Higher exposure to 1,3-butadiene is associated with more severe hearing loss.

While volatile organic compounds (VOCs) impair various organs, their influence on hearing loss (HL) has not been extensively researched. We aimed to identify the association between VOCs and HL or high-frequency hearing loss (HFHL). We extracted data on age, sex, pure tone audiometry, hypertension, occupational noise exposure, and creatinine-corrected urine VOC metabolite concentrations from the eighth Korea National Health and Nutrition Survey. Among the VOC metabolites, N-acetyl-S-(benzyl)-L-cysteine (BMA, P = 0.004), N-acetyl-S-(phenyl)-L-cysteine (SPMA, P = 0.027), and N-acetyl-S-(3,4-dihydroxybutyl)-L-cysteine (DHBMA, P < 0.001) showed associations with HL. Additionally, HFHL exhibited significant associations with BMA (P = 0.005), 3- and 4-methylhippuric acid (3, 4 MHA, P = 0.049), mandelic acid (MA, P = 0.015), SPMA (P < 0.001), N-acetyl-S-(3-hydroxypropyl)-L-cysteine (3-HPMA, P < 0.001), and DHBMA (P < 0.001). After controlling other factors, DHBMA were associated with HL (P = 0.021) and HFHL (P = 0.014) and exhibited a linear association with the mean hearing level (ß = 0.054, P = 0.024) and high-frequency hearing level (ß = 0.045, P = 0.037). Since 1,3-butadiene may act as an ototoxic material, early screening for workers exposed to 1,3-butadiene and reducing exposure to 1,3-butadiene in everyday life may be helpful to prevent further HL.

Nationwide Prevalence of Video Head Impulse Test Abnormality and its Risk Factors in South Korea.

OBJECTIVE: To identify the prevalence of and relevant information for video head impulse test (vHIT) abnormality in a large population. STUDY DESIGN: A cross-sectional design. SETTING: Korean National Health and Nutrition Examination Survey, 2021. METHODS: The sample was representative of the Korean population, with 2237 participants aged ≥40 years. A vHIT was performed to evaluate vestibular function. The vestibulo-ocular reflex (VOR) gain and the presence of reproducible catch-up saccades was assessed in a vHIT. Participants also completed questionnaires for demographics, socioeconomic status, and basic information regarding systemic diseases and dizziness and underwent hearing tests with automated pure-tone audiometry. RESULTS: The prevalence of vHIT abnormality was 22.5%, with unilateral (14.3%) being more common than bilateral (8.2%). The prevalence of vHIT abnormality increased significantly with age, with the highest rate observed in individuals aged >70 years (42.5%). Both hearing and VOR gain deteriorated with age, but the patterns of age-related progression were different. While hearing loss (HL) deteriorated gradually and progressively throughout adulthood, VOR gain deterioration was markedly evident after 70 years of age. CONCLUSION: Considering the high prevalence of vHIT abnormality, appropriate social and medical policies are needed to prevent associated injuries and improve patients' quality of life. The distinct age-related changes in HL and objective findings of vestibular dysfunction indicate the need for different approaches to address these social problems in aging countries.

Insufficient nutrient intake in individuals with disabling hearing loss and the restoration of nutritional sufficiency in hearing aid users.

Hearing loss affects some nutrient intake. Disabling hearing loss may exacerbate these issues. We aimed to evaluate nutrient intake and assess deficiencies based on functional hearing status. The study included 6907 participants with information on demographic factors, nutrient intake, weight, height, disease status, and hearing level in the eighth Korea National Health and Nutrition Examination Survey, conducted from 2019 to 2021. We categorized the participants into 3 groups based on their functional hearing status: bilateral hearing, unilateral hearing, and disabling hearing loss. The disabling hearing loss group showed lower intake of most major nutrients (P < 0.05), dietary fiber (P < 0.001), and most minerals and vitamins (P < 0.05), with some insufficiencies. The unilateral hearing group showed lower intake only for potassium (P = 0.036) compared to the bilateral hearing group and significantly higher intake of hydration (P = 0.039), dietary fiber (P = 0.039), and calcium (P = 0.009) than the disabling hearing loss group. Nutrient insufficiency in the disabling hearing loss group was more prominent in women, and was partially resolved by using hearing aids. Clinicians and nutritionists should consider undernourishment in these patients, and appropriate interventions for nutrition and hearing aids should be recommended.

Biosafety and potency of high-molecular-weight hyaluronic acid with intratympanic dexamethasone delivery for acute hearing loss.

