Mechanisms of aspirin sensitivity.
In some asthma patients, nonsteroidal anti-inflammatory drugs (NSAIDs) induce bronchospasm, rhinorrhea, and nasal obstruction. NSAID-induced reactions appear to be caused by the inhibition of cyclooxygenase-1 (Cox-1); this in turn activates the lipoxygenase pathway, which eventually increases the release of cysteinyl leukotrienes (Cys-LTs) that induces bronchospasm and nasal obstruction. With regard to the metabolism of arachidonic acid (AA) in NSAID-intolerant asthmatic patients, the following changes have been observed: 1) A low production of prostaglandin E2, seemingly due to deficient Cox-2 regulation; 2) an increased expression of leukotriene-C4 synthase; and 3) a reduced production of metabolites (lipoxins) released through the transcellular metabolism of AA. NSAID-intolerant asthmatics have higher basal levels of Cys-LT than NSAID-tolerant asthmatics. Moreover, Cys-LT levels in NSAID-intolerant asthmatics increase remarkably following NSAID provocation testing. There has been no explanation to date that connects all these findings, although an anomaly in the regulation of Cox-2 is probably accountable.
Picado
César
C
Pneumology and Respiratory Allergy Service, University of Barcelona Hospital Clinic, Villarroel 170, 08036 Barcelona, Barcelona, Spain. cpicado@ub.edu
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000139:chemically induced / Q000378:metabolism*; D004342:Drug Hypersensitivity / Q000378:metabolism*; D006801:Humans; D044045:Lipoxins / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D044045:Lipoxins; D016718:Arachidonic Acid; D001093:Arachidonate 15-Lipoxygenase; D001094:Arachidonate 5-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin