Implementation of Head of Bed Elevation Using Adjustable Bed and Its Effects on Sleep: A Pilot Randomized Trial.

Background: Although mild head of bed elevation (HBE) is a proven method to reduce obstructive sleep apnea, there is no study to apply mild HBE in daily life using an adjustable bed. Objective: We aimed to explore the applicability of mild HBE using an adjustable bed in daily life by investigating adverse events and discomforts induced by mild HBE. This pilot randomized trial additionally investigated the objective effects of mild HBE on sleep using polysomnography (PSG). Methods: Pilot randomized controlled trial. With a two-tailed alpha of 0.05 and a power of 0.95, the minimum number of participants for each group; control group slept on flat bed and study group slept on bed with mild HBE on follow-up PSG; was calculated to be 12. Considering a 20% follow-up loss, we enrolled a total of 32 participants (16 participants for each group). Setting: Dongguk University, Ilsan hospital. Participants: A total of 37 individuals complained of subjective sleep disturbance in the Republic of Korea, 32 of whom met the inclusion criteria between September 2021 to July 2022. 23 participants completed the study and participants were randomly assigned into two groups. Intervention: A mild HBE of 7.5 degrees using an adjustable bed was implemented. PSG results and questionnaires were evaluated. Results: There was no difference in the proportion of adverse events between groups after post-intervention which was adjusting mild HBE on study group. Changes in sleep satisfaction from baseline to post-intervention showed no significant difference between groups either. However, changes in respiratory distress index (RDI) (F = 6.088, 95% CI, 17.0% to 26.4%; P = .023) and apnea-hypopnea index (AHI) (F = 5.542, 95% CI, 13.6% to 23.5%; P = .029) were significantly different. Conclusions: Mild HBE is an implementable method for changing sleep posture without definitely causing discomfort or worsening sleep satisfaction. Since an easily applicable way to implement mild HBE using an adjustable bed in daily life reduces RDI and AHI in both subjects complaining of sleep disturbance and obstructive sleep apnea, it can be an alternative treatment for obstructive sleep apnea.

Predicting Obstructive Sleep Apnea Based on Computed Tomography Scan Using Deep Learning Models.

RATIONALE: The incidence of clinically undiagnosed obstructive sleep apnea (OSA) is high among the general population due to limited access to polysomnography. Computed tomography (CT) of craniofacial regions obtained for other purposes can be beneficial in predicting OSA and its severity. OBJECTIVES: To predict OSA and its severity based on paranasal CT using a 3-dimensional deep learning algorithm. METHODS: One internal dataset (n=798) and two external datasets (n=135 and 85) were used in this study. In the internal dataset, 92 normal, 159 mild, 201 moderate, and 346 severe OSA participants were enrolled to derive the deep learning model. A multimodal deep learning model was elicited from the connection between a 3-dimensional convolutional neural network (CNN)-based part treating unstructured data (CT images) and a multi-layer perceptron (MLP)-based part treating structured data (age, sex, and body mass index) to predict OSA and its severity. MEASUREMENTS AND MAIN RESULTS: In four-class classification for predicting the severity of OSA, the AirwayNet-MM-H model (multimodal model with airway-highlighting preprocessing algorithm) showed an average accuracy of 87.6% (95% confidence interval [CI] 86.8-88.6) in the internal dataset and 84.0% (95% CI 83.0-85.1) and 86.3% (95% CI 85.3-87.3) in the two external datasets, respectively. In the two-class classification for predicting significant OSA (moderate to severe OSA), The area under the receiver operating characteristics (AUROC), accuracy, sensitivity, specificity, and F1 score were 0.910 (95% CI 0.899-0.922), 91.0% (95% CI 90.1-91.9), 89.9% (95% CI 88.8-90.9), 93.5% (95% CI 92.7-94.3), and 93.2% (95% CI 92.5-93.9), respectively, in the internal dataset. Furthermore, the diagnostic performance of the Airway Net-MM-H model outperformed that of the other six state-of-the-art deep learning models in terms of accuracy for both four- and two-class classifications and AUROC for two-class classification (p<0.001). CONCLUSIONS: A novel deep learning model, including a multimodal deep learning model and an airway-highlighting preprocessing algorithm from CT images obtained for other purposes, can provide significantly precise outcomes for OSA diagnosis.

