Defining Breath VOC Biomarkers to Improve Respiratory Health of Exposed Veterans

重新提交申请的目的是定义呼出气体挥发性有机物的特征 化合物（挥发性有机化合物）的退伍军人暴露于有毒物质，并制定一个有效的便携式呼出 呼吸健康监测系统，为有患呼吸道疾病风险的士兵提供服务。这个项目 将推出一套便携式传感器投入使用，目的是支持大规模 流行病学研究在军队呼吸系统健康。具体而言，我们的建议回应了 呼吁研究慢性阻塞性肺疾病的病因、治疗和预防 疾病，包括生物标志物和疾病表型的鉴定和验证，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被认为是呼吸道疾病的关键因素， 同时测量健康指标和环境暴露一直是一个挑战， 把两者联系起来。此外，对于便携式监测系统存在技术差距， 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的概念，有可能改变军事和医疗保健。 美国的平民。我们的首要假设是一个微型呼吸分析 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 现场暴露以及暴露士兵肺功能的变化。这将允许 医生和研究人员定义对呼吸系统健康有不利影响的野外暴露， 包括哮喘恶化和COPD的发展。在目标#1中，我们建议定义 暴露于有毒物质后肺产生的VOC生物标志物。我们已经开发出一种 可靠的方法来测量非常少量的挥发性有机化合物排放的井- 分化的气管支气管上皮（TBE）细胞。我们将利用这个系统来识别 有毒有害物质和交通运输环境中TBE释放VOCs的特征和细胞来源 相关的空气污染物。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，我们将执行一个短期的，一个- 在VANCHCS和UC Davis研究中心的4个队列中进行为期一周的临床研究，以定义以下特征 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4年内共招募100名退伍军人和平民受试者。一起，数据 将使军医、研究人员和其他人能够更全面地了解哮喘 以及其他呼吸道疾病的发病率， 以前

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.