Establishment of a murine asthma exacerbation model by combining OVA exposure with either RSV or influenza infection

Background: Asthma exacerbations are characterized by a sudden decrease in lung function associated with increased inflammation in the lung and enhanced numbers of eosinophils, lymphocytes and neutrophils. Patients often need to take oral steroids and are hospitalized. . Respiratory infections particularly viral infections are a leading cause for the escalating inflammation and impairment in lung function. Aim: Develop a murine asthma exacerbation model which depicts hallmarks of the human disease by combining OVA exposure, inducing an allergen-specific Th2 response with either Respiratory syncytial Virus (RSV) or Influenza virus infections. Methods: BALB/c mice were sensitized with ovalbumin on day 0, 14 and 21 followed by two challenges with ovalbumin aerosol on day 26 and 27. The infection with RSV was performed either on day 21 (single infection) or on day 17 and 27 or 21 and 27 (re-infection). The infection with Influenza Virus was performed on day 25.Mice were sacrificed on day 28. Results: OVA exposure and single RSV infection did not lead to enhanced AHR or eosinophilic or neutrophilic inflammation. In the RSV re-infection model increased neutrophilic inflammation was observed, which did not lead to enhanced AHR. Combining OVA exposure with Influenza infection lead to eosinophilic and neutrophilic inflammation and enhanced AHR. Conclusion: Only the Influenza infection/OVA exposure model was able to mimic the human asthma exacerbation phenotype consisting of increased AHR and increased airway inflammation.