Improvement of morning headache in adults with obstructive sleep apnea after positive airway pressure therapy.

The aim of this study was to evaluate the association between obstructive sleep apnea and morning headache and to assess the improvement of morning headache following positive airway pressure therapy. One hundred and sixteen participants were enrolled in this study; all of them received positive airway pressure therapy for at least 3 months. We checked the differences in various sleep apnea-related parameters according to the presence of morning headache and evaluated the improvement of morning headache following positive airway pressure therapy. Among the 116 study participants, 103 were men, with a mean age and body mass index of 50.34 ± 10.23 years and 28.00 ± 4.21 kg/m2, respectively. The severity of morning headache was higher in the severe obstructive sleep apnea group than in the mild to moderate group (2.16 ± 1.70 vs. 1.50 ± 1.57, P = 0.027). However, the various polysomnographic parameters did not significantly differ according to the presence of headache. The Epworth sleepiness scale score was significantly higher in the morning headache presence group than in the absence group (10.90 ± 5.45 vs. 8.13 ± 4.27, P = 0.003). Furthermore, a notable correlation was observed between the reduction in daytime sleepiness and the improvement in morning headache following PAP treatment (r = 0.503, P < 0.001). Morning headache significantly improved following positive airway pressure therapy (prevalence: 53.4-16.4%; severity: 1.92 ± 1.67 vs. 0.86 ± 0.80, all P < 0.001), especially in the patients with morning headache before positive airway pressure therapy. Morning headache is significantly associated with daytime sleepiness and positive airway pressure therapy improves morning headache.

Hydrogen peroxide attenuates rhinovirus-induced anti-viral interferon secretion in sinonasal epithelial cells.

Background: Altered innate defense mechanisms, including an imbalance between oxidants and antioxidants release, have been implicated in the pathogenesis of chronic rhinosinusitis (CRS). The aim of this study is to investigate whether oxidative stress may attenuate the secretion of anti-viral interferons in human sinonasal mucosa. Methods: The levels of H2O2 in nasal secretion were increased in patients with CRS with nasal polyps, compared with that of CRS patients without nasal polyps and control subjects. Normal sinonasal epithelial cells derived from healthy subjects were cultured under an air-liquid interface. The cultured cells were infected with rhinovirus 16 (RV 16) or treated with poly (I: C), TLR3 agonist, after being pretreated with an oxidative stressor, H2O2 or antioxidant, N-acetylcysteine (NAC). Thereafter, the expression levels of type I (IFN-ß) and type III (IFN-λ1 and λ2) interferons and interferon-stimulated genes (ISGs) were evaluated with RT-qPCR, ELISA, and western blot. Results: The data showed that the production of type I (IFN-ß) and type III (IFN-λ1 and λ2) interferons and ISGs was upregulated in cells infected with RV 16 or treated with poly (I: C). However, their up-regulated expression was attenuated in cells pretreated with H2O2, but not inhibited in cells pretreated with NAC. In line with these data, the up-regulated expression of TLR3, RIG-1, MDA5, and IRF3 was reduced in cells pretreated with H2O2, but not attenuated in cells treated with NAC. Furthermore, cells transfected with Nrf2 siRNA showed decreased secretion of anti-viral interferons whereas sulforaphane treatment enhanced the secretory capacity of antiviral interferons. Conclusions: These results suggest that the production of RV16-induced antiviral interferons may be attenuated by oxidative stress.

Rhinovirus-induced anti-viral interferon secretion is not deficient and not delayed in sinonasal epithelial cells of patients with chronic rhinosinusitis with nasal polyp.

