Consensus Statements on the Definition, Classification, and Diagnostic Tests for Tinnitus: A Delphi Study Conducted by the Korean Tinnitus Study Group

Background@#Tinnitus is a bothersome condition associated with various symptoms. However, the mechanisms of tinnitus are still uncertain, and a standardized assessment of the diagnostic criteria for tinnitus is required. We aimed to reach a consensus on diagnosing tinnitus with professional experts by conducting a Delphi study with systematic review of the literature. @*Methods@#Twenty-six experts in managing tinnitus in Korea were recruited, and a two-round modified Delphi study was performed online. The experts evaluated the level of agreement of potential criteria for tinnitus using a scale of 1–9. After the survey, a consensus meeting was held to establish agreement on the results obtained from the Delphi process. Consensus was defined when over 70% of the participants scored 7–9 (agreement) and fewer than 15% scored 1–3 (disagreement). To analyze the responses of the Delphi survey, the content validity ratio and Kendall’s coefficient of concordance were evaluated. @*Results@#Consensus was reached for 22 of the 38 statements. For the definition of tinnitus, 10 out of 17 statements reached consensus, with three statements achieving complete agreement including; 1) Tinnitus is a conscious perception of an auditory sensation in the absence of a corresponding external stimulus, 2) Tinnitus can affect one’s quality of life, and 3) Tinnitus can be associated with hearing disorders including sensorineural hearing loss, vestibular schwannoma, Meniere’s disease, otosclerosis, and others. For the classification of tinnitus, 11 out of 18 statements reached consensus. The participants highly agreed with statements such as; 1) Vascular origin is expected in pulse-synchronous tinnitus, and 2) Tinnitus can be divided into acute or chronic tinnitus. Among three statements on the diagnostic tests for tinnitus only Statement 3, “There are no reliable biomarkers for sensory or emotional factors of tinnitus.”reached consensus. All participants agreed to perform pure-tone audiometry and tinnitus questionnaires, including the Tinnitus Handicap Inventory and Tinnitus Questionnaire. @*Conclusion@#We used a modified Delphi method to establish a consensus-based definition, a classification, and diagnostic tests for tinnitus. The expert panel reached agreement for several statements, with a high level of consensus. This may provide practical information for clinicians in managing tinnitus.

Difference Between the Preferred Gain and the NAL-NL2 Gain in Korean Hearing Aid Users / 대한이비인후과학회지

Background and Objectives@#The purpose of this study was to compare the preferred gain and the National Acoustic Laboratories Nonlinear 2nd edition (NAL-NL2) gain value in Korean language hearing aid users.Subjects and Method In this retrospective study, preferred gain and NAL-NL2 gain data were obtained from 199 monaural hearing aids users who were satisfied with their hearing aid devices. The gain value data were collected from three different sound levels at various frequencies. Several factors were also evaluated to determine a potential impact on the preferred gain. @*Results@#The preferred gain was significantly higher than the NAL-NL2 target gain (p=0.01). This difference was highest with the gain measured with a medium-level sound (65 dB) with 1 kHz tone. There was a tendency of reduced preferred gain with the increased age of the participant (p=0.049). @*Conclusion@#The results indicate that Korean hearing aid users require more gain than the NAL-NL2 target gain. Linguistic characteristics, age, degree of hearing loss, and many other factors may be implicated in this result.

Clonazepam Usage Improves Chronic Tinnitus and Sleep Quality: A Prospective Cohort Study / 대한이비인후과학회지

Background and Objectives@#Tinnitus, although being a common chronic disease, can be an intractable disease that causes depression and insomnia. This study aimed to analyze the results of the Tinnitus Handicap Inventory (THI), Beck Depression Inventory (BDI), and Pittsburgh Sleep Quality Index (PSQI) questionnaire surveys before and after clonazepam therapy. In addition, we analyzed the association of three pre-treatment questionnaires and evaluated whether pre-treatment factors could predict the post-treatment THI index.Subjects and Method Patients were selected from those who visited a tertiary hospital from 2019 to 2021 for the treatment of chronic tinnitus they had for more than 3 months and who were over 20 years old. Patients were excluded from the study if they were diagnosed with acute sudden hearing loss, Meniere’s disease, brain/internal auditory canal tumors, or muscular/vascular tinnitus. The questionnaire surveys of THI, BDI, PSQI were conducted before and after 3 months of clonazepam therapy (Rivotril [Roche Inc.] 0.25 or 0.5 mg). Questionnaire scores were compared using the paired t-test. Multiple regression analysis was used to determine the relationships among the three questionnaires. @*Results@#A total of 76 patients (38 males and 38 females) with the mean age of 57.2±9.01 years was analyzed. The average hearing threshold was 30.4±20.67 dB HL on the right and 31.7±17.06 dB HL on the left. The pre-treatment THI, BDI, and PSQI scores were 44.3±23.4, 7.96±2.36, and 6.85±4.68, respectively. The relationships between the THI and BDI and the THI and PSQI were significant (p=0.0027 and p<0.0001, respectively). The pre-THI score showed no significant association with age, sex, or hearing threshold (p=0.91, 0.85, and 0.23, respectively). The post-treatment THI score was 33.6±17.1, which was significantly lower than the pre-THI scores (p<0.0001). Post-BDI and post-PSQI were 7.38±2.25 and 4.04±3.20, respectively. Post-PSQI also significantly decreased compared with pre-PSQI (p=0.0002), but post-BDI did not significantly decrease (p=0.1231). In the THI survey, Question 7 (sleep disturbance) showed decrease the most, followed by Question 25 (unstable mood). The post-treatment THI could be predicted by using the formula, 0.7673+0.6947×pre-THI+0.3572×pre-PSQI. @*Conclusion@#The appropriate/optional use of clonazepam at low doses (0.25-0.5 mg) can significantly improve chronic tinnitus and sleep quality. Tinnitus was significantly associated with the scores of THI, BDI, PSQI and the usage of Clonazepam significantly reduced the THI and PSQI scores. However, clonazepam did not affect the BDI score.

Change in Self-Evaluation of Hearing Status According to Age: A Population-Based Study / 대한이비인후과학회지

Background and Objectives@#Self-reported hearing levels determined by self-report questionnaires are not always correlated with the audiometric hearing level. It is necessary to ascertain the subjectively perceived normal hearing threshold to determine the need for hearing aids at the appropriate time. The objective is to identify the level of correlation between the self-reported hearing level and the audiometric hearing level and ascertain the subjectively perceived normal hearing threshold for each age group.Subjects and Method This cross-sectional study, using the data from the Korea National Health and Nutrition Examination Survey V, looked at participants with hearing loss who were aged ≥40 years. Pure tone audiometry was conducted bilaterally. Self-reported hearing level was ascertained via survey enquiring about hearing loss. The level of correlation between self-reported hearing level and audiometric hearing level, age-specific patterns of hear-ing self-evaluation and subjectively perceived normal hearing values at which participants complained of hearing loss were main outcomes. @*Results@#Mean audiometric thresholds (MATs) increased with the age and degree of self-reported hearing level. The accuracy of self-reported hearing level compared to the audiometric threshold decreased with age both in the better-ear and worse-ear groups. Younger participants tended to overestimate their hearing impairment, while older participants tended to underestimate it. Subjectively perceived normal hearing thresholds increased with age and they were very close to the MATs for each age group. @*Conclusion@#Results can be useful for devising different age-group specific pure tone audi-ometry-based diagnostic criteria for self-reported hearing loss, which can be used to determine the need for hearing aid in a timely manner.

