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.

The past two decades have seen a high respiratory health burden for military personnel returning from deployments in Afghanistan and Iraq. Veterans have developed a variety of respiratory symptoms and been newly diagnosed with chronic obstructive pulmonary disease, asthma, and constrictive bronchiolitis. Environmental exposures including volatile organic compounds (VOCs) and particulate matter from burn pits, oil field fires, and metal alloys are thought to be causes; however, it has been challenging to concurrently measure and associate health metrics with environmental exposures. Breath testing of exhaled VOC biomarkers has the potential to transform healthcare for veterans in this regard. This project will bring a suite of portable sensors forward into development and clinical testing with the aim of identifying breath VOC signatures of exposures and help establish a “personalized exposure and medicine” platform for veterans.