Inflammatory Endotypes of Chronic Rhinosinusitis in the Korean Population: Distinct Expression of Type 3 Inflammation.

PURPOSE: Cluster analyses on inflammatory markers of chronic rhinosinusitis (CRS) in Asians from multicenter data are lacking. This multicenter study aimed to identify the endotypes of CRS in Koreans and to evaluate the relationship between the endotypes and clinical parameters. METHODS: Nasal tissues were obtained from patients with CRS and controls who underwent surgery. The endotypes of CRS were investigated by measuring interleukin (IL)-5, interferon (IFN)-γ, IL-17A, IL-22, IL-1ß, IL-6, IL-8, matrix metalloproteinase-9, eotaxin-3, eosinophil cationic protein, myeloperoxidase (MPO), human neutrophil elastase (HNE), periostin, transforming growth factor-ß1, total immunoglobulin E (IgE), and staphylococcal enterotoxin (SE)-specific IgE. We performed hierarchical cluster analysis and evaluated the phenotype, comorbidities, and Lund-Mackay computed tomography (LM CT) score in each cluster. RESULTS: Five clusters and 3 endotypes were extracted from 244 CRS patients: cluster 1 had no upregulated mediators compared to the other clusters (mild mixed inflammatory CRS); clusters 2, 3, and 4 had higher concentrations of neutrophil-associated mediators including HNE, IL-8, IL-17A, and MPO (T3 CRS); and cluster 5 had higher levels of eosinophil-associated mediators (T2 CRS). SE-specific IgE was undetectable in T3 CRS and had low detectable levels (6.2%) even in T2 CRS. The CRS with nasal polyps (CRSwNP) phenotype and LM CT scores showed no significant differences between T2 and T3 CRS, while the incidence of comorbid asthma was higher in T2 CRS than T3 CRS. In T3 clusters, higher levels of neutrophilic markers were associated with disease severity and CRSwNP phenotype. CONCLUSIONS: In Koreans, there is a distinct T3 CRS endotype showing a high proportion of CRSwNP and severe disease extent, along with T2 CRS.

Effect of Ambient Air Pollutants on the Medical Costs of Allergic Rhinitis in Seoul, Korea.

BACKGROUND: Ambient air pollutants are considered significant factors that influence allergic diseases. This study aimed to evaluate the effect of ambient air pollution on the medical costs of allergic rhinitis (AR) through a time-series analysis. METHODS: We used data from the Korean National Health Insurance Database from January 2016 to December 2019. The total cost for medical management and outpatient prescriptions for AR, estimated by the National Health Insurance Service for 25 districts, was summed as the total medical costs. The monthly concentrations of PM10 , PM2.5 , NO2 , CO, O3 , and SO2 were calculated, and time-series analysis was performed to evaluate the effect of ambient air pollutants on the medical cost of AR using the seasonal autoregressive integrated moving average (SARIMA) model. RESULTS: Time-series analysis revealed that the concentrations of PM10 , NO2 , and CO were significantly associated with an increased medical cost of AR when adjusting for monthly differences and seasonality (p = 0.048, p = 0.001, and p = 0.001 respectively). The increase in medical costs of AR was 6.22% (95% confidence interval [CI]: 0.0%-12.37%), 11.27% (95% CI: 6.03%-16.50%), and 11.05% (95% CI: 7.09%-15.01%) per one standard deviation increase in PM10 , NO2, and CO respectively. CONCLUSIONS: The monthly concentrations of PM10 , NO2 , and CO were significantly associated with the increased medical costs of AR when adjusting for monthly differences and seasonality. This analysis provides a better understanding of the health and economic effects of ambient air pollutants on AR. LEVEL OF EVIDENCE: N/A Laryngoscope, 133:1828-1833, 2023.

Distinct Endotypes of Pediatric Rhinitis Based on Cluster Analysis.

