title: Airway tissue mast cells in persistent asthma: predictor of treatment failure when patients discontinue inhaled corticosteroids.
abstract: OBJECTIVE
  To determine if persistent airway tissue mast cells are associated with treatment failure when patients discontinue inhaled corticosteroids (ICS).
  
  
  METHODS
  Double-blind, randomized, placebo-controlled trial.
  
  
  METHODS
  Multicenter, tertiary referral centers.
  
  
  METHODS
  Forty-five subjects with asthma recruited from six medical centers in the United States.
  
  
  METHODS
  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.
  
  
  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.
authors.affiliation: National Jewish Medical and Research Center, Denver, CO 80206, USA. kraftm@njc.org
authors.forename: Monica
authors.initials: M
authors.lastname: Kraft
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Martin
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Lazarus
authors.forename: John V
authors.initials: JV
authors.lastname: Fahy
authors.forename: Homer A
authors.initials: HA
authors.lastname: Boushey
authors.forename: Robert F
authors.initials: RF
authors.lastname: Lemanske
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Szefler
mesh_terms: D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000627:therapeutic use; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000473:pathology; D001706:Biopsy; D001992:Bronchoalveolar Lavage Fluid; D001999:Bronchoscopy; D002452:Cell Count; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis; D008297:Male; D008407:Mast Cells / Q000473:pathology*; D000068299:Salmeterol Xinafoate; D012697:Serine Endopeptidases / Q000032:analysis; D013997:Time Factors; D017211:Treatment Failure; D014222:Triamcinolone Acetonide / Q000008:administration & dosage / Q000627:therapeutic use*; D053802:Tryptases
chemical_list: D000318:Adrenergic beta-Agonists; D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D000068299:Salmeterol Xinafoate; D012697:Serine Endopeptidases; D053802:Tryptases; D014222:Triamcinolone Acetonide; D000420:Albuterol