Eosinophil extracellular trap formation is closely associated with disease severity in chronic rhinosinusitis regardless of nasal polyp status

Abstract

Chronicrhinosinusitis(CRS) is a heterogeneous inflammatory airwaydiseaseinvolving non-eosinophilic and eosinophilic phenotypes, which translate to various endotypes. Activated eosinophils and neutrophils are known to generateextracellulartraps consisting of DNA and cytotoxic granule proteins. We sought to investigate the presence ofeosinophiland neutrophilextracellulartraps (EETs and NETs, respectively) in human CRS tissues and to clarify the associations with their clinical features.Nasalpolyp(NP) or ethmoid tissue slides of 43 subjects from endoscopic sinus surgery for CRS were analysed. Quantitative analysis of EETs and NETs was performed by confocal microscopy using immunofluorescent staining. For correlation study, the presence of NPs, number of infiltrating tissue eosinophils, preoperative Lund-Mackay scores, and other comorbidities were analysed. EETformationwas observed to varying degrees in all CRS groups and was correlated with the number of tissue eosinophils (r = 0.83, p < 0.001)regardlessof the presence of NPs. Patients with more EETs demonstrated higher Lund-Mackay scores (r = 0.51, p = 0.009), blood eosinophilia (r = 0.80, p < 0.001), and decreased olfactory function (r = -0.65, p < 0.001). No correlation between the extent of EETformationand the presence of atopy or asthma was apparent. However, none of the CRS groups containing neutrophils formed NETs in this study. Eosinophilic CRS indicates the presence of EETs.Formationof EETs could have a role in clinical decision-making and prediction of treatment outcome of CRS,regardlessof NPstatus.