The effects of a 5-lipoxygenase inhibitor on asthma induced by cold, dry air

Arachidonic acid is the grandfather of many compounds which play roles in the mediation of inflammation. Many of the compounds believed to be important in the bronchoconstriction and inflammation which occurs in asthma are synthesized through the metabolism of arachidonic acid by the enzyme 5-lipoxygenase. While these products have been demonstrated to induce attacks of asthma, attempts to prevent asthmatic attacks by inhibiting 5-lipoxygenase have been disappointing. This may be due at least in part to the failure of some enzyme inhibitors to achieve satisfactory blockade of enzymatic activity within the human body. For this reason, an attempt was made to evaluate a novel inhibitor of 5-lipoxygenase, A-64077, which has previously been shown to be effective at inhibiting 5-lipoxygenase activity in laboratory animals. The compound was experimentally evaluated in 13 asthmatic volunteers who induced bronchoconstriction by hyperventilating in cold, dry air. Prior to breathing the cold, dry air, the patients received either a placebo or a capsule of A-64077. The response of the patient was measured biochemically through the analysis of blood specimens taken before and after the drug treatment. The response was also monitored physiologically, by the period of cold exposure which is necessary to produce a specific change in the FEV1, the volume of air which can be forcibly expelled in one second. The results showed that treatment with A-64077 resulted in a 74 percent reduction in the 5-lipoxygenase activity which could be induced in the blood samples. The treatment also increased by almost half the amount of time in the cold necessary to produce a 10 percent reduction in FEV1. The results show that inhibition of 5-lipoxygenase can result in significant reductions in the asthmatic response induced by cold, dry air. (Consumer Summary produced by Reliance Medical Information, Inc.)