Objective: This study evaluated the potential of high-molecular-weight hyaluronic acid (HHA) as an intratympanic (IT) drug delivery vehicle for dexamethasone (D) in treating acute hearing loss. We compared the efficacy, safety, and residence time of HHA to the standard-of-care IT drug delivery method. Methods: Endoscopic examinations were used to track tympanic membrane (TM) healing post-IT injection. Micro-computed tomography (CT) was used to gauge drug/vehicle persistence in the bulla air space. Histological analyses covered the middle ear, TM, and hair cell counts. Auditory brainstem responses (ABR) were used to measure hearing thresholds, while high-performance liquid chromatography (HPLC) was employed to quantify cochlear perilymph dexamethasone concentrations. Results: The HHA + D group had a notably prolonged drug/vehicle residence time in the bulla (41 ± 27 days) compared to the saline + D group (1.1 ± 0.3 days). Complete TM healing occurred without adverse effects. Histology revealed no significant intergroup differences or adverse outcomes. Hearing recovery trends favored the HHA + D group, with 85.0% of ears showing clinically meaningful improvement. D concentrations in cochlear perilymph were roughly double in the HHA group. Conclusion: HHA is a promising vehicle for IT drug delivery in treating acute hearing loss. It ensures extended residence time, augmented drug concentrations in targeted tissues, and safety. These results highlight the potential for HHA + D to excel beyond existing standard-of-care treatments for acute hearing loss.

Neural correlation of speech envelope tracking for background noise in normal hearing.

Everyday speech communication often occurs in environments with background noise, and the impact of noise on speech recognition can vary depending on factors such as noise type, noise intensity, and the listener's hearing ability. However, the extent to which neural mechanisms in speech understanding are influenced by different types and levels of noise remains unknown. This study aims to investigate whether individuals exhibit distinct neural responses and attention strategies depending on noise conditions. We recorded electroencephalography (EEG) data from 20 participants with normal hearing (13 males) and evaluated both neural tracking of speech envelopes and behavioral performance in speech understanding in the presence of varying types of background noise. Participants engaged in an EEG experiment consisting of two separate sessions. The first session involved listening to a 12-min story presented binaurally without any background noise. In the second session, speech understanding scores were measured using matrix sentences presented under speech-shaped noise (SSN) and Story noise background noise conditions at noise levels corresponding to sentence recognitions score (SRS). We observed differences in neural envelope correlation depending on noise type but not on its level. Interestingly, the impact of noise type on the variation in envelope tracking was more significant among participants with higher speech perception scores, while those with lower scores exhibited similarities in envelope correlation regardless of the noise condition. The findings suggest that even individuals with normal hearing could adopt different strategies to understand speech in challenging listening environments, depending on the type of noise.

Molecular Genetic Etiology and Revisiting the Middle Ear Surgery Outcomes of Branchio-Oto-Renal Syndrome: Experience in a Tertiary Referral Center.

OBJECTIVES: To explore the phenotypes and genotypes of patients with branchio-oto-renal (BOR) and branchio-otic (BO) syndrome, and to analyze the middle ear surgery outcomes qualitatively and quantitatively, proposing a factor usefully prognostic of surgical outcomes. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary referral center. PATIENTS: Eighteen patients with BOR/BO syndrome in 12 unrelated Korean families. INTERVENTION: Middle ear surgery, including either stapes surgery or ossicular reconstruction. MAIN OUTCOME MEASURE: Clinical phenotypes, genotypes, and middle ear surgery outcomes. RESULTS: Eight probands (66.7%) were confirmed genetically; the condition segregated as a dominant or de novo trait. Six EYA1 heterozygous variants were identified by exome sequencing and multiplex ligation-dependent probe amplification. All variants were pathogenic or likely pathogenic based on the ACMG/AMP guidelines. Two novel EYA1 frameshift variants (p.His373Phefs*4 and p.Gln543Asnfs*90) truncating a highly conserved C-terminal Eya domain were identified, expanding the genotypic spectrum of EYA1 in BOR/BO syndrome. Remarkably, middle ear surgery was individualized to ensure optimal audiological outcomes and afforded significant audiological improvements, especially in BOR/BO patients without enlarged vestibular aqueducts (EVAs). A significant difference in air-bone gap closure after middle ear surgery was noted between the two groups even after adjusting for confounders: -20.5 dB in ears without EVAs (improvement) but 0.8 dB in ears with EVAs (no change or deterioration). Furthermore, the success rate was significantly associated with the absence of EVA. CONCLUSIONS: The results of this study were against the notion that middle ear surgery is always contraindicated in patients with BOR/BO syndrome, and an EVA could be a negative prognostic indicator of middle ear surgery in BOR/BO patients. This may aid to determine the strategy of audiological rehabilitation in patients with BOR/BO syndrome.

