Sinonasal seromucinous hamartoma: a single institution case series combined with a narrative review of the literature.

PURPOSE: This study aimed to investigate the clinical and histopathological characteristics of sinonasal seromucinous hamartomas (SHs). METHODS: Eight patients with sinonasal SH and treated at a tertiary hospital between November 2005 and September 2023 were included. Additionally, a systematic review of published articles was conducted, analyzing 48 cases of SH described in the literature. RESULTS: Among the eight patients treated at our institution, tumors originated from the posterior nasal cavity in four patients and middle turbinate and middle meatus were the primary origin in two patients each. Coexistence of inflammatory nasal polyps (NPs) was observed in four cases. Histopathologically, four patients exhibited focal respiratory epithelial adenomatoid hamartoma (REAH) features, and low-grade dysplasia was found in one patient. A combined analysis with previous literature revealed that 46.3% of all cases originated in the anterior nasal cavity. The proportions of cases accompanied by NPs and those with focal REAH features were 20.5% and 39.1%, respectively. Additionally, the frequencies of cases exhibiting dysplastic features (5.4%) and recurrence (2.1%) were low. Remarkably, tumors originating from the anterior region tended to have a higher frequency of dysplasia than those originating from the posterior region, although this difference was not statistically significant (p = 0.0996). CONCLUSION: Patients with sinonasal SH showed favorable treatment outcomes following surgical resection. Focal REAH features and accompanying NPs were frequently observed. A substantial proportion of cases originate in the anterior nasal cavity, and these tumors may exhibit a high tendency for dysplasia.

IL-4 drastically decreases deuterosomal and multiciliated cells via alteration in progenitor cell differentiation.

BACKGROUND: Allergic inflammation affects the epithelial cell populations resulting in goblet cell hyperplasia and decreased ciliated cells. Recent advances in single-cell RNA sequencing (scRNAseq) have enabled the identification of new cell subtypes and genomic features of single cells. In this study, we aimed to investigate the effect of allergic inflammation in nasal epithelial cell transcriptomes at the single-cell level. METHODS: We performed scRNAseq in cultured primary human nasal epithelial (HNE) cells and in vivo nasal epithelium. The transcriptomic features and epithelial cell subtypes were determined under IL-4 stimulation, and cell-specific marker genes and proteins were identified. RESULTS: We confirmed that cultured HNE cells were similar to in vivo epithelial cells through scRNAseq. Cell-specific marker genes were utilized to cluster the cell subtypes, and FOXJ1+ -ciliated cells were sub-classified into multiciliated and deuterosomal cells. PLK4 and CDC20B were specific for deuterosomal cells, and SNTN, CPASL, and GSTA2 were specific for multiciliated cells. IL-4 altered the proportions of cell subtypes, resulting in a decrease in multiciliated cells and loss of deuterosomal cells. The trajectory analysis revealed deuterosomal cells as precursor cells of multiciliated cells and deuterosomal cells function as a bridge between club and multiciliated cells. A decrease in deuterosomal cell marker genes was observed in nasal tissue samples with type 2 inflammation. CONCLUSION: The effects of IL-4 appear to be mediated through the loss of the deuterosomal population, resulting in the reduction in multiciliated cells. This study also newly suggests cell-specific markers that might be pivotal for investigating respiratory inflammatory diseases.

Unraveling the Role of Epithelial Cells in the Development of Chronic Rhinosinusitis.

The pathophysiology of CRS is multifactorial and complex yet needs to be completed. Recent evidence emphasizes the crucial part played by epithelial cells in the development of CRS. The epithelial cells act as physical barriers and play crucial roles in host defense, including initiating and shaping innate and adaptive immune responses. This review aims to present a comprehensive understanding of the significance of nasal epithelial cells in CRS. New research suggests that epithelial dysfunction plays a role in developing CRS through multiple mechanisms. This refers to issues with a weakened barrier function, disrupted mucociliary clearance, and irregular immune responses. When the epithelial barrier is compromised, it can lead to the passage of pathogens and allergens, triggering inflammation in the body. Furthermore, impaired mucociliary clearance can accumulate pathogens and secretions of inflammatory mediators, promoting chronic inflammation. Epithelial cells can release cytokines and chemokines, which attract and activate immune cells. This can result in an imbalanced immune response that continues to cause inflammation. The interaction between nasal epithelial cells and various immune cells leads to the production of cytokines and chemokines, which can either increase or decrease inflammation. By comprehending the role of epithelial cells in CRS, we can enhance our understanding of the disease's pathogenesis and explore new therapeutics.