PURPOSE: Despite the wide spectrum of pediatric rhinitis, endotyping of rhinitis based on type 2 inflammation and bronchial hyper-responsiveness (BHR) is lacking. This study aimed to investigate endotypes of pediatric rhinitis using cluster analysis. METHODS: Cluster analysis was performed on data from 241 children with rhinitis by using 12 variables reflecting clinical characteristics of skin prick, laboratory, and pulmonary function tests. After extracting clusters, between-cluster differences in clinical features, such as nasal symptom scores and asthma comorbidity, were assessed to investigate the association between the endotypes and clinical features. RESULTS: Four clusters were extracted by hierarchical cluster analysis. Cluster 1 (n = 32 [13.3%]) was the non-allergic rhinitis dominant cluster with low type 2 inflammation and the lowest rate of BHR. Patients in cluster 1 had the mildest nasal symptoms and no asthma comorbidity. Cluster 2 (n = 114 [47.3%]) was the largest cluster and exhibited intermediate type 2 inflammation and low BHR. Cluster 3 (n = 65 [27.0%]) showed high type 2 inflammation and intermediate BHR. However, the severity of nasal symptoms and asthma comorbidity in this cluster were comparable with those in cluster 2. Cluster 4 (n = 30 [12.4%]) revealed high type 2 inflammation and BHR with potential functional airway impairment. Additionally, cluster 4 displayed the most severe nasal symptoms and frequent asthma comorbidity. CONCLUSIONS: Four distinct endotypes of pediatric rhinitis based on allergen sensitization, type 2 inflammation, and BHR correlate to symptoms and asthma comorbidity. These endotypes may aid clinicians in understanding the wide spectrum of pediatric rhinitis.

Automation of generative adversarial network-based synthetic data-augmentation for maximizing the diagnostic performance with paranasal imaging.

Thus far, there have been no reported specific rules for systematically determining the appropriate augmented sample size to optimize model performance when conducting data augmentation. In this paper, we report on the feasibility of synthetic data augmentation using generative adversarial networks (GAN) by proposing an automation pipeline to find the optimal multiple of data augmentation to achieve the best deep learning-based diagnostic performance in a limited dataset. We used Waters' view radiographs for patients diagnosed with chronic sinusitis to demonstrate the method developed herein. We demonstrate that our approach produces significantly better diagnostic performance parameters than models trained using conventional data augmentation. The deep learning method proposed in this study could be implemented to assist radiologists in improving their diagnosis. Researchers and industry workers could overcome the lack of training data by employing our proposed automation pipeline approach in GAN-based synthetic data augmentation. This is anticipated to provide new means to overcome the shortage of graphic data for algorithm training.

Changes in the Laryngeal Mucosa After Thyroid Surgery: A Rat Model.

BACKGROUND/AIM: Thyroidectomy can cause various airway symptoms affecting the quality of life. We investigated the changes in extracellular matrix (ECM) composition and markers for inflammation and microcirculation of laryngeal mucosa. MATERIALS AND METHODS: Sixty Sprague-Dawley rats were categorized into control and three surgical groups based on the extent of surgeries, 1) flap elevation (FE) group, 2) thyroid and trachea exposure (TE) group, and 3) thyroid isthmectomy (TI) group. We analyzed the expression of TGF-ß1, VEGFR-3, CD31, and MMP- 9 in relation to the inflammatory and microcirculatory changes in the lamina propria on postoperative days (PODs) 3, 7, and 21. ECM composition of hyaluronic acid (HA) and collagen in the subglottic area (SA) was also evaluated. RESULTS: All parameters increased in surgical groups at each postoperative phase except collagen deposition. On POD 3, TGF-ß1 expression and SA increased in relation to the surgical extent and decreased over time, but more than the control in all surgical groups on POD 21. Surgical groups had more HA and less collagen composition, causing a higher HA to collagen ratio in relation to the surgical extent. VEGFR-3 and CD31 expression increased with time at all postoperative phases according to the surgical extent. Expression of MMP-9 increased in TI groups compared to TE and FE groups on POD 7 and POD 21. CONCLUSION: This study demonstrated that thyroid surgery exposing the thyroid and trachea induces an increase in the SA with a higher HA and lesser collagen composition. Furthermore, the markers for acute inflammation and microcirculation with tissue remodeling increased in the laryngeal mucosa.

