Too many COX (cyclo-oxygenase) spoil the broth: aspirin-sensitive asthma and 5-lypoxygenase.

10 as a hypothesis driven article. Nevertheless, at the time it in the current issue of Thorax confirms that COX-2 is was thought to be too controversial and unsubstantiated present in asthmatic tissue. Why then are NSAIDs un-by any scientific evidence. However, with the publication successful in the treatment of asthmatic symptoms? More-by the journal of Sousa's work showing that COX-2 is over, in a subpopulation of asthmatic subjects aspirin increased in asthmatic airways, our original hypothesis is actually causes asthma typified by generalised flush, ocular better supported. The potential for COX-2 in asthma and and nasal congestion, and an acute (often severe) asthmatic aspirin-sensitive asthma is discussed below. attack. These patients also appear to have an increased Constitutive COX-1 or inducible COX-2 convert number of COX-2 expressing mast cells. 10 The answer to arachidonic acid to prostaglandins, thromboxanes, and this question may lie in the biochemical processes that prostacyclin (prostanoids). Prostanoids have both pro-occur in this group of " aspirin-sensitive " asthmatic sub-tective properties – for example, in the gastric mucosa – jects. To date, aspirin-sensitive asthma has been attributed, and inflammatory properties. Indeed, non-steroidal anti-at least in part, to the shunting of arachidonic acid from inflammatory drugs (NSAIDs) such as aspirin inhibit the COX pathway to the 5-lipoxygenase (5-LO) pathway both COX-1 and COX-2 1 resulting in therapeutic (anti-resulting in the production of leukotrienes. 11 The " shunting inflammatory and analgesic) and deleterious (gastric ulcers hypothesis " has been an attractive one as leukotrienes and kidney failure) effects. Traditional NSAIDs such as contribute to allergic and inflammatory reactions by several aspirin tend to display COX-1 selectivity, 1 2 raising the mechanisms including constriction of smooth muscle and speculation that COX-1 inhibition is responsible for stimulation of airway mucus production. In addition, in-their well described side effects. This has recently been creased levels of leukotrienes have been detected in the strengthened by reports demonstrating that selective in-urine of sensitive patients after aspirin. However, aspirin-hibitors of COX-2 are anti-inflammatory without being tolerant asthmatics do not produce more leukotrienes after ulcerogenic. 2 The induction of COX-2 in lung structures inhibition of the COX pathway, calling into question the may be of particular importance since prostaglandin E 2 validity of the " shunting hypothesis ". 12 We would like to put modulates various pulmonary functions including airway forward an alternative hypothesis to explain how aspirin-and vascular tone, plasma exudation, inflammatory cell sensitive …