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.

Amelioration of SARS-CoV-2 infection by ANO6 phospholipid scramblase inhibition.

As an enveloped virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) delivers its viral genome into host cells via fusion of the viral and cell membranes. Here, we show that ANO6/TMEM16F-mediated cell surface exposure of phosphatidylserine is critical for SARS-CoV-2 entry and that ANO6-selective inhibitors are effective against SARS-CoV-2 infections. Application of the SARS-CoV-2 Spike pseudotyped virus (SARS2-PsV) evokes a cytosolic Ca2+ elevation and ANO6-dependent phosphatidylserine externalization in ACE2/TMPRSS2-positive mammalian cells. A high-throughput screening of drug-like chemical libraries identifies three different structural classes of chemicals showing ANO6 inhibitory effects. Among them, A6-001 displays the highest potency and ANO6 selectivity and it inhibits the single-round infection of SARS2-PsV in ACE2/TMPRSS2-positive HEK 293T cells. More importantly, A6-001 strongly inhibits authentic SARS-CoV-2-induced phosphatidylserine scrambling and SARS-CoV-2 viral replications in Vero, Calu-3, and primarily cultured human nasal epithelial cells. These results provide mechanistic insights into the viral entry process and offer a potential target for pharmacological intervention to protect against coronavirus disease 2019 (COVID-19).

Effectiveness of cross-linked human acellular dermal matrix in primary and revision augmentation rhinoplasty.

BACKGROUND: 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. METHODS: 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. RESULTS: The study cohort comprised 145 subjects (75.2% with primary DAR; 39.3% females) with a mean age of 30.7 ±â€¯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. CONCLUSION: 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.

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.

Differential Correlations among Allergy Tests According to Indoor Allergens in Allergic Rhinitis.

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.

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.

Association between obesity and chronic rhinosinusitis with nasal polyps: a national population-based study.

OBJECTIVES: We 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). DESIGN: Retrospective cross-sectional analysis of health survey data. SETTING: Voluntary survey of representative South Korean populations. PARTICIPANTS: In total, 32 384 individuals aged 19 years or older with available data on CRS and obesity were included. PRIMARY AND SECONDARY OUTCOME MEASURES: Diagnosis 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. METHODS: A 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. RESULTS: The prevalence of CRSwNP was higher in the general (OR, 1.438; 95% CI, 1.170 to 1.768; p<0.001) and central (OR, 1.251; 95% CI, 1.031 to 1.520; p=0.033) obesity groups than in the control group. Prevalence of CRSsNP was not correlated with obesity. In a logistic regression analysis, olfactory dysfunction (OR, 1.329; 95% CI, 1.137 to 1.553; p<0.001) and purulent discharge (OR, 1.383; 95% CI, 1.193 to 1.603; p<0.001) showed a higher incidence in the central obesity group than in the control group. CONCLUSIONS: We 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.

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.

The effect of tonsillectomy with adenoidectomy on medical services used in association with otitis media based on Korean national sample cohort data.

BACKGROUND: The effect of tonsillectomy with adenoidectomy (T&A) on otitis media has been investigated, but there have been no reports of the relationship between T&A and medical services used in association with otitis media. We investigated the effect of T&A on otitis media with regard to the number and cost of medical services used. METHODS: From the National Health Insurance Service National Sample Cohort data in Korea, we selected patients 7 years old or younger in 2002 who had T&A in 2005 while between the ages of three and ten. A control group was established matching the patient group with similar propensities of demographic characteristics. The number and cost of medical services used in association with otitis media were analyzed for 3 years before T&A through 8 years after T&A. RESULTS: The total number of patients was 1,338, with 227 in the T&A group and 1,111 in the non-T&A group. The number of medical services used was not significantly different between the T&A and non-T&A groups before and after surgery. The cost of medical services used was significantly higher in the T&A group than in the non-T&A group one year before surgery. The cost of medical services used was not significantly different between the two groups after surgery. CONCLUSIONS: There were no significant differences between the T&A and non-T&A groups in the number and cost of medical services used in association with otitis media after surgery.

Prevalence and clinical characteristics of allergic rhinitis in the elderly Korean population.

PURPOSE: The proportion of elderly people aged ≥ 65 years is increasing worldwide. Although the reported prevalence of sinonasal disease can vary according to the diagnostic methods used, differences in allergic rhinitis prevalence in the elderly according to diagnostic method have not been reported. We thus aimed to evaluate allergic rhinitis prevalence in the elderly according to diagnostic criteria obtained from questionnaires, physician diagnoses, and allergy tests. METHODS: We compared the allergic rhinitis prevalence in the elderly aged ≥ 65 years with adults aged 19-64 years, using data from the Korean National Health and Nutrition Examination Survey 2008-2012. Total serum IgE and IgE levels specific to allergens of Dermatophagoides farina, cockroach, and dog dander were examined, and factors affecting specific IgE levels were investigated. RESULTS: Allergic rhinitis prevalence according to the questionnaire responses, physician diagnoses, and allergy test results was 35.02%, 14.89%, and 17.56%, respectively. The prevalence based on all diagnostic methods assessed was significantly lower in the elderly than in the general adult group (p < 0.001). Rhinorrhea incidence was significantly increased in the elderly (p = 0.018). Sensitization to Dermatophagoides farina was significantly decreased in the elderly (p = 0.006) and did not correlate with socioeconomic status and/or general health factors. CONCLUSIONS: The elderly population has a distinct clinical presentation, including a low prevalence of allergic rhinitis, and an increased incidence of rhinorrhea symptoms, compared with the general adult population. The management of allergic rhinitis in elderly patients may therefore require a different therapeutic approach to improve rhinorrhea rather than nasal obstruction.

