The goal of this review is to discuss current developments in understanding the protective function of prostaglandin E2 (PGE2) in aspirin-exacerbated respiratory disease (AERD), also known as NSAID-exacerbated respiratory illness in Europe (N-ERD). In individuals with AERD, decreased PGE2 signalling via the EP2 receptor leads to an increase in leukotriene production and signalling. Leukotriene signalling not only activates group 2 innate lymphoid cells and mast cells, but it also enhances IL-33 and thymic stromal lymphopoietin production. These cytokines are thought to induce Th2 inflammation in AERD patients via a feed-forward mechanism.

Recent discoveries on the function of PGE2 in leukotriene production and signalling in AERD, as well as downstream effects on group 2 innate lymphoid cells and mast cells, provide a more complete knowledge of the disease’s pathophysiology. These findings also point to new avenues of study and potential treatment targets for AERD.