Beclomethasone dipropionate dry-powder inhalation compared with conventional aerosol in chronic asthma.

In a double-blind study beclomethasone dipropionate inhaled as a dry powder in doses of 100 microgram four times daily and 150 microgram four times daily was compared with the conventional aerosol dose of 100 microgram four times daily in 20 outpatients with chronic asthma. Each of the three treatments was given for four weeks. The dry powder in a dose of 150 microgram four times daily had advantages over the other two treatments in terms of FEV1 and the number of exacerbations of asthma during the study. There were no adverse reactions to inhaling dry-powder beclomethasone. It was concluded that this new way of administering the drug was effective in chronic asthma, and should allow most patients with chronic asthma who cannot use conventional pressurised aerosols efficiently to benefit from inhaled corticosteroid treatment.     

Induction of drug-metabolizing enzymes and transporters in human bronchial epithelial cells by beclomethasone dipropionate

Inhaled steroids are the most potent anti-inflammatory therapy commonly used in bronchial asthma. There are, however, a small number of asthmatic patients who do not respond to inhaled steroid-treatment. The stimulation of metabolism and excretion of inhaled drugs at bronchial tissues might lead to a decrease in the effect of the drugs, although the molecular mechanism of this resistance is unclear. In this study, we found that beclomethasone dipropionate (BDP) stimulated the expression of mRNAs for uridine 5'-diphosphate glucuronosyl transferase 2B4 and 2B11, and transporters such as multidrug resistance P-glycoprotein, multidrug resistance-associated protein 1 and 2 in cultured bronchial epithelial cells. It is possible that the individual differences of expression of drug metabolizing enzymes and transporters and their enhancement with BDP are implicated in the individual differences of reactivity over steroid medical treatment.     

Cell surface antigen expression by peripheral blood monocytes in allergic asthma: results of 2.5 years therapy with inhaled beclomethasone dipropionate

At present, inhaled glucocorticoids are widely accepted as the therapy of choice in chronic asthma. Treatment with inhaled glucocorticoids significantly suppresses local airway inflammation in asthmatics, but may also have systemic effects, e.g. a reduction of the number of circulating hypodense eosinophils or a down-modulation of HLA-DR antigen (Ag) expression by T lymphocytes in peripheral blood. However, the effect of long-term therapy with inhaled glucocorticoids on peripheral blood monocytes (PBM), which are the precursors of the most numerous cell type in the lung, the alveolar macrophage, have not yet been evaluated. We therefore investigated the expression of various cell surface Ag on PBM from non-smoking patients with allergic asthma who were treated for 2.5 years with a beta(2)-receptor agonist plus either an inhaled glucocorticoid (beclomethasone dipropionate, BDP) (n = 4) or an anticholinergic or placebo (n = 8). We compared the results with healthy volunteers (n = 7). Long-term treatment of allergic asthmatics with inhaled BDP, but not anticholinergic or placebo therapy, was associated with a significantly lower CDllb Ag expression (p < 0.04) and higher expression of CD13, CD14 and CD18 Ag (p < 0.05, p < 0.02 and p < 0.04, respectively) when compared with the healthy control subjects (n = 7). Most interestingly, PBM of asthmatics treated with inhaled BDP expressed an almost two-fold higher level of CD14 Ag on their cell surface than PBM of patients treated with anticholinergic or placebo (p < 0.03). No significant differences in the expression of CD16, CD23, CD25, CD32 and CD64 Ag or HLA-DR were observed between PBM from the different patient groups or healthy controls. Taken together, this study shows that long-term local therapy with inhaled BDP coincides with an altered expression of at least one cell surface Ag on PBM from allergic asthmatics.     

Effect of calcium channel blockers on histamine liberation from isolated basophils and bronchial reactivity in patients with bronchial asthma]

An effect of verapamil and nifedipine on the cellular histamine release and non-specific reactivity of the bronchi measured with methacholine test was studied. In vitro tests were carried out in basophils isolated from 19 asthmatic patients. Reactivity of the bronchi was investigated in 5 patients. Both verapamil and nifedipine significantly inhibited histamine release from the cells in vitro in all examined concentrations (10(-7)-10(-4) M) while a single dose of these drugs administered to the asthmatic patients did not exert a significant effect on the airway constriction in vivo.     

Effect of cimetidine and ranitidine on bronchial reactivity in patients with asthma

The results of studies on the effect of cimetidine and ranitidine on the bronchial reactivity in a group of 10 patients with atopic bronchial asthma are discussed. The patients received 800 mg of cimetidine daily for 6 days and, after a three-day interval, 300 mg of ranitidine daily for a further 6 days. Bronchial reactivity was determined with the histamine test, according to Spector and Farr, before the administration of each drug and on the third and sixth days of each course of the treatment. A comparison of the effect of cimetidine and ranitidine on the bronchial reactivity in the same patients revealed that a 3-day exposure to each of the two drugs, cimetidine enhanced bronchial reactivity to a greater extent than ranitidine; the difference between the action of the two drugs being statistically significant (p less than 0.05). Bronchial reactivity was found to increase significantly after a 6-day treatment with each of the drugs but no statistically significant differences were noted comparing the effect of these drugs.     

Association between airway hyperreactivity and bronchial macrophage dysfunction in individuals with mild asthma

Little is known about the functional capabilities of bronchial macrophages (BMs) and their relationship to airway disease such as asthma. We hypothesize that BMs from asthmatics may be modulated in their function compared with similar cells from healthy individuals. BMs obtained by induced sputum from mild asthmatics (n = 20) and healthy individuals (n = 20) were analyzed using flow cytometry for CD16, CD64, CD11b, CD14, and human leukocyte antigen-DR expression, phagocytosis of IgG opsonized yeast, and oxidant production. Asthma status was assessed by lung function [percent predicted forced vital capacity and forced expiratory volume in 1 s (FEV(1))], percent sputum eosinophils, and nonspecific airway responsiveness [provocative concentration that produces a 20% fall in FEV(1) (PC(20,FEV1))]. Asthmatics with >5% airway eosinophils (AEo+) had decreased BM CD64 expression and phagocytosis compared with asthmatics with <5% eosinophils (AEo-). Among asthmatics, a significant correlation was found between CD64 expression and BM phagocytosis (R = 0.7, P < 0.009). Phagocytosis was also correlated with PC(20,FEV1) (R = 0.6, P < 0.007), lung function (%predicted FEV(1), R = 0.7, P < 0.002) and percent eosinophils (R = -0.6, P < 0.01). In conclusion, BM from asthmatics are functionally modulated, possibly by Th2 cytokines involved in asthma pathology.     

Effects of cortisol on calcium contents of lymphocytes in patients with bronchial asthma]

A fluorescent probe was used to study hydrocortisone (10 microM) action on mitogen-stimulated free cytoplasmic calcium level in lymphocytes of patients with bronchial asthma. The patients were divided into two groups according to their sensitivity to glucocorticoid therapy. Hydrocortisone-specific calcium-blocking effect was absent in hormone-resistant patients. Lymphocytes of hormone-sensitive patients responded to hydrocortisone administration by a decline of mitogen-induced calcium level.