Effects of Neutrophil and Eosinophil Extracellular Trap Formation on Refractoriness in Chronic Rhinosinusitis With Nasal Polyps

PURPOSE: This study investigated the clinical implications of neutrophil extracellular trap (NET) formation (NETosis) and eosinophil extracellular trap (EET) formation (EETosis) regarding refractoriness in chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP). METHODS: Nasal polyp specimens were obtained from 117 patients with CRSwNP who received endoscopic sinus surgery. Disease control status at postoperative 1 year was assessed. Refractory cases were defined as partly controlled or uncontrolled cases according to the EPOS 2020 guidelines. NETosis and EETosis were evaluated through immunofluorescence staining (citrullinated histone H3-human neutrophil elastase and citrullinated histone-galectin-10, respectively) followed by manual counting. The z-score of NET and EET counts was used to define the following four groups: low extracellular trap formation (ETosis), NETosis-predominant, EETosis-predominant, and high-ETosis. RESULTS: The refractory and non-refractory groups showed significant differences in the tissue eosinophil count (P = 0.005) and EET count (P = 0.029). The tissue neutrophil count and the NET/neutrophil ratio were significantly different between the refractory and non-refractory groups of patients with neutrophilic CRS (P = 0.045, 0.031, respectively). Refractoriness significantly differed among the low-ETosis (30.77%), NETosis-predominant (47.83%), EETosis-predominant (56.67%), and high-ETosis (83.33%) groups (P = 0.005). CONCLUSIONS: The results of this study suggest that tissue Eosinophilia and EETosis may play a prognostic role, primarily in CRSwNP and thattissue neutrophilia and NETosis can play as prognostic biomarkers in neutrophilic CRSwNP.