INHALED LOOP DIURETICS AND BASAL AIRWAY RESPONSIVENESS IN MAN - EVIDENCE OF A ROLE FOR CYCLOOXYGENASE PRODUCTS

Inhaled frusemide protects asthmatic airways against a wide variety of bronchoconstrictor stimuli by unknown mechanisms. To investigate whet her inhaled loop diuretics modulate baseline bronchial responsiveness, a randomized, double-blind, placebo-controlled study was conducted to test the ability of frusemide (40 mg) and bumetanide (2 mg) to displa ce concentration-response curves with methacholine in 14 healthy volun teers. In addition, separate randomized, double-blind studies were car ried out to evaluate the effects of oral flurbiprofen, a potent cyclo- oxygenase inhibitor, on the protective action of frusemide against met hacholine-induced bronchoconstriction. Inhaled loop diuretics signific antly increased the provocative concentration of methacholine causing a 15% decrease in forced expiratory volume in one second (PC15FEV(1)) from the geometric mean (range) value of 58.6 (9.2-2331 mg . ml(-1) af ter placebo administration, to 129 (13.8-505) and to 106 (6.6-510) mg . ml(-1) after administration of frusemide and bumetanide, respectivel y, Similar results were obtained when data from partial flow-volume cu rves were used for analysis. In the eight subjects studied, pretreatme nt with oral placebo and inhaled frusemide reduced airway responsivene ss to methacholine, with a geometric mean (range) PC15FEV(1) value of 116 (25.4-405) mg . ml(-1), and premedication with oral flurbiprofen a bolished this protective effect, the geometric mean (range) PC15FEV(1) methacholine being reduced to a value of 50.3 (16.6-189) mg . ml(-1). In addition, oral flurbiprofen alone failed to alter airway responsiv eness to methacholine. In view of these findings, it is suggested that bronchoprotective prostaglandins may mediate the effects of loop diur etics against methacholine-induced bronchoconstriction in man.