Role of TRPC3 in Right Ventricular Dilatation under Chronic Intermittent Hypoxia in 129/SvEv Mice.

Patients with obstructive sleep apnea (OSA) exhibit a high prevalence of pulmonary hypertension and right ventricular (RV) hypertrophy. However, the exact molecule responsible for the pathogenesis remains unknown. Given the resistance to RV dilation observed in transient receptor potential canonical 3(Trpc3)-/- mice during a pulmonary hypertension model induced by phenylephrine (PE), we hypothesized that TRPC3 also plays a role in chronic intermittent hypoxia (CIH) conditions, which lead to RV dilation and dysfunction. To test this, we established an OSA mouse model using 8- to 12-week-old 129/SvEv wild-type and Trpc3-/- mice in a customized breeding chamber that simulated sleep and oxygen cycles. Functional parameters of the RV were evaluated through analysis of cardiac cine magnetic resonance images, while histopathological examinations were conducted on cardiomyocytes and pulmonary vessels. Following exposure to 4 weeks of CIH, Trpc3-/- mice exhibited significant RV dysfunction, characterized by decreased ejection fraction, increased end-diastole RV wall thickness, and elevated expression of pathological cardiac markers. In addition, reactive oxygen species (ROS) signaling and the endothelin system were markedly increased solely in the hearts of CIH-exposed Trpc3-/- mice. Notably, no significant differences in pulmonary vessel thickness or the endothelin system were observed in the lungs of wild-type (WT) and Trpc3-/- mice subjected to 4 weeks of CIH. In conclusion, our findings suggest that TRPC3 serves as a regulator of RV resistance in response to pressure from the pulmonary vasculature, as evidenced by the high susceptibility to RV dilation in Trpc3-/- mice without notable changes in pulmonary vasculature under CIH conditions.

Comparison of clinical features and surgical outcomes between hypopnea- and apnea-predominant obstructive sleep apnea.

OBJECTIVES: This study is aimed to investigate the differences in the clinical features and surgical outcomes between hypopnea- and apnea-predominant obstructive sleep apnea (OSA). DESIGN: Cohort study. SETTING: Single tertiary care centre. PARTICIPANTS: This study included 190 patients with OSA who underwent multilevel upper airway surgery between September 2012 and September 2021. The patients were divided into two groups according to the proportion of each respiratory event: hypopnea-predominant (n = 102) and apnea-predominant (n = 88). MAIN OUTCOME MEASURES: The primary outcome measure was the percentage improvement in the apnea-hypopnea index (AHI) from baseline AHI after surgery. RESULTS: The apnea-predominant group included more male patients and had higher AHI, respiratory disturbance index (RDI) and oxygen desaturation index (ODI) than the hypopnea-predominant group. Both groups showed significant improvements in AHI, apnea index, RDI, supine AHI, REM AHI, non-REM AHI, ODI, lowest O2 saturation and Epworth Sleepiness Scale scores following the surgery. Notably, hypopnea index increased after surgery in the apnea-predominant OSA group. Although the improvement in the absolute value of AHI by surgery was significantly greater in the apnea-predominant group than in the hypopnea-predominant group, the two groups showed no significant difference in the percentage improvement in AHI from baseline AHI. CONCLUSION: Patients with apnea-predominant OSA had more severe disease than those with hypopnea-predominant OSA; however, surgical outcomes, as evaluated by percentage AHI improvement, were comparable between the two groups. In addition, multilevel upper airway surgery may induce the transition from apnea to hypopnea in patients with apnea-predominant OSA.

Cell-Type-Specific Expression of Hyaluronan Synthases HAS2 and HAS3 Promotes Goblet Cell Hyperplasia in Allergic Airway Inflammation.

Allergic rhinitis (AR) is a multifactorial airway disease characterized by basal and goblet cell hyperplasia. Hyaluronic acid (HA) is a major component of extracellular matrix and a critical contributor to tissue repair and remodeling after injury. We previously demonstrated that the intermediate progenitor cell (IPC) surface marker CD44v3 is upregulated in the basal and suprabasal layers of well-differentiated primary human nasal epithelial (HNE) cells after stimulation with the Th2 (T-helper cell type 2) cytokine IL-4, and an antibody blocking the CD44v3-HA interaction suppressed IL-4-induced goblet cell hyperplasia. We now show that the expression of HA and two HA synthases, HAS2 and HAS3, was upregulated in both the nasal surface epithelium of subjects with AR and IL-4-stimulated HNE cells. Inhibition of HA synthesis by 4-methylumbelliferone suppressed IL-4-induced goblet cell hyperplasia. Moreover, HAS2 and HAS3 were expressed in IPCs depending on the differentiation events, as follows: the rapid, transient upregulation of HAS2 induced basal IPC proliferation and basal-to-suprabasal transition, whereas the delayed upregulation of HAS3 promoted the transition of suprabasal IPCs to a goblet cell fate. 4-methylumbelliferone treatment in a house dust mite-induced murine AR model attenuated goblet cell metaplasia. Last, HA concentrations in nasal epithelial lining fluids from patients with AR positively correlated with the concentrations of mediators causing allergic inflammation. These data suggest that HA produced after the sequential upregulation of HAS2 and HAS3 contributes to goblet cell hyperplasia in allergic airway inflammation and modulates disease progression.

Detecting serum galactomannan to diagnose acute invasive Aspergillus sinusitis: a meta-analysis.

PURPOSE: The serum galactomannan test has been used for diagnosing acute invasive fungal sinusitis (AIFS), especially invasive Aspergillus. We aimed to assess the accuracy of the test to diagnose acute invasive Aspergillus sinusitis (AIAS). METHODS: We searched all relevant articles published in PubMed, Embase, the Cochrane Library, and Web of Science databases up until September 14, 2020. The available data for serum galactomannan test to diagnose AIAS from selected studies were assessed. The diagnostic odds ratio (DOR), summary receiver operating characteristics (SROC), sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were estimated. Additionally, we analysed four studies with a cut-off value of 0.5. RESULTS: Five eligible articles were selected in this study. The total number of enrolled patients was 118, and 62 patients had confirmed AIAS. Among these 62 patients, the summary estimates of the serum galactomannan assay were as follows: DOR, 3.37 (95% confidence interval [CI]: 1.47-6.66); sensitivity, 0.63 (95% CI 0.50-0.74); specificity, 0.65 (95% CI 0.51-0.76); PLR, 1.83 (95% CI 1.21-2.74); NLR, 0.58 (95% CI 0.39-0.83). The SROC was 0.68. CONCLUSION: In this current meta-analysis, the serum galactomannan test was classified as less accurate for purposes of diagnosing confirmed AIAS. These results suggest that the initial diagnosis of AIAS should not solely be dependent upon serum galactomannan test results. More studies of the test are needed in patients with AIAS to more accurately assess its diagnostic value.

Protein arginine methyltransferase 1 contributes to the development of allergic rhinitis by promoting the production of epithelial-derived cytokines.

BACKGROUND: Arginine methylation is a posttranslational modification mediated by protein arginine methyltransferases (PRMTs). Although previous studies have shown that PRMT1 contributes to the severity of allergic airway inflammation or asthma, the underlying mechanism is poorly understood. OBJECTIVE: This study aimed to explore the role of PRMT1 and its relevant mechanism in the development of allergic rhinitis (AR). METHODS: The expression levels of PRMTs and cytokines were determined by RT-PCR, and the localization of PRMT1 was determined by immunohistochemistry and confocal microscopy. The levels of house dust mite (HDM)-specific immunoglobulins in serum and of cytokines in nasal lavage fluids were determined by ELISA. PRMT1 inhibition was achieved by siRNA and treatment with the pan PRMT inhibitor arginine N-methyltransferase inhibitor-1. RESULTS: PRMT1 expression was significantly increased in the nasal mucosa of patients and mice with AR. The degree of eosinophilic infiltration in the nasal mucosa was reduced in PRMT1+/- AR mice compared with wild-type mice. PRMT1 haploinsufficiency reduced the levels of HDM-specific immunoglobulins in serum and those of TH2 (IL-4, IL-5, and IL-13) and epithelial (thymic stromal lymphopoietin [TSLP], IL-25, and IL-33) cytokines in the nasal lavage fluids of AR mice. In nasal epithelial cells, HDM and IL-4 cooperate to enhance PRMT1 expression through a mitogen-activated protein kinase-dependent pathway. In addition, PRMT1 was essential for the production of TSLP, IL-25, and IL-33 in response to HDM and IL-4. Arginine N-methyltransferase inhibitor-1 treatment alleviated AR in the mouse model. CONCLUSIONS: PRMT1 plays an important role in AR development by regulating epithelial-derived cytokine production and might be a new therapeutic target for AR.

Integrated genetic and epigenetic analyses uncover MSI2 association with allergic inflammation.

BACKGROUND: The relationship between allergic and eosinophilic inflammation, either systemic or local, in allergic diseases remains unclear. OBJECTIVE: We performed combined genome-wide association study (GWAS) and epigenome-wide (EWAS) for atopy and tissue eosinophilia to identify both genetic and epigenetic signatures between systemic and local allergic inflammation, and to capture global patterns of gene regulation. METHODS: We included 126 subjects for atopy analysis and 147 for tissue eosinophilia analysis, as well as 18 normal nasal tissue samples. We identified differentially methylated positions (DMPs) and genes associated with atopy and tissue eosinophilia. Furthermore, we performed mendelian randomization analysis and penalized regression along with replication in an independent cohort. RESULTS: EWAS identified genes, including Musashi RNA binding protein 2 (MSI2), associated with atopy, which contained enriched DMPs that genetically affect atopy. A direct association was observed between MSI2 single-nucleotide polymorphisms and atopy, as was a causal effect of changes in MSI2 expression and methylation on atopy, which was replicated in a Costa Rican population. Regarding tissue eosinophilia, EWAS identified genes with enriched DMPs directly contributing to tissue eosinophilia at the gene level, including CAMK1D. The gene ontology terms of the identified genes for both phenotypes encompassed immune-related terms. CONCLUSION: EWAS combined with GWAS identified novel candidate genes, especially the methylation of MSI2, contributing to systemic allergic inflammation. Certain genes displayed a greater association with either systemic or local allergic inflammation; however, it is expected that a harmonized effect of these genes influences immune responses.

Association between diabetes mellitus and chronic rhinosinusitis with nasal polyps: A population-based cross-sectional study.

OBJECTIVE: To investigate the association between physician-diagnosed diabetes mellitus (DM) and chronic rhinosinusitis (CRS) phenotypes in a national population-based study. STUDY DESIGN: Retrospective cross-sectional study. SETTING: Population-based survey data were collected by the Korean National Health and Nutrition Survey between January 2008 and December 2012. PARTICIPANTS AND METHODS: A total of 34 670 participants aged over 19 years were enrolled in the Korea National Health and Nutrition Examination Surveys from 2008 to 2012. The relationship of CRS prevalence, with and without nasal polyps, with physician-diagnosed DM and non-DM were assessed. Differences in sinonasal symptoms between patients with and without DM were analysed in this cross-sectional study. RESULTS: A significant association was observed between DM and CRS with nasal polyps after adjustment for multiple variables. No substantial association was observed between DM and CRS without nasal polyps. Among patients with CRS, olfactory dysfunction for >3 months was significantly more frequent in the DM group than in the non-DM group. CONCLUSION: We demonstrated significant associations between DM and CRS with nasal polyps and olfactory dysfunction among patients with CRS in a large national clinical cohort study. The direct mechanism of the association between DM and CRS with nasal polyps should be further investigated to clarify the pathogenesis of CRS with nasal polyps.

Th2 cytokines-DUOX2-ROS-HMGB1 translocation axis is important in the pathogenesis of allergic rhinitis.

The function of high-mobility group box 1 (HMGB1) varies according to its location. However, the translocation mechanism behind HMGB1 remains unclear. We hypothesize that type 2 helper T cell (Th2) cytokines are involved in the translocation of HMGB1 in the upper airway epithelium. We investigated the mechanism behind HMGB1 translocation using Th2 cytokine stimulation and examined the clinical significance of HMGB1 translocation in allergic rhinitis (AR). Cytoplasmic and extracellular HMGB1 were increased in AR. Inhibiting HMGB1 translocation with glycyrrhizic acid (GA) decreased the level of antigen-specific immunoglobulin E (IgE), the degree of Periodic Acid-Schiff (PAS), and Sirius Red staining in the murine model. The in vivo reactive oxygen species (ROS) level in the nasal mucosa was higher in the mice with AR than in the controls. Th2 cytokine-induced up-regulation of the ROS and translocation of HMGB1 by Th2 cytokines was dependent on the generated ROS. The ROS level also increased in the murine model. We suggest that the Th2 cytokine-dual oxidase (DUOX)2-ROS-HMGB1 translocation axis is important in AR pathogenesis.

