Ji-Hyeon Shin

Effect of oral tolerance in a mouse model of allergic rhinitis

Objective: Induction of oral tolerance (OT) is known to prevent allergic inflammation in models of asthma. This study investigated the preventive effect of OT and airway remodeling in a mouse model of allergic rhinitis (AR). Study Design: An in vivo study using an animal model. Setting: Catholic Research Institutes of Medical Science. Methods: Forty six-week-old, female BALB/c mice were divided into four groups: control, AR, low-dose OT, and high-dose OT. To induce OT, mice were fed ovalbumin (OVA) before sensitization with OVA/aluminum hydroxide, 1 mg for six days in the low-dose OT group and a 25 mg single dose in the high-dose OT group. Mice in the AR group were fed phosphate-buffered saline. After sensitization followed by challenges with OVA during six weeks, nasal behaviors, interleukin (IL)-13 and interferon gamma (IFN-γ) levels in nasal lavage (NAL) fluids, as well as OVA-specific IgE levels in serum, were measured. The degree of goblet cell hyperplasia and thickness of lamina propria were observed in nasal tissues by periodic acid-Schiff and Massons trichrome stain. A P value < 0.05 was accepted as statistically significant. Results: Both OT groups showed a significant decrease in inflammatory cells, IL-13 and IFN-γ in NAL fluids, as well as OVA-specific IgE levels in serum compared with the AR group. In addition, the degree of goblet cell hyperplasia and thickness of lamina propria were attenuated in both OT groups compared with the AR group. Further, these alterations did not differ significantly between the two OT groups. Conclusion: These results suggest that OT may effectively reduce allergic inflammation as well as airway remodeling in a mouse model of AR.

The Onodi cell: an obstacle to sellar lesions with a transsphenoidal approach.

Objective. The Onodi cell is the posterior-most ethmoid air cell and an important anatomical variant because of the intimate spatial relationship with the optic nerve, internal carotid artery, and sellar floor during sphenoid sinus surgery. The authors evaluated the incidence of Onodi cells, their clinical importance, and the association between preoperative radiological findings and surgical findings. Study Design. Case series with chart review. Setting. Tertiary care medical center. Methods. The authors retrospectively reviewed the medical records of 162 cases, including preoperative paranasal sinus computed tomography (PNS CT) findings and the findings with the endoscopic endonasal transsphenoidal approach (EETSA). They evaluated the prevalence of Onodi cells and the clinical manifestations in the patients with these cells. They also examined the clinical significance of these cells during EETSA. Results. Onodi cells were identified in the preoperative PNS CT of 53 patients, whereas Onodi cells were observed in 54 (33.3%) of the 162 patients at EETSA. The Onodi cells were bilateral in 23 patients and unilateral in 31. In all cases, the Onodi cells limited the exposure of the sellar floor. Only after removing these cells was the entire sellar floor exposed so that the tumors could be removed completely. Conclusion. Onodi cells were observed more frequently than in previous studies, and 98.1% of them were identified on preoperative PNS CT. When reviewing PNS CT images preoperatively, one needs to identify the presence of Onodi cells. The Onodi cells must be removed to completely resect tumors located in the sellar region during EETSA.

Three-dimensional morphometric analysis of paranasal sinuses and mastoid air cell system using computed tomography in pediatric population.

OBJECTIVES To evaluate the volumetric relationship between the mastoid air cell (MAC) and paranasal sinus (PNS) in the pediatric population using three-dimensional reconstruction and the analysis technique of CT. STUDY DESIGN Retrospective cross-sectional study was conducted at a university-based, secondary referral hospital. METHODS PNS CT imaging data of 62 children (40 boys and 22 girls; mean age=13.4 ± 4.0 years) was reconstructed to the three-dimensional model with the surface-rendering algorithm (lower threshold of -1024 HU and upper threshold of -318 HU), and subsequently measuring the volume of the three PNSs (frontal, maxillary and sphenoid) and MAC. Hierarchical linear regression analysis was used to control the effect of age. RESULTS Controlling the effect of age, no significant linear regression relationship was found between the volume of MAC and PNSs. It was observed that PNSs and MAC showed a significant linear relationship with age. The regression slopes of PNSs were larger than that of MAC, especially the growth of maxillary and sphenoid sinuses was faster and larger than that of the frontal sinus and MAC. As the coefficient of determination was extremely small, the aging process itself could not effectively explain the volume variation of PNSs and MAC. CONCLUSION No interaction was observed in the pneumatization of the three PNSs (frontal, maxillary, and sphenoid) and MAC. It was found that the growths of PNSs and MAC are influenced by age. Further, maxillary and sphenoid sinuses tend to grow faster and become larger than the frontal sinus and mastoid air cell system. Thus, it is verified that environmental factors could be involved in the postnatal pneumatization process of the PNSs and MAC, which might influence MAC to a greater extent than the PNSs.

Anatomical analysis of nasal obstruction: nasal cavity of patients complaining of stuffy nose.

To evaluate the relationship between subjective symptoms of nasal obstruction and the corresponding nasal anatomical parameters using paranasal computed tomography (PNS CT).

