Despite several epidemiological studies showing that infections caused by respiratory virus, particularly rhinovirus (RV), are associated with over 80% of asthma exacerbations, the exact mechanism by which RV provoke asthma exacerbations is unknown. When asthmatic subjects are experimentally inoculated with RV, fewer than 5% develop asthma exacerbations, whereas the vast majority suffers only colds of same severity as non-asthmatic healthy subjects. Thus, other factors must influence the outcome of RV infections in asthmatic non-asthmatic healthy subjects. Thus, other factors must influence the outcome of RV infections in asthmatics people. To test the hypothesis that differences among strains of RV determine the severity of respiratory symptoms during colds, we will study asthmatic subjects at the time of common colds and of asthma exacerbations (Study 1) to culture respiratory viruses from their nasal samples and follow the severity of their symptoms using several clinical and physiological measurements. The RV's isolated form asthmatic subjects who suffer mild colds, severe colds, and asthma exacerbations will be concerned in vitro (Project 1 and Core B), and these in vitro results will be correlated with the clinical symptoms. A cohort study of asthmatic subjects and these in vitro results will be correlated with the clinical symptoms. A cohort study of asthmatic subjects (Study 2) characterized at baseline and followed for 1 year will aim at: 1) examining the effects of different with the clinical symptoms. A cohort study of asthmatic subjects (Study 2) characterized at baseline and followed for 1 year will aim at: 1) examining the effects of different natural RV colds in the same asthmatic subjects in regards to their ability to indue asthma exacerbations and; 2) determining whether baseline characteristics can predict who is at risk for exacerbations during colds. In Study 3, asthmatic subjects will be inoculated with different passages of RV serotype 16 that indue (low passage) or do not induce (high passage) secretion of cytokines by cultured epithelial cells in vitro, to determine whether they cause respiratory symptoms of different severity. To test the hypothesis that differences in the responsiveness of epithelial cells to RV infection determines the severity of airway symptoms, we will assess the responsiveness of epithelial cells to RV infection determines the severity of airway symptoms, we will assess the change in cytokine and chemokine profile induced by RV16 infection in vitro of epithelial cells cultured from change in cytokine and chemokine profile induced by RV16 infection in vitro of epithelial cells cultured from asthmatic subjects before they develop natural colds (Study 2) or are inoculated with RV16 (Study 3). We will correlate these changes with the respiratory symptoms during colds. To test whether nasal and bronchial epithelial cells respond similarly to RV, we will culture cells from nasal scrapings and bronchial brushings from the same asthmatic subjects and will compare their response to RV in vitro (Study 4). These studies will potentially identify new inflammatory-mediator targets for therapy and prevention of asthma attacks caused by rhinovirus colds.
