Extracellular Hsp70 Is Involved in the CXCL12/CXCR4 Pathway in Primary Human Nasal Epithelial Cells: A Preliminary Study

Background and Objectives@#To date, no studies have been conducted on the interaction between extracellular heat shock protein 70 (Hsp70) and C-X-C chemokine receptor type 4 (CXCR4) in the upper airway. We aimed to evaluate the relationship between extracellular Hsp70 and CXCR4 and their role in the primary human nasal epithelium. @*Methods@#We cultured primary human nasal epithelial (HNE) cells in an air–liquid interface. Macrogen performed single-cell quantitative polymerase chain reaction and sequencing. We conducted western blot analysis for the CXCR4 and mitogen-activated protein kinase (MAPK) pathways. @*Results@#Extracellular Hsp70 treatment significantly increased the genetic expression and protein levels of CXCR4 in primary HNE cells. Phospho-ERK expression was increased by cotreatment with Hsp70 and CXCL12, but inhibited by pretreatment with AMD3100, a CXCR4 inhibitor. Pretreatment with an anti-Hsp70 antibody reduced phospho-ERK expression upregulation induced by cotreatment with Hsp70 and CXCL12. @*Conclusion@#Extracellular Hsp70 participates in the activation of the CXCR4-dependent downstream signaling pathway in HNE cells. Further studies should evaluate the extracellular Hsp70-CXCL12/CXCR4 axis and the role of its components in the development of inflammatory diseases.

Subjective Gustatory Dysfunction Is Correlated With Subjective Olfactory Dysfunction in Geriatric Patients Regardless of Cognitive Function / 대한이비인후과학회지

Background and Objectives@#Fewer studies are available on geriatric patients’ gustatory dysfunction than on their olfactory dysfunction. Here we aimed to evaluate the relationship between subjective gustatory dysfunction and subjective or objective olfactory dysfunction according to cognitive function in geriatric patients.Subjects and Method We prospectively enrolled patients who underwent both cognitive function test and olfactory function test between August 2018 and May 2019. The correlation between subjective gustatory dysfunction and subjective olfactory dysfunction or conventional olfactory function scores was evaluated for geriatric patients with or withhout cognitive dysfunction. Participants with a threshold-discrimination-identification (TDI) score (<21) on the YSK olfactory function test were diagnosed with olfactory dysfunction. Subjective gustatory function and olfactory function were evaluated using the visual analog scale. The Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease Assessment Packet and Mini-Mental State Examination were administered to all participants. Overall, 120 patients (27 male, 93 female; mean age, 73.00±7.50 years) were enrolled. @*Results@#We found that the subjective gustatory function score did not correlate with the threshold, discrimination, identification, or the summation of TDI scores of the olfactory function test but was significantly associated with the subjective olfactory function score (p<0.001). Further, there was no significant correlation between the subjective gustatory function score and cognitive function. @*Conclusion@#The subjective olfactory function score was the only factor significantly correlated with the subjective gustatory function score. Based on these results, we suggest evaluating gustatory function in geriatric patients with olfactory dysfunction.

Impacted Foreign Body in the Anterior Nasal Cavity Presenting With Tooth Pain

Foreign bodies pose a diagnostic challenge to clinicians, and nasal foreign bodies have the potential to lead to significant morbidity. Although foreign bodies in the nasal cavity are a commonly encountered problem in pediatric patients, a foreign body in the nasal cavity not associated with a trauma history is rare in adults. We recently experienced a 35-year-old man who presented with a foreign body in his right nasal cavity and anterior tooth pain. He was not sure what the material was, and we were not able to confirm the material type preoperatively. However, we found that a very large and thick material was impacted and totally obstructed the right anterior nasal cavity. We surgically removed it as a bone block and confirmed postoperatively that the material was glass. This case provided several lessons, and we would like to share our experience.

