Using Breath Metabolites to Determine Specific Virus Infection in Asthmatic Patients

 描述(申请人提供)：甲型流感病毒(IAV)和人类鼻病毒(HRV)会引发哮喘患者的严重恶化。这些病毒的早期诊断可能会改善临床结果，避免不适当的抗生素使用，并降低病情恶化的程度。虽然基于聚合酶链式反应的检测是黄金标准，但时间和成本限制了广泛使用。分析呼气中的挥发性有机化合物(VOCs)是一项创新的技术，可能是一种非侵入性、成本效益高的护理方法，可以快速诊断早期病毒感染，尽管对这种方法的研究还很缺乏。我们的主要假设是，呼气VOC分析将区分病毒感染的哮喘患者和未感染哮喘的对照组，哮喘患者呼气中的VOCs来自呼吸道上皮细胞，即病毒感染的部位。我们将研究从我们著名的UC哮喘网络诊所招募的有病毒感染和没有病毒感染的哮喘患者的呼吸VOCs。我们还将使用从研究支气管镜获得的哮喘呼吸道上皮细胞来研究实验性IAV和HRV感染后VOC的产生。长期目标是能够对目前检测有限的呼吸道病毒感染进行早期、快速和特异的检测。我们研究计划的最终目标是降低哮喘恶化的严重程度，使患者和临床医生能够在办公室和家里迅速做出适当的治疗决定。我们独特的细胞培养挥发性有机化合物收集系统的使用提供了一个强大的体外模型，最终测试各种对细胞挥发性有机化合物产生的干预措施(例如药物)，最终将为未来的临床呼吸研究提供信息。我的长期职业目标是领导一家慢性肺病中心的研究任务，专注于临床呼气测试。我最终计划建立一个联盟，将多个临床呼气测试地点连接起来，以推进呼吸研究。这有可能加快许多肺部疾病的诊断，包括病毒感染。受试者招募和研究团队管理方面的进一步培训；先进的呼气收集；细胞培养技术；以及为病毒感染的VOC分析开发共培养模型将有助于实现这些目标。来自K23的培训将为使用VOC分析测试哮喘、肺部感染和其他肺部疾病的临床干预措施的研究生涯奠定基础。加州大学戴维斯分校的研究和培训环境包括NIH临床和转化科学中心(CTSC)；加州大学哮喘网络(UCAN)诊所，其强大的研究基础设施和几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呼吸道生物学的合作研究人员；以及临床和高级统计与细胞培养技术研究生课程。CTSC的建立是为了促进临床和转化性研究，并作为一个环境来支持各级研究人员的职业生涯。加州大学戴维斯分校在以患者为导向的研究和协作的多学科研究努力方面拥有卓越的记录。

 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.