Spatial autocorrelation may bias the risk estimation: An application of eigenvector spatial filtering on the risk of air pollutant on asthma.

Air pollutants are major risk factors for respiratory diseases, particularly asthma, socially and spatially correlated. Many existing environment-asthma-related studies, however, have evaluated the impact of crude trends at the largest district level, which accounts only for temporal effects and may produce biased results with spatial autocorrelation. This study aimed to investigate how the spatial autocorrelation affects the air pollution effect estimations (sulfur dioxide [SO2], nitrogen dioxide [NO2], carbon monoxide [CO], and particulate matter [PM10]) on daily asthma emergency department (ED) visits in two metropolitan areas in Korea (Seoul Metropolitan Area [SMA] and Busan Metropolitan City, Ulsan Metropolitan City, Gyeongsangnamdo [BUG]). We applied eigenvector spatial filter (ESF) to the spatio-temporal model to remove spatial autocorrelation and distributed lag nonlinear model (DLNM) to explore nonlinear patterns between air pollutant concentration and lagged days on the three models including aggregated model (a temporal model), spatial model without ESF, and spatial model with ESF (both are spatio-temporal models). The effect of SO2 was not statistically significant for asthma ED visits in the aggregated model for SMA (cumulative relative risks [CRR] = 0.99, confidence intervals [CI]: 0.93-1.05), while the effect was statistically significant in the spatial model with ESF (CRR = 1.10, CI: 1.08-1.12). NO2 and CO were positively correlated to asthma ED visits in the spatial model without ESF (CRR = 0.84, CI: 0.81-0.86; 0.91, 0.89-0.94, respectively), but the spatial model with ESF showed significant risks (CRR = 1.21, CI: 1.18-1.24; 1.13, 1.11-1.16). Moreover, the spatial model with ESF successfully removed spatial autocorrelation (P-values for Moran's I 0.83-0.98) and demonstrated the highest model fit (McFadden's pseudo R2 0.42-0.43 for SMA and 0.26-0.27 for BUG) among the three models. Our findings demonstrate how ESF can be introduced into spatial correlation to remove bias and construct more reliable models.

Inverted Papilloma of the Maxillary Sinus: A Recurrence Analysis According to Surgical Approaches.

(1) Background: Various surgical approaches have been introduced to resect inverted papillomas (IP) stemming from the maxillary sinus (MS). This study aimed to compare the recurrence rates of IPs originating from the MS according to various surgical modalities. (2) Methods: A total of 155 surgical cases of sinonasal IPs originating from the MS were categorized into three groups according to the surgical approach adopted: endoscopic resection via middle or inferior meatus antrostomy (ESS), ESS with Caldwell−Luc approach or canine fossa trephination (ESS with CL), and expanded endoscopic approaches (ExEA) including endoscopic medial maxillectomy or a prelacrimal recess approach. A Kaplan−Meier curve was generated to examine the recurrence rates. (3) Results: The overall recurrence rate was 5.8% (9/155) with a mean follow-up period of 24.2 months. The recurrence rates for the ESS, ESS with CL, and ExEA groups were 10.0% (7/70), 3.5% (2/57), and 0% (0/28), respectively. The ExEA group had a significantly lower recurrence rate than the ESS group (p = 0.024) and there was a tendency for lower recurrence compared to the ESS within the CL group (p = 0.145). The ExEA required a shorter postoperative hospitalization period than in ESS with CL (p < 0.001). (4) Conclusions: ExEAs to the maxillary sinus such as the PLR and EMM approaches are excellent surgical options for IPs originating from the MS.

Efficacy of Subcutaneous and Sublingual Immunotherapy for House Dust Mite Allergy: A Network Meta-Analysis-Based Comparison.

