title: Evidence of ongoing mast cell and eosinophil degranulation in symptomatic asthma airway.
abstract: To assess whether mast cell and eosinophil (EOS) degranulation occurs in the airway of subjects with moderately symptomatic asthma, we have measured levels of preformed mast cell-derived mediators (histamine and tryptase) and EOS-derived mediators (major basic protein and EOS-derived neurotoxin) in bronchoalveolar lavage fluid (BALF) obtained from patients with symptomatic (N = 14) and asymptomatic asthma (N = 9) and patients without asthma (N = 6). Both the FEV1 (1.52 +/- 0.33 L:55% +/- 15% of predicted FEV1) and the forced expiratory flow at 50% (FEF50) (1.11 +/- 0.62 L/sec:26% +/- 14% of predicted FEF50) in the patients with symptomatic asthma were significantly lower than the corresponding values for FEV1 (3.16 +/- 0.45 L:86% +/- 10% of predicted FEV1) and the FEF50 (4.04 +/- 1.54 L/sec:71% +/- 25% of predicted FEF50) in the patients with asymptomatic asthma. Levels of histamine (4.8 +/- 5.0 ng/ml versus 0.2 +/- 0.2 ng/ml) (p = 0.05), EOS-derived neurotoxin (420.6 +/- 959.4 ng/ml versus 12.6 +/- 7.7 ng/ml) (p = 0.05), major basic protein (31.4 +/- 46.6 ng/ml versus less than 9 ng/ml) (p = 0.05), and percent EOSs (10.6% +/- 7.0% versus 1.1% +/- 0.9% of BAL cells) (p = 0.0006) were all significantly elevated in BALF from symptomatic compared to asymptomatic patients with asthma. The elevated levels of tryptase (13.2 +/- 14.8 ng/ml versus 3.9 +/- 3.9 ng/ml) in BALF from symptomatic compared to asymptomatic patients with asthma approximated, but did not reach, statistical significance. Spontaneous histamine release from BAL mast cells of symptomatic patients with asthma was 46% +/- 5% compared to 5% +/- 2% in asymptomatic patients with asthma. In response to antihuman IgE, histamine release from BAL mast cells recovered from asymptomatic patients with asthma increased to 25% +/- 10%, whereas in BAL mast cells of symptomatic patients with asthma, no anti-IgE potentiation of histamine release occurred. This study suggests that mast cell and EOS degranulation is ongoing in the airway of patients with moderately symptomatic asthma.
authors.affiliation: Department of Medicine, University of California, San Diego.
authors.forename: D H
authors.initials: DH
authors.lastname: Broide
authors.forename: G J
authors.initials: GJ
authors.lastname: Gleich
authors.forename: A J
authors.initials: AJ
authors.lastname: Cuomo
authors.forename: D A
authors.initials: DA
authors.lastname: Coburn
authors.forename: E C
authors.initials: EC
authors.lastname: Federman
authors.forename: L B
authors.initials: LB
authors.lastname: Schwartz
authors.forename: S I
authors.initials: SI
authors.lastname: Wasserman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001249:Asthma / Q000473:pathology* / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D002452:Cell Count; D015550:Cell Degranulation; D004804:Eosinophils / Q000502:physiology*; D005260:Female; D005541:Forced Expiratory Volume; D006636:Histamine Release; D006801:Humans; D008297:Male; D008407:Mast Cells / Q000378:metabolism / Q000502:physiology*; D008875:Middle Aged