Cognitive Behavioral Therapy in Korean Tinnitus Patients / 대한이비인후과학회지

Cognitive behavioral therapy, first introduced by Beck in the 1950s to treat depression by integrating cognitive and behavioral therapies, is now an established psychotherapy technique used to treat insomnia, chronic pain, and anxiety. Currently, cognitive behavioral therapy is widely used to treat tinnitus in European countries, and the efficacy and safety of the treatment have been proven through randomized clinical trials and meta-analyses. Although interest in cognitive behavioral therapy for tinnitus is increasing in Korea, there are limited reports. Because many studies so far have targeted patients in Western countries, it is difficult to apply the same to domestic patients due to cultural and linguistic differences, the absence of standardized guidelines, and limitations in clinic hours. We experienced various cases in which tinnitus was effectively treated simultaneously with pharmacotherapy and cognitive behavioral therapy, so here we report an introduction to the program along with a literature review. Cognitive behavioral therapy was performed as a 4-week program in our hospital, and progress was evaluated through Visual Analogue Scales (VAS) and tinnitus handicap inventory (THI). After each weekly 20-minute individual counseling session, a take-home writing task was given to the patient. The main goal was to guide the patient to discover and correct automatic thoughts related to their tinnitus symptoms. This paper aimed to introduce a specific scheme on how to perform cognitive behavioral therapy for domestic tinnitus patients.

Sleep Disorder in Tinnitus Patients / 대한이비인후과학회지

Background and Objectives@#One of the most common complaint of tinnitus patients has been sleep disorder. The aim of this study was to evaluate the relationship between sleep disorder and tinnitus.Subjects and Method Patients with tinnitus from July 2018 till August 2019 were enrolled. Subjects who had any acute/chronic disease in the inner and middle ear or external auditory canal, sleep apnea and had more than 3 caffeinated beverages a day was excluded. Study participants completed Beck Depression Inventory (BDI), the tinnitus symptom questionnaire, tinnitus handicap inventory (THI), Pittsburg Sleep Quality Inventory (PSQI), pure tone audiometry, a full otologic examination and an interview on past medical history. @*Results@#THI was correlated with PSQI global score and BDI. The PSQI subscale most relevant to THI was PSQI 1 (subjective sleep quality). Hearing impairment was correlated with the THI functional subscale. BDI was individually related to PSQI. @*Conclusion@#Tinnitus is found to be highly related to sleep disorder, suggesting a common pathway of aggravation and treatment target. Tinnitus is also more affected by sleep disorder than by depression. A further examination and treatment of comorbid sleep disorder in tinnitus patients is recommended.

Tumor Necrosis Factor-Alpha and Interleukin-4 Levels in Patients With Idiopathic Sudden Sensorineural Hearing Loss / 대한이비인후과학회지

Background and Objectives@#The pathogenesis of idiopathic sudden sensorineural hearing loss (ISSNHL), an otologic emergency disease, remains unclear. Several studies have attempted to illustrate the association between cytokines and ISSNHL. The purpose of this study was to evaluate the prognostic significance of various cytokines in patients with ISSNHL. Subjects and Method In this case-control study, a total of 55 patients with ISSNHL underwent treatment with oral prednisolone for 2 weeks. Serum cytokine levels, including interleukins (ILs) (IL-1a, IL-1b, IL-2, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12), and tumor necrosis factors (TNF-α and TNF-β), were measured using human cytokine panels at first visit. Patient characteristics such as age, gender, the status of hypertension, diabetes mellitus, vertigo, time from onset to visit, and initial hearing levels were also evaluated. @*Results@#Serum levels of cytokines were correlated with the prognosis of ISSNHL patients. IL-4 ≥0.225 (pg/mL) and TNF-α ≥5.155 (pg/mL) were significantly associated with poor therapeutic outcomes (OR=44.317, p=0.015 and OR=269.465, p=0.006, respectively). In addition, age and initial hearing levels were also significant prognostic factors. @*Conclusion@#Patients’ age, initial hearing levels, and serum levels of IL-4 and TNF-α prior to treatment are associated with hearing recovery and can be used as prognostic factors for patients with ISSNHL.