BACKGROUND: Meta-analyses comparing the efficacy of sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) for house dust mite allergy are lacking. OBJECTIVE: To compare the efficacy of SLIT drops, SLIT tablets, and SCIT in patients with perennial allergic rhinitis through network analysis. METHODS: Frequentist network meta-analyses estimated the standardized mean difference (SMD) across the three immunotherapy modalities on allergic rhinitis symptom and medication score data from double-blind randomized clinical trials. Random effects models were investigated. RESULTS: We included 26 double-blind randomized clinical trials in this meta-analysis for the symptom score and 18 for the medication score. In the direct pairwise meta-analysis, a significant reduction of the symptom score was observed for all immunotherapy modalities compared with the placebo: pooled SMDs of -0.461 (95% confidence interval [CI], -0.795 to -0.127) for SLIT drop, -0.329 (95% CI, -0.426 to -0.231) for SLIT tablet, and -1.669 (95% CI, -2.753 to -0.585) for SCIT. For the medication score, a significant reduction was observed for all modalities. In network meta-analysis, the clinical efficacy of SCIT based on the symptom score was greater than for SLIT drop or SLIT tablet (SMD: -0.697, 95% CI, -1.105 to -0.288; and SMD: -0.819, 95% CI, -1.242 to -0.397). However, there was no significant difference in the symptom score between SLIT drop and SLIT tablet. CONCLUSIONS: This study demonstrated the clinical efficacy of all house dust mite immunotherapy modalities and suggests that SCIT may be more effective than SLIT drops or tablets in controlling symptoms of allergic rhinitis.

Machine learning-based preoperative datamining can predict the therapeutic outcome of sleep surgery in OSA subjects.

Increasing recognition of anatomical obstruction has resulted in a large variety of sleep surgeries to improve anatomic collapse of obstructive sleep apnea (OSA) and the prediction of whether sleep surgery will have successful outcome is very important. The aim of this study is to assess a machine learning-based clinical model that predict the success rate of sleep surgery in OSA subjects. The predicted success rate from machine learning and the predicted subjective surgical outcome from the physician were compared with the actual success rate in 163 male dominated-OSA subjects. Predicted success rate of sleep surgery from machine learning models based on sleep parameters and endoscopic findings of upper airway demonstrated higher accuracy than subjective predicted value of sleep surgeon. The gradient boosting model showed the best performance to predict the surgical success that is evaluated by pre- and post-operative polysomnography or home sleep apnea testing among the logistic regression and three machine learning models, and the accuracy of gradient boosting model (0.708) was significantly higher than logistic regression model (0.542). Our data demonstrate that the data mining-driven prediction such as gradient boosting exhibited higher accuracy for prediction of surgical outcome and we can provide accurate information on surgical outcomes before surgery to OSA subjects using machine learning models.

Bone morphogenetic protein-2 as a novel biomarker for refractory chronic rhinosinusitis with nasal polyps.

BACKGROUND: Bone morphogenetic proteins (BMPs), which are members of the TGF-ß superfamily, regulate bone remodeling by stimulating osteoblasts and osteoclasts. Although the association between osteitis and poor surgical outcomes is well known in patients with chronic rhinosinusitis (CRS), BMPs have not been fully investigated as potential biomarkers for the prognosis of CRS. OBJECTIVE: Our aim was to investigate the role of BMPs in osteitis in patients with CRS with nasal polyps (NPs) (CRSwNPs), as well as associations between BMPs and inflammatory markers in sinonasal tissues from patients with CRSwNP. METHODS: We investigated the expression of 6 BMPs (BMP-2, BMP-4, BMP-6, BMP-7, BMP-9, and BMP-10) and their cellular origins in NPs of human subjects by using immunohistochemistry and ELISA of NP tissues. Exploratory factor analysis was performed to identify associations between BMPs and inflammatory markers. Air-liquid interface cell culture of human nasal epithelial cells was performed to evaluate the induction of the epithelial-mesenchymal transition by BMPs. RESULTS: Of the 6 BMPs studied, BMP-2 and BMP-7 were associated with refractoriness. Only BMP-2 concentrations were higher in patients with severe osteitis and advanced disease extent according to the computed tomography findings. Eosinophils and some macrophages were identified as cellular sources of BMP-2 in immunofluorescence analysis. An in vitro experiment revealed that BMP-2 induced epithelial-mesenchymal transition in air-liquid interface-cultured human nasal epithelial cells, particularly in a TH2 milieu. CONCLUSION: BMP-2 could reflect the pathophysiology of mucosa and bone remodeling and may be a novel biomarker for refractory CRSwNP.

