Chae-Seo Rhee

Histological and immunological features of non-eosinophilic nasal polyps

Objective The aim of this study was to investigate the his-toimmunological features of non-eosinophilic nasal polyps (NPs). METHODS Thirty patients with chronic rhinosinusitis and NPs were included in this study. NPs were grouped into eosinophilic and non-eosinophilic types according to the amount of eosinophils in the NPs. The amount of serum total IgE and peripheral blood eosinophils were measured. Basement membrane (BM) thickness was measured, along with the expression of chemokine receptor 5 (CCR5) and chemokine receptor 3 (CCR3) in NP lymphocytes. RESULTS Non-eosinophilic NPs comprised 66.7% of the total NPs included in this study. The amount of eosinophils in NPs was related to eosinophilia of the peripheral blood, but not to elevated serum IgE. BM was significantly thinner in non-eosinophilic than in eosinophilic NPs. Lymphocytes expressing CCR5 or CCR3 were less frequently found in non-eosinophilic than in eosinophilic NPs. CONCLUSION Histoimmunological characteristics of non-eo-sinophilic NPs differ from those of eosinophilic NPs; non-eosino-philic NPs may be featured by thinner BM and fewer CCR5- and CCR3-positive lymphocytes.

Changes of Nasal Function After Temperature-Controlled Radiofrequency Tissue Volume Reduction for the Turbinate

Objectives Temperature‐controlled and temper‐ature‐monitored radiofrequency tissue volume reduction (RFTVR) for the turbinate is a new treatment modality for nasal obstruction secondary to turbinate hypertrophy. We compared the nasal functions after the treatment of RFTVR and laser vaporizing turbinoplasty (LVT) using subjective symptom scores and objective tests.

Adenoid Cystic Carcinoma of the Sinonasal Tract: Treatment Results

Objectives: Malignancies arising from the sinonasal tract, which includes the nose, paranasal sinuses, and nasopharynx, are uncommon. Although adenoid cystic carcinoma (ACC) is the second most common cancer occurring in the sinonasal tract, only few studies have been reported. This retrospective review was performed to identify the clinical features and treatment outcomes of sinonasal ACC.

Cytokine gene expression in nasal polyps

Nasal polyps are the most common mass lesion of the nasal cavity. Various pathogenetic mechanisms have been proposed. However, the cause is still largely unknown, and treatment methods have not been changed for several hundred years. In order to investigate the role of cytokines in the pathogenesis of nasal polyps, expression of cytokine messenger RNAs (mRNAs) in nasal polyps was investigated. We performed reverse transcriptase-polymerase chain reaction and Southern blot to examine gene expression of the cytokines interleukin (IL)-1ß, IL-6, IL-8, transforming growth factor (TGF)-ß, IL-4, IL-5, and interferon (IFN)-Γ and compared the results with the gene expressions of these cytokines in normal nasal mucosa. Nasal polyp tissues were obtained from 14 patients undergoing polypectomy for nasal obstruction. Among them, 4 patients suffered from associated perennial allergic rhinitis. The mRNAs of IL-4 and IL-5 (Th2 cytokines) as well as IFN-γ (Thl cytokine) were expressed in all of the nasal polyps obtained from the 14 patients, irrespective of the presence or absence of allergy, while 2, 0, and 4 of 6 normal turbinate mucosae expressed IL-4, IL-5, and IFN-γ mRNAs, respectively. The mRNAs of IL-1ß, IL-6, IL-8, and TGF-ß were expressed in 6, 1, 2, and 3 of 6 normal turbinate mucosae, respectively, while the mRNAs of these cytokines were expressed in all of the 14 polyp tissues except IL-6 mRNA, which was expressed in 13 nasal polyp tissues. There were no differences in the mean density ratios of each cytokine band on Southern blot between polyp tissues with allergy and those without allergy. These results suggest that many cytokines are produced in nasal polyps, that they may play important roles in the pathogenesis of nasal polyps, and that allergy per se may not play a fundamental role in the pathogenesis of nasal polyps.

