THE INFLUENCE OF MISOPROSTOL (SYNTHETIC ANALOG OF PROSTAGLANDIN E(1))ON ASPIRIN-INDUCED BRONCHOCONSTRICTION IN ASPIRIN-SENSITIVE ASTHMA

It is believed that aspirin (ASA) and other nonsteroidal anti-inflamma tory drugs elicit dyspnea in ASA-sensitive asthmatics by blocking cycl ooxygenase. It is unclear whether this bronchospasm is due to the shun ting of arachidonic acid into the lipoxygenase pathway or to the remov al of a cyclooxygenase product which prevents bronchospasm. Diminished tissue concentration of PGE may cause bronchoconstriction. PGE also m odulates mast cells, decreasing the release of anaphylaxis mediators. The authors investigated the influence of a synthetic analogue of PGE( 1) - misoprostol (Cytotec, Searle) - on post-aspirin bronchoconstricti on in seven ASA-sensitive asthmatics. On the first day, the effect of a placebo was studied. On the second day, the bronchodilatory effect o f misoprostol (Cytotec, Searle) alone was examined. After a few days, a predetermined threshold dose of ASA was administered. Seven days lat er, at least 400 mu g of misoprostol + 200 mu g 2 h later, together wi th a predetermined ASA dose, were administered. in all but one patient , the protective influence of misoprostol on ASA-induced bronchoconstr iction was observed. The maximum drop in FEV(1) (forced expiratory vol ume in one second) in % after ASA in each of the patients was 40, 25, 24, 33, 33, 47 and 54, and after ASA with misoprostol 10, 9, 4, (+8), 10, (+2) and 45, respectively. Misoprostol given together with ASA att enuated aspirin-induced bronchoconstriction, reaching statistical sign ificance at 3 and 3.5 h. It also diminished extrapulmonary symptoms.