Preventive effects of oral tolerance on allergic inflammation and airway remodeling in a murine model.

Background Oral tolerance (OT) is considered as a preventive and therapeutic strategy for treating asthma and allergic rhinitis (AR). We investigated the preventive effects of OT on allergic inflammation and remodeling in the upper and lower airways in a mouse model of allergy. Methods BALB/c mice were divided into four groups: control, allergy, low-dose OT, and high-dose OT. To induce OT, mice were fed ovalbumin (OVA) before sensitization with OVA/Al(OH)3 at a dose of 1 mg for 6 days in low-dose OT group and a single dose of 25 mg in high-dose OT group. After sensitization followed by OVA challenge, nasal symptoms, interleukin (IL)-13, interferon (IFN)-gamma, IL-10, and transforming growth factor (TGF) beta-1 levels in nasal lavage (NAL) and bronchoalveolar lavage (BAL) fluids were measured, and OVA-specific IgE, IgG1, and IgG2a levels were measured in the serum. The airway hyperresponsiveness (AHR) was measured by enhanced pause. The goblet cell hyperplasia and the thickness of lamina propria were observed in the upper and lower airways. Results In the allergy group, the allergic behavior scores, AHR, and OVA-specific IgE, IgG1, and IgG2a levels; inflammatory cells; IFN-gamma levels; and IL-13 levels in NAL/BAL fluids were elevated compared with the control group, low-dose OT group, and high-dose OT group. The allergy group had higher levels of IL-10 and TGF-beta-1 in BAL fluids when compared with the other groups. The goblet cell hyperplasia and the thickness of the lamina propria were attenuated in both OT groups compared with the allergy group. Conclusion OT may effectively prevent AHR, allergic inflammation, and airway remodeling in the upper and lower airways.

The Serine Protease Inhibitor, 4-(2-aminoethyl) Benzene Sulfonyl Fluoride Hydrochloride, Reduces Allergic Inflammation in a House Dust Mite Allergic Rhinitis Mouse Model

Purpose Serine protease inhibitors are involved in immune development, anti-inflammatory mechanisms, and tissue repair. In the present study, the serine protease inhibitor 4-(2-aminoethyl) benzene sulfonyl fluoride hydrochloride (AEBSF) was evaluated for its prophylactic and therapeutic applications in a mouse model of allergic rhinitis (AR). Methods BALB/c mice were divided into 5 groups: contol (CON), Dermatophagoides farinae (Derf), AR mice treated with AEBSF before sensitization (S), AR mice treated with AEBSF after challenge (C), and steroid groups. Derf was used as an allergen. AEBSF was administered before S or after C. Allergic symptom scores, eosinophil counts, proteolytic activity, interferon-γ, interleukin (IL)-10 levels and serum Derf-specific IgE levels were measured. T-bet, GATA-3, Foxp3, IL-13, and transforming growth factor (TGF)-β mRNA levels were determined using real-time polymerase chain reaction. CD4+CD25+Foxp3+ T cells were assessed using flow cytometry. Results Symptom scores, serum Derf-specific IgE levels, GATA-3 mRNA levels, IL-13 mRNA levels, and tissue eosinophil counts decreased in both the S and C groups (P<0.05). Additionally, the percentage of CD4+CD25+Foxp3+ T cells, IL-10 levels, and Foxp3 mRNA levels increased in the S and C groups compared with those in the Derf group (P<0.05). AEBSF treatment decreased the proteolytic activity in the S and C groups (P<0.05). Conclusions Prophylactic and therapeutic treatment with AEBSF significantly reduces allergic airway inflammation and can induce regulatory T cells in a murine model of AR.

The effect of topical FK506 (tacrolimus) in a mouse model of allergic rhinitis.

Background The management of allergic rhinitis (AR) encompasses education, pharmacotherapy, immunotherapy, and surgery. FK506 (tacrolimus) is an immunosuppressant that inhibits allergic reactions. The purpose of this study was to reveal whether FK506 treatment reduces allergic inflammation in an AR mouse model and to elucidate the mechanisms. Methods Forty mice were divided into four groups: control, AR, FK (FK506), and dexamethasone (DEX). All mice except for the control group were sensitized by an i.p. injection of ovalbumin (OVA). After sensitization, the FK and DEX groups were treated with FK506 and DEX intranasally. All sensitized mice were challenged intranasally with OVA. Allergic symptoms and tissue eosinophil counts were recorded. Interleukin (IL)-5, interferon gamma, and IL-10 levels in nasal lavage fluid (NALF) and serum OVA-specific IgE levels were measured. T-bet, GATA-3, and Foxp3 mRNA expression in splenic mononuclear cells were determined by real-time polymerase chain reaction. Results In the FK group and DEX group, allergic symptoms, serum OVA-specific IgE, tissue eosinophil counts, IL-5 in NALF, and GATA-3 mRNAs expression decreased (p < 0.05), and IL-10 in NALF and Foxp3 mRNAs expression increased compared with the AR group (p < 0.05). No significant difference was observed between the FK group and the DEX group. Conclusion These results suggest that topical FK506 may reduce allergic inflammation and have potency equal to DEX in the AR model. This mechanism may involve not only Th2 cells but also regulatory T cells. Additional studies are needed on FK506, but in the future, we can consider FK506 as an alternative to topical steroids in the treatment of AR.

