Using Breath Metabolites to Determine Specific Virus Infection in Asthmatic Patients

使用呼吸代谢物确定哮喘患者的特定病毒感染

基本信息

批准号：
9264582
负责人：
Michael Schivo
金额：
$ 17.52万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-05-01 至 2019-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9264582
关键词：
Address Anti-Bacterial Agents Antibiotics Asthma Biological Markers Biology Breath Tests Bronchoscopy Cell Culture System Cell Culture Techniques Cells Center for Translational Science Activities Chronic lung disease Clinic Clinical Clinical Research Clinical Sciences Coculture Techniques Collection Data Analyses Detection Development Diagnosis Early Diagnosis Engineering Environment Epithelial Epithelial Cells Exhalation Foundations Future Goals Gold Heat shock proteins Home environment Hour Human Immune Infection Influenza Influenza A Virus, H3N2 Subtype Influenza A virus Interdisciplinary Study Intervention Lead Link Lung Lung diseases Measures Medicine Mentors Methodological Studies Methods Mission Modeling Morbidity - disease rate Nose Outcome Oxidative Stress Participant Patients Pharmaceutical Preparations Production Recruitment Activity Research Research Infrastructure Research Personnel Research Training Rhinovirus Sampling Severities Signal Transduction Site Speed Structure of respiratory epithelium Swab Symptoms System Techniques Testing Time Tracheobronchial Training Translational Research United States National Institutes of Health Virus Virus Diseases airway epithelium asthmatic asthmatic airway asthmatic patient base career college comparative cost cost effective falls high dimensionality improved in vivo innovation medical schools metabolomics patient oriented research point of care prevent programs public health relevance rapid diagnosis respiratory respiratory infection virus sensor skills statistics viral detection volatile organic compound

项目摘要

DESCRIPTION (provided by applicant): Influenza A virus (IAV) and human rhinovirus (HRV) trigger severe exacerbations in asthma patients. Early diagnosis of these viruses may improve clinical outcomes, avoid inappropriate antibiotic use, and reduce the severity of exacerbations. While PCR-based tests are the gold standard, time and cost limit widespread use. The analysis of volatile organic compounds (VOCs) in exhaled human breath is an innovative technique that may be a non- invasive, cost-effective, point-of-care method to rapidly diagnose early viral infections, although studies of this methodology are lacking. Our main hypotheses are that breath VOC analysis will distinguish virus-infected asthma patients from un-infected asthmatic controls, and that the VOCs seen in asthmatic human breath derive from airway epithelial cells the sites of viral infection. We will study breath VOCs from asthmatic patients with and without virus infections recruited from our well-established UC Asthma Network clinics. We will also use asthmatic airway epithelial cells obtained from research bronchoscopies to study VOC production following experimental IAV and HRV infection. The long-term goal is to enable early, rapid, and specific detection of respiratory virus infections for which current tests are limited. The ultimate goal of our research program is to reduce the severity of asthma exacerbations and enable patients and clinicians to make rapid and appropriate treatment decisions , both in the office and at home. The use of our unique VOC collection system for cell cultures provides a robust ex vivo model to ultimately test a variety of interventions (e.g., drugs) on cellular VOC production which will eventually inform future clinical breath studies. My long-term career goals are to lead the research mission of a chronic lung disease center with a focus on clinical breath testing. I ultimately plan to build a consortium linking multiple clinical breath testing sites undr the purpose of advancing breath research. This has the potential to speed diagnosis of many lung diseases including viral infections. Further training in subject recruitment and research team management; advanced breath collection; cell culturing techniques; and developing co-culture models for VOC analysis of virus infections will facilitate these goals. The training from this K23 will lay the foundation for a research career using VOC analysis to test clinical interventions for asthma, pulmonary infections, as well as other lung diseases. The research and training environment at UC Davis includes the NIH Clinical and Translational Science Center (CTSC); the UC Asthma Network (UCAN) clinics with a robust research infrastructure and several ongoing clinical studies; the Center for Comparative Respiratory Biology and Medicine (CCRBM) which includes many collaborative investigators focused on airway biology; and graduate classes in clinical and advanced statistics and cell culturing techniques. The CTSC has been established to facilitate clinical and translational research, and as an environment to support researchers at all levels in their careers. UC Davis has an established track record of excellence in patient-oriented research and collaborative, multidisciplinary research efforts.

描述（由申请人提供）：甲型流感病毒 (IAV) 和人鼻病毒 (HRV) 会引发哮喘患者的严重病情加重。在 PCR 过程中，这些病毒的早期诊断可以改善临床结果，避免不适当的抗生素使用，并降低病情加重的严重程度。基于测试的黄金标准、时间和成本限制了人类呼出气体中挥发性有机化合物 (VOC) 的分析是一种非侵入性、经济高效的创新技术。快速诊断早期病毒感染的护理点方法，尽管缺乏对该方法的研究，但我们的主要假设是呼吸挥发性有机化合物分析将区分病毒感染的哮喘患者和未感染的哮喘对照，以及哮喘患者中观察到的挥发性有机化合物。人类呼吸源自气道上皮细胞，我们将研究从我们完善的 UC 哮喘网络诊所招募的有或没有病毒感染的哮喘患者的呼吸 VOC。从研究性支气管镜检查中获得的上皮细胞，用于研究实验性 IAV 和 HRV 感染后的 VOC 产生。长期目标是能够早期、快速和特异性地检测当前测试有限的呼吸道病毒感染。旨在降低哮喘恶化的严重程度，使患者和新来者能够在办公室和家里做出快速、适当的治疗决定。使用我们独特的细胞培养 VOC 收集系统提供了一个强大的离体模型，以最终测试哮喘。各种我的长期职业目标是领导一个慢性肺病中心的研究任务，重点是我最终计划建立的临床呼吸测试。一个联合多个临床呼气测试站点，以推进呼气研究，这有可能加速许多肺部疾病的诊断，包括进一步培训受试者招募和研究团队管理；开发 VOC 共培养模型病毒感染分析将有助于实现这些目标。K23 的培训将为使用 VOC 分析来测试哮喘、肺部感染以及其他肺部疾病的临床干预措施的研究生涯奠定基础。包括 NIH 临床和转化科学中心 (CTSC)；UC 哮喘网络 (UCAN) 诊所，拥有强大的研究基础设施和多项正在进行的临床研究；比较呼吸生物学和医学中心 (CCRBM)，其中包括许多专注于气道的合作研究人员CTSC 的成立旨在促进临床和转化研究，并为加州大学戴维斯分校的各个级别的研究人员提供良好的职业支持。以患者为中心的研究和协作、多学科研究工作。