Defining Breath VOC Biomarkers to Improve Respiratory Health of Exposed Veterans

此重新提交的申请的目标是定义特征呼气挥发性有机 退伍军人接触毒物后挥发性有机化合物(VOCs)及便携式呼气机的研制 为有患呼吸道疾病风险的士兵建立呼吸健康监测系统。这个项目 将推出一套便携式传感器，目的是支持大规模 军队呼吸系统健康的流行病学研究。具体地说，我们的建议回应了 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，包括识别和确认生物标记物和疾病表型，以及 在临床研究和疾病管理中采用个性化医学方法。 虽然环境因素长期以来一直被认为是呼吸系统疾病的关键因素，但它 一直在挑战同时测量健康指标和环境暴露，以及 将两者联系起来。此外，便携式监控系统也存在技术差距，这些系统可以 在连续记录数据的同时同时执行这些功能。呼气呼气测试 VOC生物标记物是一个新概念，有可能改变军事和医疗保健 美国的平民人口。我们最重要的假设是一个微型的呼吸分析 传感器可以实时测量呼出的VOCs的特征，并将其与环境相关联 野外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健康有不利影响的现场暴露， 包括哮喘加重和慢性阻塞性肺疾病的发展。在目标1中，我们建议定义 接触毒物时肺部产生的挥发性有机化合物生物标志物。我们已经开发出一种 可靠的方法来测量从油井排放的极少量的VOCs- 体外分化的气管、支气管壁上皮细胞。我们将利用这个系统来识别 接触毒物和交通的TBE排放的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。 以便与活体研究相关联。在目标2中，我们计划扩大我们的库存 便携式呼吸采样器，用于临床研究。在目标3中，我们将执行一个短期的，一 在VANCHCS和加州大学戴维斯分校的4个队列中进行的一周临床研究，以确定 呼气生物标志物，包括二十烷类化合物，与疾病的存在相关，即 哮喘。将在4年内招收100名退伍军人和文职人员。数据结合在一起 我们的工具将使军医、研究人员和其他人更充分地了解哮喘 以及其他暴露在野外士兵身上的呼吸道疾病，其方式是前所未有的 在此之前。

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.