Immunomodulatory Role of Histamine H2 Receptor in Allergen-Specific Immunotherapy A Mouse Model of Allergic Rhinitis

Objective. The purpose of this pilot study was to investigate the effects of HR2 on allergen-specific immunotherapy in a mouse model of allergic rhinitis. Study Design. An in vivo study using an animal model. Setting. Catholic Research Institutes of Medical Science. Methods. Fifty mice were divided into 5 groups: control, allergic rhinitis (AR), immunotherapy (IT), immunotherapy with HR2 agonist (HI), and immunotherapy with HR2 antagonist (HB). All mice except for the control group were sensitized with ovalbumin (OVA). After 1 week, mice in the IT, HI, and HB groups underwent immunotherapy by intradermal injections of OVA. During immunotherapy, the HI group was injected with HR2 agonist, whereas the HB group was injected with HR2 antagonist. All sensitized mice were challenged with intranasal OVA. After the final challenge, allergic behavior was evaluated. Interleukin (IL)–13, interferon-γ, IL-10, and transforming growth factor (TGF)–β levels in nasal lavage fluid (NALF), as well as OVA-specific IgE levels in serum, were measured. The number of eosinophils in lamina propria was evaluated. Results. The levels of serum OVA-specific IgE and IL-13 in NALF were significantly increased in the HB group compared with the IT group (P < .05). Also, the tissue eosinophil counts were higher in the HB group than in the IT group (P < .05). Conclusion. HR2 antagonist impaired OVA-specific immunotherapy in mice. Although confirmation of this preliminary result is needed, these findings suggest that HR2 receptors may have inhibitory effects on immune tolerance. The authors suggest that application of this property could enhance the efficiency of allergen-specific immunotherapy.

The Effect of Pneumococcal Polysaccharide Vaccine in a Mouse Model of Allergic Rhinitis

Objectives This study aimed to determine if pneumococcal polysaccharide vaccine (PPV) could suppress allergic inflammation in an allergic rhinitis mouse model and to explore whether differences exist regarding the effect of PPV according to timing of administration. Study Design In vivo study using an animal model. Setting Catholic Research Institutes of Medical Science. Subjects and Methods BALB/c mice were divided into control, Der f, Pre-S, and Post-S groups. The allergen was Dermatophagoides farinae (Der f). Pneumococcal polysaccharide vaccine was administered before (Pre-S) or after (Post-S) sensitization. Allergic symptoms and eosinophils in nasal mucosa, interferon-γ, interleukin (IL)–13, and IL-10 in nasal lavage fluid and serum Der f–specific IgE were measured. T-bet, GATA-3, and Foxp3 mRNA in spleen were determined by real-time polymerase chain reaction. Flow cytometry of CD4+CD25+Foxp3+ T cells in spleen was analyzed. Results In the Pre-S group, symptom score, serum Der f–specific IgE, eosinophils, IL-13, and GATA-3 mRNA were decreased (P < .05), and IL-10, Foxp3 mRNA, and CD4+CD25+Foxp3+ T cells were increased compared with those in Der f group (P < .05). In the Post-S group, symptom score, serum Der f–specific IgE, and GATA-3 mRNA were decreased (P < .05), and Foxp3 mRNA and CD4+CD25+Foxp3+ T cells were increased compared with those in the Der f group (P < .05). Conclusion These results suggest that PPV administered before or after sensitization suppresses Th2 response and enhanced induction of regulatory T cells in an allergic rhinitis model. In addition, there was no significant difference between the degrees of effects in these 2 conditions. In the future, we can consider PPV to be a preventative agent for allergic rhinitis.

Psychological stress as a measure for treatment response prediction in idiopathic sudden hearing loss

OBJECTIVE Early prediction of therapeutic outcomes could reduce exposure to ineffective treatments and optimize clinical outcomes. However, none of the known otologic predictors is amenable to therapeutic intervention for idiopathic sudden sensorineural hearing loss (ISSNHL). The aims of this study were to investigate psychological stress as a potential predictor to discriminate outcomes in ISSNHL. METHODS Various psychological measures were conducted including structured interview assessment tools in patients with recently diagnosed ISSNHL before initiating treatment. Using logistic regression analysis, we identified the predictors of treatment response and estimated the probability of treatment response in 50 ISSNHL patients who participated in a clinical trial. RESULTS Treatment non-responders were significantly differentiated from responders by various psychological problems. The depression subscore of Modified form of Stress Response Inventory (SRI-MF) (p=0.007) and duration of hearing loss (p=0.045) significantly predicted treatment response after controlling other clinical correlates. The same predictors were identified from different treatment response measured using Siegels criteria. The most discriminative measure for treatment response was SRI-MF depression score with an overall classification accuracy of 73%. CONCLUSIONS We found depressive stress response to be the strong predictor of treatment response in patients with ISSNHL. Our results highlight the potential use of the psychiatric approach as a tool for enhancing therapeutic outcomes. Future stress intervention studies with larger number of ISSNHL patients are needed.