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Defining Breath VOC Biomarkers to Improve Respiratory Health of Exposed Veterans

定义呼吸 VOC 生物标志物以改善接触过的退伍军人的呼吸健康

基本信息

批准号：
10553150
负责人：
Richart W Harper
金额：
--
依托单位：
VA NORTHERN CALIFORNIA HEALTH CARE SYS
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-01-01 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10553150
关键词：
Address Adverse effects Afghanistan Air Pollutants Alloys Area Asia Asthma Biological Markers Breath Tests Bronchiolitis California Cell Culture Techniques Cells Chronic Obstructive Pulmonary Disease Clinic Clinical Research Data Development Devices Disease Disease Management Down-Regulation Eicosanoids Engineering Enrollment Environmental Exposure Environmental Science Epithelial Cells Epithelium Equipment and supply inventories Exhalation Exposure to Fire - disasters Funding Goals Health Healthcare Healthcare Systems Human In Vitro Inflammatory Iraq Laboratories Lung Lung diseases Mass Spectrum Analysis Measures Mediating Medicine Metals Methods Military Personnel Monitor Newly Diagnosed Oils Particulate Particulate Matter Pathway interactions Patients Physical condensation Population Positioning Attribute Prevention Recording of previous events Research Research Personnel Respiratory Disease Respiratory Signs and Symptoms Risk Sampling Site Soldier Source System Technology Time Tracheobronchial Up-Regulation Veterans active duty airway epithelium asthma prevention asthmatic asthmatic patient biobank biomarker discovery biomarker validation burn pit cohort combustion product disease phenotype epidemiology study experimental study human tissue improved in vivo metabolomics mobile sensor novel personalized medicine pilot test portability portable monitoring pulmonary function research clinical testing research study respiratory health sensor tool toxicant volatile organic compound

项目摘要

The goal of this resubmitted application is to define signature exhaled breath volatile organic compounds (VOCs) in veterans exposed to toxicants and to develop an effective portable exhaled breath health monitoring system for soldiers at risk of developing respiratory disease. This project will bring a suite of portable sensors forward into use with the aim of supporting large scale epidemiological studies in military respiratory health. Specifically, our proposal responds to the call for research on the causes, treatment and prevention of chronic obstructive pulmonary disease, including identification and validation of biomarkers and disease phenotypes, as well as employing personalized medicine approaches in clinical research and disease management. While environmental triggers have long been recognized as key factors in respiratory disease, it has been challenging to concurrently measure health metrics and environmental exposures and associate the two. Also, a technology gap has existed for portable monitoring systems that can perform these functions simultaneously while continuously logging data. Breath testing of exhaled VOC biomarkers is a new concept that has the potential to transform healthcare for military and civilian populations in the US. Our overarching hypothesis is that a miniature breath analysis sensor can measure signatures of exhaled breath VOCs in real-time and correlate this to ambient field exposures as well as changes in lung function among exposed soldiers. This will allow doctors and researchers to define field exposures that have adverse effects on respiratory health, including worsening of asthma and the development of COPD. In aim #1, we propose to define VOC biomarkers produced by the lung upon exposure to the toxicants. We have developed a reliable method to measure the exceptionally small amount of VOCs emitted from well- differentiated tracheobronchial epithelial (TBE) cells in vitro. We will utilize this system to identify the signature and cellular source of VOCs emitted from TBEs exposed to toxicants and traffic related air pollutants. These experiments will be performed in primary cells from the lungs of humans in order to correlate with in vivo studies. In aim#2, we plan to expand our inventory of portable breath samplers for the clinical studies. In aim #3, we will perform a short-term, one- week clinical study in 4 cohorts at the VANCHCS and UC Davis sites to define a signature of breath biomarkers, including eicosanoids, that correlate with the presence of disease, namely asthma. A total of 100 veteran and civilian subjects will be enrolled over 4 years. Together, data from our tools will allow military doctors, researchers and others to more fully understand asthma and other respiratory diseases in exposed field soldiers in ways that has never been possible before.

此次重新提交的申请的目的是定义特征性呼出气挥发性有机物化合物（挥发性有机化合物）的退伍军人暴露于有毒物质，并开发一种有效的便携式呼气针对有患呼吸道疾病风险的士兵的呼吸健康监测系统。这个项目将推出一套便携式传感器投入使用，旨在支持大规模军事呼吸系统健康的流行病学研究。具体来说，我们的提案回应了呼吁对慢性阻塞性肺疾病的病因、治疗和预防进行研究疾病，包括生物标志物和疾病表型的识别和验证，以及在临床研究和疾病管理中采用个性化医疗方法。虽然环境触发因素长期以来一直被认为是呼吸道疾病的关键因素，但它同时测量健康指标和环境暴露一直具有挑战性，将两者联系起来。此外，便携式监控系统也存在技术差距，该系统可以在连续记录数据的同时执行这些功能。呼气测试 VOC 生物标志物是一个新概念，有潜力改变军事和医疗保健领域美国的平民。我们的首要假设是微型呼吸分析传感器可以实时测量呼出气体 VOC 的特征，并将其与环境相关联野外暴露以及暴露士兵的肺功能变化。这将允许医生和研究人员定义对呼吸系统健康产生不利影响的现场暴露，包括哮喘恶化和慢性阻塞性肺病（COPD）的发展。在目标#1中，我们建议定义肺部接触毒物后产生的 VOC 生物标志物。我们开发了一个测量井中排放的极少量 VOC 的可靠方法体外分化的气管支气管上皮（TBE）细胞。我们将利用该系统来识别暴露于有毒物质和交通的 TBE 释放的 VOC 的特征和细胞来源相关空气污染物。这些实验将在来自肺的原代细胞中进行人类以便与体内研究相关联。在目标#2中，我们计划扩大我们的库存用于临床研究的便携式呼吸采样器。在目标#3中，我们将执行一项短期的、一- 为期一周的临床研究，在 VANCHCS 和加州大学戴维斯分校的 4 个队列中进行，以确定特征呼吸生物标志物，包括类二十烷酸，与疾病的存在相关，即哮喘。四年内将总共招募 100 名退伍军人和平民受试者。一起，数据我们的工具将使军医、研究人员和其他人更全面地了解哮喘和其他呼吸道疾病在暴露的野战士兵中以前所未有的方式发生前。