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Updated: Jun 5, 2026

A Novel Inhalation Mask System to Deliver High Concentrations of Nitric Oxide Gas in Spontaneously Breathing Subjects
Published on: May 4, 2021
Nasal nitric oxide is inversely associated with radiologic severity and eosinophilic inflammation in chronic
Keiichiro Kiyohara1, Sachio Takeno1, Sakura Hirokane1
1Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
Objective:
Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory disease in which subjective symptoms often poorly correlate with objective radiologic findings, complicating diagnosis and disease stratification. Nasal nitric oxide (nNO) reflects sinonasal mucosal function and ventilation. However, its clinical utility and reference values in the Japanese population remain unclear. This study evaluated whether nNO measurements could serve as an objective biomarker for CRS severity and phenotypic differentiation.
Methods:
In this retrospective cross-sectional study, nNO levels were measured using the NIOX VERO® device in 30 patients with CRS (15 eosinophilic CRS (ECRS), 15 non-ECRS) and 30 healthy controls. CRS was diagnosed based on clinical symptoms, nasal endoscopy, and computed tomography (CT). Disease severity was assessed using a modified Lund-Mackay (Zinreich) CT scoring system. Clinical correlations between nNO levels and CT scores, peripheral blood eosinophil counts, symptom severity (SNOT-22), and nasal polyp scores were analyzed. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic performance of nNO.
Results:
Mean nNO levels were significantly lower in CRS patients than in controls (controls: 477.5 ± 211.2 ppb; non-ECRS: 303.2 ± 210.6 ppb; ECRS: 251.4 ± 154.1 ppb). nNO levels showed a significant inverse correlation with CT scores (r = -0.5537, p < 0.0001) and a weak inverse correlation with peripheral blood eosinophil counts (r = -0.3657, p = 0.0065). In contrast, no significant correlations were observed between nNO levels and SNOT-22 scores or nasal polyp scores. ROC analysis demonstrated moderate discriminatory ability of nNO for identifying CRS (AUC = 0.7933) and ECRS (AUC = 0.8156), with optimal cutoff values of 263.5 ppb and 276.0 ppb, respectively.
Conclusion:
Nasal nitric oxide levels are significantly reduced in CRS patients and inversely associated with radiologic disease severity, suggesting that nNO primarily reflects impaired sinus ventilation rather than symptom burden. Although its diagnostic performance is moderate, nNO measurement represents a simple, non-invasive adjunctive biomarker for objective assessment and phenotypic stratification of CRS in the Japanese population. Larger prospective studies are warranted to establish standardized reference values and validate its clinical utility.
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