Dysregulated innate and adaptive immune response to rhinoviral infection plays an important role in the exacerbation or progressive course of chronic rhinosinusitis (CRS). However, few studies have evaluated whether rhinovirus-induced production of anti-viral interferon is deficient or delayed in inflammatory epithelial cells of patients with CRS with nasal polyps. The aim of the present study is to investigate the replication rates of rhinovirus 16 (RV 16), RV16-induced antiviral interferon secretion, and the expression levels of pattern recognition receptors after RV 16 infection or TLR3 stimulation with poly (I: C) in normal and inflammatory epithelial cells. Inflammatory epithelial cells were obtained from CRS patients with nasal polyps and normal epithelial cells were derived from ethmoid sinus mucosa during endoscopic reduction of blowout fracture or uncinate process mucosa of patients with septal deviation. Cultured cells were infected with RV 16 or treated with poly (I: C) for 24, 48, and 72 h. Cells and media were harvested at each time point and used to evaluate RV16 replication rates, the secretion of IFN-ß, -λ1, -λ2, viperin, Mx, and OAS, and the expression levels of TRL3, RIG-I, MDA5, phospho-NFκB, and phospho-IRF3. RV replication rates reached peak levels 48 h after inoculation in both normal and inflammatory epithelial cells and showed no difference between both groups of epithelial cells at any time point. The release of IFN-ß, -λ1, and -λ2 in normal and inflammatory epithelial cells was also strongly induced 48 h after RV16 inoculation but reached peak levels 24 h after poly (I: C) treatment. The expression levels of viperin, Mx, OAS, TLR3, RIG-I, MDA5, phospho-NFκB, and phospho-IRF3 showed similar patterns in both groups of epithelial cells. These results suggest that the production of RV16-induced antiviral interferons is not deficient or delayed in inflammatory epithelial cells from CRS patients with nasal polyps.

Long-Term Outcomes of Nasoseptal Perforation Repair Using Anterior Maxillary Sinus Wall as an Interpositional Graft.

BACKGROUND: Various graft materials have been used to repair nasoseptal perforation, but there is no standardized treatment method. The anterior maxillary sinus wall is flattened in appearance and can be easily obtained in a sufficient amount for a large-sized nasoseptal perforation. OBJECTIVES: The aim of this study is to determine whether the anterior maxillary sinus wall is suitable as an interpositional graft in the surgical repair of septal or nasoseptal perforation. METHODS: This is a retrospective review of 21 patients who underwent repair of nasoseptal perforation using anterior maxillary sinus wall as an interpositional graft. The etiology, pre- and post-operative NOSE and GBI score, and perforation size were reviewed. The surgical outcome was considered successful if total closure was achieved after postoperative follow-up. RESULTS: 19 of the 21 perforations were successfully repaired with anterior maxillary sinus wall. Failure of the repair was found in 2 patients. Causal etiology of perforation was previous septoplasty in 10 patients, and electrocautery in 1 case, but not identified in 10 cases. The largest size was 2.7 × 2.2 cm. The most common symptoms were epistaxis, crusting, and nasal obstruction. Closure of septal perforation resulted in improved subjective symptoms and quality of life which were evaluated with NOSE and GBI score. CONCLUSION: Anterior maxillary sinus wall as interpositional graft between mucoperichondrial flaps can be used to reliably repair nasoseptal perforations.

Association Between Microbiota and Nasal Mucosal Diseases in terms of Immunity.

The pathogenesis of nasal inflammatory diseases is related to various factors such as anatomical structure, heredity, and environment. The nasal microbiota play a key role in coordinating immune system functions. Dysfunction of the microbiota has a significant impact on the occurrence and development of nasal inflammation. This review will introduce the positive and negative roles of microbiota involved in immunity surrounding nasal mucosal diseases such as chronic sinusitis and allergic rhinitis. In addition, we will also introduce recent developments in DNA sequencing, metabolomics, and proteomics combined with computation-based bioinformatics.

Auditory brainstem response test results in normal hearing adolescents with subjective tinnitus.

