The importance of COX-2 inhibition for aspirin induced asthma.

There have been recent reviews of aspirin induced asthma (AIA), 2 the use of the COX-2 preferential inhibitor nimesulide in asthmatic patients intolerant to non-steroidal anti-inflammatory drugs (NSAIDs), and of nimesulide in general. 5 This paper discusses the importance of inhibiting prostaglandin E2 (PGE2) synthesis in AIA, and the relative safety of NSAIDs that preferentially inhibit COX-2. Aspirin and other NSAIDs cause bronchoconstriction in about 10% of asthmatic subjects but NSAIDs relieve asthma in about 0.3%. This variability helps to show the complexity of the problem. Prostaglandins in human lung are formed by various tissues and cells, including bronchial muscle, epithelium, and inflammatory cells, 2 so the inhibition of prostaglandin formation can have numerous eVects. In addition, the prostanoids (prostaglandins and thromboxanes) formed have different, and sometimes opposite, eVects on the lungs. Furthermore, NSAIDs may alter the synthesis of various prostaglandins diVerently in patients with AIA—for example, aspirin reduces the synthesis of PGE2 but not of the bronchoconstrictors PGD2 and PGF2á. 6 Inhibition of PGE2 synthesis seems to be particularly important in AIA for several reasons: PGE2 can relax bronchial muscle, inhibit the formation or release of various bronchoconstrictor agents such as leukotrienes and histamine (levels of which are raised in patients with AIA), and PGE2 administered as an aerosol inhibits aspirin induced bronchoconstriction. 2 Since PGE2 and other prostanoids are formed by both constitutive COX-1 and induced COX-2, the eVect on the lung may partly reflect the relative activities of each NSAID on the enzymes. Generally, in various tissues and organs such as the gastrointestinal mucosa and kidney, COX-1 produces prostaglandins that have physiological protective roles, whereas COX-2 induced at sites of inflammation forms prostaglandins that contribute to the disease. It is generally agreed that blocking COX-1 can damage the stomach and kidneys, at least when other factors are involved, and perhaps this applies to the lungs.