Noritsugu Ono

Subclassification of chronic rhinosinusitis with nasal polyp based on eosinophil and neutrophil.

Japanese patients with chronic rhinosinusitis with nasal polyps (CRSwNP), differing from European and U.S. patients, are suggested to show two distinct phenotypes: Th2‐polarized and Th1‐shifted immunity. The purpose of this study was to conduct clinical subgrouping of CRSwNP based on inflammatory cell infiltration, which was evaluated and supported by clinical backgrounds and immunological characteristics.

Relationships between IL-17A and macrophages or MUC5AC in eosinophilic chronic rhinosinusitis and proposed pathological significance.

Recently, some researchers have reported that macrophages and neutrophils were related to severe asthma. Mucus hypersecretion and persistent airway inflammation result from increased expression of mucin gene (MUC5AC). Eosinophilic chronic rhinosinusitis (ECRS) is considered as intractable rhinosinusitis. From the viewpoint of “one way one disease,” we examined whether ECRS is associated with infiltrating macrophages, neutrophils, their promotive factors, and MUC5AC. We examined 21 nasal polyps with CRS. Each specimen was fixed in 10% phosphate-buffered formalin, embedded in paraffin, processed routinely, and then prepared as semithin sections (3.5 μm). We immunohistochemically observed the macrophages by using CD68, neutrophils by using neutrophil elastase and the promotive factors, monocyte chemotactic protein (MCP) 1, IL-17A, and IL-8, in both ECRS and non-ECRS. The number of macrophages (CD68+ cells), IL-17A, and MUC5AC+ cells in ECRS were significantly greater than in non-ECRS. The mean number of MCP-1+ cells in ECRS was greater than that in non-ECRS, but not significantly. There was a significant correlation in all cases between IL-17A and macrophages or MUC5AC+ cells. Neither the numbers of neutrophils (positive cells for neutrophil elastase) nor the IL-8+ cells showed any significant differences between ECRS and non-ECRS. Our study suggested that infiltrating macrophages, IL-17A and MUC5AC, as well as eosinophils could have roles in the development of ECRS.

Fungal extracts detected in eosinophilic chronic rhinosinusitis induced cytokines from the nasal polyp cells

The role of fungi in chronic rhinosinusitis (CRS) is still controversial. The present study was conducted to detect and identify fungal species from the nasal polyp tissues of eosinophilic and noneosinophilic CRS, and to determine the role of fungal antigens in cytokine production.

Reduction in Superoxide Dismutase Expression in the Epithelial Mucosa of Eosinophilic Chronic Rhinosinusitis with Nasal Polyps

Background: Eosinophils generate large amounts of oxidant species. The eosinophil-dominant type of chronic rhinosinusitis (CRS) with nasal polyps is related to more extensive disease and a decreased likelihood of surgical success. Superoxide dismutase (SOD) is the first-line and only antioxidant enzyme that converts superoxide to hydrogen peroxide. Methods: The patients with CRS with nasal polyps were divided into eosinophilic and noneosinophilic groups. The expression of three isoforms of SOD, intracellular copper-zinc SOD (CuZnSOD), mitochondrial manganese SOD (MnSOD) and extracellular SOD (ECSOD), were examined by enzyme activity assay, immunohistochemistry and quantitative real-time RT-PCR sampled by laser capture microdissection. Results: SOD activity in the eosinophilic and noneosinophilic groups was significantly reduced compared to that of the control groups. Immunostaining of both CuZnSOD and MnSOD in the eosinophilic group was significantly decreased compared with that in the noneosinophilic and control groups. CuZnSOD mRNA of the eosinophilic group was significantly decreased compared with that of the control group, whereas MnSOD mRNA in the eosinophilic group was significantly decreased compared with that in the noneosinophilic and control groups. Neither immunoreactivity nor mRNA of ECSOD was different among the three groups. The degree of epithelial damage and disease severity were inversely correlated with CuZnSOD and MnSOD immunoreactivity. Conclusions: The reduction in SOD activity and the downregulation of the SOD message are suggested to be related to eosinophil recruitment and epithelial damage of CRS with nasal polyps.

Heme oxygenase-1 expression in chronic rhinosinusitis with eosinophilic infiltration

OBJECTIVES Chronic rhinosinusitis (CRS) with eosinophilic infiltration is a type of intractable rhinosinusitis often associated with asthma. The oxidants are well known to induce aggravate asthma. Heme oxygenase-1 (HO-1), a cytoprotective enzyme against oxidant, has been extensively studied in airway diseases. However, no study that observed HO-1 in both epithelial and subepithelial tissues of CRS has been reported. METHODS Part of each specimen derived from the nasal polyps of CRS with and without eosinophilic infiltration was promptly fixed for hematoxylin-eosin staining and immunohistochemical analysis for HO-1 and macrophages. RESULTS We found that the expression of HO-1 in the epithelial layers of CRS without eosinophilic infiltration was significantly enhanced as compared with that of CRS with eosinophilic infiltration. On the other hand, the number of macrophages with HO-1 positive reactions was significantly greater in CRS with eosinophilic infiltration compared with CRS without eosinophilic infiltration. CONCLUSIONS Our study suggests that both a reduction of HO-1 expression in epithelial cells and an increase of infiltration of macrophages positive for HO-1 are related to the epithelial damage of CRS with eosinophilic infiltration.