OBJECTIVES: The objective of the study was to analyze the auditory brainstem response (ABR) test results of adolescents with normal hearing threshold who have subjective tinnitus in an effort to determine the probable site of origin of tinnitus. METHODS: Among the patients who visited the outpatient clinic of the Department of Otolaryngology at our tertiary hospital from January 2016 to December 2019, adolescents aged 13-18 years with the chief complaint of unilateral subjective tinnitus and pure tone audiometry (PTA) within 25 dB HL were enrolled and retrospectively reviewed. The ABR test parameters (amplitudes and latencies of waves I, III, and V and interpeak latencies [IPLs] of waves I-III, III-V, and I-V) were analyzed and compared between tinnitus ears and contralateral ears without tinnitus. Study participants were divided into the chronic tinnitus (tinnitus duration ≥6 months) and non-chronic tinnitus (tinnitus duration <6 months) groups, and the difference between the two groups was analyzed. RESULTS: Ten adolescents were included in the study, and their ABR test results were reviewed. IPL III-V was significantly prolonged in tinnitus ears compared to non-tinnitus ears (p = 0.035). Although other parameters were found to be statistically non-significant, there was preponderance in ABR wave I amplitude; it was smaller in tinnitus ears of chronic tinnitus adolescents than in those of non-chronic tinnitus adolescents (p = 0.114). CONCLUSION: The probable site of origin of tinnitus in adolescents with normal hearing might be in the upper brainstem of the auditory pathway. Further analysis of ABR test results in adolescents with tinnitus and normal hearing can help clarify the pathophysiology of tinnitus in adolescents.

Variation in Sleep Stability with Differences in Severity of Sleep-Disordered Breathing in Children.

OBJECTIVES: The aim of this study was to analyze the association between obstructive sleep apnea (OSA) severity and various cardiopulmonary coupling (CPC) parameters in children with OSA. STUDY DESIGN: Retrospective cross-sectional study. METHODS: A cross-sectional study was conducted among 117 children (aged 7.96 ± 3.54 years, 86 male) who underwent both full-night polysomnography (PSG) and CPC for suspicion of sleep-disordered breathing (SDB). We analyzed the association between various CPC and PSG findings. RESULTS: The apnea-hypopnea index (AHI) was negatively correlated with high frequency coupling (HFC, r = -0.374, P < .001) and very low frequency coupling (VLFC, r = -0.192, P = .038) and positively correlated with low frequency coupling (LFC, r = 0.503, P < .001), elevated low frequency coupling (e-LFC, r = 0.475, P < .001), and narrow and broad band e-LFC (e-LFCNB and e-LFCBB ; r = 0.221, P = .016 and r = 0.468, P < .001, respectively). The arousal index was negatively correlated with HFC (r = - 0.466, P < .001) and positively correlated with LFC, e-LFC, e-LFCNB , and e-LFCBB (r = 0.543, r = 0.460, r = 0.239, and r = 0.445, respectively; all P < .001). In addition, we also found a significant difference in various CPC values according to OSA severity. CONCLUSION: CPC parameters accurately reflect sleep fragmentation and OSA severity in children. Thus, we can verify objective sleep quality using CPC analysis, which is a simple method of analyzing sleep stability in children with SDB. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:435-439, 2021.

The Expression of ephrinA1/ephA2 Receptor Increases in Chronic Rhinosinusitis and ephrinA1/ephA2 Signaling Affects Rhinovirus-Induced Innate Immunity in Human Sinonasal Epithelial Cells.

EphA2 receptor and its ephrin ligands are involved in virus infection, epithelial permeability, and chemokine secretion. We hypothesized that ephrinA1/ephA2 signaling participates in rhinovirus (RV)-induced antiviral immune response in sinonasal mucosa of patients with chronic rhinosinusitis (CRS). Therefore, we investigated the expression of ephrinA1/ephA2 in normal and inflamed sinonasal mucosa and evaluated whether they regulate chemokine secretion and the production of antiviral immune mediators including interferons (IFNs) in RV-infected human primary sinonasal epithelial cells. For this purpose, the expression and distribution of ephrinA1/ephA2 in sinonasal mucosa were evaluated with RT-qPCR, immunofluorescence, and western blot. Their roles in chemokine secretion and the production of antiviral immune mediators such as type I and III IFNs, and interferon stimulated genes were evaluated by stimulating ephA2 with ephrinA1 and inactivating ephA2 with ephA2 siRNA or inhibitor in cells exposed to RV and poly(I:C). We found that ephrinA1/ephA2 were expressed in normal mucosa and their levels increased in inflamed sinonasal mucosa of CRS patients. RV infection or poly(I:C) treatment induced chemokine secretion which were attenuated by blocking the action of ephA2 with ephA2 siRNA or inhibitor. The production of antiviral immune mediators enhanced by rhinovirus or poly (I:C) is increased by blocking ephA2 compared with that of cells stimulated by either rhinovirus or poly(I:C) alone. In addition, blocking ephA2 attenuated RV replication in cultured cells. Taken together, these results describe a novel role of ephrinA1/ephA2 signaling in antiviral innate immune response in sinonasal epithelium, suggesting their participation in RV-induced development and exacerbations of CRS.