The Sniffing Bead System as a Useful Diagnostic Tool for Olfactory Dysfunction in COVID-19 / 대한이비인후과학회지

We present a sniffing bead system used to diagnose olfactory dysfunction in coronavirus disease 2019 (COVID-19) patients. A 25-year-old male presented with the loss of olfaction one week after he was diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). He had no other symptoms such as fever or myalgia but only showed an absence of respiratory distress. Nasal endoscopy and paranasal sinus CT showed that the patient had no bilateral sinus diseases; cranial nerve MRI showed no abnormal signal intensity or enhancement. A sniffing bead system was applied using 2-phenylethyl alcohol for the objective assessment of olfactory dysfunction to confirm the presence of anosmia. Anosmia was diagnosed early by objective evaluation using a sniffing bead system and early intervention with olfactory training. This case report suggests that a verified, one-off system for objective measurement of olfactory dysfunction in COVID-19 with olfactory training in patients could facilitate the recovery of olfactory function.

Clinical Practice Guideline: Nasal Irrigation for Chronic Rhinosinusitis in Adults

The Korean Society of Otorhinolaryngology-Head and Neck Surgery and Korean Rhinologic Society appointed a guideline development group (GDG) to establish a clinical practice guideline, and the GDG developed a guideline for nasal irrigation for adult patients with chronic rhinosinusitis (CRS). The guideline focuses on knowledge gaps, practice variations, and clinical concerns associated with nasal irrigation. Nasal irrigation has been recommended as the first-line treatment for CRS in various guidelines, and its clinical effectiveness has been demonstrated through a number of studies with robust evidence. However, no guidelines have presented a consistent nasal irrigation method. Several databases, including OVID Medline, Embase, the Cochrane Library, and KoreaMed, were searched to identify all relevant papers using a predefined search strategy. When insufficient evidence was found, the GDG sought expert opinions and attempted to fill the evidence gap. Evidence-based recommendations for practice were ranked according to the American College of Physicians grading system. The committee developed 11 evidence-based recommendations. This guideline focuses on the evidence-based quality improvement opportunities deemed the most important by the GDG. Moreover, the guideline addresses whether nasal lavage helps treat CRS, what type of rinsing solution should be used, and the effectiveness of using additional medications to increase the therapeutic effect.

Removal of Knotted Nasogastric Tube: A Literature Review and Lessons From Our Case

Nasogastric tube placement is a common practice, and complications are rarely reported. We recently encountered and successfully managed a knotted nasogastric tube in a chronically bedridden patient. His nasal and nasopharyngeal mucosa were exceptionally dry, and the tube was not well advanced. The attending physician had difficulty removing the tube, and unsuccessful removal attempts resulted in the patient experiencing epistaxis and respiratory discomfort. Imaging and endoscopic evaluation revealed that the tube was knotted at the choanal level, obstructing the posterior airway. We cut the tube within the middle nasal cavity and removed the knotted part through the mouth; the remaining parts of the tube were removed through the nasal cavity. Herein, we describe our case and other previously reported cases of nasogastric tube knotting to guide healthcare workers who may encounter similar scenarios.

Correlations Between the Adenotonsillar Microbiome and Clinical Characteristics of Pediatric Patients With Snoring

Objectives@#. Few studies have reported combined analyses of the microbiome of the adenoids and tonsils in pediatric patients with snoring, and correlations of the adenotonsillar microbiome with clinical characteristics have not been evaluated to date. The aim of this study was to characterize the adenotonsillar microbiome and to determine its correlations with the subjective symptoms of pediatric patients with snoring and with levels of regional mucosal immune molecules. @*Methods@#. Twenty-four children who underwent tonsillectomy with adenoidectomy owing to snoring were enrolled in this cross-sectional study conducted between August 2017 and December 2018. The microbiome of the adenoids and tonsils was characterized, and its alpha- and beta-diversity was determined. Clinical characteristics, including subjective discomfort during sleep (assessed using the obstructive sleep apnea-18 questionnaire), the presence of allergic rhinitis, concentrations of heat shock protein (Hsp)27, Hsp70, and interleukin-8 (IL-8) in lavage fluids, and white blood cell (WBC) counts, were measured. @*Results@#. At the phylum level, the microbiome was not significantly different between the adenoids and tonsils; the alpha and beta indices were likewise not significantly different between these two regions. The alpha-diversity of the entire adenotonsillar microbiome was associated with sex, emotional stress, and IL-8 levels in the tonsil lavage fluids. Beta-diversity was associated with Hsp27 levels in the tonsil lavage fluids and WBC counts. Multiple allergen simultaneous test results were not significant, although total serum immunoglobulin E levels were significantly associated with the beta-diversity of the adenotonsillar microbiome. @*Conclusion@#. The data reported herein suggest, for the first time, that the adenotonsillar microbiome interacts with the regional mucosal immune system. The observed association of the microbiome with subjective discomfort is a novel finding that warrants further investigation.

