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Chronic rhinosinusitis (CRS) is characterized by prolonged inflammation of the nasal and paranasal sinus mucosa lasting over 12 weeks. CRS is divided into two main types based on the presence of nasal polyps: CRS without nasal polyps and CRS with nasal polyps. The condition is further classified into endotypes based on type 1, type 2, and type 3 inflammatory signatures, with differences in terms of disease severity, prognosis, and treatment response. Recent studies have emphasized the importance of the epithelial-mesenchymal transition (EMT) in CRS progression. In CRS, the EMT can be triggered by infections, allergens, hypoxia, and environmental pollutants. Specifically, EMT induction proceeds through the following mechanisms: viral and bacterial infections disrupt the epithelial barrier, house dust mites and other allergens activate the TGF-β and EGFR signaling pathways, hypoxia increases HIF-1α and other mesenchymal markers, and diesel exhaust particles and particulate matter cause oxidative stress. Maintaining the integrity of the epithelial barrier is essential for nasal mucosa homeostasis. In CRS, barrier damage activates repair processes that trigger the EMT, resulting in barrier dysfunction and tissue remodeling. Epithelial barrier dysfunction allows antigens and pathogens to penetrate, perpetuating inflammation and promoting the EMT. This disruption is a hallmark of CRS, emphasizing the importance of barrier integrity in the development of the disease. Key signaling pathways regulating the EMT in CRS include TGF-β, Wnt, HMGB1, AGE/ERK, TNF-α, and various miRNAs. These signaling pathways connect to various downstream pathways, such as the Smad2/3, GSK-3β/β-catenin, RAGE, and NF-κB pathways. This review focuses on the complex mechanisms of the EMT in CRS, emphasizing the role of epithelial barrier dysfunction and subsequent EMT processes in driving the disease’s development and progression. A deeper understanding of these EMT-driven mechanisms will help identify the potential therapeutic targets aimed at restoring epithelial integrity and reversing the EMT.

Background and Objectives In 2021, biologics were approved for treating chronic rhinosinusitis with nasal polyps (CRSwNP) in Korea. However, CRS is a heterogeneous disease, and its characteristics are thought to differ between Western and Korean populations. This study aimed to evaluate the experiences of members of the Korean Rhinologic Society during the first year of biologic usage for the treatment of nasal polyps. Methods An anonymous survey consisting of 15 items was conducted from November to December 2021. The survey included questions about participant demographics, use of biologics for treating CRSwNP, and expectations regarding the effectiveness of biologics for treating CRSwNP. Results In total, 44 members participated in the survey. Approximately half of the respondents were in their 40s (50.0%) and had 5–9 years of clinical experience as otorhinolaryngologists (47.7%). The majority of participants held academic positions (95.4%). About half of them worked in Gyeonggi Province. The utilization of biologics did not differ significantly based on clinical experience (p=0.192). When asked about the factors considered for prescribing biologics, the most common reason was recurrence of polyps after surgery (87.2%). The most frequent reason for discontinuing biologics was cost (48.6%). When asked about the extent to which they expected that the availability of biologics for CRSwNP treatment would reduce endoscopic sinus surgery (ESS), 45.5% of members expected a reduction of approximately 10%–29%. In addition, 20.5% expected a reduction of 50% or more. However, 61.4% expected a reduction of less than 10% in primary ESS. In addition, most respondents (93.2%) agreed with the need for Korea-specific guidelines for biologic treatment. Conclusion There are discrepancies between the current guidelines for biologic treatment of CRSwNP and the reality of the situation, highlighting the need for the development of Korea-specific guidelines.

Background and Objectives Turbinoplasty may be an option in patients with persistent symptoms of allergic rhinitis (AR) despite adequate medication. The two most frequently used surgical techniques for turbinoplasty are radiofrequency ablation and microdebriderassisted turbinoplasty. This study compared the outcomes of these two surgical techniques and assessed the long-term treatment effects. Methods This study included patients with AR who underwent turbinoplasty between January 2010 and June 2017. We examined the medication scores, overall treatment satisfaction scores, and medical records. Based on the type of surgery, patients were classified into microdebrider and coblator groups. A telephone survey was conducted to collect data on the 5-year post-treatment efficacy parameters. Scores for allergic symptoms, prescription medicines taken after surgery, and general satisfaction were compared. Results Of the total 241 patients, 192 (79.7%) and 49 (20.3%) underwent microdebrider-assisted turbinoplasty and radiofrequency ablation turbinoplasty, respectively. Both the microdebrider and coblator groups showed remarkable improvements in AR symptoms at the 5-year follow-up (p

