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.
Rhinovirus and influenza can aggravate asthma, and early detection of these viruses can lead to improved asthma control and reduced anti-bacterial use. Current tests for respiratory virus infection are expensive or slow, and breath analysis is emerging as a way to diagnose viruses quickly, non-invasively, and at the point-of-care. This proposal will test if asthmatic patients with confirmed rhinovirus or influenza infections have unique volatile breath compounds that can distinguish them from uninfected asthmatic patients, and it will also aim to determine if the respiratory epithelium alone is the site of volatile breat compound production or if other cells are involved.
| Zamuruyev, Konstantin O; Borras, Eva; Pettit, Dayna R et al. (2018) Effect of temperature control on the metabolite content in exhaled breath condensate. Anal Chim Acta 1006:49-60 |
| Yamaguchi, Mei S; McCartney, Mitchell M; Linderholm, Angela L et al. (2018) Headspace sorptive extraction-gas chromatography-mass spectrometry method to measure volatile emissions from human airway cell cultures. J Chromatogr B Analyt Technol Biomed Life Sci 1090:36-42 |
| Schivo, Michael; Albertson, Timothy E; Haczku, Angela et al. (2017) Paradigms in chronic obstructive pulmonary disease: phenotypes, immunobiology, and therapy with a focus on vascular disease. J Investig Med 65:953-963 |
| Schivo, Michael; Aksenov, Alexander A; Pasamontes, Alberto et al. (2017) A rabbit model for assessment of volatile metabolite changes observed from skin: a pressure ulcer case study. J Breath Res 11:016007 |
| Aksenov, Alexander A; Zamuruyev, Konstantin O; Pasamontes, Alberto et al. (2017) Analytical methodologies for broad metabolite coverage of exhaled breath condensate. J Chromatogr B Analyt Technol Biomed Life Sci 1061-1062:17-25 |
| Zamuruyev, Konstantin O; Aksenov, Alexander A; Pasamontes, Alberto et al. (2016) Human breath metabolomics using an optimized non-invasive exhaled breath condensate sampler. J Breath Res 11:016001 |
