Prognostic Significance of Eosinophil Extracellular Traps in Chronic Rhinosinusitis and Innovative Nanosheets‐Based Clearance Therapy

ABSTRACT Background Chronic rhinosinusitis with nasal polyps (CRSwNP) can be classified into Eosinophilic CRSwNP (ECRSwNP) and non‐Eosinophilic CRSwNP (nECRSwNP) based on eosinophilic infiltration in nasal polyps. However, no consensus criteria exist for eosinophilic infiltration in nasal polyps, including different cutoffs for eosinophil (EOS) counts or different EOS proportions among inflammatory cells. Methods Inferior turbinate (IT) tissues from controls ( n = 27) and nasal polyp (NP) tissues from ECRSwNPs ( n = 50) were collected. ECRSwNPs ( n = 38) underwent 2‐year post‐FESS follow‐up. Clinical assessments (SNOT‐22, Lund‐Mackay, Lund‐Kennedy scores), eosinophil indicators (polyp/blood EOS counts, EETs area), and Th2 cytokines pre/post‐FESS were recorded for correlation analysis and prognostic model building. Subsequently, functional nanosheets TLPG A targeting EETs were synthesized and tested for EETs clearance in human EOS, epithelial cell models, and NP models. Results Our findings demonstrated positive correlations between EETs area and ECRSwNP severity, including Lund‐Mackay CT scores ( r = 0.72, p < 0.001), Lund‐Kennedy Endoscopic score ( r = 0.57, p < 0.001), IL‐4 ( r = 0.50, p < 0.001), IL‐5 ( r = 0.50, p < 0.001), IL‐13 ( r = 0.39, p < 0.01), and Periostin ( r = 0.34, p < 0.05). And we first demonstrated that increased preoperative EETs area predicts both impaired mucosal recovery and elevated nasal polyp uncontrolled risk within 2 years post‐FESS. Furthermore, we developed novel nanosheets TLPG A and demonstrated that TLPG A effectively scavenges EETs and alleviates the type 2 inflammatory cascade in human nasal polyp tissues and epithelial cell model. Conclusion These findings highlight the potential of EETs and EOS morphology in assessing preoperative ECRSwNP severity and predicting postoperative prognosis. Moreover, this also supports TLPG A as a promising therapeutic approach for managing ECRSwNP with high EETs levels.