Fine dust and bioaerosols are significant public health concerns, showing the importance of protective measures. In this study, natural-based trimethyl chitosan, permanently burdened with a positive charge, was successfully distributed on the surface of melt-blown polypropylene sheets through a metal rod coating process. This surface modification was confirmed through scanning electron microscopy and X-ray photoelectron spectroscopy, indicating the surface adsorption of trimethyl chitosan without chemical bonding. Modifying polypropylene mask filters yielded a positive surface zeta potential for 10–20 g/m2 coat weight, increasing the filtration efficiency to 55–94 % in a standard particle filtration test using paraffin oil as a liquid aerosol. The filtration efficiency remained higher than conventional non-treated mask filters even after the humidification of sheets. In addition, the filtration test against fine dust particles, such as titanium dioxide, was performed with trimethyl chitosan-modified mask filters that captured up to 100–800 µg/m3 titanium oxide particle concentrations, showing better filtration than conventional mask filters in high fine dust events. Trimethyl chitosan-modified mask filters also exhibited potent inhibition, bactericidal, and antiviral effects against HCoV-OC43, reducing the virus infection rate by 93.69 %. Thus, trimethyl chitosan could be applied to several existing filter membranes to protect against particulate matter and dangerous airborne pathogens.

The Korean Society of Otorhinolaryngology-Head and Neck Surgery and Korean Rhinologic Society appointed a guideline development group (GDG) to establish a clinical practice guideline, and the GDG developed a guideline for nasal irrigation for adult patients with chronic rhinosinusitis (CRS). The guideline focuses on knowledge gaps, practice variations, and clinical concerns associated with nasal irrigation. Nasal irrigation has been recommended as the first-line treatment for CRS in various guidelines, and its clinical effectiveness has been demonstrated through a number of studies with robust evidence. However, no guidelines have presented a consistent nasal irrigation method. Several databases, including OVID Medline, Embase, the Cochrane Library, and KoreaMed, were searched to identify all relevant papers using a predefined search strategy. When insufficient evidence was found, the GDG sought expert opinions and attempted to fill the evidence gap. Evidence-based recommendations for practice were ranked according to the American College of Physicians grading system. The committee developed 11 evidence-based recommendations. This guideline focuses on the evidence-based quality improvement opportunities deemed the most important by the GDG. Moreover, the guideline addresses whether nasal lavage helps treat CRS, what type of rinsing solution should be used, and the effectiveness of using additional medications to increase the therapeutic effect.

Background & aimsChronic rhinosinusitis (CRS) is one of the most prevalent upper respiratory tract diseases. However, little is known the effect of CRS on the cardiovascular aspects of patients. This study aimed to investigate the incidence of acute myocardial infarction (AMI) in patients with CRS compared with that in the general population.MethodsThis retrospective cohort study was performed using the Korean National Health Insurance Service (NHIS) database. To minimize confounding, age, sex, and cardiovascular risk profiles were adjusted. The primary endpoint was newly diagnosed AMI in patients between January 2005 and December 2018. The relative risk of AMI in patients with CRS was compared with that in controls. Kaplan-Meier survival curves and Cox proportional regression tests were used for statistical analyses.ResultsAmong 5,179,981 patients from the NHIS database, 996,679 patients with CRS were selected. The control group was 10 times (n = 9,966,790) the number of individuals in the CRS group. The CRS group had better cardiovascular profiles than those of the control group and had an adjusted hazard ratio of 0.99 (95% confidence interval, 0.97-1.02) for AMI.ConclusionThere was no significant association between the two groups regardless of the presence of nasal polyps. This is the first study adjusting cardiovascular risk profiles and analyzing the relationship between CRS and AMI. CRS was not associated with a high incidence of AMI after adjusting for cardiovascular risk factors.