Hypoxia-inducible Factor 1 Mediates Nasal Polypogenesis by Inducing Epithelial-to-Mesenchymal Transition

RATIONALE Nasal polyposis implies a refractory clinical course in case of chronic rhinosinusitis (CRS). Although hypoxia is believed to be associated with nasal polyposis, little is known about the mechanism underlying polypogenesis. OBJECTIVES To determine if hypoxia drives nasal polyposis by epithelial-to-mesenchymal transition (EMT). METHODS Immunoblotting, immunofluorescence, flow cytometry, and real-time polymerase chain reaction were performed to evaluate EMT and hypoxic markers in human nasal epithelial cells (hNECs) and in sinonasal tissues from patients with CRS with or without polyps. In addition, the effects of hypoxia-inducible factor (HIF)-1α inhibitors on nasal polypogenesis were investigated in a murine model. MEASUREMENTS AND MAIN RESULTS E-cadherin and α-smooth muscle actin (α-SMA) were down-regulated and up-regulated, respectively, in patients with polyps as compared with patients without polyps. Under hypoxia, hNECs transformed to a mesenchymal shape, and demonstrated representative changes in EMT markers; that is, mesenchymal markers (α-SMA, vimentin, and twist) increased but epithelial markers (E-cadherin and β-catenin) decreased. Mechanistically, E-cadherin level was recovered in hypoxia by silencing HIF-1α and decreased in normoxia by expressing HIF-1α. Furthermore, hypoxia was found to down-regulate PP2Ac phosphatase and up-regulate pSmad3, which led to α-SMA induction. In CRS sinonasal specimens, HIF-1α expression was found to correlate with E-cadherin loss and α-SMA expression. Finally, HIF-1α inhibitors suppressed nasal polypogenesis in a murine model. CONCLUSIONS hNECs undergo EMT during hypoxia and this process is critically mediated by HIF-1α and pSmad3. This study shows that hypoxia-induced EMT is likely to contribute to nasal polyposis in CRS, and suggests that HIF-1α be viewed as a therapeutic target for nasal polyposis.

Staphylococcus aureus enterotoxin B contributes to induction of nasal polypoid lesions in an allergic rhinosinusitis murine model.

Background Studies on the pathophysiology of nasal polyps in human subjects have been limited; thus an animal model is needed. There is increasing evidence supporting the role of Staphylococcus aureus enterotoxin B (SEB) in the pathogenesis of nasal polyposis. The aim of this study was to investigate the histological and immunologic effects of SEB on the formation of nasal polypoid lesions in an allergic rhinosinusitis murine model. Methods After induction of an ovalbumin (OVA)-induced allergic rhinosinusitis, OVA with SEB (5 or 500 ng) was instilled into the nasal cavity of mice for 8 weeks. Control mice did not receive SEB or OVA instillation. Histopathological changes were observed using hematoxylin and eosin, Sirius red, Giemsa, Massons trichrome, and Alcian blue stains. The levels of interleukin (IL)-4, IL-5, IL-8, IL-13, eotaxin, interferon gamma, total IgE, and OVA-specific IgE from serum or nasal lavage fluid were measured using enzyme-linked immunosorbent assay. Results The group treated with OVA plus 5 ng of SEB had significantly more mucosal lesions with epithelial disruption and nasal polypoid lesions than mice treated with OVA only, showing a significant increase in the infiltration of total inflammatory cells, eosinophils, and lymphocytes than the other groups. Levels of IL-5, eotaxin, and OVA-specific IgE in nasal lavage fluid were increased in the group treated with OVA plus 5 ng of SEB than in the other groups. A higher number of secretory cells in the groups treated with OVA plus SEB was observed than in other groups. Conclusion Low-dose SEB induced nasal polypoid lesions with an increased eosinophilic infiltration in an allergic rhinosinusitis murine model.

Bronchial hyperresponsiveness in young children with allergic rhinitis and its risk factors

Background:  Subjects with allergic rhinitis but no clinical evidence of asthma have greater bronchial hyperresponsiveness (BHR), and several factors have been implicated as its determinants. However, studies in young children are lacking. The aims of this study were to evaluate the prevalence of BHR in young children with allergic rhinitis and to investigate its risk factors.

Nasal septal perforation repair: predictive factors and systematic review of the literature.

