Distinct eicosanoid patterns in severe recalcitrant nasal polyposis

Although 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. Levels of leukotriene (LT) E , LTB , prostaglandin (PG) D , PGE 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. Patients with recurrent NPs had pronounced pre-surgical levels of nasal 15(S)-HETE, PGD and LTE . From pre-surgery to 12 months post-surgery, NPR was associated with significant decreases of 15(S)-HETE and PGD relative to non-recurrence, whereas levels of LTE 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 LTE and PGD , lower levels of PGE and LTB , and more cases of recurrent NPs and previous NP surgeries. Elevated nasal LTE 12 months post-surgery in NP recurrent subjects suggests that postoperative LTE 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.