Distinct eicosanoid patterns in severe recalcitrant nasal polyposis

Abstract

AbstractBackgroundAlthough altered eicosanoid levels are related to disease severity in chronic rhinosinusitis with nasal polyps (CRSwNP), identifying patients prone to recurrent nasal polyps (NPs) is still difficult. We investigated levels of nasally secreted eicosanoids before and after NP surgery in patients with or without NP recurrence (NPR) and explored potential endotypes based on pre‐surgical eicosanoid levels.MethodsLevels of leukotriene (LT) E4, LTB4, prostaglandin (PG) D2, PGE2 and 15(S) hydroxyeicosatetraenoic acid (15[S]‐HETE) were measured in nasal secretions with specific immunoassays at pre‐surgery (n = 38) and 6 and 12 months post‐surgery (n = 35), with NPR identified endoscopically. Pre‐ and post‐surgical levels were compared between patients with and without NPR. Eicosanoid patterns among patients were explored with cluster analysis and evaluated with clinical parameters.ResultsPatients with recurrent NPs had pronounced pre‐surgical levels of nasal 15(S)‐HETE, PGD2 and LTE4. From pre‐surgery to 12 months post‐surgery, NPR was associated with significant decreases of 15(S)‐HETE and PGD2 relative to non‐recurrence, whereas levels of LTE4 decreased at 6 months but increased again at 12 months. Clustering revealed three potential endotypes. Clusters 1 and 3 featured high and low eicosanoid levels, respectively. Cluster 2 had higher levels of LTE4 and PGD2, lower levels of PGE2 and LTB4, and more cases of recurrent NPs and previous NP surgeries.ConclusionElevated nasal LTE4 12 months post‐surgery in NP recurrent subjects suggests that postoperative LTE4 measurements may indicate rapid NP regrowth. A distinct nasal eicosanoid profile may be used for the identification of the most severe recalcitrant patients in need of targeted immunomodulatory therapies.