Lipid Mediators in Aspirin-Exacerbated Respiratory Disease

Abstract

Aspirin-exacerbated respiratory disease (AERD) is a syndrome of severe asthma and rhinosinusitis with nasal polyposis with exacerbations of baseline eosinophil-driven and mast cell-driven inflammation after nonsteroidal antiinflammatory drug ingestion. Although the underlying pathophysiology is poorly understood, dysregulation of the cyclooxygenase and 5-lipoxygenase pathways of arachidonic acid metabolism is thought to be key. Central features of AERD pathogenesis are overproduction of proinflammatory and bronchoconstrictor cysteinyl leukotrienes and prostaglandin (PG) D₂ and inhibition of bronchoprotective and antiinflammatory PGE₂. Imbalance in the ratio of these lipid mediators likely leads to the increased eosinophilic and mast cell inflammatory responses in the respiratory tract.

Keywords: 5-LO (5-lipoxygenase); AA (arachidonic acid); AERD (aspirin-exacerbated respiratory disease); Asthma; COX (cyclooxygenase); Leukotriene; NSAID (nonsteroidal inflammatory drug); Prostaglandin.