A proportion (10to 30070) of subjects with asthma are intolerant of aspirin. In these persons, aspirin ingestion is followed by the onset of bronchoconstriction, rhinitis, and/or urticaria within I to 2 h (1). Aspirin-induced asthma tends to occur in the third to fourth decade of life. Subjects are characteristically nonatopic and have asthma that may be difficult to control with medication. Nasal polyps are common. The majority of subjects with aspirin sensitivity may be desensitized to aspirin by the administration of increasing doses of aspirin orally. This may lead to an improvement in the severity of asthma and of nasal symptoms (2). The mechanism of aspirin sensitivity is unknown. Subjects with aspirin-induced asthma are also intolerant of other nonsteroidal anti-inflammatory drugs, and the capacity of these agents to provoke asthma is related to their potencies and inhibitors of the cyclooxygenaseenzyme (3). After successfuldesensitization to aspirin, subjects are then able to ingest other nonsteroidal anti-inflammatory drugs without adverse effects. Asthmatic attacks may be precipitated by several analgesics with different chemical structures, making chemical cross-reactivity most unlikely (4). In recent years, the concept of aspirin-precipitated attacks that are linked to inhibition of cyclooxygenase in the respiratory tract of sensitive patients has gained support.

Arachidonic acid is released from cellmembrane phospholipids by the action phospholipase A2• This substrate may be metabolized by the cyclooxygenase pathway to the prostaglandins and thromboxane A2, or by the 5-lipoxygenase pathway to leukotrienes. The 5-lipoxygenase generates LTA. from arachidonic acid and this is metabolized by an epoxide hydrolase to LTB. or by glutathionyl-S-transferase, termed LTC. synthetase, to LTC•. LTC. is cleaved to LTD. and to LTE. by gamma-glutamyl transpeptidase and by dipeptidase, respectively. The sulfidopeptide leukotrienes, LTC., LTD., and LTE., are potent spasmogens for nonvascular smooth muscle and comprise the activity previously recognized as slow-reacting substance of anaphylaxis.