Airway tissue mast cells in persistent asthma: predictor of treatment failure when patients discontinue inhaled corticosteroids.
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.
Kraft
Monica
M
National Jewish Medical and Research Center, Denver, CO 80206, USA. kraftm@njc.org
Martin
Richard J
RJ
Lazarus
Stephen C
SC
Fahy
John V
JV
Boushey
Homer A
HA
Lemanske
Robert F
RF
Szefler
Stanley J
SJ
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
D000318:Adrenergic beta-Agonists; D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D000068299:Salmeterol Xinafoate; D012697:Serine Endopeptidases; D053802:Tryptases; D014222:Triamcinolone Acetonide; D000420:Albuterol