Purpose of reviewAlthough numerous surgical techniques have been introduced thus far in order to achieve the surgical closure of nasal septal perforation, the repair of nasal septal perforation is still challenging for surgeons and operative techniques are not standardized. Furthermore, predictive factors for successful closure have not been elucidated. This review aimed to investigate predictive factors for complete closure of nasal septal perforation. Recent findingsThe size of perforation was the most significant factor for complete closure. Surgical failure occurred more frequently in patients with large perforation (>2 cm) than those with small-to-moderate perforation (⩽2 cm). The bilateral coverage over the perforation with vascularized mucosal flap also helped complete closure. Interposition of grafts appeared to assist complete closure, although it was statistically insignificant. SummaryThis review provides information for surgeons on how to predict surgical outcomes of the repair of nasal septal perforation and which surgical techniques to choose in order to obtain better results.

Class III β-tubulin, but not ERCC1, is a strong predictive and prognostic marker in locally advanced head and neck squamous cell carcinoma

BACKGROUND Recent researches revealed that class III beta-tubulin (TUBB3) is a prognostic marker in various tumors and role of TUBB3 in head and neck squamous cell carcinoma (HNSCC) is not defined yet. We analyzed the significance of TUBB3 expression along with p53 and ERCC1 in locally advanced HNSCC patients receiving cisplatin-based induction chemotherapy. MATERIALS AND METHODS Retrospective review of medical records at Seoul National University Hospital between 1998 and 2007 was carried out. Immunohistochemical stain of TUBB3, p53, and ERCC1 was done in paraffin-embedded tumor tissue. We assessed response to treatment, progression-free survival (PFS), overall survival (OS), and cancer-specific survival (CSS). RESULTS Eighty-five patients with oropharyngeal, hypopharyngeal, and laryngeal cancers received induction chemotherapy with 5-fluorouracil (5-FU) and cisplatin (n = 55), or 5-FU, cisplatin, and docetaxel (Taxotere) (n = 30). Eighty-three received definitive treatment after induction chemotherapy, where 62 received radiotherapy and 21 received surgery. TUBB3-positive patients showed lower response rate than TUBB3-negative patients (69% versus 88%, P = 0.039). Shorter median PFS was observed in TUBB3-positive group (12 versus 47 months, P = 0.001). Shorter median OS was observed in TUBB-positive group not reaching statistical significance (30 versus 59 months, P = 0.072). TUBB3 status significantly influenced CSS (35 months versus not reached, P = 0.017). Positive p53 status was related to poorer OS and CSS. ERCC1 showed no influence on chemotherapy response, PFS, OS, and CSS. CONCLUSION TUBB3 is a predictive and prognostic marker along with well-known p53 in HNSCC patients receiving cisplatin-based induction chemotherapy. Clinical impact of ERCC1 is not evident in this setting.

Allergen-independent immunostimulatory sequence oligodeoxynucleotide therapy attenuates experimental allergic rhinitis

While effective for the prevention and treatment of allergic rhinitis (AR) symptoms, currently available medications do not reverse allergen specific hypersensitivities. Therefore, pharmacotherapeutics are not curative and their daily use is often required for years. These investigations were conducted to determine whether immunostimulatory sequence oligodeoxynucleotide (ISS‐ODN) delivery protects previously sensitized mice from AR hypersensitivity responses and modulates their allergen specific immune profiles. Mice were first sensitized with ovalbumin (OVA) and alum, twenty‐four hr before beginning a series of seven daily intranasal (i.n.) allergen challenges, subsets of mice received a single i.n. or intradermal (i.d.) dose of ISS‐ODN or control oligodeoxynucleotide (C‐ODN), a single intraperitoneal (i.p.) injection of dexamethasone (DXM), or no intervention. Mice receiving i.d. or i.n. ISS‐ODN were found to have attenuated immediate and late phase effector cell responses to i.n. OVA challenge. Specifically, ISS‐ODN treated mice had less histamine and cysteinyl leukotriene release and eosinophilic inflammation in their nasal passages than mice treated with C‐ODN. In addition, splenocytes from ISS‐ODN but not C‐ODN treated mice displayed attenuated OVA‐specific interleukin (IL)‐4, IL‐5, and IL‐13 but increased interferon‐γ responses. Finally, ISS‐ODN was generally a more effective treatment than DXM, both in blunting AR hypersensitivity responses and in shifting T helper 2 Th2‐biased immune parameters towards Th1 dominance. As ISS‐ODN delivery rapidly attenuated effector cell responses in this AR model in an allergen independent manner, the present results suggest that therapy with ISS‐ODN alone may be an effective alternative to corticosteroid medications for the clinical management of AR.