Effects of ketotifen on symptoms and on bronchial mucosa in patients with atopic asthma.
Ketotifen is marketed throughout the world as an antiallergy drug, but whether it affects infiltration of inflammatory cells into airway mucosa is not known. We studied the effects of ketotifen on symptoms, pulmonary function, and airway inflammation in 25 patients with atopic asthma. Patients took ketotifen (1 mg twice daily) or a matching placebo for 8 weeks in a double-blind, parallel-group study. Data recorded on diary cards were used for 2 weeks before treatment began, and they were used for the last 2 weeks of treatment to study asthma symptoms, use of beta 2-agonists, and peak expiratory flow (PEF). Pulmonary function tests, bronchial responsiveness to methacholine, and fiberoptic bronchoscopy were performed before and after treatment. Biopsy specimens were obtained by bronchoscopy. Specimens were stained immunohistochemically with monoclonal antibodies against stored eosinophil cationic protein (EG1), the secreted form of eosinophil cationic protein (EG2), mast-cell tryptase (AA1), neutrophil elastase (NP57), CD3, CD4, CD8, and CD25. The numbers of positively stained cells in the lamina propria were counted. Compared with the placebo, the ketotifen-treated group exhibited significant improvement of asthma symptoms (P < 0.05) and bronchial responsiveness (P < 0.05). This was accompanied by a reduction of EG2+ eosinophils (P < 0.05), CD3+ T cells (P < 0.001), CD4+ T cells (P < 0.01), and CD25+ activated T cells (P < 0.01) in the bronchial mucosa. These results suggested that the beneficial effects of ketotifen in bronchial asthma may result from consequent inhibition of activated eosinophils and T-cell recruitment into the airway. Moreover, ketotifen may relieve allergic inflammation in bronchial asthma.
Hoshino
M
M
Second Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan.
Nakamura
Y
Y
Shin
Z
Z
Fukushima
Y
Y
D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000627:therapeutic use; D000328:Adult; D018926:Anti-Allergic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015703:Antigens, CD / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols; D001249:Asthma / Q000188:drug therapy*; D001706:Biopsy; D001798:Blood Proteins / Q000378:metabolism; D001980:Bronchi / Q000187:drug effects / Q000276:immunology; D001985:Bronchial Provocation Tests; D001999:Bronchoscopy; D003561:Cytarabine / Q000378:metabolism; D004311:Double-Blind Method; D004317:Doxorubicin / Q000378:metabolism; D047091:Eosinophil Granule Proteins; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000188:drug therapy; D007665:Ketotifen / Q000008:administration & dosage / Q000627:therapeutic use*; D019272:Leukocyte Elastase / Q000378:metabolism; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D008875:Middle Aged; D010366:Peak Expiratory Flow Rate; D012260:Ribonucleases; D013601:T-Lymphocytes / Q000276:immunology
D000318:Adrenergic beta-Agonists; D018926:Anti-Allergic Agents; D015703:Antigens, CD; D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D003561:Cytarabine; D016210:Methacholine Chloride; D004317:Doxorubicin; D012260:Ribonucleases; D019272:Leukocyte Elastase; D007665:Ketotifen