CMA: Pulmonary and Systemic Effects of Deployment Related Particulate Matter Exposures

超过270万军事人员被部署到阿富汗，伊拉克和其他西南亚国家 并暴露于高水平的直径≤2.5 µm的颗粒物（PM2.5，小到足以存款的颗粒 在小气道和肺泡），从频繁的沙尘暴，焚烧坑烟雾（废物燃烧）， 受管制的工业和车辆来源。以前的研究报告说，部署的人员 出现了与慢性呼吸道疾病相符的症状但是，客观的暴露证据- 相关的健康影响有限。为了解决这一问题，VA合作研究#595“服务和健康” 在部署的退伍军人（阴影）”正在进行检查的假设，更大的累积 在展开时暴露于PM2.5与通过肺活量测定法评估的较低肺功能相关。一个关键 SHADE强度是一种利用历史卫星和区域能见度的暴露评估方法 记录，以重建部署相关的PM2.5在5000退伍军人在6个中心进行评估。 肺量测定法的局限性在于它对早期肺部疾病不敏感。该提案是三个提案之一 开展合作项目，系统地检查部署期间暴露的肺部后果。 我们将在四个研究中心（西雅图，波士顿， 明尼阿波利斯和休斯顿），有和没有呼吸道症状（咳嗽，喘息，呼吸困难）， 根据CSP #595呼吸健康问卷进行评估，并且几乎没有吸烟史（前吸烟者 <10包年或从不吸烟者）。我们的假设是，在部署到 西南亚和阿富汗与早期和经常未确诊的肺部疾病有关。 在VA Puget Sound提案中，我们将完成3项额外的肺生理学测量，以评估 气体交换和小气道功能异常可能表明早期肺部疾病。我们将 测量一氧化碳弥散量（DLCO），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。我们还将测量 两种检查小气道功能的临床试验：（1）脉冲呼吸测量法，其使用强制振荡， 测量小气道阻力（R5-R20），和（2）氮气多次呼吸冲洗试验，以确定 肺清除指数，一种通气异质性的测量方法。MBW测试还提供了功能 残余容量，肺容量的测量不能单独使用肺活量测定法。我们将研究是否 这些临床测试与部署期间的呼吸道症状和空气污染（PM2.5）有关。 除了本提案中的生理测试外，作为整体合作提案的一部分，参与者还将 还具有：（a）通过CT扫描对肺部进行结构评估（由波士顿VA的Garshick博士领导的项目）， (b)系统性生物标志物和免疫细胞活化的评估（由Wendt博士领导的项目， Minneapolis VA和Houston VA的Kheradmand博士）。使用波士顿VA项目的CT数据， 建议将检查DLCO、R5-R20和LCI与CT结构异常之间的关系， 肺气肿和气体滞留 在合作分析中，我们将检验以下假设： 导致特异性气道和肺实质内型，其可以通过功能，结构， 和生化机制。我们的三个协调提案将通过以下方式补充CSP #595： 全面表征与PM2.5暴露相关的早期部署相关肺部发现， 未来可以用来评估疾病。通过识别不同的与糖尿病相关的疾病类型，这项研究将 帮助识别和治疗退伍军人与部署相关的肺部疾病。

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.