The Role of Fractional Exhaled Nitric Oxide in Diagnosing Asthmatic Type 2 Chronic Rhinosinusitis With Nasal Polyps.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) is useful in the management of asthma and predicting the efficacy of standard corticosteroids and biologics. However, the diagnostic value of FeNO in asthmatic chronic rhinosinusitis with nasal polyps (CRSwNP) remains unclear. OBJECTIVE: We assessed FeNO levels in patients with CRSwNP and evaluated the diagnostic value of FeNO for screening type 2 CRSwNP (T2-CRSwNP) with asthma. METHODS: We enrolled 94 patients who were diagnosed with CRSwNP and underwent functional endoscopic sinus surgery. FeNO levels, the blood eosinophil percentage, total IgE, spirometry tests (FEV1/FVC), Lund-Mackay CT score, and percentage of patients with comorbid asthma were compared among CRSwNP subgroups. Spearman rank correlation test was used to assess the degree of association between variables. ROC curve analysis was conducted to evaluate the diagnostic capability to differentiate T2-CRSwNP based on clinical and histological classifications. RESULTS: FeNO levels and the blood eosinophil percentage were significantly higher in patients with T2-CRSwNP(h) based on histological data (P < .05). FeNO was correlated with the blood eosinophil percentage (r = 0.420, P < .001) and FEV1/FVC (r = -0.324, P = .001). A FeNO level of 27 ppb had a good ability to discriminate patients with asthmatic T2-CRSwNP(h) (AUC = 0.848; 95% CI = 0.7602-0.9361; sensitivity = 90.9%; specificity = 63.9%). The optimal cutoff values for FeNO and the blood eosinophil percentage for diagnosing asthmatic T2-CRSwNP(h) were 68 ppb and 5.6% (sensitivity = 95.5%; specificity = 86.1%; AUC = 0.931; 95% CI = 0.8832-0.9791). In the diagnosis of severe T2-CRSwNP(c) based on clinical data, a FeNO level of 36 ppb showed the highest AUC (0.816; 95% CI = 0.7173-0.914; sensitivity = 72.7%; specificity = 79.2%). CONCLUSION: FeNO is a useful marker for screening asthmatic T2-CRSwNP even prior to biopsy or asthma evaluation and may assist in selecting a proper treatment.

Effects of Neutrophil and Eosinophil Extracellular Trap Formation on Refractoriness in Chronic Rhinosinusitis With Nasal Polyps.

PURPOSE: This study investigated the clinical implications of neutrophil extracellular trap (NET) formation (NETosis) and eosinophil extracellular trap (EET) formation (EETosis) regarding refractoriness in chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP). METHODS: Nasal polyp specimens were obtained from 117 patients with CRSwNP who received endoscopic sinus surgery. Disease control status at postoperative 1 year was assessed. Refractory cases were defined as partly controlled or uncontrolled cases according to the EPOS 2020 guidelines. NETosis and EETosis were evaluated through immunofluorescence staining (citrullinated histone H3-human neutrophil elastase and citrullinated histone-galectin-10, respectively) followed by manual counting. The z-score of NET and EET counts was used to define the following four groups: low extracellular trap formation (ETosis), NETosis-predominant, EETosis-predominant, and high-ETosis. RESULTS: The refractory and non-refractory groups showed significant differences in the tissue eosinophil count (P = 0.005) and EET count (P = 0.029). The tissue neutrophil count and the NET/neutrophil ratio were significantly different between the refractory and non-refractory groups of patients with neutrophilic CRS (P = 0.045, 0.031, respectively). Refractoriness significantly differed among the low-ETosis (30.77%), NETosis-predominant (47.83%), EETosis-predominant (56.67%), and high-ETosis (83.33%) groups (P = 0.005). CONCLUSIONS: The results of this study suggest that tissue Eosinophilia and EETosis may play a prognostic role, primarily in CRSwNP and thattissue neutrophilia and NETosis can play as prognostic biomarkers in neutrophilic CRSwNP.

Endotype-related recurrence pattern of chronic rhinosinusitis in revision functional endoscopic sinus surgery.

OBJECTIVE: The recurrence of chronic rhinosinusitis (CRS) after functional endoscopic sinus surgery (FESS) is influenced by various factors, potentially including the endotype based on the molecular pathophysiology of CRS. This study investigated differences in the recurrence pattern of CRS by endotype after primary FESS. METHODS: This retrospective study enrolled patients who had undergone revision FESS for recurrent CRS. Based on their clinical diagnosis, the patients were divided into two endotype groups: recurrent eosinophilic CRS (rECRS) and recurrent non-eosinophilic CRS (rNECRS). We compared and analyzed preoperative computed tomography (CT) findings, including typical anatomical findings of recurred CRS such as lateralized middle turbinate and retained uncinate process, the sinus where recurrence took place, and previous surgical completeness of the sinuses, between the rECRS and rNECRS groups. RESULTS: In total, 142 patients were enrolled (48 rECRS, 94 rNECRS). No significant difference was found in the typical anatomic findings of recurrent CRS between the rECRS and rNECRS groups. The rates of the completeness of previous surgeries was significantly higher in rECRS than in rNECRS(P=.031). Despite the completeness of previous surgeries, the recurrence rate of frontal and ethmoidal sinuses was higher in the rECRS than rNECRS(P=.012, P<.001, respectively). In subgroup analysis according to the severity of ECRS, the number of involved sinuses and the rates of CRS recurrence and surgical completeness in frontal and anterior ethmoidal sinuses increased with ECRS severity. CONCLUSIONS: CT findings of revision FESS cases differed by CRS endotype. The rECRS group showed higher recurrence in the frontal and ethmoidal sinuses despite a higher surgical completeness rate. Incomplete surgery was more often found in the rNECRS group.