A1lerg.v 1996: 51: zyxwvutsrqpon 394-400 zyxwvutsrqponm Priiited in UK zyxwvutsrqponm ~ all rights reserved Copyright zyx 0 Munksgaard 1996 ALLERGY ISSN zyxw 0105 -4538 Ex vivo zyxw pharmacologic modulation of basophil histamine release in asthmatic patients Lebel zyxwvutsrq B, Arnoux B, Chanez P, Bougeard Y-H, Daures JP, Bousquet J, Campbell AM. Ex vivo pharmacologic modulation of basophil histamine release in asthmatic patients. Allergy 1996: 51: 394-400. 0 Munksgaard 1996. Histamine is one of a range of mediators which play an important role in asthma, and the “releasability” of basophils has been shown to be upregulated in this disease. In vitro, P,-agonists and to a lesser extent corticosteroids have been shown to reduce histamine release. The ex vivo effects of salmeterol and inhaled corticosteroids on histamine release were studied in 78 asthmatic patients with variable disease severity and 20 control subjects. Spontaneous and anti-IgE-induced histamine release was measured in all subjects. Fifteen patients were not receiving any form of treatment, 42 were treated with inhaled corticosteroids, and 21 received inhaled corticosteroids and salmeterol. Seven patients treated with inhaled corticosteroids and seven patients treated with inhaled corticosteroids and salmeterol were tested twice to assess the effect of salmeterol on histamine release. Nine patients treated with inhaled corticosteroids were tested before and after 1 month of salmeterol treatment to determine the possible inhibition by salmeterol. Patients who were treated with inhaled corticosteroids and salmeterol showed significantly lower levels of spontaneous histamine release (median: 2.5%) than untreated (5.2%) and inhaled corticosteroids-treated asthmatics (3.4%). No tachyphylaxis to salmeterol was observed when patients were tested twice at a 3-month interval. This study suggests that salmeterol may have an additive anti- inflammatory effect with inhaled corticosteroids, although this hypothesis must be tested by further studies involving cells obtained by bronchoalveolar lavage and studies with bronchial biopsies. Metachromatic cells are found in the bronchi of normal and asthmatic subjects (1, 2). In asthmatic subjects, these cells have been shown to be degranu- lated by both direct methods such as electron micro- scopy (3) or immunocytochemistry and indirectly as demonstrated by increased levels of tryptase, histamine, and prostaglandin ( PG)D2 in the bron- choalveolar lavage (BAL) fluid (4-9). Basophils play an important role in the late-phase reaction both after allergen challenge (10, 11) and in acute asthma (12), but their role in chronic asthma remains to be clarified. Some authors have observed an increase in the spontaneous release of histamine from peripheral blood basophils of asthmatic sub- jects (13-19), an increase which is reduced when asthma symptoms are controlled. In some asth- matics, there is also an increased release of histamine in response to immunologic stimuli (20, 21). zyxwvu B. Lebel, B. Amoux, P. Chanez, Y.-H. Bougeard, J. P. Daures, J. Bousquet, A. M. Campbell Clinique des Maladies Respiratoires and Unite 454 INSERM, HBpital Arnaud de Villeneuve. Montpellier, and Departement de Biostatistiques, CHU Montoellier, France Key words- asthmatic patients; basophil histamine release; inhaled corticosteroids; salmeterol. Jean Bousquet. MU Clinique des Maladies Respiratoires HBpital Arnaud de Villeneuve Centre Hospitalier Universitaire 34295 Montpellier Cedex-5 France Accepted for publication 4 March 1996 Pharmacologic studies have examined the in vitro inhibitory activity of various antiasthma drugs on the immunologic or nonimmunologic release of histamine from blood basophils and mast cells. p2- Agonists have been found to be potent inhibitors of histamine release, but differences exist among the cell types studied (22-26). These in vitro effects have been confirmed during bronchial allergen chal- lenge (27), exercise challenge (28), or skin tests with allergens (for review, see Bousquet & Michel [29]). However, it is not known whether tachyphyl- axis can develop when P,-agonists are administered over long periods of time. Corticosteroids can block in vitro histamine release (30), but only one study has shown that orally administered steroids can inhibit histamine release (31). Salmeterol, a long-acting 0,-agonist (32), may possess some anti-inflammatory properties in 394