Correlations Between the Adenotonsillar Microbiome and Clinical Characteristics of Pediatric Patients With Snoring

Objectives@#. Few studies have reported combined analyses of the microbiome of the adenoids and tonsils in pediatric patients with snoring, and correlations of the adenotonsillar microbiome with clinical characteristics have not been evaluated to date. The aim of this study was to characterize the adenotonsillar microbiome and to determine its correlations with the subjective symptoms of pediatric patients with snoring and with levels of regional mucosal immune molecules. @*Methods@#. Twenty-four children who underwent tonsillectomy with adenoidectomy owing to snoring were enrolled in this cross-sectional study conducted between August 2017 and December 2018. The microbiome of the adenoids and tonsils was characterized, and its alpha- and beta-diversity was determined. Clinical characteristics, including subjective discomfort during sleep (assessed using the obstructive sleep apnea-18 questionnaire), the presence of allergic rhinitis, concentrations of heat shock protein (Hsp)27, Hsp70, and interleukin-8 (IL-8) in lavage fluids, and white blood cell (WBC) counts, were measured. @*Results@#. At the phylum level, the microbiome was not significantly different between the adenoids and tonsils; the alpha and beta indices were likewise not significantly different between these two regions. The alpha-diversity of the entire adenotonsillar microbiome was associated with sex, emotional stress, and IL-8 levels in the tonsil lavage fluids. Beta-diversity was associated with Hsp27 levels in the tonsil lavage fluids and WBC counts. Multiple allergen simultaneous test results were not significant, although total serum immunoglobulin E levels were significantly associated with the beta-diversity of the adenotonsillar microbiome. @*Conclusion@#. The data reported herein suggest, for the first time, that the adenotonsillar microbiome interacts with the regional mucosal immune system. The observed association of the microbiome with subjective discomfort is a novel finding that warrants further investigation.

Pharmacologic therapy of olfaction disroders induced by COVID-19 upper respiratory infection

Postviral olfactory disorder refers to the sensorineural olfactory loss caused by upper respiratory tract infections. With the increasing awareness of olfactory or gustatory dysfunction as a potential early symptom of coronavirus disease 2019, postviral olfactory disorder has been attracting much attention. Postviral olfactory disorder is the most common type of olfactory disorder, especially among women aged over 50 years. Systemic or topical corticosteroids have commonly been used for treating this disorder, but the mechanism of corticosteroid action is unclear. Other medical treatment options such as alpha-lipoic acids and caroverine that stimulate nerve growth factor expression or prevent glutamatergic neurotoxicity have also been used. Although these drugs have been found to be useful in the treatment of postviral olfactory disorder in previous studies, the efficacy has not been statistically proven through a meta-analysis. Recently, olfactory training has been introduced in the treatment strategy for postviral olfactory disorder. It is a safe option without side effects that can be used for treating olfactory disorders caused by upper respiratory tract infections. Further rigorous studies are needed to determine the efficacy of the combination of drug treatment and olfactory training.

Olfactory Function Test for Early Diagnosis of Vascular Dementia / 가정의학회지

Olfactory impairment occurs in patients with Alzheimer’s disease, and olfactory function tests are performed for the diagnosis of Alzheimer’s disease. However, the diagnosis and patient status are not currently outlined for vascular dementia, and many physicians do not consider concurrent vascular dementia in patients complaining of olfactory dysfunction. Here, we report a case of vascular dementia with no symptoms of dementia other than olfactory dysfunction. This case suggested that the olfactory function test is helpful not only for the diagnosis of Alzheimer’s disease but also for the early diagnosis of vascular dementia.