Can the sensitisation to staphylococcal enterotoxin predict the severity of chronic rhinosinusitis?

BACKGROUND: Evidence is accumulating that Staphylococcus aureus plays an important role as a disease modifier in upper and lower airway disease. We aimed to assess the association of staphylococcal enterotoxins (SEs) with allergic multimorbidity as well as the severity of chronic rhinosinusitis. METHODS: We retrospectively reviewed the medical records of 97 subjects aged 6 years or older between March 2018 and June 2019 and analysed symptom scores, computed tomography scores, serum IgE levels to SEs, serum total and specific IgE levels to inhalant allergens. To evaluate eosinophilic chronic rhinosinusitis (ECRS), we used refractory ECRS score from the Japanese epidemiological survey. RESULTS: Of the 97 patients enrolled, 29 (29.9%) were non-sensitised, 33 (34.0%) were mono-sensitised, and 35 (36.1%) were poly-sensitised. Sensitisation to SEs was closely associated with poly-sensitisation to inhalant allergens. SE-sensitised participants had higher median values for total and specific IgE levels to inhalant allergens than did non-SE-sensitised participants. SE sensitisation was associated with allergic multimorbidity and severe allergic diseases, such as ECRS. CONCLUSIONS: This preliminary study suggested that sensitisation to SEs may play a role in the initiation of type-2 inflammatory responses, such as allergic rhinitis, ECRS, and allergic multimorbidity. Furthermore, sensitisation to SEs correlated with the severity of ECRS.

A Unified Approach to Spatial Proximity Query Processing in Dynamic Spatial Networks.

Nearest neighbor (NN) and range (RN) queries are basic query types in spatial databases. In this study, we refer to collections of NN and RN queries as spatial proximity (SP) queries. At peak times, location-based services (LBS) need to quickly process SP queries that arrive simultaneously. Timely processing can be achieved by increasing the number of LBS servers; however, this also increases service costs. Existing solutions evaluate SP queries sequentially; thus, such solutions involve unnecessary distance calculations. This study proposes a unified batch algorithm (UBA) that can effectively process SP queries in dynamic spatial networks. With the proposed UBA, the distance between two points is indicated by the travel time on the shortest path connecting them. The shortest travel time changes frequently depending on traffic conditions. The goal of the proposed UBA is to avoid unnecessary distance calculations for nearby SP queries. Thus, the UBA clusters nearby SP queries and exploits shared distance calculations for query clusters. Extensive evaluations using real-world roadmaps demonstrated the superiority and scalability of UBA compared with state-of-the-art sequential solutions.

Role of specific IgE on staphylococcal enterotoxin B in chronic rhinosinusitis severity.

OBJECTIVE: To investigate the clinical significance of specific IgE-staphylococcal enterotoxin B (IgE-SEB) in CRS (chronic rhinosinusitis). DESIGN: Retrospective analysis of patients who were positive for specific IgE-staphylococcal enterotoxin B. SETTING: Tertiary rhinology clinic. PARTICIPANTS: A total of 965 patients who were tested for specific IgE-staphylococcal enterotoxin B from December 2016 to December 2017. MAIN OUTCOME MEASURES: We retrospectively reviewed the records of 965 patients who were tested for specific IgE-staphylococcal enterotoxin B from December 2016 to December 2017. Patient demographics, titre-specific IgE to staphylococcal enterotoxin B levels, MAST, serologic test and medical records were reviewed. RESULTS: IgE-SEB (KU/L) was higher in CRS patients than non-CRS patients (0.13 ± 0.37 vs 0.08 ± 0.22, respectively; P-value: .044), and the IgE-SEB (+, ≥0.35) rate was also higher (10.06% vs 4.46%, respectively; P-value: .030). IgE-SEB (KU/L) was higher in the CRS group than in the fungal sinusitis group (0.13 ± 0.37 vs 0.03 ± 0.05, respectively; P-value: <.001), and the IgE-SEB (+, ≥0.35) rate was also higher (10.06% vs 0%, respectively; P-value: .015). Between the CRSsNP (chronic rhinosinusitis without nasal polyps) and CRSwNP (chronic rhinosinusitis with nasal polyps) groups, there were no differences in IgE-SEB (KU/L) or IgE-SEB (+) rates. IgE-SEB positivity was not associated with the presence of polyps, concomitant asthma or postoperative recurrence. As the values of IgE-SEB (KU/L) and the IgE-SEB (+, >0.1) rate increased, the CRS severity also increased. CONCLUSIONS: IgE-SEB showed a positive correlation with Lund-Mackay CT severity score, but not with postoperative recurrence or nasal polyps. Further studies are needed to obtain clear evidence that IgE-SEB can be considered as an independent CRS endotype.

