Background Aspirin-exacerbated respiratory disease (AERD) is characterized by tissue eosinophilia and mast cell activation, including abundant production of prostaglandin D2 (PGD2). Group 2 innate lymphoid cells (ILC2s), which promote tissue eosinophilia and mast cell responses, undergo chemotaxis and cytokine production in response to PGD2 but it is unknown whether ILC2s are active in AERD. Objective We sought to determine whether ILC2 numbers change in peripheral blood and nasal mucosa during cyclooxygenase-1 (COX-1) inhibitor-induced reactions in patients with AERD. Methods Blood and nasal scrapings were collected at baseline, during reaction, and after completion of ketorolac/aspirin challenge/desensitization in twelve patients with AERD. ILC2s and eosinophils were quantitated by flow cytometry. Urine was also collected and quantification of PGD2 metabolite and leukotriene E4 (LTE4) was done by ELISA. Baseline and NSAID-reaction clinical data was correlated with cell changes. Results ILC2s significantly increased in nasal mucosal samples and decreased in blood at the time of COX-1 inhibitor reactions in 12 patients with AERD. These changes were not observed in two patients without AERD. Further, eosinophils decreased in blood concurrently with significant increases in urinary PGD2 metabolite and LTE4. The magnitude of increases in nasal mucosal ILC2s positively correlated with maximum symptom score during the challenges. Further, the levels of blood ILC2s during the reaction correlated with the time for the reaction to resolve, possibly reflecting reaction severity. Conclusions ILC2s are recruited to the nasal mucosa during COX-1 inhibitor-induced reactions in patients with AERD, correlating with enhanced production of prostaglandins and leukotrienes.

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