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.