Effects of Amniotic Membrane Extract on the Hyperplastic Response of the Middle Ear Mucosa in a Bacterially-Induced Otitis Media Rat Model: A Preliminary Study

Objectives@#. Human amniotic membrane extract (AME) is known to contain numerous bioactive factors and anti-inflammatory substances. However, the anti-inflammatory effects of AME on the middle ear (ME) mucosa are unclear. This study assessed the effects of AME on the growth of the ME mucosa in response to bacterially-induced otitis media (OM). @*Methods@#. OM was induced by inoculating nontypeable Haemophilus influenzae (NTHi) into the ME cavity of rats. ME mucosal explants were cultured in AME concentrations of 0, 5, 10, or 50 μg/mL. The area of explant outgrowth was measured in culture and analyzed at 1, 3, 5, and 7 days after explantation. The expression of Ki-67, mucin 5AC (MUC5AC), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10) in the explants was also evaluated using quantitative polymerase chain reaction (PCR) and immunocytochemistry (ICC). @*Results@#. The NTHi-induced ME mucosa growth increased gradually over the 7-day culture period in all explants at different AME concentrations. There was a trend for mucosal growth inhibition at higher concentrations of AME, although the growth was not significantly different among the groups until day 5. The ME mucosal explants treated with the 50 μg/mL concentration of AME showed significantly suppressed growth on postexplantation day 7 compared with other explants on the same day. PCR and ICC staining revealed that the expression of Ki-67, MUC5AC, TNF-α, and IL-10 further decreased in the explants with higher concentrations of AME than in those with lower concentrations of AME. @*Conclusion@#. Our results showed that higher concentrations of AME reduced the mucosal proliferative response in bacterial OM in rats. These findings provide evidence that AME has an influence on the inflammatory and proliferative responses to NTHi infection in ME mucosa.

Comparison of Functional Outcomes after PoweredIntracapsular Tonsillectomy with Adenoidectomy andConventional Extracapsular Tonsillectomy withAdenoidectomy for Pediatric Obstructive Sleep Apnea / 대한이비인후과학회지

Background and Objectives@#This study was investigated to compare the clinical outcomes and complications of powered intracapsular tonsillectomy and adenoidectomy (PITA) with those of conventional extracapsular tonsillectomy and adenoidectomy (ECTA) in treatment of pediatric obstructive sleep apnea (OSA).Subjects and Method Eighty-one children with adenotonsillar hyperplasia underwent tonsillectomy and adenoidectomy (46 PITA and 35 ECTA) from December 2016 to July 2017 for OSA. The choice of surgical procedure (PITA vs. ECTA) was determined by the number of episodes of acute tonsillitis. The quality of life measurement was performed using Korean Obstructive Sleep Apnea Survey (KOSA-18) score. Postoperative bleeding was assessed as number of revisit or readmission. Postoperative pain was evaluated by visual analog scale (VAS) at postoperative day 1, 3, and 7. @*Results@#PITA and ECTA significantly reduced KOSA-18 scores postoperatively (p＜0.01, p＜0.01, respectively) and were equally effective in pediatric OSA treatment. Postoperative bleeding was lower in the PITA group, but there was no statistical difference due to small number of cases. VAS score for postoperative pain was significantly lower in the PITA group at day 1, 3, and 7 (p=0.03, p＜0.01, and p＜0.01, respectively). @*Conclusion@#PITA is effective in pediatric OSA treatment with less morbidity, and less complications.

Virtual Reality for Vestibular Rehabilitation

No abstract available.

The Study of Standardization for a Korean Dizziness Handicap Inventory for Patient Caregivers / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Several questionnaires had been developed to assess the handicap due to dizziness. The questionnaires for adults were used and these had been translated into Korean with validity and reliability. However, there is no Korean translation of dizziness inquiry form owing to the little concern of the pediatric dizziness. The objective of this study was to determine the reliability and validity of a Korean Dizziness Handicap Index for Patient Caregivers (KDHI-PC), and revealed the factor analysis of this index. SUBJECTS AND METHOD: We sampled the 24 pediatric patients who had dizziness-related symptoms and visited the hospitals. The patients completed a questionnaire (DHI-PC) that had been translated and reverse translated into Korean. The results of this investigation were analyzed using exploratory factor analysis, Cronbach's α coefficient and internal consistency reliability. RESULTS: By exploratory factor analysis, KDHI-PC was divided into two scales. This questionnaire showed a good internal consistency (Cronbach's α=0.945). All items had good item-total correlations. CONCLUSION: The KDHI-PC is a reliable tool for evaluating the dizziness of pediatric patients.

