Perspective of the regulatory and functional roles of nasal nitric oxide in chronic rhinosinusitis

Measurement of factional exhaled NO (FeNO) and nasal NO has the potential to be useful for diagnosis and assessment in paranasal sinus infection. NO production is regulated by activities of three isoforms of nitric oxide synthase (NOS) and bioavailability of L-arginine as a substrate. We consider measuring FeNO can be a valid marker to differentiate chronic rhinosinusitis (CRS) phenotypes based on distinct difference in arginase and NOS isoform activities. Although previous studies have reported that nasal NO levels generally decreased in CRS patients, the usefulness of NO measurement remains controversial. We found that eosinophilic CRS (ECRS) patients showed higher oral FeNO levels compared to non-ECRS patients. The increased FeNO levels in the ECRS patients are possibly related with augmented inducible NOS (NOS2) expression and airway eosinophilia. In addition, the role of endothelial NOS (NOS3) in nasal polyp formation has been proposed. NOS3 expression was found to be in glands, epithelial and vascular endothelial cells, the positive staining of which accounting for secretion and vascular dilatation. NOS2 gene expression is predominantly transcriptionally regulated. The existence of NOS2 promoter gene polymorphisms may influence CRS pathophysiology as shown in asthmatic patients. As for NOS3, several stimuli have been shown to initiate or enhance the enzyme activity and consequently the NO production both in calcium-dependent and -independent manners. The post-translational modification such as phosphorylation also influences eNOS activities. Further studies are needed in order to clarify the deeper role of the NOS isoforms in the pathogenesis of CRS phenotypes.