Well-characterized in chronic rhinosinusitis, type 2 inflammation is frequently associated with nasal polyps, comorbid asthma, and nonsteroidal anti-inflammatory drug hypersensitivity. Despite medical and surgical treatment, it recurs in a significant proportion of patients. Thus, severe uncontrolled type 2 chronic rhinosinusitis with nasal polyps is the most difficult-to-treat phenotype of chronic rhinosinusitis. Recently, dupilumab, a monoclonal antibody against IL-4 receptor α, and omalizumab, a monoclonal antibody against immunoglobulin E, were approved for patients with chronic rhinosinusitis with nasal polyps in the United States, Europe, and Korea. Therefore, rhinologists should understand novel biologics and their use. Here, we provide a literature review of several biologics with their indications, effectiveness, and safety.

The novel SARS-CoV-2 virus that causes COVID-19 has emerged rapidly and the virus has caused a global pandemic since it was first diagnosed in December 2019. SARS-CoV-2 is the seventh virus associated with human transmission among corona viruses. Otorhinolaryngologists could be vulnerable to this viral transmission due to the high viral load in the nasal cavity and nasopharynx. Hence, it is essential to understand the novel COVID-19 from the perspective of otorhinolaryngologists. We provide literature reviews of previous human coronaviruses and the novel COVID-19 with clinical hallmarks, diagnostic approaches, and possible treatment options. Further study is necessary to elucidate viral features and standardize treatment protocols with curable anti-viral agents and vaccines.

Otorhinolaryngologic symptoms such as cough, rhinorrhea, anosmia, ageusia, and fever can precede development of COVID-19. Otolaryngologists are vulnerable to potential COVID-19 infection because early cases of COVID-19 have been asymptomatic or show mild manifestations. Otolaryngologists should wear adequate personal protective equipment (PPE) according as location or situation. PPE includes medical masks, goggles, and fluid-resistant gown and gloves. Authors provide clinical recommendations based on PPE for otorhinolaryngologists during the COVID-19 pandemic. In addition, we reviewed the literature related to clinical guidelines of foreign otorhinolaryngology societies with regard to COVID-19.

Objectives. Limited information is available regarding strain-related differences in mouse models of allergic rhinitis induced by Dermatophagoides farinae (Der f1). In this study, we compared differences between two mouse strains and determined the optimal dose of Der f1 for allergic rhinitis mouse models. Methods. Forty-eight mice were assigned to the following six groups (n=8 per group): group A (control, BALB/c), group B (Der f1-sensitized BALB/c, 25 µg), group C (Der f1-sensitized BALB/c, 100 µg), group D (control, C57BL/6), group E (Der f1-sensitized C57BL/6, 25 µg), and group F (Der f1-sensitized C57BL/6, 100 µg). Allergic inflammation was induced with Der f1 and alum sensitization, followed by an intranasal challenge with Der f1. Rubbing and sneezing scores, eosinophil and neutrophil infiltration, and immunoglobulin, cytokine, and chemokine levels in the nasal mucosa and from splenocyte cultures were assessed. Results. Rubbing and sneezing scores were higher in groups B, C, E, and F than in groups A and D, with a similar pattern in both strains (i.e., group B vs. E and group C vs. F). Serum immunoglobulin levels were significantly elevated compared to the control in groups B and C, but not in groups E and F. Eosinophil and neutrophil infiltration increased (all P0.05). BALB/c mice (group B) showed a greater elevation of splenic interleukin (IL)-4 (P

Taste bud cell differentiation is extremely important for taste sensation. Immature taste bud cells cannot function during taste perception transmission to the nerve. In this study, we investigated whether hedgehog signaling affected taste bud cell differentiation and whether transient receptor potential vanilloid 1 (TRPV1) played a key role in dry mouth. The induction of dry mouth due to salivary gland resection (SGR) was confirmed on the basis of reduced salivation and disrupted fungiform papillae. The expression of keratin 8 (K8) of taste bud cells, neurofilament (NF), sonic hedgehog (Shh), and glioma-associated oncogene homolog 1 (Gli1) around taste bud cells was downregulated; however, the expression of TRPV1, P2X purinoceptor 3 (P2X3), and hematopoietic stem cell factor (c-Kit) was upregulated at the NF ends in the dry mouth group. To investigate the effect of TRPV1 defect on dry mouth, we induced dry mouth in the TRPV-/- group. The K8, NF, and P2X3 expression patterns were the same in the TRPV1 wild-type and TRPV1-/- dry mouth groups. However, Shh and c-Kit expression decreased regardless of dry mouth in the case of TRPV1 deficiency. These results indicated that TRPV1 positively regulated proliferation during taste bud cell injury by blocking the Shh/Gli1 pathway. In addition, not only cell proliferation but also differentiation of taste bud cells could not be regulated under TRPV1-deficiency conditions. Thus, TRPV1 positively regulates taste bud cell innervation and differentiation; this finding could be valuable in the clinical treatment of dry mouth-related taste dysfunction.

