6个中心评估的5000名退伍军人中，在5000名退伍军人中重建与部署相关的PM2.5的记录。 肺活量测定法的局限性是它对早期肺部疾病不敏感。该提议是三个 协作项目以系统地检查部署过程中暴露的肺后果。 我们将在四个地点的280个阴影参与者的子集（西雅图，波士顿，波士顿， 明尼阿波利斯和休斯顿）都有和没有呼吸道症状（咳嗽，喘息，呼吸困难） 在CSP＃595呼吸道健康问卷中进行评估，几乎没有吸烟史（前吸烟者 <10包或从未吸烟）。我们的假设是部署期间暴露于PM2.5 西南亚和阿富汗与早期且经常未诊断的肺部疾病有关。 在VA Puget Sound提案中，我们将完成3个额外的肺部生理测量值以评估 气体交换和小气道功能的异常，可能表明早期肺部疾病。我们将 测量一氧化碳（DLCO）的扩散能力，这是一种间接测量氧气的呼吸测试 从空气转移到血液，是气体交换异常和肺损伤的标志。我们还将衡量 两项检查小气道功能的临床测试：（1）使用强制振荡的冲动振荡法 测量小气道电阻（R5-R20），以及（2）氮多重呼吸刷测试以确定 肺间隙指数，通风异质性的度量。 MBW测试还提供了功能 残留容量，仅肺活量测定法无法获得肺部体积的度量。我们将检查是否 这些临床测试与部署期间的呼吸道症状和空气污染有关（PM2.5）。 除了本建议中的生理测试之外，作为整体协作建议的一部分，参与者还将 也有：（a）CT扫描对肺的结构评估（由弗吉尼亚州波士顿的Garshick领导的项目）和 （b）评估系统性生物标志物和免疫细胞激活（Wendt博士领导的项目 弗吉尼亚州的明尼阿波利斯VA和Kheradmand博士在弗吉尼亚州休斯顿）。使用来自波士顿VA项目的CT数据，此 提案将检查DLCO，R5-R20和LCI与CT结构异常之间的关系 作为肺气肿和气体捕获。 在协作分析中，我们将检验以下假设：与部署相关的PM2.5的暴露更大 导致特定的气道和肺实质内型可以通过功能，结构， 和生化机制。我们的三个协调提案将完成CSP＃595 全面表征与PM2.5暴露有关的早期部署相关发现可能 未来可用于评估疾病。通过识别不同的暴露相关疾病类型，这项研究将 帮助识别和治疗与部署相关的肺部疾病的退伍军人。