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Background  Chronic rhinosinusitis with polyps (CRSwNP) is a global health concern. Nasal nitric oxide (nNO), a clinical biomarker, have been studied to assess the presence of airway mucosal inflammation. This study aimed to clarify the roles of nNO in diagnosis and endotypes of CRSwNP.    Methods  Eighty-two CRSwNP patients and thirty healthy volunteers were recruited for this study. The patients were classified into eosinophilic CRSwNP (Eos CRSwNP) and non⁃eosinophilic CRSwNP (Non-Eos CRSwNP) endotypes by tissue eosinophil percentage. nNO levels were measured with an electrochemical sensor-based device. nNO levels and clinical factors were compared among the groups. Receiver-operating characteristic (ROC) curve and logistic regression analyses were performed to evaluate the predictive ability of the nNO for diagnosis and endotypes of CRSwNP.    Results  Eos CRSwNP patients(143.9 ± 106.2, ppb) had lower nNO levels than Non-Eos CRSwNP(228.3 ± 109.2, ppb,  p  = 0.013) and healthy subjects(366.5 ± 88, ppb,  p  < 0.0001). Patients with atopy exhibited significantly higher levers of nNO compared with patients without atopy ( p  < 0.05). For Eos CRSwNP diagnosis, nNO had high predictive value for Eos CRSwNP (AUC: 0.939; sensitivity: 76.74%; specificity: 96.67%; cut-off value: 231 ppb,  p  < 0.001). Furthermore, nNO levels were associated with CRSwNP endotypes (odds ratio: 1.010; 95% confidence interval: 1.003, 1.016%;  p =  0.002). When the nNO concentration was 158 ppb, we could discriminate Eos CRSwNP from Non-Eos CRSwNP (AUC = 0.710, sensitivity: 76.92%; specificity, 60.47%,  P  = 0.001). After it was combinated by nNO, peripheral blood eosinophil count (PEAC) and VAS score, the AUC was increased to 0.894 (95%CI = 0.807 to 0.951,  p  < 0.0001, sensitivity:76.74%, specificity: 89.74%).    Conclusions  nNO may have potential for non-invasive diagnosis and endotype of CRSwNP. nNO combined with PEAC and VAS score may be a good diagnostic tool for endotyps of Eos CRSwNP. However, the atopic status of the patients influenced the levels of nNO.

The roles of nasal nitric oxide in diagnosis and endotypes of chronic rhinosinusitis with nasal polyps