Abstract
Background: Mast cells play a key role in airway hyperresponsiveness (AHR) in asthma but infiltration of airway mast cells and the effect of inhaled corticosteroids (ICS) across Type 2 high (T2-high) and T2-low disease have only been poorly described.
Aims and Objectives: To study the effect of inhaled corticosteroids (ICS) on airway mast cell density and phenotypes in patients with T2-high and T2-low asthma.
Methods: The RECONSTRUCT-study was a prospective intervention study with 50 steroid-free patients with asthma stratified into T2-high (FeNO≥25 ppb) and T2-low (FeNO<25 ppb) asthma at baseline, and 10 healthy controls. Bronchoscopy with obtainment of mucosal cryobiopsies was performed before and after 6 weeks of daily treatment with 1600 µg budesonide and examined histologically for tissue densities of tryptase (MCT) and chymase (MCTC) mast cell phenotypes.
Results: MCT density was higher in T2-low asthma: Median: 0.20% (IQR: 0.18) than in T2-high asthma: 0.09% (IQR: 0.16), P=0.025. In comparison, MCTC density was higher in T2-high asthma: 0.39% (IQR: 0.30) than T2-low asthma: 0.17% (IQR: 0.09), p<0.001 and healthy controls: 0.16% (IQR:0.41), P=0.023. In patients with T2-high asthma, both MCT and MCTC density decreased after ICS to: 0.05% (IQR: 0.10), P=0.019 and 0.28% (IQR: 0.34), P=0.022, respectively. In patients with T2-low asthma, only MCT decreased to 0.06% (IQR: 0.08), P<0.001 in response to ICS.
Conclusion: T2-low asthma is characterized by an MCT-predominant mast cell infiltration, whereas T2-high asthma is characterized by a higher density of MCTC. ICS decreases mast cell density in T2-high and T2-low asthma, suggesting infiltrating mast cells to be steroid-sensitive disease drivers in T2-low asthma.
Footnotes
Cite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 3698.
This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2020