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

Chest. 2003 Jul;124(1):42-50. doi: 10.1378/chest.124.1.42.

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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Inhalation
  • Adrenergic beta-Agonists / administration & dosage
  • Adrenergic beta-Agonists / therapeutic use
  • Adult
  • Albuterol / administration & dosage
  • Albuterol / analogs & derivatives*
  • Albuterol / therapeutic use
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / therapeutic use*
  • Asthma / drug therapy*
  • Asthma / pathology
  • Biopsy
  • Bronchoalveolar Lavage Fluid
  • Bronchoscopy
  • Cell Count
  • Double-Blind Method
  • Female
  • Humans
  • Inflammation Mediators / analysis
  • Male
  • Mast Cells / pathology*
  • Salmeterol Xinafoate
  • Serine Endopeptidases / analysis
  • Time Factors
  • Treatment Failure
  • Triamcinolone Acetonide / administration & dosage
  • Triamcinolone Acetonide / therapeutic use*
  • Tryptases

Substances

  • Adrenergic beta-Agonists
  • Anti-Inflammatory Agents
  • Inflammation Mediators
  • Salmeterol Xinafoate
  • Serine Endopeptidases
  • Tryptases
  • Triamcinolone Acetonide
  • Albuterol