EFFECTS OF FLUTICASONE PROPIONATE ON ARACHIDONIC-ACID METABOLITES IN BAL-FLUID AND METHACHOLINE DOSE-RESPONSE CURVES IN NONSMOKING ATOPIC ASTHMATICS

Hyperresponsiveness of the airways to nonspecific stimuli is a charact eristic feature of asthma. Airway responsiveness is usually characteri zed in terms of the position and shape of the dose-response curve to m ethacholine (MDR). In the study we have investigated the influence of fluticasone propionate (FP), a topically active glucocorticoid, on ara chidonic acid (AA) metabolites in broncho-alveolar lavage (BAL) fluid (i.e. TxB(2), PGE(2), PGD(2), 6kPGF(1 alpha) and LTC(4)) on the one ha nd and MDR curves on the other hand. The effect of FP was studied in a randomized, double-blind, placebo-controlled design in 33 stable non- smoking asthmatics; 16 patients received FP (500 mu g b.i.d.) whereas 17 patients were treated with placebo. We found that the forced expira tory volume in 1 s (FEV(1) % predicted) increased, the log(2)PC(20) me thacholine increased and the plateau value (% fall in FEV(1)) decrease d after a 12 week treatment period. No changes in AA-metabolites could be determined after treatment except for PGD(2) which decreased nearl y significantly (p = 0.058) within the FP treated group, whereas chang e of PGD(2) differed significantly (p = 0.05) in the FP treated group from placebo. The levels of the other AA metabolites (i.e. TxB(2), PGE (2), 6kPGF(1 alpha) and LTC(4)) remained unchanged after treatment and were not significantly different from the placebo group. Our results support the hypothesis that although FP strongly influences the positi on, the shape and also the maximum response plateau of the MDR curve, this effect is not mainly achieved by influence on the level of AA. me tabolites, Other pro-inflammatory factors may be of more importance fo r the shape of the MDR curve. It is suggested that these pro-inflammat ory factors are downregulated by FP.