Evidence of ongoing mast cell and eosinophil degranulation in symptomatic asthma airway

• Published in: Journal of allergy and clinical immunology Vol. 88; no. 4; pp. 637 - 648
• Main Authors: Broide, David H., Gleich, Gerald J., Cuomo, Anthony J., Coburn, David A., Federman, Edward C., Schwarte, Lawrence B., Wasserman, Stephen I.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.10.1991; Elsevier
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Analysis of Variance; Asthma; Asthma - pathology; Asthma - physiopathology; Biological and medical sciences; Bronchoalveolar Lavage Fluid - cytology; Cell Count; Cell Degranulation; eosinophil; eosinophil-derived neurotoxin; Eosinophils - physiology; Female; Forced Expiratory Volume; histamine; Histamine Release; Humans; Immunological methods for diagnosis and exploration; Immunopathology; major basic protein; Male; mast cell; Mast Cells - metabolism; Mast Cells - physiology; Medical sciences; Middle Aged; Other methods; tryptase; eosinophil-derived neurotoxin; histamine; Ag; BALF; mast cell; EOS; FEF 50; EDN; Asthma; major basic protein; MDI; UCSD; MBP; eosinophil; EIA; tryptase; Assay; Human; Allergy; Immunopathology; Biological fluid; Bronchioalveolar; Respiratory disease; Degranulation; Chemical mediator; Mast cell; Eosinophil
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/0091-6749(91)90158-K

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 FEV 1 (1.52 ± 0.33 L:55% ± 15% of predicted FEV 1) and the forced expiratory flow at 50% (FEF 50) (1.11 ± 0.62 L/sec:26% ± 14% of predicted FEF 50) in the patients with symptomatic asthma were significantly lower than the corresponding values for FEV 1 (3.16 ± 0.45 L:86% ± 10% of predicted FEV 1) and the FEF 50 (4.04 ± 1.54 L/sec:71% ± 25% of predicted FEF 50) 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 < 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.