Fractional exhaled nitric oxide and nasal nitric oxide as biomarkers in chronic rhinosinusitis

This article summarizes current evidence on the role of fractional exhaled nitric oxide (FeNO) and nasal nitric oxide (nNO) as noninvasive biomarkers in chronic rhinosinusitis with nasal polyps (CRSwNP), focusing on their potential to refine endotype-driven diagnosis and monitoring in the context of united airways disease.

Recent studies show that nNO levels are markedly reduced in CRSwNP, especially in eosinophilic phenotypes, where they correlate inversely with radiologic severity and may reflect both ostiomeatal obstruction and epithelial nitric oxide synthase dysfunction. FeNO, conversely, is often elevated in CRSwNP, even in the absence of overt asthma, is higher than in chronic rhinosinusitis without nasal polyps, and associates with type 2 inflammatory markers, symptom burden, and extended nitric oxide parameters indicating diffuse lower airway involvement. Surgical and biologic therapies targeting type 2 inflammation rapidly modify FeNO and nNO, with postoperative nNO increases and FeNO reductions, and early parallel improvements during dupilumab treatment suggesting that both indices can serve as dynamic markers of treatment response.

FeNO and nNO capture complementary aspects of CRSwNP pathophysiology, integrating information on sinonasal ventilation, epithelial function, and type 2 inflammation along the nose-lung axis, but their routine clinical use is currently limited by methodological heterogeneity, lack of validated cut-offs, and scarcity of longitudinal, combined assessments. Standardized measurement protocols and multicenter studies are needed to validate FeNO and nNO as reliable tools for endotype-based stratification, early detection of lower airway involvement, and personalized selection and monitoring of medical or surgical interventions in CRSwNP.