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: 10092809
• 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 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10092809
• 关键词: Address; Afghanistan; Air; Air Pollution; Airway Disease; Airway Resistance; Asia; Biochemical; Biological Markers; Blood; Boston; Breath Tests; Bronchiolitis; Caliber; Carbon Monoxide; Case Series; Chronic; Clinical; Clinical Research; Cluster Analysis; Complement; Coughing; Country; Data; Deposition; Development; Diffuse; Diffusion; Disease; Dust; 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 Signs and Symptoms; Services; Shortness of Breath; Site; Smoke; Smoker; Smoking History; Solid; Source; Spirometry; Structural defect; Structure; Symptoms; Testing; Thick; Time; Veterans; Wheezing; X-Ray Computed Tomography; airway obstruction; associated symptom; base; burn pit; constriction; cooperative study; disorder subtype; eosinophilic inflammation; epidemiology study; experience; fine particles; former smoker; health assessment; imaging biomarker; immune activation; indexing; injured airway; interstitial; lung injury; lung volume; 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.

向阿富汗、伊拉克等西南亚国家部署了超过270万军事人员 并暴露于高浓度的直径≤2.5 µm 的颗粒物（PM2.5，小到足以沉积的颗粒） 频繁的沙尘暴、燃烧坑烟雾（废物燃烧）和不良 受监管的工业和车辆来源。此前的研究报告称，部署的人员 出现与慢性呼吸道疾病一致的症状。然而，暴露的客观证据—— 相关的健康影响有限。为了解决这一问题，VA 合作研究#595“服务与健康 正在部署的退伍军人中（SHADE）”正在进行，以检验以下假设：更大的累积 部署期间暴露于 PM2.5 与肺活量测定法评估的肺功能较低有关。一把钥匙 SHADE 的优势是一种暴露评估方法，将使用历史卫星和区域能见度 记录以重建在 6 个中心评估的 5000 名退伍军人中与部署相关的 PM2.5。 肺活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 合作项目系统地检查部署期间暴露对肺部的影响。 我们将对四个地点（西雅图、波士顿、 明尼阿波利斯和休斯顿）有或没有呼吸道症状（咳嗽、喘息、呼吸困难） 根据 CSP #595 呼吸健康调查问卷进行评估，并且几乎没有吸烟史（以前吸烟者） <10包年或从不吸烟者）。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常常未被诊断的肺部疾病有关。 在 VA 普吉特海湾提案中，我们将完成 3 项额外的肺部生理学测量，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 测量一氧化碳扩散能力 (DLCO)，这是一种间接测量氧气的呼气测试 从空气转移到血液，是气体交换异常和肺损伤的标志。我们也会测量 检查小气道功能的两项临床测试：(1) 脉冲振荡测量法，使用受迫振荡来测量小气道功能。 测量小气道阻力 (R5-R20)，以及 (2) 氮气多次呼吸冲洗试验以确定 肺清除指数，通气不均匀性的衡量标准。 MBW 测试还提供了功能 残余容量，一种仅用肺活量测定法无法获得的肺容量测量值。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（PM2.5）有关。 除了本提案中的生理测试之外，作为整体合作提案的一部分，参与者将 还有：(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）以及 (b) 评估全身生物标志物和免疫细胞激活（由 Wendt 博士领导的项目） 弗吉尼亚州明尼阿波利斯市和弗吉尼亚州休斯敦市的 Kheradmand 博士）。使用波士顿 VA 项目的 CT 数据， 该提案将检查 DLCO、R5-R20 和 LCI 与 CT 结构异常之间的关系，例如 如肺气肿和气滞。 在协作分析中，我们将检验以下假设：更多地接触与部署相关的 PM2.5 结果产生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补充 CSP #595 全面描述与 PM2.5 暴露相关的早期部署相关肺部检查结果，可能会 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 帮助识别和治疗患有与部署相关的肺部疾病的退伍军人。