The effect of topic familiarity and volatility of auditory scene on selective auditory attention.

Selective auditory attention has been shown to modulate the cortical representation of speech. This effect has been well documented in acoustically more challenging environments. However, the influence of top-down factors, in particular topic familiarity, on this process remains unclear, despite evidence that semantic information can promote speech-in-noise perception. Apart from individual features forming a static listening condition, dynamic and irregular changes of auditory scenes-volatile listening environments-have been less studied. To address these gaps, we explored the influence of topic familiarity and volatile listening on the selective auditory attention process during dichotic listening using electroencephalography. When stories with unfamiliar topics were presented, participants' comprehension was severely degraded. However, their cortical activity selectively tracked the speech of the target story well. This implies that topic familiarity hardly influences the speech tracking neural index, possibly when the bottom-up information is sufficient. However, when the listening environment was volatile and the listeners had to re-engage in new speech whenever auditory scenes altered, the neural correlates of the attended speech were degraded. In particular, the cortical response to the attended speech and the spatial asymmetry of the response to the left and right attention were significantly attenuated around 100-200 ms after the speech onset. These findings suggest that volatile listening environments could adversely affect the modulation effect of selective attention, possibly by hampering proper attention due to increased perceptual load.

Dual viscosity mixture vehicle for intratympanic steroid treatment modifies the ROS and inflammation related proteomes.

Until recently, the most standard treatment for sensorineural or sudden hearing loss, which is caused by inner ear damage or deterioration, has been systemic oral steroid administration. In recent, intratympanic steroid injections such as dexamethasone have been used for the treatment of sudden hearing loss as well. It is injected into the tympanic cavity through its membrane and is expected to diffuse over the round window located between the tympanic cavity and the inner ear. However, in clinical situations, the delivery time of steroids to the inner ear is shorter than 24 h, which does not allow for a sufficient therapeutic effect. Therefore, we applied a previously invented dual viscosity mixture vehicle (DVV) for intratympanic dexamethasone to a guinea pig model, which could reduce the side effects of systemic steroid administration with sufficient dwelling time for the treatment of hearing loss, and we investigated the physiological changes with a global proteomic approach. In this study, we extracted perilymph in three different conditions from guinea pigs treated with dexamethasone-embedded DVV, dexamethasone mixed in saline, and control groups to compare proteomic changes using tandem mass spectrometry analysis. After liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) analysis, we first identified 46 differentially expressed proteins (DEPs) that were statistically significant after one-way ANOVA multiple-sample test. We also performed pairwise comparisons among each group to identify DEPs closely related to the treatment response of dexamethasone-embedded DVV. Gene ontology enrichment analysis showed that these DEPs were mostly related to inflammation, immune, actin remodeling, and antioxidant-related processes. As a result, the proteome changes in the DVV-treated groups revealed that most upregulated proteins activate the cell proliferation process, and downregulated proteins inhibit apoptosis and inflammatory reactions. Moreover, the reactive oxygen process was also regulated by DEPs after DVV treatment.

Feasibility of an inertial measurement unit sensor-based guiding system for benign paroxysmal positional vertigo treatment: A pilot study.

