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.

该重新提交应用的目的是定义签名呼出的呼吸挥发性有机暴露于有毒物质的退伍军人中的化合物（VOC），并开发有效的便携式呼气呼吸健康监测系统，适合患有呼吸道疾病风险的士兵。这个项目将带一套便携式传感器，以支持大规模军事呼吸健康的流行病学研究。具体来说，我们的建议回应呼吁研究原因，治疗和预防慢性阻塞性肺部疾病，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学方法。尽管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，但同时衡量健康指标和环境暴露和环境暴露和使两个。此外，对于可移植监视系统的技术差距也存在同时执行这些功能，同时连续记录数据。呼气的呼吸测试 VOC生物标志物是一个新概念，有可能改变军事医疗保健和美国的平民人口。我们的总体假设是微型呼吸分析传感器可以实时测量呼出呼吸VOC的签名，并将其与环境相关联野外暴露以及暴露士兵中肺功能的变化。这将允许医生和研究人员定义对呼吸健康有不良影响的现场暴露，包括哮喘的恶化和COPD的发展。在AIM＃1中，我们建议定义肺暴露于毒物后产生的VOC生物标志物。我们已经开发了可靠的方法来测量从良好的频率中发出的少量VOC 分化的气管支气管上皮（TBE）细胞体外。我们将利用此系统来识别暴露于有毒物质和交通的TBE发出的VOC的签名和细胞来源相关的空气污染物。这些实验将在原代细胞中的肺中进行为了与体内研究相关。在AIM＃2中，我们计划扩大我们的清单用于临床研究的便携式呼吸采样器。在AIM＃3中，我们将执行短期，一 Vanchcs和UC Davis站点的4个队列中的周临床研究，以定义呼吸生物标志物，包括与疾病的存在相关的类花生酸的生物标志物哮喘。总共100名老将和平民受试者将在4年内招收。在一起，数据我们的工具将使军事医生，研究人员和其他人更充分了解哮喘以及裸露的现场士兵中的其他呼吸道疾病，以永远无法实现的方式前。