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.

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.

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.

CD44v3-Positive Intermediate Progenitor Cells Contribute to Airway Goblet Cell Hyperplasia.

In allergic airway diseases, intermediate progenitor cells (IPCs) increase in number in the surface epithelium. IPCs arise from basal cells, the origin of hallmark pathological changes, including goblet cell hyperplasia and mucus hypersecretion. Thus, targeting IPCs will benefit future treatment of allergic airway diseases. However, the lack of adequate cell surface markers for IPCs limits their identification and characterization. We now show that CD44 containing exon v3 (CD44v3) is a surface marker for IPCs that are capable of both proliferating and generating differentiated goblet cells in allergic human nasal epithelium. In primary human nasal epithelial cells that had differentiated at an air-liquid interface, IL-4 upregulated mRNA expression of three CD44v variants that include exon v3 (CD44v3-v6, CD44v3,v8-v10, and CD44v3-v10), and it induced expression of CD44v3 protein in the basal and suprabasal layers of the culture. FACS analysis revealed two subpopulations differing in CD44v3 concentrations, as follows: CD44v3low cells expressed high amounts of proliferative and basal cell markers (Ki-67 and TP63), whereas CD44v3high cells strongly expressed progenitor and immature and mature goblet cell markers (SOX2, CA2, and SPDEF). Importantly, a blocking anti-CD44 antibody suppressed IL-4-induced mucin production by human nasal epithelial cells. Furthermore, CD44v3 was coexpressed with TP63, KRT5, or SOX2 and was upregulated in the basal and suprabasal layers of the nasal surface epithelium of subjects with allergic rhinitis. Taken together, these data demonstrate that high CD44v3 expression contributes to goblet cell hyperplasia in inflammation of the allergic airway.

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.

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.

Fms-Like Tyrosine Kinase 3-Independent Dendritic Cells Are Major Mediators of Th2 Immune Responses in Allergen-Induced Asthmatic Mice.

Dendritic cells (DCs) are the main mediators of Th2 immune responses in allergic asthma, and Fms-like tyrosine kinase 3 ligand (Flt3L) is an important growth factor for the development and homeostasis of DCs. This study identified the DC populations that primarily cause the initiation and development of allergic lung inflammation using Fms-like tyrosine kinase 3 (Flt3) knockout (KO) mice with allergen-induced allergic asthma. We observed type 2 allergic lung inflammation with goblet cell hyperplasia in Flt3 KO mice, despite a significant reduction in total DCs, particularly CD103+ DCs, which was barely detected. In addition, bone marrow-derived dendritic cells (BMDCs) from Flt3 KO mice directed Th2 immune responses in vitro, and the adoptive transfer of these BMDCs exacerbated allergic asthma with more marked Th2 responses than that of BMDCs from wild-type (WT) mice. Furthermore, we found that Flt3L regulated the in vitro expression of OX40 ligand (OX40L) in DCs, which is correlated with DC phenotype in in vivo models. In conclusion, we revealed that Flt3-independent CD11b+ DCs direct Th2 responses with the elevated OX40L and are the primary cause of allergic asthma. Our findings suggest that Flt3 is required to control type 2 allergic inflammation.

Integrins αvß5 and αvß6 Mediate IL-4-induced Collective Migration in Human Airway Epithelial Cells.

