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Airway tissue mast cells in persistent asthma: predictor of treatment failure when patients discontinue inhaled corticosteroids.

Abstract：

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 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 salmeterol (42 micro g 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.

journal_name

Chest

journal_title

Chest

authors

Kraft M,Martin RJ,Lazarus SC,Fahy JV,Boushey HA,Lemanske RF Jr,Szefler SJ,Asthma Clinical Research Network.

doi

10.1378/chest.124.1.42

subject

Has Abstract

pub_date

2003-07-01 00:00:00

pages

42-50

issue

eissn

0012-3692

issn

1931-3543

pii

S0012-3692(15)35987-0

journal_volume

124

pub_type

临床试验,杂志文章,多中心研究,随机对照试验

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Airway tissue mast cells in persistent asthma: predictor of treatment failure when patients discontinue inhaled corticosteroids.