TY - JOUR
T1 - Airway tissue mast cells in persistent asthma
T2 - Predictor of treatment failure when patients discontinue inhaled corticosteroids
AU - Kraft, Monica
AU - Martin, Richard J.
AU - Lazarus, Stephen C.
AU - Fahy, John V.
AU - Boushey, Homer A.
AU - Lemanske, Robert F.
AU - Szefler, Stanley J.
N1 - Funding Information:
Supported by grants U10 HL-51810, U10 HL-51834, U10 HL-51831, U10 HL-51823, U10 HL-51845, U10 HL-51843, and U10 HL-56443 from the National Heart, Lung, and Blood Institute. Financial disclosure statements for all authors are on file.
PY - 2003/7/1
Y1 - 2003/7/1
N2 - Study objectives: To determine if persistent airway tissue mast cells are associated with treatment failure when patients discontinue inhaled corticosteroids (ICS). Design: Double-blind, randomized, placebo-controlled trial. Setting: Multicenter, tertiary referral centers. Patients or participants: Forty-five subjects with asthma 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 asthma. 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 triamcinolone acetonide (TAA), 400 μg 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 salmeterol (42 μg bid), placebo, or continue TAA 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 salmeterol 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 TAA (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 TAA predict treatment failure in patients for whom discontinuation of ICS is being considered.
AB - Study objectives: To determine if persistent airway tissue mast cells are associated with treatment failure when patients discontinue inhaled corticosteroids (ICS). Design: Double-blind, randomized, placebo-controlled trial. Setting: Multicenter, tertiary referral centers. Patients or participants: Forty-five subjects with asthma 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 asthma. 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 triamcinolone acetonide (TAA), 400 μg 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 salmeterol (42 μg bid), placebo, or continue TAA 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 salmeterol 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 TAA (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 TAA predict treatment failure in patients for whom discontinuation of ICS is being considered.
KW - Asthma
KW - Bronchoscopy
KW - Mast cell
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U2 - 10.1378/chest.124.1.42
DO - 10.1378/chest.124.1.42
M3 - Article
C2 - 12853500
AN - SCOPUS:0037484793
VL - 124
SP - 42
EP - 50
JO - Diseases of the chest
JF - Diseases of the chest
SN - 0012-3692
IS - 1
ER -