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This study is aimed to investigate the differences in the clinical features and surgical outcomes between hypopnea- and apnea-predominant obstructive sleep apnea (OSA).Cohort study.Single tertiary care centre.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).The primary outcome measure was the percentage improvement in the apnea-hypopnea index (AHI) from baseline AHI after surgery.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 OPatients 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.

Among the materials used for dorsal augmentation rhinoplasty (DAR), cross-linked human acellular dermal matrix (ADM) has been claimed for its low risk of infection and extrusion. The aim of this study was to compare the effectiveness of ADM in subjects undergoing primary versus revision dorsal augmentation rhinoplasties.Using a retrospective cohort study design, the investigators enrolled a cohort set of DAR patients operated by a single surgeon during a 65-month interval. The predictor variable was the treatment group (primary or revision DAR). The main outcome variables were postoperative changes with regard to the degree of augmentation (ratio of the dorsal height [DH] and radix height [RH] to the nasal length) and patients' and surgeons' satisfaction with the aesthetic and functional results. Other study variables were grouped into the following categories: demographic, surgical, and pathological. Descriptive, uni-, and bivariate statistics were computed using P ≤ 0.05 as a cutoff value.The study cohort comprised 145 subjects (75.2% with primary DAR; 39.3% females) with a mean age of 30.7 ± 9.4 years (range, 19-58). DAR was linked to the significant changes in DH and RH in both the treatment groups. Comparison of the two groups revealed that there was no significant difference in DH and RH between both the groups. Surgeons' and patients' satisfaction rates were comparable between the two surgery groups, neither of which experienced serious complications. Microscopic findings of the removed ADM showed abundant collagen tissue with newly formed vessels without signs of foreign body reaction.Despite significant differences in patient characteristics (age; number of osteotomy, tip plasty, and hump reduction surgeries), the results of this study suggest that ADM can be used in both primary and revision DAR, with minimal complications.

Accumulating evidence suggests that two chronic respiratory diseases, nontuberculous mycobacterium (NTM)-pulmonary disease (PD) and allergic asthma, are frequently present together and that they likely influence the disease development and progression of each other. However, their precise interactions regarding the pathogenesis of comorbid diseases versus that of individual diseases are not well understood. In this study, comorbid diseases (i.e., Mycobacteria avium (Mav) pulmonary infection (PI) (Mav-PI) and ovalbumin-induced allergic asthma) were established in mice in different orders and at different time periods. Individual disease-specific characteristics, including alterations in immune cell populations and antigen-specific immune responses, were analyzed and compared. To assess Mav-PI pathogenesis, lung inflammation and bacterial burden levels were also determined. Allergic asthma induction in the presence of Mav-PI markedly aggravated Mav-PI pathogenesis by increasing the bacterial burden and the severity of lung inflammation. Interestingly, the general outcome of allergic asthma with goblet cell hyperplasia was alleviated at a chronic stage in the comorbid mouse model. Overall, the increase in the number of Mav CFUs was inversely correlated with the Mav-specific Th17 response, as confirmed by comparing BALB/c and C57BL/6J mice. Overall, the pathogenesis of existing Mav-PI is more severely affected by allergen exposure than vice versa. This Mav-PI exacerbation is associated with disruption of Mav-specific Th17 responses. This study provides the first evidence that the Mav-specific Th17 response plays an important role in the control of Mav pathogenesis in the presence of allergic asthma, indicating that targeting the Th17 response has therapeutic potential for NTM-PD accompanied by allergic asthma.

