Abstract
BACKGROUND: The etiology of otitis media with effusion (OME) is multifactorial and complex, with increasing evidence implicating bacterial infection as a potential contributor. Neutrophil extracellular traps (NETs) have been identified as key participants in the pathophysiological processes of various infectious diseases. However, to date, no studies have quantitatively assessed NETs in OME or explored its role in the middle ear. OBJECTIVE: This study aims to quantitatively assess NETs and mucins in different types of middle ear effusion (MEE) in children with OME, investigate the correlations between NETs, mucins, and clinical phenotypes, and explore the potential role of NETs in OME. METHODS: We included fifty-five pediatric OME patients underwent tympanostomy tube insertion (March-November 2024). Seventy MEE specimens were collected for detection and analysis. General demographics, disease duration, hearing thresholds and blood cell levels were documented. All samples were characterized into two main types (serous and mucoid) by the same surgeon based on their appearance and viscosity. NET-related biomarkers (citrullinated histone H3 [CitH3], double-stranded DNA [dsDNA], myeloperoxidase-DNA complex [MPO-DNA], and Nucleosome), along with mucins (mucin5AC [MUC5AC] and mucin5B [MUC5B]) were detected using enzyme-linked immunosorbent assay (ELISA), modified ELISA or fluorometry. RESULTS: Subjects in the mucoid group demonstrated more severe hearing impairment than those in the serous group (p = 0.015). Compared to the serous group, specimens from the mucoid group exhibited higher levels of CitH3, dsDNA, MPO-DNA, MUC5B and MUC5AC (p < 0.05). Within the hearing severity subgroups, CitH3, dsDNA, and MUC5B levels were higher in patients with poorer hearing. Correlation analysis revealed strong positive correlations between NET-related biomarkers with MUC5B and MUC5AC expression (p < 0.05). CitH3 (r = 0.306, p = 0.010), dsDNA (r = 0.135, p = 0.049), and MUC5B (r = 0.242, p = 0.043) were positively correlated with patients' hearing levels. CONCLUSIONS: NET-related biomarkers were significantly increased in mucoid effusions with a notable positive correlation to MUC5AC, MUC5B, and hearing levels.