A positive link between persistent cellular motion and a defective tight junction barrier allows increased antigenic penetration and contact between ligand-receptor pairs, leading to exacerbated allergic airway inflammation and remodeling. Given that collective cell migration involves cell-cell and cell-extracellular matrix adhesions, and given that IL-4 induces epithelial barrier dysfunction and decreases cell-extracellular matrix adhesions, we hypothesized that IL-4 may induce collective migration in the well-differentiated primary human nasal epithelial cells (HNECs). Well-differentiated HNECs were treated with IL-4, and the effects of IL-4 on cell migration were investigated using genetic and pharmacological approaches, live-cell imaging, a vertex model, and immunostaining. IL-4 disrupted the expression and localization of the tight junction proteins zonula occludens 1 and occludin, and it induced the cleavage and asymmetric distribution of E-cadherin in the HNEC layers. It also induced collective epithelial migration and cell shape changes driven by actin cytoskeleton reorganization. In addition, the effect of IL-4 on collective HNEC migration was reversed by pharmacologic and genetic inhibition of the αv-integrin-activating enzyme furin, and function-blocking antibodies for αvß5 or αvß6. In IL-4-stimulated cells, both anti-αvß5 and anti-αvß6 inhibited the phosphorylation of focal adhesion kinase. Furthermore, both ß5- and ß6-integrins were enriched in basal cells in the injured airway epithelium with allergic rhinitis. These findings suggest that αvß5 and αvß6 serve as critical mechanoreceptors in IL-4-induced collective HNEC migration through the focal adhesion kinase signaling pathway. These results have implications for targeting treatment of exacerbation of respiratory allergic diseases.

Association of Elevated Plasma Interleukin-18 Level With Increased Mortality in a Clinical Trial of Statin Treatment for Acute Respiratory Distress Syndrome.

OBJECTIVE: A high plasma level of inflammasome mediator interleukin-18 was associated with mortality in observational acute respiratory distress syndrome cohorts. Statin exposure increases both inflammasome activation and lung injury in mouse models. We tested whether randomization to statin therapy correlated with increased interleukin-18 in the ARDS Network Statins for Acutely Injured Lungs from Sepsis trial. DESIGN: Retrospective analysis of randomized controlled clinical trial. SETTING: Multicenter North American clinical trial, the ARDS Network Statins for Acutely Injured Lungs from Sepsis. PATIENTS: Six hundred eighty-three subjects with infection-related acute respiratory distress syndrome, representing 92% of the original trial population. INTERVENTIONS: Random assignment of rosuvastatin or placebo for up to 28 days or 3 days after ICU discharge. MEASUREMENTS AND MAIN RESULTS: We measured plasma interleukin-18 levels in all Statins for Acutely Injured Lungs from Sepsis patients with sample available at day 0 (baseline, n = 683) and day 3 (after randomization, n = 588). We tested the association among interleukin-18 level at baseline, rising interleukin-18, and the impact of statin therapy on 60-day mortality, adjusting for severity of illness. Baseline plasma interleukin-18 level greater than or equal to 800 pg/mL was highly associated with 60-day mortality, with a hazard of death of 2.3 (95% CI, 1.7-3.1). Rising plasma interleukin-18 was also associated with increased mortality. For each unit increase in log2 (interleukin-18) at day 3 compared with baseline, the hazard of death increased by 2.3 (95% CI, 1.5-3.5). Subjects randomized to statin were significantly more likely to experience a rise in plasma interleukin-18 levels. Subjects with acute kidney injury, shock, low baseline interleukin-18, and those not receiving systemic corticosteroids were more likely to experience rising interleukin-18. Randomization to statin therapy was associated with rising in interleukin-18 in all of those subsets, however. CONCLUSIONS: Elevated baseline plasma interleukin-18 was associated with higher mortality in sepsis-induced acute respiratory distress syndrome. A rise in plasma interleukin-18 was also associated with increased mortality and was more common in subjects randomized to statin therapy in this clinical trial.

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.

Geographic and demographic variations of inhalant allergen sensitization in Koreans and non-Koreans.

BACKGROUND: To diagnose and treat respiratory allergic diseases, it is important to identify the specific allergens involved. Many differences exist between common inhalant allergens depending on the residential environment and demographic factors. This study aimed to compare common inhalant allergens between Koreans and non-Koreans according to their residential region, age, and sex. METHODS: This study evaluated 15,334 individuals who underwent serum tests for multiple allergen-specific immunoglobulin E at a tertiary academic medical center between January 2010 and December 2016. The individuals included 14,786 Koreans and 548 non-Koreans. The AdvanSure™ Allostation assay (LG Life Science, Korea) was used to test for 33 inhalant allergens. RESULTS: The house dust mite (HDM) was the most common allergen in both Koreans and non-Koreans, although the proportion of individuals with HDM sensitization was greater among Koreans. High sensitization rates for various pollen types were detected among Koreans in Gangwon region, whereas Japanese cedar pollen was unique among Koreans in Jeju region. Grass pollen and animal dander were relatively common among individuals from the Americas, whereas weed and grass pollen accounted for the 10 most common allergens for individuals from Central Asia. The total sensitization rate, sensitization to HDM, and sensitization to animal dander peaked among adolescents and young adults, then subsequently decreased with age. CONCLUSIONS: This large-scale study demonstrates that various regional and age-related differences exist in the allergen sensitization rates of Koreans and non-Koreans. These data could be useful for development of avoidance measures, immunotherapy for causative allergens, and policymaking regarding allergic diseases.