Comparison of bacterial examinations between eosinophilic and neutrophilic chronic rhinosinusitis with nasal polyps

Abstract Conclusion: We found no significant differences in the bacterial features of the maxillary sinuses between eosinophilic and neutrophilic chronic rhinosinusitis (CRS) with nasal polyps. Objectives: Since neutrophilic CRS is often influenced by a predisposition to bacterial infection, and eosinophilic CRS is likely to be developed by allergic antigens, differences in the microbiology between the two pathologies of CRS can be expected. The present study was designed to investigate the bacterial findings from the maxillary sinus in eosinophilic and neutrophilic CRS. Methods: Seventy patients with CRS with nasal polyps were divided into eosinophilic and neutrophilic types based on histopathological observations of the nasal polyps. The specimens for bacterial culture were obtained from the maxillary sinus during endoscopic sinus surgery. Results: In all, 29 and 41 patients were classified as having eosinophilic and neutrophilic CRS with nasal polyps, respectively. The isolation rate of bacteria showed no significant difference between eosinophilic (90%) and neutrophilic CRS (98%). Aerobic bacteria were found in 25 patients (86%) with eosinophilic CRS, which was not significantly different from that in neutrophilic CRS (40 patients, 98%). The isolation rate for aerobic and anaerobic bacteria showed no significant differences.

Comparative analysis of cytokine release from epithelial cell cultures of the upper airway.

INTRODUCTION Upper airway epithelial cells show a multi-potential ability to produce a variety of cytokines/chemokines in the steady-state and under external stimuli. OBJECTIVE To compare various cytokines/chemokines released from primary cultures of human nasal epithelial cells (HNECs) derived from healthy controls and subjects with allergic rhinitis (AR), chronic rhinosinusitis with nasal polyps (CRSwNPs) in non- stimulated and IL-17A-stimulated conditions. METHODS The supernatants derived from HNECs of healthy control, AR, CRSwNPs were used to measure 20 of cytokines/chemo- kines in the non-stimulated and IL-17A-stimulated conditions. RESULTS AR and CRSwNPs showed significant up-regulation in the release of IL-6, IL-33, and thymic stromal lymphopoietin (TSLP), and the release of IL-6, TSLP, granulocyte macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor α (TNFα) in comparison with normal controls, respectively. Secretion of GM-CSF and TNFα were enhanced in patients with nasal polyps as compared with AR. Stimulation with IL-17A enhanced the secretion of IL-8 and granulocyte-colony stimulating factor (G-CSF) in the normal control, IL-6 and IL-8 in AR, and IL-6, TSLP, G-CSF, GM-CSF and TNFα in nasal polyps. CONCLUSION Epithelial cells derived from AR and CRSwNPs showed up-regulation of secretion of several cytokines/chemokines both in the steady state and after IL-17A stimulation, which may contribute to the inflammatory responses of AR and CRSwNPs.

Maxillary sinus infundibulum narrowing influences sinus abnormalities in spite of the presence or absence of allergy

Abstract Conclusion. Maxillary sinus abnormalities were demonstrated to be associated with maxillary sinus infundibulum narrowing as well as nasal airflow resistance secondary to nonspecific nasal inflammation. Objectives. There is no consensus regarding the pathogenetic roles of allergy and anatomic variations in sinus mucosa abnormalities. We investigated the correlation between allergy and anatomic variations in sinus abnormalities in chronic rhinitis patients in the presence or absence of allergy. Methods: In all, 148 adult patients with allergic rhinitis (AR) and non-allergic rhinitis (NAR) were enrolled. Opacification of sinuses, the size of the maxillary sinus infundibulum, Haller cells, and concha bullosa were evaluated based on computed tomography (CT) images. Simultaneously, nasal airflow resistance was measured. Results: The AR group comprising 105 patients showed maxillary sinus opacification in 45 patients. In the NAR group including 43 patients, soft tissue opacification was observed in 13 patients. There was no significant difference in the incidence of sinus opacification between the AR and NAR groups. Both nasal resistance and the infundibulum size in both the AR and NAR groups with sinus opacification showed significant differences from those without sinus abnormalities. The presence of concha bullosa influenced the sinus opacification in both the AR and NAR groups.

Postoperative Management of Eosinophilic Chronic Rhinosinusitis with Nasal Polyps: Impact of High-Dose Corticosteroid Nasal Spray

Introduction  Eosinophilic chronic rhinosinusitis (ECRS) is characterized by an eosinophilic inflammation driven by Th2-type cytokines. Glucocorticosteroids are the most common first-line treatment for ECRS with nasal polyps. Objective  We have evaluated the long-term treatment with double-dose intranasal corticosteroids in refractory ECRS nasal polyps resistant to the conventional dose and assessed the risk of adverse systemic effects Methods  Sixteen subjects were enrolled in this study. All subjects had ECRS after endoscopic sinus surgery that resulted in recurrent mild and moderate nasal polyps and were undergoing a postoperative follow-up application of mometasone furoate at a dose of 2 sprays (100 μg) in each nostril once a day (200 μg). All the patients were prescribed mometasone furoate, administered at a dose of 2 sprays (100 μg) in each nostril twice a day (400 μg) for 6 months. Results  The average scores of the symptoms during the regular dose of intranasal steroid treatment were 5.2 ± 2.2, but 6 months after the high-dose application, they had significantly decreased to 2.5 ± 1.4 ( p  < 0.05). The polyp size showed an average score of 1.38 during the regular dose which was significantly reduced to 0.43 ( p  < 0.01) by the double dose. Glycated hemoglobin (HbA1c) showed normal ranges in all the patients tested. The cortisol plasma concentration was also normal. Conclusion  Doubling the dose of the nasal topical spray mometasone furoate might be recommended for the treatment of recurrent nasal polyps in the postoperative follow-up of intractable ECRS.

Low‐grade intraductal carcinoma of the salivary gland with prominent oncocytic change: a newly described variant

Low‐grade intraductal carcinoma (LG‐IDC) is a clinically indolent malignant tumour of the salivary glands. Because of its rarity, the histological variants of LG‐IDC have not been well characterised. Herein, we describe five LG‐IDC cases with prominent oncocytic change in the major salivary glands.