Performing an accurate canalith repositioning procedure (CRP) is important for treating benign paroxysmal positional vertigo, because inadequate rotational head angles can result in ineffective otolith mobilization and consequent treatment failure. Specialists-guided Epley maneuver reportedly had mean errors of 13.7°-24.4° while they were significantly larger (40.0°-51.5°) when self-administered. Similar results were obtained for the Barbeque maneuver: mean errors were 9.2°-13.0° by the specialists while they were significantly larger (22.9°-28.6°) when self-administered. Our study aimed to validate the feasibility of an inertial measurement unit sensor-based CRP (IMU-CRP) by analyzing the differences in accuracy in the rotational angles, comparing them with education-based conventional CRP (EDU-CRP). A pilot validation was also performed by analyzing the treatment success rate of IMU-CRP in patients with BPPV. This single-institution prospective, comparative effectiveness study examined 19 participants without active vertigo or prior knowledge of benign paroxysmal positional vertigo and CRP. Participants conducted the Epley and Barbeque roll maneuvers without and with auditory guidance (EDU-CRP vs. IMU-CRP, respectively) twice, and head rotation accuracies were compared. Differences in target angles based on the American Academy of Otolaryngology-Head and Neck Surgery guidelines were considered errors. For BPPV participants, treatment success was assessed based on the presence or absence of nystagmus, vertigo, and dizziness. For all the Epley and Barbeque roll maneuvers steps, the absolute errors were smaller for IMU- than for EDU-CRPs, with significant differences in steps 2-4 and 3-6 of the Epley and Barbeque roll maneuvers, respectively. A learning effect was found in steps 4 and 5 of the Barbeque roll maneuver but not in the Epley maneuver. The treatment success rates after 1 h were 71.4% and 100% for the Epley and Barbeque roll maneuvers, respectively. Real-time feedback on head rotation angles induced more appropriate movements in the Epley and Barbeque roll maneuvers. A guiding device based on head monitoring providing real-time auditory feedback may increase the self-administered CRP success rates in treating benign paroxysmal positional vertigo.

The Treatment Outcome of Smart Device-Based Tinnitus Retraining Therapy: Prospective Cohort Study.

BACKGROUND: Tinnitus retraining therapy (TRT) is a standard treatment for tinnitus that consists of directive counseling and sound therapy. However, it is based on face-to-face education and a time-consuming protocol. Smart device-based TRT (smart-TRT) seems to have many advantages, but the efficacy of this new treatment has been questioned. OBJECTIVE: The aim of this study was to compare the efficacy between smart-TRT and conventional TRT (conv-TRT). METHODS: We recruited 84 patients with tinnitus. Results were compared between 42 patients who received smart-TRT and 42 control participants who received conv-TRT. An interactive smart pad application was used for directive counseling in the smart-TRT group. The smart pad application included detailed education on ear anatomy, the neurophysiological model of tinnitus, concept of habituation, and sound therapy. The smart-TRT was bidirectional: There were 17 multiple choice questions between each lesson as an interim check. The conv-TRT group underwent traditional person-to-person counseling. The primary outcome measure was the Tinnitus Handicap Inventory (THI), and the secondary outcome measure was assessed using a visual analogue scale (VAS). RESULTS: Both treatments had a significant treatment effect, which comparably improved during the first 2 months. The best improvements in THI were -23.3 (95% CI -33.1 to -13.4) points at 3 months and -16.8 (95% CI -30.8 to -2.8) points at 2 months in the smart-TRT group and conv-TRT group, respectively. The improvements on the VAS were also comparable: smart-TRT group: -1.2 to -3.3; conv-TRT: -0.7 to -1.7. CONCLUSIONS: TRT based on smart devices can be an effective alternative for tinnitus patients. Considering the amount of time needed for person-to-person counseling, smart-TRT can be a cost-effective solution with similar treatment outcomes as conv-TRT.

Intratympanic steroid treatment can reduce ROS and immune response in human perilymph investigated by in-depth proteome analysis.

Intratympanic (IT) steroid treatment is one of the most widely used and effective treatments for inner ear disorders such as sudden sensorineural hearing loss (SNHL). However, a clear mechanism of IT steroids in inner ear recovery has not yet been revealed. Therefore, we investigated proteome changes in extracted human perilymph after steroid treatment. In this study, we applied a tandem mass spectrometry (MS/MS)-based proteomics approach to discover global proteome changes by comparing human perilymph after steroid treatment with non-treated perilymph group. Using liquid chromatography-MS/MS analysis, we selected 156 differentially expressed proteins (DEPs) that were statistically significant according to Student's t-test. Functional annotation analysis showed that upregulated proteins after steroid treatment are related to apoptosis signaling, as well as reactive oxygen species (ROS) and immune responses. The protein-protein interaction (PPI) clusters the proteins associated with these processes and attempts to observe signaling circuitry, which mediates cellular response after IT steroid treatments. Moreover, we also considered the interactome analysis of DEPs and observed that those with high interaction scores were categorized as having equivalent molecular functions (MFs). Collectively, we suggest that DEPs and interacting proteins in human perilymph after steroid treatment would inhibit the apoptotic and adaptive immune processes that may lead to anti-inflammatory effects.

Endolymphatic hydrops asymmetry distinguishes patients with Meniere's disease from normal controls with high sensitivity and specificity.

