EX-VIVO PHARMACOLOGICAL MODULATION OF BASOPHIL HISTAMINE-RELEASE IN ASTHMATIC-PATIENTS

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, beta(2)-agonists and to a less er extent corticosteroids have been shown to reduce histamine release. The ex vivo effects of salmeterol and inhaled corticosteroids on hist amine release were studied in 78 asthmatic patients with variable dise ase severity and 20 control subjects. Spontaneous and anti-IgE-induced histamine release was measured in all subjects. Fifteen patients were not receiving ally form of treatment, 42 were treated with inhaled co rticosteroids, and 21 received inhaled corticosteroids and salmeterol. Seven patients ?reared with inhaled corticosteroids and seven patient s treated with inhaled corticosteroids and salmeterol were tested twic e to assess the effect of salmeterol on histamine release. Nine patien ts 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 an d salmeterol showed significantly lower levels of spontaneous histamin e release (median: 2.5%) than untreated (5.2%) and inhaled corticoster oids-treated asthmatics (3.4%). No tachyphylaxis to salmeterol was obs erved when patients were tested twice at a 3-month interval. This stud y suggests that salmeterol may have an additive anti-inflammatory effe ct with inhaled corticosteroids, although this hypothesis must be test ed by further studies involving cells obtained bronchoalveolar lavage and studies with bronchial biopsies.