Bronchoalveolar lavage tryptase levels are correlated with type 2 airway inflammation in mild asthma

Abstract

Background: Tryptase, the major protein product of mast cells, can mediate multiple pathologic manifestations of asthma. Objectives: Determine whether airway tryptase levels are related to manifestations of type 2 airway inflammation in asthma patients of varying severity. Methods: Bronchoscopy in healthy controls (N=20), patients with mild-moderate asthma (N=23) before and after an 8-week course of inhaled corticosteroid (ICS) treatment, moderate asthma (N=33) on chronic ICS treatment, and severe asthma (N=64) uncontrolled despite high-dose ICS treatment. Assessments include: bronchoalveolar lavage (BAL) tryptase, bronchial epithelial gene expression, FeNO, and peripheral blood levels of eosinophils, periostin, tryptase, and IgE. Results: In mild asthma patients not taking ICS, BAL but not plasma tryptase levels were significantly higher than in controls. BAL tryptase was significantly correlated with the expression of a bronchial epithelial “Th2 signature”, FeNO, blood eosinophils, and plasma periostin and IgE, but not with plasma tryptase levels. Mild asthma patients with elevated BAL tryptase at baseline exhibited significant decreases in BAL tryptase after ICS treatment. In moderate asthma patients on stable ICS doses and severe asthma patients uncontrolled despite high-dose ICS, BAL tryptase levels were elevated vs. healthy controls but were not strongly correlated with indices of type 2 airway inflammation. Conclusions: BAL tryptase levels and measures of type 2 airway inflammation are concordant in mild asthma patients, but discordant in moderate and severe asthma patients, which may reflect different mast cell phenotypes, localization, and effects of steroid exposure.