Background: Many endolymphatic hydrops (EH) MRI studies in the literature do not include a normal control group. Consequently, it remains unclear which outcome measure in EH MRI can most effectively distinguish between MD patients and normal controls. Methods: Gadolinium-enhanced EH imaging was performed to quantitatively evaluate the extents of hydrops in MD patients and age-/sex-matched normal controls. Four hours after intravenous injection of contrast agent, MRI was performed using a 3-T MR platform fitted with a 32-channel phased-array coil receptor. MR images (10-15 slices) covering an inner ear were 3D-stacked. Analyses of all images that included the vestibule or the cochlea yielded the volumes (in µL) of the endolymphatic and perilymphatic spaces. Results: For the vestibule, they were significantly greater EH% in ipsilateral (52.4 ± 12.5) than in contralateral MD ears (40.4 ± 8.5, p = 0.001) and in ipsilateral MD ears than in control ears (42.4 ± 13.7, p = 0.025). For the cochlea, the values were slightly higher EH% in ipsilateral MD ears (49.7 ± 10.4, p = 0.061) but did not significantly differ from contralateral (41.3 ± 12.6) or control ears (39.6 ± 18.9, p = 0.858). In the MD group, the EH asymmetries were 12.0 ± 10.2% (vestibule) and 8.4 ± 8.6% (cochlea), significantly larger than those of controls. Conclusion: Compared to conventional semiquantitative grading or quantitative EH% analysis, EH asymmetry may better distinguish MD patients from normal controls. Quantitative hydrops volumetric analysis yields clinically relevant information on inner ear function.

Synaptic Remodeling of the Auditory Cortex Following Bilateral Blindness: Evidence of Cross-modal Plasticity.

We aimed to evaluate structural dynamic changes of neurons in the auditory cortex after visual deprivation. We longitudinally tracked dendritic spines for 3 weeks after visual deprivation in vivo using a two-photon microscope. GFP-labeled dendritic spines in the auditory cortex were serially followed after bilateral enucleation. The turnover rate, density, and size of the spines in the dendrites were evaluated 1, 2, and 3 weeks after visual deprivation. The turnover rate of the dendritic spines in the auditory cortex increased at 1 week (20.1±7.3%) after bilateral enucleation compared to baseline (12.5±7.9%); the increase persisted for up to 3 weeks (20.9±11.0%). The spine loss rate was slightly higher than the spine gain rate. The average spine density (number of spines per 1 µm of dendrite) was significantly lower at 2 weeks (2W; 0.22±0.06 1/µm) and 3 W (0.22±0.08 1/µm) post-nucleation compared to baseline (0.026±0.09 1/µm). We evaluated the change of synaptic strength in the stable spines at each time point. The normalized spine size in the auditory cortex was significantly increased after bilateral blindness at 1 W postoperatively (1.36±0.92), 2 W postoperatively (1.40±1.18), and 3 W postoperatively (1.36±0.88) compared to baseline. Sensory deprivation resulted in remodeling of the neural circuitry in the spared cortex, via cross-modal plasticity in the direction of partial breakdown of synapses, and enhanced strength of the remaining synapses.

Patterns of vestibular function in patients with dizziness after COVID-19 vaccination; dual tertiary referral center study.

BACKGROUND: Although dizziness is a common symptom after vaccination, the mechanism, and prognosis are not well understood. AIMS/OBJECTIVES: This study aimed to investigate patients with dizziness after COVID-19 vaccination by analyzing objective information. METHODS: A retrospective study of patients who visited the outpatient clinics of two institutes with a complaint of dizziness occurring within 72 h after a COVID-19 vaccination. RESULTS: In most cases, patients experienced only a single event of dizziness, and the subjective symptom was relieved after a few weeks. All patients decreased gain of vestibular ocular reflex (VOR). The vestibular function test results showed signs of central vestibulopathy in some cases. We separated patients into two groups; the direction-fixed nystagmus (DFN) group and the direction-changing nystagmus (DCN) group. All patients showed decreased gain on the rotational chair test (RCT). The DFN group showed an 80% decrease in video head impulse test (vHIT) gain, whereas the DCN group only showed a decrease of 25%. In RCT, 66% of the DFN group showed asymmetry compared to 20% showing asymmetry in the DCN group. CONCLUSION AND SIGNIFICANCE: The patients who suffered from dizziness after the COVID-19 vaccination exhibited decreased VOR gain and in some cases signs of central vestibulopathy.

Intratympanic Administration of Dieckol Prevents Ototoxic Hearing Loss.