Introduction: Serum level of high-mobility group box 1 protein is reportedly correlated with the severity of obstructive sleep apnea. Objective: We tried to evaluate the possibility of using the serum high-mobility group box 1 protein level as a biologic marker in obstructive sleep apnea patients. Methods: We generated a chronic intermittent hypoxia murine model that reflected human obstructive sleep apnea. Obstructive sleep apnea patients who underwent polysomnography were prospectively enrolled. Serum samples were obtained from mice and obstructive sleep apnea patients, and the serum high-mobility group box1 protein level was measured by enzyme-linked immunosorbent assay. Results: Serum high-mobility group box 1 protein level was 56.16 ± 30.33 ng/mL in chronic intermittent hypoxia and 18.63 ± 6.20 ng/mL in control mice (p0.05). Instead, this protein level was significantly correlated with lowest arterial oxygen concentration (SaO2) (p

By affecting the tongue position and oropharyngeal airway volume, torus mandibularis is an anatomical factor associated with obstructive sleep apnea (OSA). This study aimed to investigate the influence of torus mandibularis on the surgical outcomes of multilevel upper airway surgery with tongue base resection (TBR) in patients with OSA. Patients with OSA who underwent palatal surgery and TBR were retrospectively analyzed. The patients were divided into two groups according to the presence or absence of torus mandibularis upon physical examination or on computed tomography images. The anatomical characteristics of the upper airway and pre/postoperative polysomnography were analyzed. The control and torus mandibularis groups comprised 69 and 35 patients, respectively, with all of them showing improved sleep quality after surgery. Apnea-hypopnea index (AHI) scores decreased from 42.1 ± 22.2 preoperatively to 23.9 ± 21.4 postoperatively in the control group (p 0.001), and from 45.2 ± 19.9 to 22.5 ± 13.5 in the torus mandibularis group (p 0.001). Comparing the postoperative changes in AHI, the AHI of the torus mandibularis group improved by 22.7 ± 23.4, whereas that of the control group improved by 18.1 ± 19.6 (p = 0.296). Sleep efficiency improved from 90.0 ± 7.5 to 92.8 ± 6.8 in the control group, and from 90.3 ± 8.7 to 93.6 ± 6.5 in the torus mandibularis group; however, there was no statistical difference between the two groups (p = 0.816). The presence of torus mandibularis did not appear to significantly affect the surgical results in OSA patients, but it did elicit significant changes in polysomnographic parameters compared with the control group. Therefore, following the identification of torus mandibularis in OSA patients, TBR should be considered as part of planning, as it may help to predict surgical outcomes.

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.

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.

Objectives: Several allergy tests are used for the diagnosis of allergic rhinitis; however, few studies have reported a direct comparison of the skin prick test (SPT), multiple allergen simultaneous test (MAST), and ImmunoCAP according to specific allergens. This study aimed to evaluate the correlations between each test and allergic rhinitis symptoms and to evaluate the correlations of the MAST and ImmunoCAP with the SPT for representative indoor allergens in Korea. Methods: Electronic medical charts were retrospectively reviewed, and 698 patients with allergic rhinitis who had performed SPT, MAST, and ImmunoCAP were enrolled. Correlations between each allergy test for 4 representative indoor allergens and the symptoms of allergic rhinitis were analyzed. Agreements of the MAST and ImmunoCAP with the SPT were compared according to each allergen. Results: The SPT showed higher correlations with allergic rhinitis symptoms for 4 indoor allergens ( Dermatophagoides pteronyssinus, Dermatophagoides farinae, cat, and dog allergens) than the MAST or ImmunoCAP. In comparison between the MAST and SPT, the least correlation was observed for the dog allergen, whereas between the ImmunoCAP and SPT, the least correlation was observed for the cat allergen. The correlation between the ImmunoCAP and SPT was higher than that between the MAST and SPT for the dog allergen, whereas no significant differences were noted for other allergens. Conclusions: Overall, the SPT showed a higher correlation with allergic rhinitis symptoms than the MAST or ImmunoCAP for 4 indoor allergens. ImmunoCAP showed similar reactivity to MAST; however, it showed better positivity with dog allergen in patients who were reactive to the allergen in the SPT. Care should be taken while evaluating dog allergen sensitization using the MAST.

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

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.

