COX-2 specific inhibitors in NSAID-intolerant patients.

Most adverse NSAID-induced respiratory and skin reactions appear to be precipitated by the inhibition of cyclooxygenase-1 (COX-1); this in turn activates the lypoxygenase pathway, which eventually increases the release of cysteinyl leukotrienes (Cys-LTs). Recent studies have reported that patients with NSAID-induced asthma have a low production of PGE2 in respiratory epithelial cells, bronchial fibroblast and peripheral blood cells. Low production of PGE2 may be due to an insufficient cyclooxygenase-2 (COX-2) expression in the inflammatory response underlying asthma. Since PGE2 administered by inhalation inhibits NSAID-induced bronchoconstriction and the parallel increase in Cys-LTs release, a reduced PGE2 synthesis may render NSAID-patients more susceptible to the COX-1 inhibitory effects of NSAIDs. Recent studies have shown that selective COX-2 inhibitors (rofecoxib and celecoxib), unlike COX-1 inhibitors, are very well tolerated by NSAID-sensitive patients and do not elicit increased Cyst-LTs production. However, these drugs can still can precipitate cutaneous reactions in a significant proportion of patients with skin reactions to NSAID. The heterogeneity of the NSAID-intolerance syndrome suggests that subjects who do not tolerate NSAID can use coxibs only after first having been exposed to the drug under the supervision of a specialist with experience in these procedures.