Airway hyperresponsiveness reflects corticosteroid-sensitive mast cell involvement across asthma phenotypes

Area of Science:

• Pulmonary Medicine
• Immunology
• Allergy

Background:

• Airway hyperresponsiveness (AHR) is a key feature of asthma, irrespective of phenotype.
• Mannitol-induced AHR is specifically associated with airway mast cell infiltration.
• Inhaled corticosteroids (ICS) may reduce mannitol response, even in low type 2 inflammation asthma.

Purpose of the Study:

• To investigate the link between AHR, mast cell infiltration, and ICS treatment response.
• To explore differences in mast cell distribution and AHR in asthma phenotypes based on fractional exhaled nitric oxide (Feno).

Main Methods:

• 50 patients with AHR to mannitol, without prior ICS use, underwent biopsies before and after 6 weeks of daily ICS (budesonide 1600 μg).
• Patients were stratified into Feno-high (≥25 ppb) and Feno-low (<25 ppb) groups.
• Mast cell density, chymase-high mast cells, thymic stromal lymphopoietin, and IL-33 levels were assessed.

Main Results:

• ICS treatment improved AHR in both Feno-high and Feno-low groups.
• In Feno-high asthma, AHR correlated with epithelial mast cell density.
• In Feno-low asthma, AHR correlated with airway smooth muscle mast cell density.
• ICS treatment led to reduced mast cells, thymic stromal lymphopoietin, and IL-33.

Conclusions:

• Mannitol-induced AHR is associated with mast cell infiltration patterns that differ between Feno-high and Feno-low asthma phenotypes.
• ICS are effective in reducing AHR across different asthma phenotypes by decreasing mast cell infiltration and related inflammatory mediators.