Development of a Korean Culture-Friendly Olfactory Function Test and Optimization of a Diagnostic Cutoff Value.

OBJECTIVES: Cultural familiarity and safety must be considered when assessing olfactory ability. The YSK olfactory function (YOF) test is a new olfactory function test using culturally familiar odorants to Koreans. METHODS: The YOF test comprises three subtests for threshold (T), discrimination (D), and identification (I). The identification test included eight universal and four Korean culture-friendly odorants, which were selected considering eight major functional groups. Data were obtained from 1,127 subjects over 19 years old. Subjects were classified as having normosmia (n=542), hyposmia (n=472), and anosmia (n=113) by self-reported olfactory function. The YOF test and the Korean version of the Sniffin' stick test (KVSS-II) were performed on the same day in random order. Diagnostic cutoffs for anosmia and hyposmia were calculated using the Youden index (J). RESULTS: The mean values for each T/D/I subtest and the total TDI score were as follows: normosmia (T, 4.6±2.3; D, 8.6±2.1; I, 11.1±1.7; TDI score, 24.2±4.5); hyposmia (T, 3.3±2.2; D, 7.1±2.5; I, 9.2±3.1; TDI score, 19.5±6.4); and anosmia (T, 1.7±1.2; D, 5.1±2.5; I, 5.0±3.2; TDI score, 11.8±5.6). The correlation coefficients between the YOF test and KVSS-II were 0.57, 0.65, 0.80, and 0.86 for T, D, I, and the TDI score, respectively (P<0.001). The diagnostic cutoffs were a TDI score ≤14.5 (J=0.67) for anosmia and 14.5(TDI score ≤21.0 (J=0.38) for hyposmia. The diagnostic efficacy of the YOF test (area under the curve [AUC], 0.88) was equivalent to that of the KVSS-II (AUC, 0.88; P=0.843; DeLong method). CONCLUSION: The YOF test is a new olfactory test using safe and Korean culture-friendly odorants. It showed equivalent validity with the conventional olfactory function test. Furthermore, the YOF test provides information on the major functional groups of odorants, potentially enabling a more comprehensive interpretation for patients with olfactory disorders.

Can drug-induced sleep endoscopy improve the success rates of tongue base surgery?

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] < 20/h and ≥ 50% reduction in preoperative AHI), and AHI improvement (%) was defined as (preoperative AHI-postoperative AHI) × 100/preoperative AHI. For comparison between the MM and DISE groups, 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 < 0.05) and occlusion at the oropharynx lateral wall (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.

Radiological comparison of inferior turbinate hypertrophy between allergic and non-allergic rhinitis: does allergy really augment turbinate hypertrophy?

BACKGROUND: Inferior turbinate hypertrophy could be a result of allergic rhinitis (AR) that leads to nasal congestion and nasal airway obstruction, which is the most bothersome complaint in patients with AR. However, evidence regarding whether patients with AR have a more hypertrophied inferior turbinate than do patients with non-AR is lacking. OBJECTIVE: We aimed to evaluate the degree of inferior turbinate hypertrophy according to the presence of AR using radiological measurements of the inferior turbinate. METHODS: For evaluating the inferior turbinate, which contributes to nasal obstruction in patients with AR, we enrolled 90 adult patients with septal deviation and divided them into two groups (AR group: n = 49; non-AR group: n = 41). Allergic rhinitis was diagnosed according to the presence of an allergic history, positive multiple allergen simultaneous test, and serological total immunoglobulin E level (≥ 100 kU/L). We analyzed the minimal cross-sectional area on acoustic rhinometry for both groups. The bilateral total width as well as medial mucosa and nasal cavity space in the anterior and posterior portions of the inferior turbinate were measured using computed tomography. RESULTS: We could not find any significant differences in the anterior and posterior dimensions of the inferior turbinate, intranasal space, and choanal spaces between the AR and non-AR groups. Instead, the anterior part of the inferior turbinate in both the groups showed significant differences between the deviated and contralateral sides. The contralateral side had a larger width than did the deviated side, but no significant difference was noted in the posterior portion of the inferior turbinate. CONCLUSION: The degree of inferior turbinate hypertrophy showed no difference between patients with and without AR. Therefore, we suggest that surgical treatment for reducing the size of the inferior turbinate hypertrophy should be considered when performing septoplasty in patients with symptoms of nasal obstruction, regardless of the presence of AR.

Overexpression of OgPAE1 from wild rice confers fungal resistance against Botrytis cinerea.

A full-length cDNA of the OgPAE1 gene encoding the alpha5 subunit of the 20S proteasome was isolated from wild rice (Oryza grandiglumis) treated by wounding or with a fungal elicitor. The deduced amino acid sequence of OgPAE1 comprises 237 amino acids (25.99 kDa), and shows 94.5% homology with Arabidopsis thaliana AtPAE1. Expression of OgPAE1 is regulated by defense-related signaling chemicals such as cantharidin, endothall and jasmonic acid. Overexpression of OgPAE1 in A. thaliana leads to resistance to the fungal pathogen Botrytis cinerea by lowering disease rate and size of necrotic lesions, and by less penetration and colonization of fungal hyphae. The results indicate that the 20S proteasome from wild rice is involved in the B. cinerea defense pathway via an as yet undetermined mechanism.