Mechanisms of aspirin hypersensitivity – What is known up to now

The association of nasal/sinus and bronchial symptoms with aspirin hypersensitivity is currently named aspirin-exacerbated respiratory disease (AERD). The application of biostatical methodology allowed us to identify unique AERD subphenotypes that can occur in regular clinical practice.According to the cyclooxygenase hypothesis, aspirin blocks cyclooxygenase enzymes (stronger – COX-1, weaker – COX-2), resulting in a decrease of the product concentration, catalyzed by those enzymes.There is a shift of arachidonic acid transformation from the cyclooxygenase pathway to 5-lipooxygenase, stimulating the synthesis of cysteinyl-leukotrienes (cys-LTs). The concentration of cys-LTs significantly increases after an aspirin challenge test in aspirin-exacerbate respiratory disease. This could be due to the fact that the pathogenesis of AERD is based on the assumption that a deficiency of prostaglandin E2 (PGE2) is responsible for bronchodilatation and cys-LTs production inhibition, which has a role in aspirin-induced bronchoconstriction. The results, non-invasively obtained induced sputum eicosanoids, have been acknowledged that a selective inhibition of PGE2 biosynthesis by aspirin shifts the 5-lipoxygenase pathway from cys-LTs.