Effectiveness and Safety of Polydioxanone Thread Embedding Acupuncture Compared to Physical Therapy in the Treatment of Patients with Non-Specific Chronic Neck Pain: An Assessor-Blinded, Randomized, Controlled, Clinical Trial.

BACKGROUND: Thread embedding acupuncture (TEA) has recently been used as a conservative treatment method for non-specific chronic neck pain (CNP). The objective of this study was to evaluate the effectiveness and safety of TEA compared to physical therapy (PT) for treating patients with CNP. METHODS: A total of 128 patients diagnosed with CNP were randomly assigned to a TEA group and a PT group at a 1:1 ratio. The TEA group received four sessions of TEA, while the PT group received eight sessions of PT over 4 weeks. Outcomes were assessed using Neck Pain and Disability Scale (NPDS), clinically important difference (CID), cervical spinal angle, Beck Depression Inventory II (BDI-II), Beck Anxiety Inventory (BAI), Patient Global Impression of Change (PGIC), and EuroQol Five-Dimension (EQ-5D) at baseline and 5, 9, and 13 weeks. RESULTS: The TEA group showed significant improvement in NPDS compared to the PT group at 5, 9, and 13 weeks. Proportions of patients with decreased NPDS scores of more than 11.5 points (minimal CID) were significantly higher in the TEA group at 5, 9, and 13 weeks. There were significant differences between the two groups at 5, 9, and 13 weeks for BDI-II, and at 5 and 9 weeks for BAI. For EQ-5D, the TEA group showed significant improvement at 5, 9, and 13 weeks. There was no significant difference in cervical spinal angle between the two groups. For PGIC, better improvement was observed at 9 and 13 weeks in the TEA group. Adverse events associated with interventions were mostly temporary and mild. CONCLUSION: For patients with CNP, TEA treatment was found to be more effective than PT treatment for improving their pain and dysfunction, quality of life, and psychological distress. Despite some post-treatment discomfort, TEA treatment can be considered as a useful treatment method for patients with CNP. TRIAL REGISTRATION: This trial has been registered 5 April 2019 in Clinical Research Information Service of South Korea (CRIS- KCT0003720).

Validation of Olfactory Questionnaire in Koreans: an Alternative for Conventional Psychophysical Olfactory Tests.

BACKGROUND: The patients with coronavirus disease 2019 (COVID-19), a worldwide pandemic infection, frequently complain of olfactory disorders. However, psychophysical olfactory tests performed by an examiner are very difficult in these highly infectious patients. This study aimed to develop and validate a questionnaire for olfactory function that can be readily used to evaluate olfactory loss. METHODS: Fourteen smell-related questions were created based on smells familiar to Koreans. Among them, questions with a κ value of 0.6 or higher were finally selected through a test-retest reliability analysis. The correlations between the scores of the olfactory questionnaire and those of olfactory function tests (Butanol Threshold Test [BTT] and Cross Cultural Smell Identification Test [CCSIT]) were analyzed. To evaluate the predictive ability of the questionnaire and elicit cutoff values, receiver operating characteristic (ROC) curves were generated. RESULTS: Out of the 14 questions in the questionnaire, 11 (κ > 0.6) were selected for the olfactory questionnaire. We analyzed 2,273 subjects, and there was a significant correlation between the total score of the olfactory questionnaire and the BTT (r = 0.643, P < 0.001) or CCSIT (r = 0.615, P < 0.001) scores. ROC curves for the olfactory questionnaire, BTT, and CCSIT all demonstrated high predictive power to discriminate anosmia and severe hyposmia from normosmia. Regarding mild to moderate hyposmia, however, ROC curve for the olfactory questionnaire alone showed high predictive power of discrimination from normosmia. Based on the results of ROC curves among the subclasses, we suggest the classification of the total score of the questionnaire as 0-4, 5-17, 18-27, 28-41, and 42-44, for anosmia, severe hyposmia, moderate hyposmia, mild hyposmia, and normosmia, respectively. CONCLUSION: The total scores of the questionnaires correlated with the BTT and CCSIT scores. The symptom questionnaire for olfactory dysfunction may be useful as an alternative tool for olfactory function testing, when unavailable.