The Study of Standardization for a Korean Dizziness Handicap Inventory for Patient Caregivers / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES@#Several questionnaires had been developed to assess the handicap due to dizziness. The questionnaires for adults were used and these had been translated into Korean with validity and reliability. However, there is no Korean translation of dizziness inquiry form owing to the little concern of the pediatric dizziness. The objective of this study was to determine the reliability and validity of a Korean Dizziness Handicap Index for Patient Caregivers (KDHI-PC), and revealed the factor analysis of this index.SUBJECTS AND METHOD: We sampled the 24 pediatric patients who had dizziness-related symptoms and visited the hospitals. The patients completed a questionnaire (DHI-PC) that had been translated and reverse translated into Korean. The results of this investigation were analyzed using exploratory factor analysis, Cronbach's α coefficient and internal consistency reliability.@*RESULTS@#By exploratory factor analysis, KDHI-PC was divided into two scales. This questionnaire showed a good internal consistency (Cronbach's α=0.945). All items had good item-total correlations.@*CONCLUSION@#The KDHI-PC is a reliable tool for evaluating the dizziness of pediatric patients.

Development of the Suicide Risk Scale for Medical Inpatients

BACKGROUND: Inpatient suicide is one of the major issues related with hospital patient safety. Although there are many studies addressing suicide in the psychiatric unit, little is known about suicide in a medical setting. This study included the development and validation of a screening tool for the assessment of suicide risk, specialized for medical inpatients. METHODS: The preliminary questionnaire was based on review of previous suicide ideation scales, mood scales, and clinical experiences of psychiatrists and clinical psychologists in Korea. Initially, the questionnaire consisted of 12 questions. One hundred adult medical inpatients were asked to perform the questionnaire. Explorative factor analysis was used to examine construct validity. Concurrent validity was evaluated by comparison with the Korean versions of the Beck Scale for Suicide Ideation (BSI), the Beck Hopelessness Scale (BHS), and the Hospital Anxiety and Depression Scale (HADS). RESULTS: Five questions were removed from the preliminary questionnaire by explorative factor analysis and seven questions remained to comprise the Suicide Risk Scale for Medical inpatients (SRSM). Explorative factor analysis showed that the SRSM is composed of a single factor. SRSM was highly reliable in terms of internal consistency (Cronbach's alpha 0.91). Concurrent validity with the BSI, BHS, and HADS was statistically significant. The proposed cut-off score of the SRSM was five. CONCLUSION: In conclusion, the SRSM is a valid and reliable measure for screening suicide risks in medical inpatients.

Pulsatile Tinnitus Related with Prominent Venous Plexus: Case Report and Literature Review / 대한이비인후과학회지

Pulsatile tinnitus coexists with patient's heartbeat and objective tinnitus is audible to other persons such as examiner. It can be disagreeable for the patient and can also be the only clue to a potentially devastating and life-threatening disease. Pulsatile tinnitus with a normal otoscopic examination often presents a diagnostic challenge, and its differential diagnosis includes a wide range of conditions. Evaluation of a patient with tinnitus requires a detailed history, a comprehensive audiological evaluation with hearing thresholds, neuro-otological physical examination with otoscopy and imaging studies. We recently experienced a case of a 28-year-old male complaining of right-sided pulsatile tinnitus. The tinnitus was objectively audible at the left side of the posterior neck. Non-contrast enhanced computed tomography of temporal bone showed a high jugular bulb on the left side. A 6-vessel angiography showed prominent left paravertebral venous plexus and prominent venous plexus around the skull base.