Chronic rhinosinusitis (CRS) is a multifactorial, heterogeneous disease characterized by persistent inflammation of the sinonasal mucosa and tissue remodeling, which can include basal/progenitor cell hyperplasia, goblet cell hyperplasia, squamous cell metaplasia, loss or dysfunction of ciliated cells, and increased matrix deposition. Repeated injuries can stimulate airway epithelial cells to produce inflammatory mediators that activate epithelial cells, immune cells, or the epithelial-mesenchymal trophic unit. This persistent inflammation can consequently induce aberrant tissue remodeling. However, the molecular mechanisms driving disease within the different molecular CRS subtypes remain inadequately characterized. Numerous secreted and cell surface proteins relevant to airway inflammation and remodeling are initially synthesized as inactive precursor proteins, including growth/differentiation factors and their associated receptors, enzymes, adhesion molecules, neuropeptides, and peptide hormones. Therefore, these precursor proteins require post-translational cleavage by proprotein convertases (PCs) to become fully functional. In this review, we summarize the roles of PCs in CRS-associated tissue remodeling and discuss the therapeutic potential of targeting PCs for CRS treatment.

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.

ObjectivesWe performed a cross-sectional analysis of data from the nationwide Korea National Health and Nutrition Examination Survey to evaluate the association between obesity and chronic rhinosinusitis with nasal polyps (CRSwNP) or without nasal polyp (CRSsNP).DesignRetrospective cross-sectional analysis of health survey data.SettingVoluntary survey of representative South Korean populations.ParticipantsIn total, 32 384 individuals aged 19 years or older with available data on CRS and obesity were included.Primary and secondary outcome measuresDiagnosis of CRSwNP or CRSsNP was performed by trained otolaryngologists through sinus endoscopy and surveys of medical history. General and central obesity was diagnosed using body mass index (BMI) and waist circumference (WC), respectively.MethodsA multivariate logistic regression analysis was used to clarify the association between CRSwNP or CRSsNP and obesity according to BMI and WC. Non-obese individuals were recruited as controls.ResultsThe prevalence of CRSwNP was higher in the general (OR, 1.438; 95% CI, 1.170 to 1.768; pConclusionsWe demonstrated an association between CRSwNP and general and central obesity. Further investigations on the mechanism underlying this correlation are necessary for an improved understanding of the pathogenesis of CRSwNP.

Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory airway disease involving non-eosinophilic and eosinophilic phenotypes, which translate to various endotypes. Activated eosinophils and neutrophils are known to generate extracellular traps consisting of DNA and cytotoxic granule proteins. We sought to investigate the presence of eosinophil and neutrophil extracellular traps (EETs and NETs, respectively) in human CRS tissues and to clarify the associations with their clinical features. Nasal polyp (NP) or ethmoid tissue slides of 43 subjects from endoscopic sinus surgery for CRS were analysed. Quantitative analysis of EETs and NETs was performed by confocal microscopy using immunofluorescent staining. For correlation study, the presence of NPs, number of infiltrating tissue eosinophils, preoperative Lund–Mackay scores, and other comorbidities were analysed. EET formation was observed to varying degrees in all CRS groups and was correlated with the number of tissue eosinophils (r = 0.83, p

Objective This study aimed to reveal diagnosis, management, and treatment outcome characteristics of sinonasal pleomorphic adenoma and to identify predictors for disease recurrence. Methods This study comprised a retrospective review of data from seven patients with sinonasal pleomorphic adenoma who were treated by the authors at a tertiary medical center between January 2005 and May 2017. In addition, the MEDLINE database was searched for literature published in English. A systematic review of the published articles was performed. Results A total of 42 articles were eligible for review. Data from the seven treated patients and 101 patients described in the literature were included in the analysis. An endoscopic approach was employed in all cases treated at our institution, and recurrence was found in one patient with a large, 5.5-cm tumor. In reviewing prior publications, the mean age at surgery was 45.4 years, and the primary sign at diagnosis was nasal obstruction. The most common primary tumor site was the nasal septum (57.4%), and the mean tumor size was 3.6 cm (range, 0.5–10 cm) in 76 cases for which detailed information was available. Endoscopic endonasal resection achieved successful oncologic control in applied cases (25/25, 100%). Recurrence was found in eight of 101 patients. Multivariate analysis identified tumor origin of the paranasal sinus (adjusted OR 31.000, p = 0.016) as being significantly associated with a high prevalence of recurrence. Conclusion Pleomorphic adenoma is a rare benign tumor of the sinonasal tract. Surgery that achieves clear margins is the treatment of choice. The tumor may be accessible via an endoscopic endonasal approach in most cases, although incomplete resection of the tumor stem may allow for tumor recurrence. In addition, our findings suggest that a tumor originating from the paranasal sinus is significantly associated with a high prevalence of recurrence.