Cut-Off Scores of an Olfactory Function Test for Mild Cognitive Impairment and Dementia

Objective@#We aimed to find the optimal cut-off scores for screening of odor detection threshold, odor discrimination, and odor identification tests for detection of mild cognitive impairment (MCI) and dementia in Korean elderly. @*Methods@#A total of 195 elderly people were divided into three groups: the normal cognition (NC), MCI, and dementia groups. All participants underwent neurocognitive and olfactory function tests. We used k-means cluster analysis and receiver operating characteristic (ROC) analysis to identify the most appropriate cut-off value. @*Results@#To distinguish the MCI from NC groups, odor identification [area under the curve (AUC)=0.670, p<0.007] with a cut-off point of 7 showed greater validity for screening (sensitivity/specificity=0.462/0.837) than did other olfactory function tests. To distinguish the MCI and dementia from NC as well, odor identification (AUC=0.817, p=0.002) with a cut-off point of 7 showed the highest validity for screening (0.785/0.654). To distinguish MCI from AD, an odor detection threshold (AUC=0.722, p=0.001) with a cut-off point of 2 showed the highest validity for screening (0.785/0.654). @*Conclusion@#Olfactory function tests may be a useful screening tool for cognitive decline before clinical symptoms of dementia have completely developed. This tool can be used as a supplementary tool to enhance the sensitivity of traditional cognitive tests to screen for dementia.

Nasal or Nasopharyngeal Tuberculosis Should be Considered in the Initial Diagnosis of Sino-Nasal Inflammatory Diseases

No abstract available.

Nasal Obstruction due to Fibrous Dysplasia Invading Inferior and Middle Turbinates: A Case Report and Literature Review / 대한이비인후과학회지

Fibrous dysplasia (FD) is a rare type of fibro-osseous lesion characterized by progressive replacement of normal bone with immature tissue. The involvement of craniofacial bones is reported in 10% of FD cases, while the involvement of sinonasal cavity is extremely rare. We report a unique case of FD in which the primary complaint was nasal obstruction. As FD cases involving the turbinate bones are very rare, we also reviewed all reported cases of FD involving the inferior or middle turbinates. Based on our experience and a review of the relevant literature, we conclude that inferior and/or middle turbinectomy via endoscopic approach and septoplasty can improve nasal symptoms.

Expression of CAIII and Hsp70 Is Increased the Mucous Membrane of the Posterior Commissure in Laryngopharyngeal Reflux Disease

PURPOSE: We tried to evaluate the difference in the expression of carbonic anhydrase (CA) III and heat shock protein (Hsp) 70 between laryngopharyngeal reflux disease (LPRD) and non-LPRD patients. MATERIALS AND METHODS: The study involved 28 patients who underwent laryngeal microsurgery due to benign laryngeal disease from March to August 2008. Reflux symptom index (RSI) and reflux finding score (RFS) were measured for each person, and they were assigned either to the LPRD group (n=10) or non-LPRD group (n=18). Tissue samples were obtained from the mucosa of posterior commissure, and immunohistochemistry (IHC) staining of CAIII and Hsp70 was performed. The IHC scores were measured and compared with clinical features including RSI and RFS. RESULTS: Total 10 patients were assigned as LPRD group, and 18 patients were as control group. The mean IHC score of CAIII and Hsp70 was 1.70+/-1.06 and 1.90+/-0.88, respectively, in LPRD patients, whereas the mean IHC score of CAIII and Hsp70 was 0.78+/-0.73 and 0.94+/-0.87, respectively, in non-LPRD patients. The difference between two groups was statistically significant (p<0.05). CONCLUSION: CAIII and Hsp70 expressions were higher in LPRD patients that in non-LPRD patients, suggesting the possibility as one of biomomarker in LPRD diagnosis.

