Exacerbations of asthma, especially those caused by rhinovirus (RV), account for a disproportionate burden on healthcare resources for children and adults who have asthma and are allergic. Following the onset of an RV infection, innate immune responses develop rapidly before symptoms peak. However, attempts to evaluate the early, innate response stimulated by RV during the onset of a natural infection have been challenging. Several investigations, predominantly ex vivo, have provided evidence that anti-viral innate responses (in particular the expression of type I and type III interferons) may be impaired in the asthmatic airway. This has been proposed as a mechanism that could increase viral burden leading to an asthma exacerbation. In our studies conducted in vivo, however, the experimental RV infection model and cross-sectional studies of RV-infected children experiencing an asthma exacerbation, have not revealed increased viral loads in the airway. To address this conundrum, the experimental RV infection model has advantages because it allows investigators to examine the kinetics of the asthmatic response to RV following virus inoculation before symptoms peak. The investigators collaborating in this research have long-standing experience and expertise using this model which also permits frequent monitoring of subjects early in the infection when innate immune responses are at play. For this reason, we will evaluate existing data sets and samples from our recently completed and published experimental RV challenges to test our central hypothesis that, during an RV infection, allergic asthmatics do not experience an increased viral load, but do generate augmented, pro- inflammatory type 2 immune responses, including eosinophilic inflammation, that begin early in the infection. We also speculate that this early response will control viral load – but at the expense of increasing airway inflammation that in turn drives the exacerbation. A rich set of data has been col