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 αvβ5 or αvβ6. In IL-4-stimulated cells, both anti-αvβ5 and anti-αvβ6 inhibited the phosphorylation of focal adhesion kinase. Furthermore, both β5- and β6-integrins were enriched in basal cells in the injured airway epithelium with allergic rhinitis. These findings suggest that αvβ5 and αvβ6 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.

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. Key words: Allergen, Epidemiology, House dust mite, Pollen, Sensitization

Recently, interest in IL-15-differentiated cells has increased; however, the phenotypic definition of IL-15-differentiated bone marrow-derived cells (IL-15-DBMCs) is still under debate, particularly the generation of IFN-γ-producing innate cells such as premature NK (pre-mNK) cells, natural killer dendritic cells (NKDCs), interferon-producing killer dendritic cells (IKDCs), and type 1 innate lymphoid cells (ILC1s), all of which are IL-15-dependent. Here, we revisited the immunophenotypic characteristics of IFN-γ-producing IL-15-DBMCs and their functional role in the control of intracellular Mycobacterium tuberculosis (Mtb) infection. When comparing the cytokine levels between bone marrow-derived dendritic cells (BMDCs) and IL-15-DBMCs upon stimulation with various TLR agonists, only the CD11cint population of IL-15-DBMCs produced significant levels of IFN-γ, decreased levels of MHC-II, and increased levels of B220. Neither BMDCs nor IL-15-DBMCs were found to express DX5 or NK1.1, which are representative markers for the NK cell lineage and IKDCs. When the CD11cintB220+ population of IL-15-DBMCs was enriched, the Thy1.2+Sca-1+ population showed a marked increase in IFN-γ production. In addition, while depletion of the B220+ and Thy1.2+ populations of IL-15-DBMCs, but not the CD19+ population, inhibited IFN-γ production, enrichment of these cell populations increased IFN-γ. Ultimately, co-culture of sorted IFN-γ-producing B220+Thy1.2+ IL-15-DBMCs with Mtb-infected macrophages resulted in control of the intracellular growth of Mtb via the IFN-γ-nitric oxide axis in a donor cell number-dependent manner. Taken together, the results indicate that IFN-γ-producing IL-15-DBMCs could be redefined as CD11cintB220+Thy1.2+Sca-1+ cells, which phenotypically resemble both IKDCs and ILC1s, and may have therapeutic potential for controlling infectious intracellular bacteria such as Mtb.

BACKGROUND AND PURPOSE: The golden-angle radial sparse parallel-volumetric interpolated breath-hold (GRASP-VIBE) sequence is a recently introduced imaging technique with high resolution. This study compared the image quality between conventional fat-suppressed T1-weighted TSE and GRASP-VIBE after gadolinium enhancement in the head and neck region. MATERIALS AND METHODS: Data from 65 patients with clinical indications for head and neck MR imaging between September 2020 and January 2021 were retrospectively reviewed. Two radiologists assessed the overall image quality, overall artifacts, and image conspicuities in the oropharynx, hypopharynx, and cervical lymph nodes according to 5-point scores (best score: 5). Interobserver agreement was assessed using weighted κ statistics. The SNR and contrast-to-noise ratio were calculated and compared between the 2 sequences using a paired Wilcoxon signed rank test. RESULTS: The analysis included 52 patients (mean age, 60 [SD, 14 ] years; male, 71.2% [37/52]) who were mostly diagnosed with head and neck malignancies (94.3% [50/52]). κ statistics ranged from slight agreement in cervical lymph node conspicuity (κ = 0.18) to substantial agreement in oropharyngeal mucosal conspicuity (κ = 0.80) (κ range, 0.18–0.80). Moreover, GRASP-VIBE demonstrated significantly higher mean scores in overall image quality (4.68 [SD, 0.41] versus 3.66 [SD, 0.73]), artifacts (4.47 [SD, 0.48] versus 3.58 [SD, 0.71]), oropharyngeal mucosal conspicuity (4.85 [SD, 0.41] versus 4.11 [SD, 0.79]), hypopharyngeal mucosal conspicuity (4.84 [SD, 0.34] versus 3.58 [SD, 0.81]), and cervical lymph node conspicuity (4.79 [SD, 0.32] versus 4.08 [SD, 0.64]) than fat-suppressed T1-weighted TSE (all, P

