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Principal Investigator: Richart W Harper
Organization: VA NORTHERN CALIFORNIA HEALTH CARE SYS
Fiscal Year: 2024
Funding agency: Veterans Affairs
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.
Terms: <Address><Adverse effects><Afghanistan><Air Pollutants><Airway health><Alloys><Area><Armed Forces Personnel><Asia><Asthma><Biological Markers><Breath Tests><Bronchial Asthma><Bronchiolitis><COPD><California><Cell Body><Cell Culture Techniques><Cells><Chronic Obstruction Pulmonary Disease><Chronic Obstructive Lung Disease><Chronic Obstructive Pulmonary Disease><Clinic><Clinical Evaluation><Clinical Research><Clinical Study><Clinical Testing><Data><Development><Devices><Disease><Disease Management><Disorder><Disorder Management><Down-Regulation><Eicosanoids><Engineering><Enrollment><Environmental Exposure><Environmental Science><Epidemiologic Research><Epidemiologic Studies><Epidemiological Studies><Epidemiology Research><Epithelial Cells><Epithelium><Equipment and supply inventories><Exhalation><Exhaling><Exposure to><Fire - disasters><Fires><Funding><Goals><Health><Health Care Systems><Healthcare><Healthcare Systems><History><Human><In Vitro><Inflammatory><Inventory><Investigators><Iraq><Laboratories><Lung><Lung Diseases><Lung Respiratory System><Mass Photometry/Spectrum Analysis><Mass Spectrometry><Mass Spectroscopy><Mass Spectrum><Mass Spectrum Analyses><Mass Spectrum Analysis><Measures><Mediating><Medicine><Metals><Methods><Military><Military Personnel><Modern Man><Monitor><Newly Diagnosed><Oils><Particulate><Particulate Matter><Pathway interactions><Patients><Physical condensation><Population><Position><Positioning Attribute><Prevention><Pulmonary Diseases><Pulmonary Disorder><Recording of previous events><Research><Research Personnel><Researchers><Respiratory Disease><Respiratory Epithelium><Respiratory Expiration><Respiratory Signs and Symptoms><Respiratory System Disease><Respiratory System Disorder><Risk><Sampling><Site><Soldier><Source><Structure of respiratory epithelium><System><Technology><Time><Tracheobronchial><Up-Regulation><Upregulation><Veterans><active duty><active service><airway epithelium><airway symptom><asthma patient><asthma prevention><asthmatic><asthmatic patient><bio-markers><biobank><biologic marker><biomarker><biomarker discovery><biomarker validation><biorepository><breath analysis><burn pit><cell culture><cell cultures><chronic obstructive pulmonary disorder><clinical test><cohort><combustion by-products><combustion product><condensation><developmental><disease of the lung><disease phenotype><disorder of the lung><enroll><epidemiologic investigation><epidemiology study><experiment><experimental research><experimental study><experiments><fire><health care><histories><human tissue><improved><in vivo><lung disorder><lung function><marker validation><metabolism measurement><metabolomics><metabonomics><military population><mobile sensor><novel><pathway><personalization of treatment><personalized medicine><personalized therapy><personalized treatment><pilot test><portability><portable monitoring><portable sensor><pulmonary><pulmonary function><research clinical testing><research study><respiratory health><respiratory symptom><respiratory tract epithelium><sensor><tool><toxicant><volatile organic chemical><volatile organic compound>