Apolipoprotein E and Periostin Are Potential Biomarkers of Nasal Mucosal Inflammation. A Parallel Approach of In Vitro and In Vivo Secretomes.

No previously suggested biomarkers of nasal mucosal inflammation have been practically applied in clinical fields, and nasal epithelium-derived secreted proteins as biomarkers have not specifically been investigated. The goal of this study was to identify secreted proteins that dynamically change during the differentiation from basal cells to fully differentiated cells and examine whether nasal epithelium-derived proteins can be used as biomarkers of nasal mucosal inflammation, such as chronic rhinosinusitis. To achieve this goal, we analyzed two secretomes using the isobaric tag for relative and absolute quantification technique. From in vitro secretomes, we identified the proteins altered in apical secretions of primary human nasal epithelial cells according to the degree of differentiation; from in vivo secretomes, we identified the increased proteins in nasal lavage fluids obtained from patients 2 weeks after endoscopic sinus surgery for chronic sinusitis. We then used a parallel approach to identify specific biomarkers of nasal mucosal inflammation; first, we selected apolipoprotein E as a nasal epithelial cell-derived biomarker through screening proteins that were upregulated in both in vitro and in vivo secretomes, and verified highly secreted apolipoprotein E in nasal lavage fluids of the patients by Western blotting. Next, we selected periostin as an inflammatory mediator-inducible biomarker from in vivo secretomes, the secretion of which was not induced under in vitro culture conditions. We demonstrated that those two nasal epithelium-derived proteins are possible biomarkers of nasal mucosal inflammation.

Geo-Social Top-k and Skyline Keyword Queries on Road Networks.

The rapid growth of GPS-enabled mobile devices has popularized many location-based applications. Spatial keyword search which finds objects of interest by considering both spatial locations and textual descriptions has become very useful in these applications. The recent integration of social data with spatial keyword search opens a new service horizon for users. Few previous studies have proposed methods to combine spatial keyword queries with social data in Euclidean space. However, most real-world applications constrain the distance between query location and data objects by a road network, where distance between two points is defined by the shortest connecting path. This paper proposes geo-social top-k keyword queries and geo-social skyline keyword queries on road networks. Both queries enrich traditional spatial keyword query semantics by incorporating social relevance component. We formalize the proposed query types and appropriate indexing frameworks and algorithms to efficiently process them. The effectiveness and efficiency of the proposed approaches are evaluated using real datasets.

Multiple airborne allergen-induced eosinophilic chronic rhinosinusitis murine model.

PURPOSE: Several murine models have been established to mimic human eosinophilic chronic rhinosinusitis (ECRS). However, in most of these models, ECRS was induced using ovalbumin, which does not cause sinusitis in humans. Thus, we aimed to develop a more clinically relevant murine model of ECRS using multiple airborne allergens. We also investigated the effects of exposure duration of the allergens on ECRS development. METHODS: C57BL/6 mice were intranasally administered multiple airborne allergens (house dust mite, Aspergillus fumigatus, Alternaria alternata, and protease from Staphylococcus aureus) three times weekly for 4, 8, 12, and 16 consecutive weeks. Histopathological changes, the levels of cytokines and chemokines in the nasal lavage fluid, and immune cells of the blood and spleen were analyzed. RESULTS: The mice administered multiple allergens showed significantly increased eosinophil infiltration, epithelial thickening and disruption, and subepithelial collagen deposition from 8 weeks compared to the control group. Goblet cell hyperplasia, polyp-like lesions, and blood eosinophils, as well as the levels of interleukin-5 and eotaxin in the nasal lavage fluid were considerably increased in the ECRS group from 12 weeks compared to those of controls. Instillation of allergens for 16 weeks exacerbated the eosinophil infiltration and eotaxin increase in the nasal lavage fluid. CONCLUSIONS: We successfully established a new murine model of ECRS using more clinically relevant multiple airborne allergens. Prolonged exposure to airborne allergens for 12 weeks or more, corresponding to the definition of human ECRS, strongly induced eosinophil infiltration as well as epithelial remodeling.

