CLINICAL POTENTIAL OF ANTI-THROMBOXANE A(2) AGENTS IN BRONCHIAL-ASTHMA

Animal and human studies have shown that various kinds of chemical med iators may participate in the pathogenesis of bronchial asthma. Among these mediators, thromboxane A(2) (TXA(2)) is recognised as important in bronchial responses and the pathogenesis of airway hyperresponsiven ess. The reasons are as follows. (i) TXA(2) (or mimetics) is a powerfu l constrictor of bronchial muscle in vitro and in vivo. (ii) Levels of TXB2, a metabolite of TXA(2), increase in blood or bronchoalveolar la vage fluid after allergen challenge in atopic asthmatic patients. (iii ) TXA(2) mimetics induce airway hyperresponsiveness to nonspecific sti muli such as acetylcholine or methacholine. (iv) TXA(2) synthetase inh ibitors or TXA(2) receptor antagonists inhibit asthmatic responses or airway hyperresponsiveness in various animal models and in patients wi th asthma. In Japan, the TXA(2) synthetase inhibitor ozagrel and the T XA(2) receptor antagonist seratrodast are now used in the treatment of patients with bronchial asthma. In multicentre double-blind studies, these 2 agents were shown to have beneficial effects in adult patients with asthma, and no serious adverse effects were reported. This revie w deals with the role of TXA(2) in the pathogenesis of bronchial asthm a and the clinical potential of anti-TXA(2) agents in the treatment of bronchial asthma.