The influence of misoprostol (synthetic analogue of prostaglandin E1) on aspirin-induced bronchoconstriction in aspirin-sensitive asthma.

It is believed that aspirin (ASA) and other nonsteroidal anti-inflammatory drugs elicit dyspnea in ASA-sensitive asthmatics by blocking cyclooxygenase. It is unclear whether this bronchospasm is due to the shunting of arachidonic acid into the lipoxygenase pathway or to the removal of a cyclooxygenase product which prevents bronchospasm. Diminished tissue concentration of PGE may cause bronchoconstriction. PGE also modulates mast cells, decreasing the release of anaphylaxis mediators. The authors investigated the influence of a synthetic analogue of PGE1-misoprostol (Cytotec, Searle)-on post-aspirin bronchoconstriction in seven ASA-sensitive asthmatics. On the first day, the effect of a placebo was studied. On the second day, the bronchodilatory effect of misoprostol (Cytotec, Searle) alone was examined. After a few days, a predetermined threshold dose of ASA was administered. Seven days later, at least 400 micrograms of misoprostol +200 micrograms 2 h later, together with a predetermined ASA dose, were administered. In all but one patient, the protective influence of misoprostol on ASA-induced bronchoconstriction was observed. The maximum drop in FEV1 (forced expiratory volume in one second) in % after ASA in each of the patients was 40, 25, 24, 33, 47 and 54, and after ASA with misoprostol 10, 9, 4, (+8), 10, (+2) and 45, respectively. Misoprostol given together with ASA attenuated aspirin-induced bronchoconstriction, reaching statistical significance at 3 and 3.5 h. It also diminished extrapulmonary symptoms.