Analysis of Fall Accidents of Dizzy Patients in a Tertiary Hospital in South Korea (2011-2015) / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: A fall refers to a sudden fall accident resulting in injury and hurt of the human body. In the hospital, fall accidents occur mainly in dizzy patients or elderly people, but can also occur even in young people who fail to adapt to the unfamiliar hospital environment. This study analyzed the incidence of fall accidents and its pattern in dizzy patients in a tertiary hospital in South Korea. SUBJECTS AND METHOD: This study was conducted using 477 fall accidents that occurred in a tertiary hospital in Korea from 2011 to 2015. Extensively investigated were related fall risk factors such as patient's sex, age, medical department, diagnosis, first witness, mental status, physical activity, patient risk factors, walking aids, medication use and treatment. RESULTS: Dizziness induced falls consisted of 20.5% of the total fall accidents. Sedative medications were frequently used in patients of dizziness induced falls (42.9%). Fall acidents were mainly detected by nurses 33%. The frequente sites of fall were the bed rooms (55%), the corridor (15%) or the bath rooms (8%). Types of physical damage were no damage (47%), abrasion or bruising (20%), laceration (10%), bath rooms (8%), fracture (3%), and head trauma (1%). In 532 treatments, observation was recommended for 68%, sterilization 15.2%, suture 4.7%, cast 1%, and surgery 1%. CONCLUSION: The study finds that the fall risk screening test and Multifactorial Fall Prevention Program should be performed for all high-risk patients of fall. About 20% of falls were associated with otologic dizziness, and otolaryngology doctors should pay attention to the fall problem and the medication related to dizziness, which may potentially increase the risk of falls.

Analysis of Eustachian Tube Dysfunction by Dynamic Slow Motion Video Endoscopy and Eustachian Tube Dysfunction Questionnaire in Chronic Otitis Media

OBJECTIVES: Eustachian tube dysfunction has been associated with most cases of middle-ear disease. We aimed to assess the effectiveness of dynamic slow motion video endoscopy (DSVE) as a test of eustachian tube dysfunction. Furthermore, we assessed the correlation of the test with the Valsalva maneuver, the seven-item Eustachian Tube Dysfunction Questionnaire (ETDQ-7), and intraoperative findings of the eustachian tube. METHODS: We retrospectively reviewed medical records from April to September 2014 to identify patients who were diagnosed with chronic otitis media (COM) at Korea University Ansan Hospital. They all underwent surgery because of COM without cholesteatoma and were assessed via the DSVE and ETDQ-7 to determine eustachian tube function. RESULTS: We reviewed 46 COM patients and examined 46 ears with COM and 46 ears on the contralateral side to COM that were thought to be normal. The mean DSVE grade in COM ears was 1.57±0.96, while the mean DSVE grade in contralateral ears was 1.15±0.94. The difference in DSVE between COM ears and normal ears was statistically significant (P=0.006). In the ETDQ-7, a higher score was related to intraoperative obstruction of the eustachian tube (P=0.012). CONCLUSION: DSVE and ETDQ-7 can provide information regarding preoperative status of eustachian tube dysfunction by measuring dynamic structural changes of the eustachian tube in combination with other diagnostic tests.

Asian Sand Dust Enhances the Inflammatory Response and Mucin Gene Expression in the Middle Ear

OBJECTIVES: Asia sand dust (ASD) is known to cause various human diseases including respiratory infection. The aim of this study was to examine the effect of ASD on inflammatory response in human middle ear epithelial cells (HMEECs) in vitro and in vivo. METHODS: Cell viability was assessed using the cell counting kit-8 assay. The mRNA levels of various genes including COX-2, TNF-a, MUC 5AC, MUC 5B, TP53, BAX, BCL-2, NOX4, and SOD1 were analyzed using semiquantitative realtime polymerase chain reaction. COX-2 protein levels were determined by western blot analysis. Sprague Dawley rats were used for in vivo investigations of inflammatory reactions in the middle ear epithelium as a result of ASD injection. RESULTS: We observed dose-dependent decrease in HMEEC viability. ASD exposure significantly increased COX-2, TNF-a, MUC5AC, and MUC5B mRNA expression. Also, ASD affected the mRNA levels of apoptosis- and oxidative stress-related genes. Western blot analysis revealed a dose-dependent increase in COX-2 production. Animal studies also demonstrated an ASD-induced inflammatory response in the middle ear epithelium. CONCLUSION: Environmental ASD exposure can result in the development of otitis media.