Regional and Chronological Variation of Chemosensory Dysfunction in COVID-19: a Meta-Analysis.

BACKGROUND: Olfactory and gustatory dysfunction are frequently reported in patients with coronavirus disease 2019 (COVID-19). However, the reported prevalence of olfactory and/or gustatory dysfunction varies widely, and the reason for the inter-study differences is unclear. Hence, in this meta-analysis, we performed subgroup analyses to investigate the factors that contribute to the inter-study variability in the prevalence of olfactory and gustatory dysfunction. METHODS: Out of 943 citations, we included 55 eligible studies with 13,527 patients with COVID-19 for a meta-analysis. Calculating the data extracted from each study, the weighted summary prevalence of olfactory and gustatory dysfunction was estimated using a Freeman-Tukey transformation with models based on random-effects assumptions. A meta-analysis of variance compared the prevalence of olfactory and gustatory dysfunction according to regional, chronological, demographic, and methodologic factors, respectively. RESULTS: The overall pooled prevalence rates of olfactory and gustatory dysfunction were 51.4% and 47.5%, respectively, in the random-effect model. In subgroup analyses, the prevalence rates of olfactory and gustatory dysfunction were significantly different among four geographical regions (both P < 0.001, respectively). Although the prevalence rates of olfactory and gustatory dysfunction did not significantly differ according to the time of enrollment, the subgroup analyses including only studies from the same geographical region (Europe) revealed a significant difference in olfactory dysfunction according to the time of enrollment. CONCLUSION: The regional and chronological differences in the prevalence rates of olfactory and gustatory dysfunctions partly explain the wide inter-study variability.

Early Response of Specific IgE can Predict Satisfaction with Sublingual Immunotherapy.

OBJECTIVE: To investigate predictive parameters at baseline and during the early response to sublingual immunotherapy (SLIT) for house dust mites in allergic rhinitis patients. STUDY DESIGN: Retrospective cohort study. METHODS: Patients were treated with SLIT for at least 3 years and serological tests performed at baseline and at 1-year follow-up to investigate predictive parameters. Satisfaction with SLIT, 4 nasal symptoms, and quality of life were evaluated before and after 3 years of SLIT. Sixty-one patients were enrolled and divided into two groups depending on their satisfaction after 3 years of SLIT: 43 were satisfied (70.5%) and 18 were not (29.5%). RESULTS: Immunological parameters at baseline did not differ significantly between the satisfactory and unsatisfactory groups. However, changes in both Dermatophagoides pteronyssinus (Dp)- and D. farinae (Df)-specific IgEs were significantly higher in the unsatisfactory group than in the satisfactory group during the early response to SLIT (P = .006 and P = .045, respectively). CONCLUSION: The changes in both Dp- and Df-specific IgE levels during early response may be indicators for favorable long-term treatment outcomes with SLIT. These results suggest that clinicians could measure these immunological parameters 1 year after Dp and Df SLIT to indicate potential responders versus nonresponders. LEVEL OF EVIDENCE: 2b Laryngoscope, 131:467-472, 2021.

Impact of Particulate Matter on the Clinical Characteristics of Rhinitis.

OBJECTIVES/HYPOTHESIS: To investigate the association between PM10 concentration and the severity of rhinitis symptoms. STUDY DESIGN: Retrospective cohort study. METHODS: Retrospective analysis of the data of 590 participants prospectively enrolled in a regional population-based cohort study was performed. The ambient PM10 concentrations were measured at 12 different observatories located in three cities. All participants were screened for allergic sensitization by skin prick tests and asked to complete questionnaires regarding their rhinitis symptoms. The severity and duration of rhinitis were analyzed and compared at different levels of PM10 concentration. RESULTS: On multivariate analysis, the PM10 concentration significantly correlated with the severity of symptoms when adjusting for age, sex, presence of sensitized allergen, region, and the time of enrolment (ß = 0.102, P = .021). Positive correlation was found between PM10 concentration and the duration of allergic rhinitis symptoms (ß = 0.082, P = .077). In the stratified analysis on the atopic status, there was a significant correlation between PM10 concentration and the severity and duration of rhinitis symptoms in those without allergic sensitization (ß = 0.104; P = .032 and ß = 0.104; P = .011, respectively). CONCLUSIONS: The significant correlation between the annual PM10 concentration and severity and duration of rhinitis symptoms suggests the necessity of intensive management of rhinitis patients exposed to elevated levels of ambient PM10 concentration. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E1753-E1759, 2021.