Cyclic AMP (cAMP) is involved in many biological processes but little is known regarding its role in shaping immunity. Here we show that cAMP-PKA-CREB signaling (a pattern recognition receptor [PRR]-independent mechanism) regulates conventional type-2 Dendritic Cells (cDC2s) in mice and reprograms their Th17-inducing properties via repression of IRF4 and KLF4, transcription factors essential for cDC2-mediated Th2 induction. In mice, genetic loss of IRF4 phenocopies the effects of cAMP on Th17 induction and restoration of IRF4 prevents the cAMP effect. Moreover, curdlan, a PRR-dependent microbial product, activates CREB and represses IRF4 and KLF4, resulting in a pro-Th17 phenotype of cDC2s. These in vitro and in vivo results define a novel signaling pathway by which cDC2s display plasticity and provide a new molecular basis for the classification of novel cDC2 and cDC17 subsets. The findings also reveal that repressing IRF4 and KLF4 pathway can be harnessed for immuno-regulation.

Background and Purpose. Recently, tonsil-derived mesenchymal stem cells (T-MSCs) have attracted great attention in various medical fields due to easier harvest of T-MSCs and more immunomodulatory effects than adipose-derived MSCs. However, there was still little evidence of the effect of conditioned media from T-MSCs (T-MSCs-CM) on allergic rhinitis (AR). Therefore, we investigated the impact of T-MSCs-CM on an AR mouse model. Methods. We isolated T-MSCs from human palatine tonsil and evaluated the ingredients of T-MSCs-CM. The effect of T-MSCs-CM was evaluated in the AR mouse model that was randomly divided into five groups (negative control, positive control, and T-MSCs-CM treated (0.1 mg, 1 mg, and 10 mg)). To investigate the therapeutic effect, we analyzed rhinitis symptoms, serum immunoglobulin (Ig), inflammatory cells, and cytokine expression. We also assessed T cell receptor signal, including MAP kinase (ERK/JNK), p65, and NFAT1. Results. We identified the increment of TGF-β1, PGE2, and HGF in the T-MSCs-CM. In an animal study, the T-MSCs-CM-treated group showed significantly reduced allergic symptoms and infiltration of eosinophils and neutrophils in the nasal mucosa, whereas there was no significant difference in total IgE and the OVA-specific IgE level. Additionally, we found that the 10 mg T-MSCs-CM-treated group showed a significantly decreased IL-4 mRNA expression, compared to the (+) Con group. In the analysis of T cell receptor signal, the phosphorylation of MAP kinases, translocation of p65, and activation of NFAT1 were inhibited after T-MSCs-CM. Conclusions. Our findings suggest that T-MSCs-CM showed a partial immunomodulatory effect on the AR mouse model by the inhibition of T cell activation via MAP kinase, p65, and NFAT1.

Abstract Background Adipocyte differentiation of human mesenchymal stem cells (hMSCs) is dependent on mitochondrial metabolism and reactive oxygen species (ROS) to initiate adipocyte differentiation. Although anethole has been known as an anti-oxidant and lipid peroxidation inhibitor, there is little investigated about its role in adipogenic differentiation. Methods The effects on cytotoxicity and proliferation of anethole in hMSCs were measured by the MTT assay. The anti-adipogenic effect of anethole on hMSCs was analyzed by Oil Red O staining and western blot analysis. The anti-oxidant activity of anethole on hMSC was assessed by flowcytometry and fluorescence staining using 2',7' –dichlorofluorescin diacetate (DCFDA). The western blotting was used to detect of phospho-Akt, phospho-mTOR, phospho-p70S6K, PPARγ, and phsopho-AMP-activated kinase (AMPK). Results Anethole suppressed the adipogenic differentiation of hMSCs through down-regulation of Akt-mTOR-p70S6K-PPARγ and up-regulation of AMPK. Anethole affected oxidative conditions through ROS generation. Anethole also rescued AMPK activity and reduced activation of mTOR-p70S6K-PPARγ under oxidative conditions in presence of exogenous hydrogen peroxide. Conclusion ROS and mTOR regulation is a crucial factor in adipogenic differentiation, anethole has an important role in regulating activities of mTOR/PPARγ and ROS control in adipogenic differentiation of hMSCs.

