Aspirin-intolerant asthma: role of cyclo-oxygenase enzymes.
Aspirin-induced asthma and rhinitis (AIAR) appear to be precipitated by the inhibition of cyclo-oxygenase (COX). By inhibiting COX pathway aspirin diverts arachidonic acid metabolites to the lipoxygenase pathway. There are two isoforms of COX, namely COX-1 and COX-2. Metabolites derived from COX-1 are involved in cellular housekeeping functions. COX-2 can be induced in cells exposed to proinflammatory substances and growth factors. Recent studies have reported that patients with AIAR have decreased activity of COX-2 and lower production of PGE(2) in the upper airway and peripheral blood cells. Considering the protective effect of exogenous PGE(2) on aspirin-induced bronchoconstriction and the interdependence of PGE(2) and cisteinyl leukotriene production, a reduced PGE(2) synthesis may render aspirin-sensitive patients more susceptible to the inhibitory effect of NSAIDs drugs and also lead to an increase in cysteinyl leukotriene release.
Picado
Cesar
C
Servicio de Neumologia y Alergia Respiratoria, Instituto de Neumologia y Cirugia Torácica, Hospital Clinic, Villaroel 170, E-08036 Barcelona, Spain.
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000494:pharmacology; D001241:Aspirin / Q000009:adverse effects* / Q000276:immunology; D001249:Asthma / Q000201:enzymology / Q000276:immunology / Q000503:physiopathology*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D004342:Drug Hypersensitivity / Q000201:enzymology / Q000209:etiology / Q000503:physiopathology*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism / Q000502:physiology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D001241:Aspirin