Hypoxia Increases Epithelial Permeability in Human Nasal Epithelia

PURPOSE: The nasal mucosa is the first site to encounter pathogens, and it forms continuous barriers to various stimuli. This barrier function is very important in the innate defense mechanism. Additionally, inflammation of the nasal sinus is known to be a hypoxic condition. Here, we studied the effect of hypoxia on barrier function in normal human nasal epithelial (NHNE) cells. MATERIALS AND METHODS: The expression levels of various junction complex proteins were assessed in hypoxia-stimulated NHNE cells and human nasal mucosal tissues. We performed real-time polymerase chain reaction analysis, western blotting, and immunofluorescence assays to examine differences in the mRNA and protein expression of ZO-1, a tight junction protein, and E-cadherin in NHNE cells. Moreover, we evaluated the trans-epithelial resistance (TER) of NHNE cells under hypoxic conditions to check for changes in permeability. The expression of ZO-1 and E-cadherin was measured in human nasal mucosa samples by western blotting. RESULTS: Hypoxia time-dependently decreased the expression of ZO-1 and E-cadherin at the gene and protein levels. In addition, hypoxia decreased the TER of NHNE cells, which indicates increased permeability. Human nasal mucosa samples, which are supposed to be hypoxic, showed significantly decreased levels of ZO-1 and E-cadherin expression compared with control. CONCLUSION: Our results demonstrate that hypoxia altered the expression of junction complex molecules and increased epithelial permeability in human nasal epithelia. This suggests that hypoxia causes barrier dysfunction. Furthermore, it may be associated with innate immune dysfunction after encountering pathogens.

Clinical Features of Obstructive Sleep Apnea That Determine Its High Prevalence in Resistant Hypertension

PURPOSE: Resistant hypertension (HTN) occurs in 15-20% of treated hypertensive patients, and 70-80% of resistant hypertensive patients have obstructive sleep apnea (OSA). The characteristics of resistant HTN that predispose patients to OSA have not been reported. Therefore, we aimed to determine the clinical, laboratory, and polysomnographic features of resistant HTN that are significantly associated with OSA. MATERIALS AND METHODS: Hypertensive patients (n=475) who underwent portable polysomnography were enrolled. The patients were categorized into controlled (n=410) and resistant HTN (n=65) groups. The risk factors for the occurrence of OSA in controlled and resistant hypertensive patients were compared, and independent risk factors that are associated with OSA were analyzed. RESULTS: Out of 475 patients, 359 (75.6%) were diagnosed with OSA. The prevalence of OSA in resistant HTN was 87.7%, which was significantly higher than that in controlled HTN (73.7%). Age, body mass index, neck circumference, waist circumference, and hip circumference were significantly higher in OSA. However, stepwise multivariate analyses revealed that resistant HTN was not an independent risk factor of OSA. CONCLUSION: The higher prevalence and severity of OSA in resistant HTN may be due to the association of risk factors that are common to both conditions.

Neck Circumference and Lowest Oxygen Saturation Are Independently Associated with High Coexistence of Hypertension in Obstructive Sleep Apnea

PURPOSE: Obstructive sleep apnea (OSA) is considered an independent risk factor for hypertension. However, it is still not clear which clinical factors are related with the presence of hypertension in OSA patients. We aimed to find different physical features and compare the sleep study results which are associated with the occurrence of hypertension in OSA patients. MATERIALS AND METHODS: Medical records were retrospectively reviewed for patients diagnosed with OSA at Severance Cardiovascular Hospital between 2010 and 2013. Males with moderate to severe OSA patients were enrolled in this study. Clinical and polysomnographic features were evaluated to assess clinical variables that are significantly associated with hypertension by statistical analysis. RESULTS: Among men with moderate to severe OSA, age was negatively correlated with hypertension (odds ratio=0.956), while neck circumference was positively correlated with the presence of hypertension (odds ratio=1.363). Among the polysomnographic results, the lowest O2 saturation during sleep was significantly associated with the presence of hypertension (odds ratio=0.900). CONCLUSION: Age and neck circumference should be considered as clinically significant features, and the lowest blood O2 saturation during sleep should be emphasized in predicting the coexistence or development of hypertension in OSA patients.

