Rhinovirus Infection Does Not Alter Bronchodilation in Human Precision Cut Lung Slices from Asthma Donors.

Abstract

Rhinovirus (RV) infection is present in 60-80% of children with asthma exacerbations in the emergency department. Recent studies suggest that during asthma exacerbations, children with RV are less likely to experience treatment failure than those with other viruses. We hypothesized that despite enhancing contraction in precision cut lung slices (PCLS) from asthma donors, RV does not affect the ability of these slices to bronchodilate. PCLS were prepared from asthmatic (n=6) and non-asthmatic (n=14) donor lungs. Baseline photomicrographs measuring airway cross-sectional area were taken before and after exposure to carbachol (2 μM), isoproterenol (4 μM), and forskolin (4 μM). PCLS were infected with RV39 for 48h or treated with 10mL/mL IL-25 for 24h. After treatments, slice responses to carbachol, isoproterenol, and forskolin were measured again. The percentage of bronchodilation for each slice was calculated using the percent difference in the airway area after exposure to carbachol and isoproterenol. Bronchodilation was compared pre- and post-treatments. PCLS from asthma donors retained their ability to bronchodilate after isoproterenol despite RV infection (pre- 55.67%, post- 61.09%; p=ns), while PCLS from non-asthma donors had reduced bronchodilation post-infection (pre- 63.33%, post- 56.67%; p<0.05). PCLS treated with IL-25 bronchodilated more post-treatment in the asthma lungs (pre- 37.86%, post- 66.65%; p<0.05). Although RV infection of PCLS causes airway hyperresponsiveness to carbachol in donors with history of asthma, it does not alter the ability of the airways to bronchodilate in response to isoproterenol. PCLS treated with IL-25 bronchodilate more post-treatment, suggesting that IL-25 enhances contraction, but does not affect bronchodilation.