Abstract Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is an inflammatory sinonasal disorder characterized by eosinophilic inflammation and T-helper 2 skewing. Eosinophil accumulation in sinonasal mucosa comprises a major feature of CRSwNP. The study aimed to investigate the effect of the flavone wogonin in nasal polyposis by assessing its ability to induce eosinophil apoptosis in vitro and attenuate eosinophilic CRSwNP in mice. Double immunofluorescence, immunohistochemistry, flow cytometry, and immunoblotting were performed to evaluate hypoxia-inducible factor (HIF)-1α, survivin, and apoptotic markers in the human eosinophilic EoL-1 cell line or sinonasal tissues from patients with CRS with or without NPs. In sinonasal specimens from patients with CRS, HIF-1α and survivin were up-regulated in eosinophils from patients with NPs compared with levels in patients without NPs. Under hypoxia, HIF-1α and survivin expression was up-regulated in EoL-1 cells. Wogonin down-regulated both HIF-1α and survivin in EoL-1 cells. In addition, overexpression of survivin protected EoL-1 cells against apoptosis in response to wogonin. Moreover, wogonin attenuated nasal polyp formation in a murine model. Our findings suggest that wogonin could induce caspase-3 activation by suppressing HIF-1α and survivin expression in EoL-1 cells. Further studies regarding novel therapeutic options for CRSwNP targeting eosinophil apoptosis are needed.

Objectives It is well known that allergic rhinitis (AR) has positive association with adenotonsillectomy. However, the impact of AR on symptom improvement after adenotonsillectomy is not well documented. Hence, we aimed to evaluate the effect of AR on the symptom improvement after adenotonsillectomy between AR and nonallergic patients. Methods A retrospective analysis was performed on 250 pediatric patients younger than 10 years old who received adenotonsillectomy from June 2009 to June 2014 in a tertiary referral hospital. All patients underwent skin prick test or multiple allergen simultaneous test (MAST) before surgery and classified into AR group and control group. Obstructive and rhinitis symptoms including snoring, mouth breathing, nasal obstruction, rhinorrhea, itching, and sneezing were evaluated before and 1 year after surgery using questionnaire and telephone survey. Results AR group was 131 and control group was 119, showing higher prevalence (52.4%) of AR among adenotonsillectomized patients. Both groups showed dramatic improvement of symptoms such as snoring and mouth breathing after surgery (all P

Objectives Postoperative bleeding and adhesion formation are the two most common complications after endoscopic sinus surgery (ESS). The former sometimes can be life threatening and the latter is the most common reason requiring revision surgery. This study was designed to evaluate the effect of newly developed chitosan gel (8% carboxymethyl chitosan, Surgi shield) on hemostasis and wound healing after ESS. Methods A prospective, randomized, double-blind controlled trial was conducted in 33 patients undergoing symmetric ESS. At the conclusion of the operation, Surgi shield was randomly applied on one side of the nasal cavity, with the opposite side acting as control and the bleeding quantity of the surgical field was evaluated every 2 minutes. And then, Merocel was placed in the ethmoidectomized areas of the both sides. Five milliliters of Surgi shield was applied to the Merocel of intervention side and saline was applied to the other side. Merocel in both nasal cavities was removed and 5 mL of Surgi shield was applied again to the intervention side on the second day after surgery. The nasal cavity was examined using a nasal endoscope and the degree of adhesion, crusting, mucosal edema, infection, and granulations were graded at 1, 2, and 4 weeks after surgery. Results Complete hemostasis was rapidly achieved in the Surgi shield applied side compared with the control side at 2, 4, 6, 8, and 10 minutes after application of Surgi shield (P#x0003d;0.007, P#x0003d;0.004, P0.05). No adverse effects were noted in the patient series. Conclusion Surgi shield containing chitosan can be used safely to achieve rapid hemostasis immediately after ESS and to prevent adhesion formation.

