Exhaled Biomarkers During Treatment of Rhinovirus

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DESCRIPTION (provided by applicant): Rhinovirus is a well-recognized, epidemiologically important cause of exacerbations of lower respiratory diseases including asthma, COPD, and cystic fibrosis. The mechanisms by which this common cold virus caused alteration in airway physiology are not well characterized in part because of the difficulty of assessing lower airway biochemistry and inflammation longitudinally. However, with the advent of high sensitivity assays, inflammatory mediators including cytokines and leukotrienes can now be measured in the fluid safely and easily condensed from exhaled breath. Additionally, chemical constituents of exhaled breath can be readily assayed for evidence of lung redox disturbances. This proposal is an ancillary study to a carefully designed NIH-funded clinical trial of Echinacea for the prophylaxis and treatment of experimentally induced nasal Rhinovirus infection. Based on preliminary data, we hypothesize that after Rhinovirus infection there will be repeatedly and safely assessed with exhaled breath condensate assays. Additionally we hypothesize that beneficial effects of Echinacea therapy correlate with amelioration of these chemical and immunologic alterations, and that development of cold symptoms can be predicted by assays of exhaled biomarkers. We will leverage the well-characterized subjects of the parent trial to identify baseline and post infection levels of exhaled inflammatory cytokines, leukotrienes, hydrogen ions, nitrogen oxides, and redox components including hydrogen peroxide and lipid oxidation products. Twenty-nine exhaled breath condensate collections will be performed by each of 168 subjects (40 placebo-treated) in a time period surrounding experimental Rhinovirus infection. Assays of these samples will provide statistically powerful data that will substantially improve our mechanistic understanding of airway chemical and immunologic effects of Rhinovirus-effects that are highly relevant to lower airway disease exacerbation. This study also will provide mechanistic data regarding efficacy of Echinacea. The project will be conducted at the University of Virginia, where expertise in the study of the common cold, airway chemistry, and exhaled biomarkers is extensive.