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).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.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.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.

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.

Background/Introduction Physiology-guided PCI in the ACS setting remains debatable. Purpose We aimed to determine the long-term prognostic utility of fractional flow reserve (FFR)- or resting distal coronary pressure to aortic pressure ratio (Pd/Pa)-directed percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) cases. Methods This study included 11,415 coronary stenoses in 7945 patients, including 1668 ACS cases who underwent FFR and resting Pd/Pa. The primary endpoint was the rate of a composite of cardiac death, spontaneous myocardial infarction (MI), and repeat revascularisation. Results During a median follow-up of 3.9 years (IQR: 2.0–4.9), 108 events (12 cardiac deaths, 9 MIs, and 100 revascularisations) of the primary endpoint occurred in 101 patients. In the deferred lesions with FFR >0.80 or Pd/Pa >0.91, the primary endpoint rate was higher in ACS patients than those with stable ischaemic heart disease (SIHD) (adjusted HR 1.87, 95% CI 1.37–2.55 for FFR; adjusted HR 1.78, 95% CI 1.34–2.38 for Pd/Pa). Among ACS patients with FFR ≤0.8 or Pd/Pa ≤0.91, performed revascularisation was associated with a lower rate of the primary endpoint compared to deferred PCI. (6.0% vs. 15.4%, adjusted HR 0.42, 95% CI 0.23–0.77 for FFR; 4.3% vs. 14%, adjusted HR 0.33–0.71, 95% CI 0.33–0.71 for Pd/Pa). However, performed and deferred groups had similar outcome rates in ACS patients with FFR >0.80 or Pd/Pa >0.91. Conclusion ACS patients who deferred revascularisation based on physiology had higher cardiovascular events than did those with SIHD. FFR- and resting Pd/Pa-directed decision-making for PCI is likely useful even in the ACS setting. Funding Acknowledgement Type of funding source: None

To investigate the clinical significance of specific IgE-staphylococcal enterotoxin B (IgE-SEB) in CRS (chronic rhinosinusitis).Retrospective analysis of patients who were positive for specific IgE-staphylococcal enterotoxin B.Tertiary rhinology clinic.A total of 965 patients who were tested for specific IgE-staphylococcal enterotoxin B from December 2016 to December 2017.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.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.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.

Nasal inflammatory diseases, including nasal polyps and acute/chronic sinusitis, are characterized by impaired mucociliary clearance and eventually inflammation and infection. Contact of nasal polyps with adjacent nasal mucosa or stagnated mucus within the maxillary sinus produces compressive mechanical stresses on the apical surface of epithelium which can induce cytoskeleton remodeling in epithelial cells. In this study, we hypothesized that compressive stress modulates ciliary beating by altering the mechanical properties of the cytoskeleton of ciliated cell basal bodies. For the primary human nasal epithelial cells, we found that the applied compressive stress higher than the critical value of 1.0 kPa increased the stroke speed of cilia leading to the enhancement of ciliary beating frequency and mucociliary transportability. Immunostained images of the cytoskeleton showed reorganization and compactness of the actin filaments in the presence of compressive stress. Analysis of beating trajectory with the computational modeling for ciliary beating revealed that the stroke speed of cilium increased as the relative elasticity to viscosity of the surrounding cytoskeleton increases. These results suggest that the compressive stress on epithelial cells increases the ciliary beating speed through cytoskeleton remodeling to prevent mucus stagnation at the early stage of airway obstruction. Our study provides an insight into the defensive mechanism of airway epithelium against pathological conditions. STATEMENT OF SIGNIFICANCE: Cilia dynamics of the nasal epithelium is critical for not only maintaining normal breathing but preventing inflammatory diseases. It has been shown that mechanical compressive stresses can alter the shape and phenotype of epithelial cells. However, the effect of compressive stress on cilia dynamics is unclear. In this study, we demonstrated that the oscillation speed of cilia in human nasal epithelial cells was increased by the applied compressive stress experimentally. The computational simulation revealed that the change of ciliary beating dynamics was attributed to the viscoelastic properties of the reorganized cytoskeleton in response to compressive stress. Our results will be beneficial in understanding the defensive mechanism of airway epithelium against pathological conditions.

