TY - JOUR T1 - Roflumilast but not dexamethasone or fluticasone reduces neutrophilic airway inflammation and hyperreactivity in a murine influenza-induced asthma exacerbation model JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2016.PA4893 VL - 48 IS - suppl 60 SP - PA4893 AU - Cornelia Tilp AU - Hannes Bucher AU - Eva Wex AU - Klaus Erb Y1 - 2016/09/01 UR - http://erj.ersjournals.com/content/48/suppl_60/PA4893.abstract N2 - Background: A major cause for severe asthma exacerbations are viral infections. Asthma exacerbations are characterized by a sudden decrease in lung function associated with increased inflammation in the lung. In severe cases exacerbations cannot be sufficiently controlled by using inhaled or oral corticosteroids.Aim: Investigate the anti-inflammatory and broncho-protective effects of the selective PDE4 inhibitor Roflumilast and the corticosteroids Dexamethasone and Fluticasone in a murine influenza-induced asthma exacerbation model.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 Influenza A virus was performed intranasally on day 25. Roflumilast, Dexamethasone or Fluticasone were given either orally or intratracheally on day 25, 26 and 27. Mice were analysed on day 28.Results: All three treatments significantly reduced the numbers of macrophages and eosinophils and Th2 cytokine levels in the airways. However, only Roflumilast attenuated pulmonary neutrophilic cell influx, KC concentrations and airway hyperresponsiveness (AHR).Conclusion: In this murine model of an acute asthma exacerbation, steroid treatment had no impact on AHR or neutrophil numbers, parameters believed to be important in human asthma exacerbations. In contrast, Roflumilast reduced both parameters. These pre-clinical data suggest that in patients where asthma exacerbations cannot be controlled by an inhaled or oral corticosteroid, a PDE4 inhibitor like Roflumilast may help to reduce symptoms and the frequency of exacerbations. ER -