House Dust Mite Sublingual Immunotherapy in Children Versus Adults With Allergic Rhinitis.

BACKGROUND: There are only a few studies in which the clinical efficacy of SLIT has been compared between children and adults. In addition, there is a lack of research on other factors, associated with the treatment, including immunological parameters and quality of life (QOL). OBJECTIVE: To compare the effects of sublingual immunotherapy (SLIT) in adults and children on various factors: clinical efficacy, quality of life (QOL), satisfaction, immunological parameters, and adverse events. METHODS: Subjects who were sensitized to house dust mites and treated with SLIT for at least 2 years were enrolled. Seventy patients who completed questionnaires measuring nasal symptoms and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores and underwent serologic tests for immunological parameters at initial, 1-year, and 2-year follow-up were selected and divided into two groups based on age: a child group (age 4-12 years, n = 44) and an adult group (age 19-59 years, n = 26). RESULTS: The Total Nasal Symptom Score (TNSS) was significantly decreased after 2 years of SLIT in both the child and adult groups (p < 0.001, both); however, changes in TNSS from baseline did not significantly differ between the two groups (p = 0.365). More patients in adult group were satisfied with SLIT than those in child group (p = 0.050), and changes in RQLQ score from baseline tended to be larger in adult group (p = 0.089). The levels of immunological parameters at baseline were significantly higher in the child group than in the adult group; however, changes in the levels of these parameters were not significantly different. CONCLUSION: Although more adult patients were satisfied with SLIT, the clinical effects of SLIT on nasal symptoms were comparable between child and adult groups. Despite different immunological values at baseline between the two groups, changing patterns of immunological parameters did not differ.

Enhanced Type 2 Immune Reactions by Increased IL-22/IL-22Ra1 Signaling in Chronic Rhinosinusitis With Nasal Polyps.

PURPOSE: Recent studies have revealed the pathogenic role of interleukin (IL)-22 in atopic dermatitis and asthma. However, little is known about the role of IL-22 in the pathophysiology of chronic rhinosinusitis with nasal polyps. We aimed to investigate the expression of IL-22 and its pathogenic function in type 2 immune reactions of nasal polyps (NP). METHODS: Protein levels of inflammatory mediators were determined by multiplex immunoassay, and principal component analysis (PCA) was performed. Immunofluorescence analysis and mast cell culture were used to determine the cellular sources of IL-22. Normal human bronchial epithelial (NHBE) cells were stimulated using IL-22 in combination with diverse cytokines, and thymic stromal lymphopoietin (TSLP) was measured. RESULTS: IL-22 expression was not up-regulated in NP compared with control tissues, but IL-22-high NP revealed distinct features characterized by type 2 inflammatory cytokines such as chemokine (C-C motif) ligand (CCL)-11, CCL-24, and IL-5 on the PCA. Additionally, IL-22 positively correlated with type 2 immune mediators and the disease severity in NP. For the localization of the cellular sources of IL-22 in eosinophilic NP, it was expressed in cells mostly composed of eosinophil peroxidase-positive cells and partially of tryptase-positive cells. The human mast cell line, LAD2 cells, released IL-22 mediated by immunoglobulin E. Moreover, IL-22 receptor subunit alpha-1 (IL-22Ra1) expression was significantly increased in NP. IL-22Ra1 was up-regulated with poly(I:C) stimulation in NHBE cells. Furthermore, TSLP production was enhanced when stimulated with a combination of IL-13, poly(I:C), and IL-22. Treatment with anti-IL-22Ra1 also inhibited IL-22-induced enhancement of TSLP production. CONCLUSION: IL-22 was associated with type 2 inflammatory reactions in NP. The IL-22/IL-22Ra1 axis was enhanced and might be involved in type 2 inflammatory reactions via TSLP production in NP.