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270万名军事人员被部署到阿富汗、伊拉克和其他西南亚国家 并暴露在直径为2.5µm的高浓度颗粒物≤(PM2.5，小到足以沉积的颗粒)中 在小气道和肺泡)，由于频繁的沙尘暴、焚烧坑烟雾(垃圾焚烧)和较差 受管制的工业和车辆污染源。以前的研究报告说，部署的人员已经 出现与慢性呼吸道疾病相一致的症状。然而，接触的客观证据- 相关的健康影响是有限的。为了解决这一问题，退伍军人事务部合作研究#595“服务与健康” 在已部署的退伍军人中(SHADE)正在进行“，以检验更大的累积 部署时暴露于PM2.5与肺功能低下有关，通过肺活量测定法进行评估。一把钥匙 阴影强度是一种暴露评估方法，它将使用历史卫星和区域能见度。 在6个中心评估的5000名退伍军人中重建与部署相关的PM2.5的记录。 肺活量测定法的一个局限性是它对早期肺部疾病不敏感。这项提议是三项建议之一 开展合作项目，系统地检查部署期间暴露的肺部后果。 我们将在四个地点(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)都是 根据CSP#595呼吸健康问卷进行评估，且几乎没有吸烟史(前吸烟者 有10年烟龄或从不吸烟)。我们的假设是，在部署期间暴露于PM2.5 西南亚和阿富汗与早期且往往未确诊的肺部疾病有关。 在退伍军人事务部普吉特湾计划中，我们将完成3项额外的肺生理测量，以评估 气体交换和小气道功能异常可能提示早期肺部疾病。我们会 测量一氧化碳扩散能力(DLCO)，这是一种间接测量氧气的呼气测试 从空气到血液的转移，是气体交换异常和肺损伤的标志。我们还将衡量 检查小气道功能的两种临床测试：(1)脉冲振荡法，它使用强迫振荡来 测量小气道阻力(R5-R20)，以及(2)氮气多次呼气冲洗试验以确定 肺清除指数，一个衡量通气量异质性的指标。MBW测试还提供了功能 剩余容量，这是肺容量的一种衡量标准，仅靠肺活量测定无法获得。我们将研究是否 这些临床测试与呼吸道症状和部署期间的空气污染(PM2.5)有关。 除了本提案中的生理测试外，作为总体协作提案的一部分，参与者将 还包括：(A)通过CT扫描对肺进行结构评估(波士顿退伍军人管理局的加希克博士领导的项目)和 (B)系统生物标记物和免疫细胞激活的评估(温特博士在 明尼阿波利斯退伍军人事务部和休斯顿退伍军人事务部的赫拉芒德博士)。使用波士顿退伍军人管理局项目的CT数据，这 建议将检查DLCO、R5-R20和LCI与CT结构异常的关系，如 如肺气肿和气体陷阱。 在协作分析中，我们将检验以下假设：更多地暴露于与部署相关的PM2.5 结果形成特殊的呼吸道和肺实质内型，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表现，可能在 未来将被用来评估疾病。通过识别不同的暴露相关疾病类型，这项研究将 帮助识别和治疗患有部署相关肺部疾病的退伍军人。