Dysbiosis of Inferior Turbinate Microbiota Is Associated with High Total IgE Levels in Patients with Allergic Rhinitis.

Abnormalities in the human microbiota are associated with the etiology of allergic diseases. Although disease site-specific microbiota may be associated with disease pathophysiology, the role of the nasal microbiota is unclear. We sought to characterize the microbiota of the site of allergic rhinitis, the inferior turbinate, in subjects with allergic rhinitis (n = 20) and healthy controls (n = 12) and to examine the relationship of mucosal microbiota with disease occurrence, sensitized allergen number, and allergen-specific and total IgE levels. Microbial dysbiosis correlated significantly with total IgE levels representing combined allergic responses but not with disease occurrence, the number of sensitized allergens, or house dust mite allergen-specific IgE levels. Compared to the populations in individuals with low total IgE levels (group IgElow), low microbial biodiversity with a high relative abundance of Firmicutes phylum (Staphylococcus aureus) and a low relative abundance of Actinobacteria phylum (Propionibacterium acnes) was observed in individuals with high total serum IgE levels (group IgEhigh). Phylogeny-based microbial functional potential predicted by the 16S rRNA gene indicated an increase in signal transduction-related genes and a decrease in energy metabolism-related genes in group IgEhigh as shown in the microbial features with atopic and/or inflammatory diseases. Thus, dysbiosis of the inferior turbinate mucosa microbiota, particularly an increase in S. aureus and a decrease in P. acnes, is linked to high total IgE levels in allergic rhinitis, suggesting that inferior turbinate microbiota may be affected by accumulated allergic responses against sensitized allergens and that site-specific microbial alterations play a potential role in disease pathophysiology.

Surgical outcomes of overlapping lateral pharyngoplasty with or without coblator tongue base resection for obstructive sleep apnea.

PURPOSE: Considerable number of patients with obstructive sleep apnea (OSA) failed to respond to positive airway pressure therapy and so turned to surgical procedures. A wide variety of surgical procedures have been developed and advanced, according to obstruction and target site through nasal cavity to trachea. We introduced our overlapping lateral pharyngoplasty (OLP) technique as a surgical option for OSA and evaluated its surgical outcomes both with and without endoscope-guided coblator tongue base resection (CobTBR). METHODS: Sixty-five patients underwent either OLP alone or OLP combined with CobTBR to treat OSA at academic tertiary center. Twenty-nine patients underwent postoperative polysomnography and were divided into two groups, as an OLP group and an OLP combined CobTBR group. Various parameters from physical examinations and polysomnographic results were compared and analyzed. RESULTS: Most enrolled patients improved on various polysomnographic parameters, including AHI and oxygen levels. In the OLP group, 91.7% of patients showed a surgical response and the overall success rate was 66.7%. Mean AHI improved significantly from 36.3 to 14.8. In the OLP + CobTBR group, all patients showed improvement in AHI and the surgical response rate was 100%. The overall success rate was 70.6% and mean AHI improved from 38.8 to 13.1. In both groups, various parameters such as RDI, lowest O2 saturation, mean O2 saturation, oxygen desaturation index, supine AHI, and ESS significantly improved after surgery. CONCLUSION: Our OLP technique appears to be safe and effective among OSA patients. Multi-level OLP surgery combined with CobTBR can be a good surgical strategy for patients experiencing retroglossal obstruction.