ObjectivesThe aim of this study was to determine the relationship between the intensity of snoring and severity of sleep apnea using Watch-PAT (peripheral arterial tone) 100.MethodsA total of 404 patients (338 males and 66 females) who underwent home-based portable sleep study using Watch-PAT 100 for obstructive sleep apnea (OSA) from January 2009 through December 2011 were included in this study. Subjects were divided into 4 groups; no OSA (PAT apnea hypopnea index [pAHI]

Background and Purpose. When house dust mite (HDM), a common allergen, comes into the mucosal membrane, it may stimulate innate immunity. However, the precise role of interleukin- (IL-) 25 in the development of HDM-induced nasal allergic inflammation is still unclear. Therefore, we investigated the role of IL-25 in allergic rhinitis (AR) patients sensitized to HDM. Methods. To confirm the production of IL-25 in human nasal epithelial cells (HNECs), we stimulated HNECs. IL-25 expression in the nasal mucosa from control, non-AR (NAR) patients, and HDM-sensitized AR patients was assessed using immunohistochemistry, and quantitative reverse transcription PCR. Correlations between IL-25 and other inflammatory markers were explored. Results. An in vitro study showed significantly elevated concentrations of IL-25 in the HNEC samples with highest doses of HDM. Nasal tissues from AR patients sensitized to HDM showed significantly higher IL-25 expression, compared to those from the control or NAR patients. Moreover, the expression of IL-25 in nasal tissues from AR patients sensitized to HDM was positively associated with Th2 markers, such as ECP and GATA3. Conclusions. IL-25 expression increased with high-dose HDM stimulation and was related to Th2 markers. Therefore, IL-25 neutralization might offer a new strategy for treating patients with HDM-sensitized AR.

Obstructive sleep apnea (OSA) is a common disorder. It usually results from the structural compromise of the upper airway. In patients with OSA, the obstruction predominantly occurs along the pharyngeal airway, and also a variety of tumors have been reported to cause such a condition. We present here the case of a thyroglossal duct cyst causing OSA in adult. This case demonstrates that thyroglossal duct cyst or some kind of mass lesions in the airway lesions should be considered in the differential diagnosis of OSA patients.

ObjectivesCartilage reshaping by laser irradiation is used to correct septal and auricular cartilage deformities. Chondrocyte viability following laser irradiation and reshaping has been well established. However, the regeneration process of chondrocyte after laser irradiation has not been revealed yet. The aims of this study were to determine the mechanism of cartilaginous thermal injury and the regenerative process of damaged cartilage following laser irradiation.MethodsLaser irradiation was performed on human septal cartilage and rabbit auricular cartilage using a 1,460-nm diode laser. We observed change in the shape of cartilage and evaluated the extent of cartilage injury using live/dead cell assay via confocal microscopy. Hoechst and propidium iodide (PI) staining was used to evaluate the mechanism of chondrocyte injury after laser irradiation. To evaluate the regeneration of cartilage, laser irradiated cartilages were reimplanted into a subperichondrial pocket and were harvested at 1, 2, and 4 weeks after reimplantation for viability assessment and histologic examination.ResultsLaser irradiation using a 1,460-nm diode laser produced a marked shape change in both human septal and rabbit auricular cartilages. Thermal damage on cartilage was correlated with the exposure time and the laser power. Hoechst and PI staining showed that chondrocyte death by laser irradiation was due to mainly necrosis, rather than apoptosis. In lower power treatment group (0.3 W and 0.5 W), all the chondrocytes regenerated within 4 weeks, however, in 1 W treatment group, chondrocytes could not regenerate until 4 weeks.ConclusionReshaping of cartilage using 1,460 nm diode laser was attained concurrently with the thermal injury to the chondrocytes. The extent of thermal damage on chondrocytes was dependent on the exposure time and the laser power and the damaged chondrocytes irradiated with lower level of laser power could be regenerated after reimplantation into subperichondrial pocket.