Serum level of high-mobility group box 1 protein is reportedly correlated with the severity of obstructive sleep apnea.We tried to evaluate the possibility of using the serum high-mobility group box 1 protein level as a biologic marker in obstructive sleep apnea patients.We generated a chronic intermittent hypoxia murine model that reflected human obstructive sleep apnea. Obstructive sleep apnea patients who underwent polysomnography were prospectively enrolled. Serum samples were obtained from mice and obstructive sleep apnea patients, and the serum high-mobility group box1 protein level was measured by enzyme-linked immunosorbent assay.Serum high-mobility group box 1 protein level was 56.16 ± 30.33 ng/mL in chronic intermittent hypoxia and 18.63 ± 6.20 ng/mL in control mice (p 0.05). The mean apnea-hypopnea index and respiratory disturbance index values of enrolled obstructive sleep apnea patients were 50.35 ± 27.96 and 51.56 ± 28.53, respectively, and the mean serum high-mobility group box 1 protein level was 30.13 ± 19.97 ng/mL. The apnea-hypopnea index and respiratory disturbance index were not significantly correlated with the serum high-mobility group box 1 protein level (p 0.05). Instead, this protein level was significantly correlated with lowest arterial oxygen concentration (SaOHigh-mobility group box 1 protein may be involved in the pathogenesis of obstructive sleep apnea, and the possibility of this protein being a useful biologic marker in obstructive sleep apnea should be further evaluated.

Background Nasal polyps in the nasal cavity and mucous discharge inside the maxillary sinus exhibit compressive stress on the nasal mucosal epithelium. However, there have been only a few studies on how compressive stress impacts the human nasal mucosal epithelium. Methodology We investigated the effect of compressive stress on collective migration, junctional proteins, transepithelial electri- cal resistance, epithelial permeability, and gene expression in well-differentiated normal human nasal epithelial (NHNE) cells and human nasal polyp epithelial (HNPE) cells. Results NHNE cells barely showed collective migration at compressive stress up to 150 mmH20. However, HNPE cells showed much greater degree of collective migration at a lower compressive stress of 100 mmH20. The cell migration of HNPE cells sub- jected to 100 mmH2O compression was significantly decreased at day 3 and was recovered to the status prior to the compressive stress by day 7, indicating that HNPE cells are relatively more sensitive to mechanical pressure than NHNE cells. Compressive stress also increased transepithelial electrical resistance and decreased epithelial permeability, indicating that the compressive stress disturbed the structural organization rather than physical interactions between cells. In addition, we found that compressive stress induced gene expressions relevant to airway inflammation and tissue remodelling in HNPE cells. Conclusion Taken together, these findings demonstrate that compressive stress on nasal polyp epithelium is capable of inducing collective migration and induce increased expression of genes related to airway inflammation, innate immunity, and polyp remo- delling, even in the absence of inflammatory mediators.

