Different Effects of Inhaled Corticosteroids on Infiltrating Mast Cells in Type 2 High and Type 2 Low Asthma

Background: Asthma is a highly heterogenous disease with a differentiated response to treatment with inhaled corticosteroids. Airway hyperresponsiveness is a key feature of asthma across disease phenotypes linked to mast cells infiltrating the airwayswhich may respond to inhaled corticosteroids. Methods: The RECONSTRUCT-study was a prospective intervention study with 50 corticosteroid-free patients with Type 2 high or low asthma and airway hyperresponsiveness to mannitol treated for 6 weeks with 1600µg budesonide. Endobronchial cryobiopsies obtained before and after treatment were examined histologically for infiltrating mast cell phenotypes. Results: Airway hyperresponsiveness was comparable at baseline and improved equally with treatment. In patients with Type 2 low asthma there was a reduction in mast cells infiltrating the airway smooth muscle after treatment: mean factor: 0.40 (95% CI: 0.19-0.83, P=0.02) and 0.61 (95% CI: 0.43-0.89. P=0.01) for tryptase and chymase high mast cells, respectively. In patients with Type 2 high asthma, reductions in tryptase and chymase high mast cells were seen only in the subepithelial layer: 0.56 (95% CI: 0.34-0.82, P=0.005) and 0.74 (95% CI: 0.58-0.95, P=0.02), respectively. Conclusions: Airway hyperresponsiveness to mannitol was reduced after treatment with inhaled corticosteroids and was associated with a reduction in infiltrating mast cells in the airway smooth muscle in patients with Type 2 low asthma and in the subepithelial layer in patients with Type 2 high asthma suggesting different underlying steroid sensitive disease drivers among the two phenotypes of asthma.