Innate and adaptive immune responses change with increasing age and affect the course of diseases. Previous study investigated immunologic alteration in Western nasal polyps (NP) which is mostly eosinophilic. However, there are no reports regarding age-related immune changes of non-eosinophilic NP (NE-NP) which is a predominant subtype in Asian population.A total of 153 subjects, including 20 with control, 63 with chronic rhinosinusitis (CRS) without NP (CRSsNP), and 70 with CRS with NP were enrolled. Age-related changes in computed tomography (CT), cytokines and clinical information were investigated. Tissue samples were analyzed for protein levels of IL-5, IL-17A, IL-23, interferon (IFN)-γ, CCL-11, and CXCL-8, using Luminex immunoassay and for mRNA expression levels of interleukin (IL)-5, IL-17A, IL-23p19, IFN-γ, CCL-11, CXCL-1, CXCL-2, CXCL-8, and CXCR2 by quantitative RT-PCR. Immunohistochemistry (IHC) was performed for the number of inflammatory cells.We observed that Lund-Mackay CT scores decreased with age in NE-NP. The number of human neutrophil elastase-positive cells and myeloperoxidase gene expression decreased in older patients with NE-NP, but not in control subjects, CRSsNP, and E-NP. Neutrophil-associated cytokines including IL-17A and IL-23, were negatively correlated with age in NE-NP at the protein and mRNA levels. Additionally, the expression of CXCR2, a receptor for CXCL-1 and CXCL-2, was decreased with age in NE-NP. However, there were no age-related changes in blood neutrophil count, and neutrophil-recruiting chemokines such as CXCL-1, CXCL-2, and CXCL-8. Elderly NE-NP patients showed better endoscopic scores at 12 months after surgery compared with the non-elderly.Age-related decline in neutrophil inflammation may favorably affect postoperative results in elderly patients with NE-NP.

Interleukin 10 (IL-10) is a potent anti-inflammatory cytokine. The dysregulation of IL-10 is associated with an enhanced immunopathologic response to infection, as well as with an increased risk for developing numerous autoimmune diseases. In this study, we investigated IL-10 expression in chronic rhinosinusitis with nasal polyps (CRSwNP) and assessed the possible role of IL-10 in the pathogenesis of CRSwNP.Thirty-five patients with CRSwNP, 12 patients with chronic rhinosinusitis without NP (CRSsNP) and 10 control subjects were enrolled in this study. NP tissues and uncinated tissues (UT) were collected for analysis. Dispersed NP cells (DNPCs) were cultured in the presence or absence of IL-25 and IL-10, and a flow cytometric assay was performed to identify the constitutive cell populations of the DNPCs. Murine NP (n = 18) models were used for the in vivo experiments. Real-time PCR, immunohistochemistry, western blotting analysis and ELISA were performed to measure the expression levels of the selected inflammatory cytokines and inflammation-associated molecules.The mRNA expression levels of IL-10, IL-5, IL-17A, IL-25 and interferon gamma (IFN-γ) were significantly higher in the NP tissues than in the UT tissues. Strong positive correlations were observed between IL-10 and a variety of inflammatory cytokines (IL-5, IL-17A, IL-25, IFN-γ) and inflammation-associated molecules (B-cell activating factor; BAFF, CD19). Other than the IL-25 to IL-10 ratio, the expression ratios of the other measured inflammatory cytokines to IL-10 were significantly lower in the CRSwNP group than in the CRSsNP or control groups. Administrating IL-25 into the cultured DNPCs significantly increased the production of IL-10, but administrating IL-10 had no effect on the production of IL-25.Increased expression of IL-10, IL-10 related inflammatory cytokine, and IL-10 related B cell activation indicated that IL-10, a potent anti-inflammatory cytokine, has a pivotal role in the pathogenesis of CRSwNPs.