This meta-analysis is aimed to investigate the association between the neutrophil-to-lymphocyte ratio (NLR) and obstructive sleep apnea (OSA). The PubMed, Web of Science, Google Scholar, and Cochrane Library databases were searched to collect all relevant articles. The pooled standardized mean difference (SMD) with a 95% confidence interval (CI) was calculated using the random effects model. In addition, subgroup analysis and meta-regression analysis were performed. Eleven eligible articles containing 2,259 patients with OSA were included in this study. Pooled outcomes revealed that the NLR was significantly higher in patients with OSA than in controls (SMD 0.62, 95% CI 0.29–0.94, P = 0.002). In subgroup analyses, differences in the NLR between patients and controls increased with worsening OSA grades. Furthermore, meta-regression analysis showed that differences in mean BMI exerted a significant effect on differences in the NLR (P = 0.0003). In summary, our meta-analysis demonstrated that the NLR in OSA patients was significantly higher than that in controls, and the difference was larger in patients with severe OSA. These results indicate that the NLR may be a reliable marker for detecting systemic inflammation and predicting disease severity in patients with OSA.

Background In the treatment of rhinosinusitis, nasal polyps are a major problem, and the epithelial-to-mesenchymal transition (EMT) process is considered pivotal in their development. Although various studies have addressed the role of high mobility group box 1 (HMGB1) nuclear protein in this setting, its impact on EMT has yet to be evaluated. Our aim was the pathogenic mechanism of HMGB1 in EMT and EMT-induced upper respiratory nasal polyps. Methods We investigated the EMT-related effects of HMGB1 in human nasal epithelial (HNE) cells using western blot analysis, transepithelial-electrical resistance (TEER) testing, wound healing assay, and immunofluorescence. HNE cells were incubated in a low-oxygen environment to evaluate the role of HMGB1 in hypoxia-induced EMT. Further support for our in vitro findings was obtained through murine models. Human nasal polyps and nasal lavage fluid samples were collected for western blotting, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA). Results HMGB1 increased mesenchymal markers and decreased epithelial markers in HNE cells. Hypoxia-induced HMGB1 in turn induced EMT, apparently through RAGE signaling. We verified HMGB1-induced EMT in the upper respiratory epithelium of mice by instilling intranasal HMGB1. In testing of human nasal polyps, HMGB1 and mesenchymal markers were heightened, whereas epithelial markers were reduced, compared with tissue controls. Conclusion HMGB1 secretion in nasal epithelium may be a major pathogenic factor in upper respiratory EMT, contributing to nasal polyps.

Background The purpose of this study was to determine the therapeutic value of drug-induced sleep endoscopy (DISE) by comparing the outcomes of tongue base surgery based on Muller’s maneuver (MM) and those based on DISE in obstructive sleep apnea (OSA) patients. Methods Ninety-five patients who underwent the tongue base surgery in combination with palatal surgery for OSA at a tertiary referral hospital between March 2012 and March 2019 were enrolled in this retrospective comparative study. Forty-seven patients underwent MM for surgical decision and 48 patients underwent DISE in addition to MM for surgical decision. Surgical success was defined according to the Sher criteria (postoperative apnea-hypopnea index [AHI] p-values were calculated using independent or paired t-tests for continuous variables and using chi-square test for categorical variables. Results By comparing the results of MM and DISE, consensus on the tongue base level showed insignificant concordance (kappa = 0.017, p = 0.865), whereas that on the oropharynx level showed fair agreement (kappa =0.241, p = 0.005). AHI, supine AHI, rapid eyeball movement (REM) AHI, non-REM AHI, and nadir oxygen saturation were all significantly improved after the tongue base surgery in both groups. The MM group showed a significant improvement in the Epworth sleepiness scale after the tongue base surgery (p = 0.014), whereas the DISE group did not (p = 0.165). However, there was no significant difference in the AHI improvement (MM group = 47.0 ± 32.0, DISE group = 48.3 ± 35.4, p = 0.852) and surgical success (MM group = 42.6%, DISE group = 45.8%, p = 0.748) between the groups. Tonsil grade (p p = 0.031) were significantly related to surgical success in the MM group. Conclusions In the judgment of the tongue base surgery, MM and DISE findings showed poor agreement. DISE might affect the surgical decision on the tongue base surgery in OSA patients; however, there was a lack of evidence regarding the superiority of DISE over MM with respect to the surgical outcomes.