Analysis of Surgical Approaches to Skull Base Tumors Involving the Pterygopalatine and Infratemporal Fossa.

Selecting an appropriate surgical approach for resection of huge skull base tumors involving pterygopalatine and infratemporal fossa is challenging because of their rarity and high possibility of vital anatomical structure injuries. To suggest the guidance of selecting the appropriate approach by analyzing outcomes and satisfactions of known surgical approaches with our previous experience, the authors retrospectively analyzed skull base tumor cases experienced for 24 years, and condensed to 4 well-known surgical approaches: maxillary swing, infratemporal fossa type C, transzygomatic, and a combined transzygomatic-midfacial degloving approach: to review indications, advantages, and limitations of these approaches. Maxillary swing approach was useful in large-sized tumors as it provided wide surgical field; however, inevitable facial scar was the main drawbacks, especially in adolescents. Infratemporal fossa approach type C was helpful in the involvement of vital vascular structures; however, long incision scar with temporal area depression and permanent conductive hearing loss were the factors of patients' dissatisfaction. Transzygomatic approach could be the good alternative to the infratemporal fossa approach type C; however, en bloc tumor resection was impossible due to its limited operative space. To overcome limitations of these approaches, transzygomatic approach was combined with midfacial degloving approach, and it enabled lateral and anterior access without prominent facial scar and/or deformity while providing wide surgical space. Based on our 24 years of surgical experience in managing huge skull base tumors, the authors recommend the combined transzygomatic-midfacial degloving approach, which enables complete resection with short postoperative healing periods and no disfiguring facial incisions.

Torus mandibularis affects the severity and position-dependent sleep apnoea in non-obese patients.

OBJECTIVE: Various anatomical structures of upper airway and physical differences are known to be risk factors for obstructive sleep apnoea (OSA). Torus mandibularis is a structure that can appear on the inside of the mandible. Therefore, it is possible for tori to influence airway volume by occupying the space for tongue and cause sleep apnoea. The purpose of this study is to investigate the effect of torus mandibularis on the severity of OSA as one of the craniofacial risk factors. DESIGN: Retrospective case-control study. SETTING: University-based tertiary medical centre. PARTICIPANTS: Adult patients over 19-years-old who visited outpatient clinics with complaints of sleep-disordered breathing symptoms between January 2010 and December 2017 were investigated. MAIN OUTCOME MEASURES: The presence of torus mandibularis in oral cavity was confirmed by physical examination or CT image. We analysed demographic findings including age, sex, medical history, previous operation history, physical findings of upper airway and result of polysomnography. To evaluate the effect of torus mandibularis on OSA, polysomnography data of the two groups according to presence or absence of torus mandibularis were compared and analysed. RESULTS: Two-hundred and thirty-two OSA patients with BMI <25 were divided into two groups, according to either the presence or absence of torus mandibularis. We analysed 138 patients of control group and 94 of torus mandibularis group. Apnoea-hypopnoea index (AHI) was 18.8 ± 14.9 in control group and 25.1 ± 18.4 in torus mandibularis group (P = 0.006). Respiratory disturbance index (RDI) was 23.1 ± 14.7 in control group and 27.9 ± 18.4 in torus mandibularis group (P = 0.035). Supine AHI showed 26.6 ± 20.3 in control group and 32.5 ± 22.6 in torus mandibularis group (P = 0.039). Patients with torus mandibularis had a trend of increase in proportion according to the severity of sleep apnoea, such as AHI (P = 0.007) or RDI (P = 0.034). CONCLUSIONS: We newly found that the presence of torus mandibularis affects not only severity of OSA and also position-dependent OSA. These results support the necessity of torus mandibularis evaluation in OSA patients, and further study is also required to investigate its consequence in the surgical outcome.