Analysis of Auditory Brainstem Response Change, according to Tinnitus Duration, in Patients with Tinnitus with Normal Hearing.

OBJECTIVES: The purpose of this study was to analyze auditory brainstem response (ABR) waveforms of patients with tinnitus with normal hearing, according to tinnitus duration, and demonstrate the possible pathophysiological mechanisms of tinnitus. MATERIALS AND METHODS: From January 2016 to December 2017, patients who presented to our hospital with tinnitus as their chief complaint were enrolled and reviewed retrospectively. Pure tone audiometry and ABR tests were performed. The patients were classified into three groups according to tinnitus duration: acute (<1 month), subacute (1-6 months), and chronic (>6 months). The amplitudes of waves I and V and the latencies of waves I, III, and V were evaluated. In this study, 177 ears of 128 patients with tinnitus with normal hearing were evaluated. RESULTS: Wave V amplitude was significantly lower during the subacute phase than during the acute phase. The absolute latency value of wave V was greater during the subacute phase than during the acute phase. The interpeak latency I-V was significantly prolonged during the subacute phase compared with the acute and chronic phases. Wave V amplitude, wave V absolute latency, and interpeak latency I-V varied significantly between cases with a 1-month and 6-month tinnitus history. CONCLUSION: The compensatory response to tinnitus decreased sharply after 1 month of symptoms. Early tinnitus identification and treatment initiation are recommended.

Comparisons among vestibular examinations and symptoms of vertigo in sudden sensorineural hearing loss patients.

OBJECTIVES: Vertigo in sudden sensorineural hearing loss (SSNHL) is hypothesized as an extension of the disease caused by the anatomical proximity of the cochlea and vestibule. The present study aimed to demonstrate the association of vestibular function test (VFT) results with SSNHL disease severity and prognosis. MATERIALS AND METHODS: This study assessed clinical records of 263 SSNHL patients admitted to our hospital, between January 2010 and October 2017. Steroid treatment comprised high-dose intravenous dexamethasone (16 mg/d) or oral methylprednisolone (64 mg/d) for 4 days and tapered oral methylprednisolone for 8 days after discharge. Caloric tests were performed in all patients, and cervical vestibular-evoked myogenic potential (c-VEMP) and ocular VEMP (o-VEMP) tests were performed in 209 and 144 patients, respectively. RESULTS: Ninety six patients had vertigo, and caloric abnormalities were observed in 119 patients. Initial PTA in patients with vertigo were worse than in those without vertigo (63.0 dB vs 72.7 dB, P = .002). Initial PTA in patients with abnormal o-VEMP was worse than in those with normal o-VEMP (61.4 dB vs 73.0 dB, P = .004). PTA improvement after steroid treatment in patients with vertigo was lower than in those without vertigo (25.0 dB vs 20.9 dB, P = .028). PTA improvement after treatment in patients with abnormal caloric results was lower than in those with normal caloric results (26.0 dB vs 18.4 dB, P = .013). CONCLUSION: The functions of vestibular organs, particularly the utricle and lateral semicircular canal, are associated with disease severity and hearing outcome in SSNHL patients.

Machine Learning Models for Predicting Hearing Prognosis in Unilateral Idiopathic Sudden Sensorineural Hearing Loss.