Analysis of Bacterial Biofilms on a Cochlear Implant Following Methicillin-Resistant Staphylococcus Aureus Infection

To demonstrate biofilm formations on a cochlear implant magnet of a pediatric patient suffering from a methicillin-resistant Staphylococcus aureus (MRSA) infection. The appearance of biofilm colonies was analyzed on different magnet sections. The appearance of MRSA biofilms on the surface of an explanted cochlear implant was analyzed by scanning electron microscopy (SEM), focusing on the pattern of extracellular polymeric substances (EPS) within the biofilms. SEM revealed unique biofilms with a three-dimensional EPS complex and tower-like formations. Biofilm configurations changed from the margin to the center of the magnet. Biofilms were solitary and scattered at the margin; large and plate-like in the center; and stacked in layers, forming towers and water channels, in the middle region. After a MRSA infection, biofilm formations were observed on the surface of a magnet. Bacterial biofilms provide optimal conditions for bacterial growth and antibiotic resistance and can cause intractable infections that lead to device failure.

Microarray Analysis of Gene Expression Alteration in Human Middle Ear Epithelial Cells Induced by Asian Sand Dust

OBJECTIVES: The primary aim of this study is to evaluate the gene expression profile of Asian sand dust (ASD)-treated human middle ear epithelial cell (HMEEC) using microarray analysis. METHODS: The HMEEC was treated with ASD (400 microg/mL) and total RNA was extracted for microarray analysis. Molecular pathways among differentially expressed genes were further analyzed. For selected genes, the changes in gene expression were confirmed by real-time polymerase chain reaction. RESULTS: A total of 1,274 genes were differentially expressed by ASD. Among them, 1,138 genes were 2 folds up-regulated, whereas 136 genes were 2 folds down-regulated. Up-regulated genes were mainly involved in cellular processes, including apoptosis, cell differentiation, and cell proliferation. Down-regulated genes affected cellular processes, including apoptosis, cell cycle, cell differentiation, and cell proliferation. The 10 genes including ADM, CCL5, EDN1, EGR1, FOS, GHRL, JUN, SOCS3, TNF, and TNFSF10 were identified as main modulators in up-regulated genes. A total of 11 genes including CSF3, DKK1, FOSL1, FST, TERT, MMP13, PTHLH, SPRY2, TGFBR2, THBS1, and TIMP1 acted as main components of pathway associated with 2-fold down regulated genes. CONCLUSION: We identified the differentially expressed genes in ASD-treated HMEEC. Our work indicates that air pollutant like ASD, may play an important role in the pathogenesis of otitis media.

Protective Effect of Hexane and Ethanol Extract of Piper Longum L. on Gentamicin-Induced Hair Cell Loss in Neonatal Cultures

OBJECTIVES: Gentamicin (GM) is a commonly used aminoglycoside antibiotic that generates free oxygen radicals within the inner ear, which can cause vestibulo-cochlear toxicity and permanent damage to the sensory hair cells and neurons. Piper longum L. (PL) is a well-known spice and traditional medicine in Asia and Pacific islands, which has been reported to exhibit a wide spectrum of activity, including antioxidant activity. In this study, we evaluated the effect of hexane:ethanol (2:8) PL extract (subfraction of PL [SPL] extract) on GM-induced hair cell loss in basal, middle and apical regions in a neonatal cochlea cultures. METHODS: The protective effects of SPL extract were measured by phalloidin staining of cultures from postnatal day 2-3 mice with GM-induced hair cell loss. The anti-apoptosis activity of SPL extract was measured using double labeling by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and myosin-7a staining. The radical-scavenging activity of SPL extract was assessed using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. RESULTS: SPL extract at a concentration of 1 microg/mL significantly inhibited GM-induced hair cell loss at basal and middle region of cochlea, while 5 microg/mL was effective against apical region hair cell loss. The protective effect of SPL extract was concentration dependent and hair cells retained their stereocilia in explants treated with SPL extract prior to treatment with 0.3 mM GM. SPL extract decreased GM-induced apoptosis of hair cells as assessed by TUNEL staining. The outer hair and inner hair counts were not decreased in SPL extract treated groups in compare to GM treated explants. Additionally, SPL extract showed concentration dependent radical scavenging activity in a DPPH assay. CONCLUSION: An anti-apoptosis effect and potent radical scavenger activity of SPL extract protects from GM-induced hair cell loss at basal, middle and apical regions in neonatal cochlea cultures.