INHIBITION OF SODIUM METABISULFITE INDUCED BRONCHOCONSTRICTION BY FRUSEMIDE IN ASTHMA - ROLE OF CYCLOOXYGENASE PRODUCTS

Background - Inhaled frusemide inhibits airway responses to sodium met abisulphite and other indirect bronchial challenges in asthma by undet ermined mechanisms which may relate to its ability to stimulate prosta glandin release. Inhalation of sodium metabisulphite provokes indirect bronchoconstriction, possibly by activating sensory nerves. To invest igate the role of cyclooxygenase products in the airway actions of fru semide and sodium metabisulphite, the effects of a potent cyclooxygena se inhibitor, flurbiprofen, alone and in combination with frusemide we re investigated against airway responsiveness to sodium metabisulphite . Methods - In a double blind double placebo controlled study, 12 mild asthmatic subjects attended on four occasions to undergo three inhala tion challenges with sodium metabisulphite. A baseline challenge was p erformed one hour before oral intake of flurbiprofen 200 mg or matched placebo, and two hours before inhalation of frusemide 40 mg or matche d placebo. A second challenge was performed immediately after inhalati on of frusemide (two hours after flurbiprofen) with a further challeng e three hours later. The log concentration provoking a 20% fall in FEV (1) (log PC20) was used to assess airway responsiveness to sodium meta bisulphite. Results - Frusemide caused an immediate 1.9 doubling dose protection and a lesser 0.7 doubling dose protection at three hours. T his protection was enhanced by flurbiprofen at both time points to 2.7 (early) and 1.9 (late) doubling doses. In addition, flurbiprofen alon e significantly reduced airway responsiveness to sodium metabisulphite by 1.1 doubling doses at both two and five hours. Conclusions - The g eneration of bronchoprotective prostaglandins is unlikely to underlie the inhibitory action of frusemide against airway responsiveness to so dium metabisulphite. Endogenous contractile prostaglandins within the airways may be involved in the bronchoconstrictor response to sodium m etabisulphite.