A Case of Multiple Complications after Treatment in Patients with the Second Primary Nasopharyngeal Cancer / 대한이비인후과학회지

Due to anatomic restrictions and presentation with advanced local-regional diseases, radiotherapy has provided the standard of care for nasopharyngeal cancer. Although the local recurrence after curative radiation therapy has been often reported in the literature, reports of changes in the histopathologic findings of the tumor in the nasopharyngeal carcinoma are rare. Due to limitation in surgical treatment of nasopharyngeal carcoma, radiotherapy has been standard treatment for nasopharyngeal carcinoma. We present a case of multiple complications after radiotherapy in patients with the second primary nasopharyngeal cancer following a change in the histopathologic findings.

Application of experion(TM) assay system for discovery of ovarian cancer serum biomarkers / 대한산부인과학회지

OBJECTIVE: The discovery of new biomarkers for ovarian cancer is clearly necessary for the detection and monitoring of the disease. Experion(TM) automated electrophoresis system can be employed in the identification of differentially expressed proteins in cancer cells. The objective of this study was to discover potential diagnostic serological biomarkers for ovarian cancer. METHODS: We performed protein expression difference analyses for 14 healthy women and 28 ovarian cancer patients with stage I, III and IV using Experion(TM) system. And then we checked the protein expression as silver staining after loading at 8~16% gradient gel for comparison with Experion(TM) gel image. The candidate biomarkers were purified and determined using MALDI-TOF mass spectrometer. RESULTS: The distinctive polypeptide peaks were detected at 115.40, 15.96, 14.8, 11.66, and 10.69 kDa and these five peaks were identified as ceruloplasmin, hemoglobin beta chain, hemoglobin sigma chain, serum amyloid A4, and amyloid related serum protein SAA, respectively. These proteins were significantly different between the sera of normal healthy women and ovarian cancer patients. CONCLUSIONS: Five proteins were found to be significantly different between the sera of normal healthy women and ovarian cancer patients. In addition, Experion(TM) assay system can provide high performance for analysis of ovarian cancer-related proteins by increasing the throughput while maintaining a high level of accuracy.

Genomic gain and loss of cervical cancer using BAC Chip / 대한산부인과학회지

OBJECTIVE: Cervical cancer has long been linked to the sexually transmitted human papillomavirus (HPV), and the oncoproteins E6 and E7 disrupt the functions of tumour suppressor genes, resulting in genetic alteration. It was shown that loss of heterozygosity at 6p is a common genetic alteration in cervical cancer. However, the molecular genetics of cancer have only recently been understood, and for the development of cervical cancer additional genetic alterations in host cell genes are required. The present study has identified the differential changes of the cervical cancer-associated genetic alterations by a genome-wide array based comparative genomic hybridization (array-CGH). METHODS: We analyzed 15 cases of cervical cancer from St. Mary's hospital of The paraffin-fixed tissue samples were microdissected under microscope and DNA was extracted by the procedures of proteinase K digestion and chloroform extraction. Array-based CGH and genomic PCR were carried out with statistical analyses such as hierarchical clustering and Gene Ontology. The BAC array used in this study consisted of 1,440 human BACs, the space among the clones were approximately 2.08 megabase (Macrogen, Seoul, Korea). RESULTS: All of 15 cases of cervical cancer showed specific gains and losses. The analysis limit of average gains and losses was 53%. A significant positive correlation was found between 1p36.32, 3p14.2, 3q27.1, 7p21.1, 8q24.3 and 11q13.1 changes through the cervical carcinogenesis. The high-level of gain regions, BAC clones encoded GSDMDC1, RECQL4, TP73, ABCF3, ALG3, HDAC9, ESRRA and RPS6KA4 genes. Frequently gained BAC clones encoded genes were PRSS8, FUS, COL18A1, PCOLN3, MAFG and ASPSCR1. The genes encoded by frequently lost BAC clones were PTPRG, GRM7, ZDHHC3, EXOSC7, LRP1B and NR3C2. Also, hierarchical clustering of the expression data readily distinguished genomic alterations in cervical cancer. A subset of cellular processes from each gene was clustered by Gene Ontology database. CONCLUSION: Using Array-CGH, genomic alterations related to cervical cancer were identified to determine whether induction of chromosomal imbalances occurs prior to carcinogenesis. The high resolution of array-CGH combined with human genome database would give a chance to find out possible target genes present in the gained or lost clones.