ObjectivesTreating olfactory dysfunction is a challenge for physicians. One of the therapeutic options could be transplantation of stem cells. In this study, neural stem cells were transplanted into anosmic mice.MethodsNeural stem cells were generated from the olfactory bulb of green fluorescent protein (GFP)-transgenic C57BL6 mice. Anosmia were induced by injection of intraperitoneal 3-methylindole. The neural stem cells were transplanted transnasally on the next day. The olfactory function was evaluated by a food-finding test once a week. The olfactory neuroepithelium was harvested for histologic examination and protein analysis at 4 weeks.ResultsTwenty-five percent (6/24) of the control mice that were not transplanted with neural stem cells survived at 4 weeks while 67% (8/12) of the transplanted mice survived (P=0.029). The food finding test showed that the transplanted mice resumed finding food at 3 weeks while the control mice resumed finding food at 4 weeks. GFP-positive cells were observed in the olfactory neuroepithelium of the transplanted mice. Western blotting revealed that the olfactory marker protein expression was significantly lower in the control mice than that in the transplanted mice.ConclusionThis study demonstrated that improvement of mouse survival was achieved and recovery of olfactory function was promoted by transnasal transplantation of neural stem cells in the anosmic mouse model. These results indicate that stem cells might be one of the future modalities for treating olfactory impairment.

ObjectivesSublingual immunotherapy (SLIT) has recently received much attention around the world as a treatment for allergic rhinitis. This study aimed to investigate the efficacy and adverse effects of SLIT in Korean patients with allergic rhinitis caused by house dust mites. The treatment compliance and the patient satisfaction with SLIT were also assessed.MethodsThe patients who were sensitized to Dermatophagoides pteronyssinus and Dermatophagoides farinae and who started SLIT between November 2007 and July 2008 were included in this study. The symptom questionnaires, which included items on rhinorrhea, sneezing, nasal obstruction, itchy nose, olfactory disturbance, eye discomfort and sleep disturbance, were obtained before and 6 months after SLIT. The patient satisfaction and the adverse effects were also investigated.ResultsOne hundred forty-two patients started SLIT and 98 of them continued SLIT for 6 months or more. Ninety-two of the 98 patients completed the questionnaires. The duration of receiving SLIT was 9.8 months on average (range, 6 to 13 months). All the symptoms of allergic rhinitis were improved with SLIT. Forty-five percent of the patients were satisfied for SLIT, while 12% were unsatisfied. The incidence of adverse effects was 12% during maintenance therapy, although it was 48% during the up-dosing phase. The drop-out rate of SLIT was 31.0%.ConclusionThe subjective symptoms were improved with SLIT in Korean patients with allergic rhinitis for house dust mites. Yet the drop out rate was high despite of the symptomatic improvement.

BACKGROUND: Asthmatic nasal polyps primarily exhibit eosinophilic infiltration. However, the identities of the immune cells that infiltrate non-asthmatic nasal polyps remain unclear. Thus, we thought to investigate the distribution of innate immune cells and its clinical relevance in non-asthmatic chronic rhinosinusitis (CRS) in Korea. METHODS: Tissues from uncinate process (UP) were obtained from controls (n = 18) and CRS without nasal polyps (CRSsNP, n = 45). Nasal polyps (NP) and UP were obtained from CRS with nasal polyps (CRSwNP, n = 56). The innate immune cells was evaluated by immunohistochemistry such as, eosinophil major basic protein (MBP), tryptase, CD68, CD163, CD11c, 2D7, human neutrophil elastase (HNE) and its distribution was analyzed according to clinical parameters. RESULTS: In comparisons between UP from each group, CRSwNP had a higher number of MPB(+), CD68(+), and CD11c(+) cells relative to CRSsNP. Comparisons between UP and NP from CRSwNP indicated that NP have a higher infiltrate of MBP(+), CD163(+), CD11c(+), 2D7(+) and HNE(+) cells, whereas fewer CD68(+) cells were found in NP. In addition, MBP(+) and CD11c(+) cells were increased from UP of CRSsNP, to UP of CRSwNP, and to NP of CRSwNP. Moreover, in UP from CRSwNP, the number of MBP(+) and CD11c(+) cells positively correlated with CT scores. In the analysis of CRSwNP phenotype, allergic eosinophilic polyps had a higher number of MBP(+), tryptase(+), CD11c(+), 2D7(+) cells than others, whereas allergic non-eosinophilic polyps showed mainly infiltration of HNE(+) and 2D7(+) cells. CONCLUSIONS: The infiltration of MBP(+) and CD11c(+) innate immune cells show a significant association with phenotype and disease extent of CRS and allergic status also may influences cellular phenotype in non-asthmatic CRSwNP in Korea.