Article

Monitoring of oral and nasal exhaled nitric oxide in eosinophilic chronic rhinosinusitis: a prospective study.

Department of Otolaryngology, Head and Neck Surgery, Division of Clinical Medical Science, Programs for Applied Biomedicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
American Journal of Rhinology and Allergy 07/2012; 26(4):255-9. DOI: 10.2500/ajra.2012.26.3772
Source: PubMed

ABSTRACT We aimed to examine the effect of different therapeutic modalities on levels of fractional concentrations of exhaled nitric oxide (FeNO) in patients with eosinophilic chronic rhinosinusitis (ECRS).
Thirty-six ECRS patients with nasal polyps were treated either medically or surgically. Oral and nasal FeNO levels were measured using an electrochemical NO analyzer initially and at 1 and 6 months. The mRNA expression and localization of nitric oxide synthase (NOS) isoforms in sinus mucosa and nasal polyps were analyzed by real-time polymerase chain reaction (PCR) and immunohistochemistry.
The mean oral FeNO levels in the surgical group had decreased significantly from 50.9 to 36.8 ppb 6 months after endoscopic sinus surgery. All patients in this group showed significantly higher nasal FeNO levels after treatment. The mean nasal FeNO levels were 62.3 ppb at 1 month and 93.6 ppb at 6 months. Mean oral and nasal FeNO levels in the medical group after treatment remained unchanged when compared with the baseline levels. Positive immunoreactivity of inducible NOS (iNOS) was observed in both epithelial cells and submucosal inflammatory cells. Real-time PCR analysis showed significant up-regulation of iNOS and IL-5 mRNA expression.
A combination of oral and nasal FeNO measurements is useful to monitor the extent of inflammation in CRS patients. The increase in nasal FeNO in the surgical group indicates prompt recovery of NO release from healed sinus mucosa through the opened sinus ostia. Reduction of oral FeNO levels may reflect a cessation of the underlying lower airway inflammation that is characteristic of ECRS.

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    ABSTRACT: OBJECTIVE: Monitoring of fractional concentrations of exhaled nitric oxide (FeNO) has become a reliable marker of inflammation in human nose and paranasal sinuses. However, it is still unknown to what extent nasal NO levels contribute to the pathology of chronic rhinosinusitis (CRS). In the present study, we aimed to examine FeNO levels and the underlying mechanism of NO production and metabolism in patients with eosinophilic chronic rhinosinusitis (ECRS) and non-ECRS. METHODS: Thirty-three untreated ECRS patients, 16 non-ECRS patients, and 38 normal subjects were enrolled in this cross-sectional study of FeNO levels. Oral and nasal FeNO levels were measured before treatment using an electrochemical NO analyzer (NObreath(®)) with a nose adaptor. The mRNA expression of three nitric oxide synthase (NOS) isoforms, interleukin-5 (IL-5), and transforming growth factor-beta (TGF-β) in the ethmoid sinus mucosa and nasal polyps were analyzed by real-time PCR. Immunohistological localization of inducible NOS (iNOS) and nitrotyrosine (NT), a marker for oxidized NO metabolites, was also examined. RESULTS: ECRS patients showed significantly higher oral FeNO levels compared to non-ECRS patients and normal subjects (mean values, 47.6, 13.5, and 15.3ppb, respectively). Nasal FeNO levels of the non-ECRS patients (30.5ppb) were significantly lower than those of the ECRS patients (53.9ppb) and normal subjects (45.5ppb). Positive correlations existed between the blood eosinophil percentage and FeNO levels in ECRS patients. Histologically, ECRS patients showed higher eosinophil accumulation in the ethmoid mucosa than non-ECRS patients (103.1 vs. 16.3cells/HPF). Real-time PCR analysis showed significant upregulation of iNOS and IL-5 mRNA expression in the ethmoid mucosa of the ECRS patients compared to those of non-ECRS patients. Positive iNOS immunoreactivity was observed in ciliated epithelial cells, submucosal glands and associated inflammatory cells in both groups. NT immunoreactivity was detected in the epithelium and around inflammatory cells. Intense NT staining was co-localized with eosinophil accumulation and ECRS patients showed significantly higher rates of NT-positive cells than non-ECRS patients. CONCLUSION: A combination of oral and nasal FeNO measurement is a valid marker for the classification and definition of different CRS subtypes in Japan. Higher levels of oral and nasal FeNO in ECRS patients may reflect the persistence of eosinophilic inflammation in sinus mucosa with concomitant iNOS upregulation and accompanying deposition of oxidized NO metabolites.
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