OBJECTIVES: Prognosticating idiopathic sudden sensorineural hearing loss (ISSNHL) is an important challenge. In our study, a dataset was split into training and test sets and cross-validation was implemented on the training set, thereby determining the hyperparameters for machine learning models with high test accuracy and low bias. The effectiveness of the following five machine learning models for predicting the hearing prognosis in patients with ISSNHL after 1 month of treatment was assessed: adaptive boosting, K-nearest neighbor, multilayer perceptron, random forest (RF), and support vector machine (SVM). METHODS: The medical records of 523 patients with ISSNHL admitted to Korea University Ansan Hospital between January 2010 and October 2017 were retrospectively reviewed. In this study, we analyzed data from 227 patients (recovery, 106; no recovery, 121) after excluding those with missing data. To determine risk factors, statistical hypothesis tests (e.g., the two-sample t-test for continuous variables and the chi-square test for categorical variables) were conducted to compare patients who did or did not recover. Variables were selected using an RF model depending on two criteria (mean decreases in the Gini index and accuracy). RESULTS: The SVM model using selected predictors achieved both the highest accuracy (75.36%) and the highest F-score (0.74) on the test set. The RF model with selected variables demonstrated the second-highest accuracy (73.91%) and F-score (0.74). The RF model with the original variables showed the same accuracy (73.91%) as that of the RF model with selected variables, but a lower F-score (0.73). All the tested models, except RF, demonstrated better performance after variable selection based on RF. CONCLUSION: The SVM model with selected predictors was the best-performing of the tested prediction models. The RF model with selected predictors was the second-best model. Therefore, machine learning models can be used to predict hearing recovery in patients with ISSNHL.

Long-term results of sleep-related quality-of-life and behavioral problems after adenotonsillectomy.

OBJECTIVES: Improvements in sleep-related quality of life (QOL) and behavioral problems have been observed in children with obstructive sleep apnea (OSA) during a short-term follow-up after adenotonsillectomy. Whether this trend continues beyond the short term remains unclear. Therefore, we aimed to evaluate the long-term effects of surgery in children with OSA. METHODS: The study participants comprised 20 children with OSA who underwent adenotonsillectomy. We used the scores from the Attention Deficit and Hyperactivity Disorder Rating Scale (ADHD-RS) and total scores from the Korean OSA-18 Survey (KOSA-18) before and after adenotonsillectomy to compare and analyze behavioral problems and OSA-specific health-related QOL, respectively, during a long-term follow-up. Respiratory disturbance parameters from standard polysomnography and subjective symptom scores for snoring and apnea were also investigated. RESULTS: The mean patient age was 6.6 ± 3.4 years (range, 3-13), and the male-to-female ratio was 15:5. The mean follow-up period was 54.5 months (range, 27-98). The total scores for both ADHD-RS (from 17.6 to 10.5; P = 0.006) and KOSA-18 (from 74.3 to 40.7; P = 0.001) decreased significantly from before to after surgery. Significant decreases were also observed in the subjective symptom scores for snoring (from 5.4 to 2.4; P = 0.000) and apnea (from 3.3 to 0.8; P = 0.002). CONCLUSION: Significant improvement was observed in sleep-related QOL and behavioral problems in children with OSA during long-term follow-up after adenotonsillectomy. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:546-550, 2020.

Comparison of the efficacy of various doses of steroids for acute facial palsy.

BACKGROUND: Although steroids are effective for multiple types of acute facial palsies, an appropriate dosage remains to be established. AIMS/OBJECTIVES: The objective of this study is to compare the efficacy of high, low, and moderate doses of steroids in patients with acute facial palsy. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 49 patients with Bell palsy, Ramsay Hunt syndrome, or traumatic facial palsy. The patients were divided into 3 groups. We determined the initial House-Brackmann (HB) grade of each patient and the HB grade at the 3-month follow-up to determine whether complete recovery was achieved. RESULTS: Results of electroneurography showed that the average and maximum rates of degeneration were not statistically different among the groups. Although the HB grade showed improvement after 3 months, the initial score was not significantly different from that at the follow-up. The degree of recovery was not significantly different among the groups. CONCLUSION AND SIGNIFICANCE: Our findings showed that a high dose of steroids did not achieve outcomes that were more clinically meaningful than did that of a moderate or a low-dose steroid. Therefore, moderate or low doses of steroids may be sufficient for the treatment of acute facial palsy.