New insights into the mechanisms of aspirin-exacerbated respiratory disease.

Abstract

Aspirin-exacerbated respiratory disease (AERD), a syndrome characterized clinically by asthma, chronic rhinosinusitis with nasal polyposis, and respiratory reactions to aspirin and other cyclooxygenase-1 inhibitors, is an inflammatory condition of the respiratory tract that is often severe and challenging to treat. There have been several recent advances in our understanding of the underlying pathology of the disease. These have been paralleled by welcome advances in the availability of targeted treatment options for patients with AERD. Spurred in part by results from trials of targeted biologic therapies, along with single cell genomics, there is now clear evidence that the chronic respiratory inflammation in AERD is driven by combination of local tissue factors. These include abnormalities in effector cell populations, with increased accumulation and activation of mast cells and plasma cells in the nasal polyp, along with notable epithelial barrier dysregulation. The key mediators now identified include high levels of both type 2 inflammatory cytokines (IL-4, IL-5, IL-13) and cytokines involved in broader inflammatory pathways (IL-33, TSLP, IL-6, oncostatin M), as well as the overproduction of cysteinyl leukotrienes, and the underproduction of prostaglandin E2. This review covers the latest insights into the immunopathogenesis of and targeted treatment of AERD, including the roles of lipids, effector cells, and inflammatory cytokines, and discusses unanswered questions regarding its pathogenesis and potential future therapies.