Airway tissue mast cells in persistent @entity565 : predictor of treatment failure when XXXX discontinue inhaled corticosteroids.

@entity1 @entity2796 @entity2995 @entity565 @entity10453
STUDY OBJECTIVES: To determine if persistent airway tissue mast cells are associated with treatment failure when @entity1 discontinue inhaled corticosteroids (ICS). DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: Multicenter, tertiary referral centers. @entity1 OR @entity1 : Forty-five subjects with @entity565 recruited from six medical centers in the United States. INTERVENTIONS: The Asthma Clinical Research Network undertook a 28-week, randomized, multicenter, double-blind, placebo-controlled trial of 164 subjects with clinically stable, persistent @entity565 . A subset of subjects (n = 45) underwent bronchoscopy with endobronchial biopsy and BAL at the end of a 6-week run-in period, during which all subjects received @entity2995 ( @entity2796 ), 400 microg bid. Airway tissue mast cells, eosinophils, neutrophils, macrophages, and T cells were quantified morphometrically along with determination of BAL tryptase. At the end of the run-in period, subjects were then randomized to receive @entity10453 (42 micro g bid), placebo, or continue @entity2796 for 16 weeks followed by a second bronchoscopy. MEASUREMENTS AND RESULTS: Outcome variables included airway tissue mast cells, eosinophils, neutrophils, macrophages, and T cells that were quantified morphometrically and BAL tryptase. Thirty-five subjects completed the treatment phase; an additional 10 subjects, who were randomized to either @entity10453 or placebo after the run-in, had treatment failure. When the bronchoscopy results performed at the end of the run-in, prior to randomization, were analyzed, the treatment failure group demonstrated significantly more tissue mast cells as compared to the nontreatment failure group despite 6 weeks of therapy with @entity2796 (p = 0.04). BAL tryptase was also significantly higher in the treatment failure group (p < 0.0001). Of those subjects who completed the study, tissue mast cells and BAL tryptase did not change significantly within any of the treatment groups during the treatment phase (p > 0.05). CONCLUSIONS: Persistent elevations in airway tissue mast cells and BAL tryptase after treatment with @entity2796 predict treatment failure in @entity1 for whom discontinuation of ICS is being considered.