OBJECTIVE: Systemic administration of dieckol reportedly ameliorates acute hearing loss. In this study, dieckol was delivered to the inner ear by the intratympanic route. The functional and anatomic effects and safety of dieckol were assessed using the rat ototoxicity model. MATERIALS AND METHODS: Dieckol in a high-molecular-weight hyaluronic acid vehicle (dieckol+vehicle group) or vehicle without dieckol (vehicle-only group) were randomly delivered into 12 ears intratympanically. Ototoxic hearing loss was induced by intravenous administration of cisplatin, gentamicin, and furosemide. The hearing threshold and surviving outer hair cells (OHC) were enumerated. Biocompatibility was assessed by serial endoscopy of the tympanic membrane (TM), and the histology of the TM and the base of bulla (BB) mucosa was quantitatively assessed. RESULTS: The hearing threshold was significantly better (difference of 20 dB SPL) in the dieckol+vehicle group than in the vehicle-only group. The number of surviving OHCs was significantly greater in the dieckol+vehicle group than in the vehicle-only group. There were no signs of inflammation or infection in the ear. The thickness of the TM and the BB mucosa did not differ between the two groups. CONCLUSION: Intratympanic local delivery of dieckol may be a safe and effective method to prevent ototoxic hearing loss.

Effects of CoQ10 Replacement Therapy on the Audiological Characteristics of Pediatric Patients with COQ6 Variants.

Primary coenzyme Q10 (CoQ10) deficiency refers to a group of mitochondrial cytopathies caused by genetic defects in CoQ10 biosynthesis. Primary coenzyme Q10 deficiency-6 (COQ10D6) is an autosomal recessive disorder attributable to biallelic COQ6 variants; the cardinal phenotypes are steroid-resistant nephrotic syndrome (SRNS), which inevitably progresses to kidney failure, and sensorineural hearing loss (SNHL). Here, we describe the phenotypes and genotypes of 12 children with COQ10D6 from 11 unrelated Korean families and quantitatively explore the beneficial effects of CoQ10 replacement therapy on SNHL. A diagnosis of SRNS generally precedes SNHL documentation. COQ10D6 is associated with progressive SNHL. Four causative COQ6 variants were identified in either homozygotes or compound heterozygotes: c.189_191delGAA, c.484C>T, c.686A>C, and c.782C>T. The response rate (no further hearing loss or improvement) was 42.9%; CoQ10 replacement therapy may thus limit and even improve hearing loss. Notably, the audiological benefit appeared to be genotype-specific, suggesting a genotype-phenotype correlation. The results of cochlear implantation were generally favorable, and the effects were sustained over time. Our results thus propose the beneficial effects of CoQ10 replacement therapy on hearing loss. Our work with COQ10D6 patients is a good example of personalized, genetically tailored, audiological rehabilitation of patients with syndromic deafness.

Effect of Angiogenesis and Lymphangiogenesis in Diesel Exhaust Particles Inhalation in Mouse Model of LPS Induced Acute Otitis Media.

Lymphangiogenesis and angiogenesis might have significant involvement in the pathogenesis of otitis media with effusion. This study investigated the effect of diesel exhaust particles (DEP) on inflammation and lymphangiogenesis in a mouse model of acute otitis media (AOM). BALB/c mice were injected with LPS and exposed to 100 µg/m3 DEP. The mice were divided into four groups: control (no stimulation), AOM, AOM + DEP, and DEP + AOM. The effects of DEP inhalation pre- and post-DEP induction were estimated based on measurements of the auditory brainstem response, mRNA levels of lymphangiogenesis-related genes and cytokines, and histology of the middle ear. Cell viability of human middle ear epithelial cells decreased in a dose-response manner at 24 and 48 hours post-DEP exposure. DEP alone did not induce AOM. AOM-induced mice with pre- or post-DEP exposure showed thickened middle ear mucosa and increased expression of TNF-α and IL1-ß mRNA levels compared to the control group, but increased serum IL-1ß levels were not found in the AOM + Post DEP. The mRNA expression of TLR4, VEGFA, VEGFAC, and VEGFR3 was increased by pre-AOM DEP exposure. The expression of VEFGA protein was stronger in the AOM + Post DEP group than in any other group. The expression of CD31 and CD45 markers in the mouse middle ear tissue was higher in the Pre DEP + AOM group than in the AOM group. This result implies that pre-exposure to DEP more strongly increases inflammation and lymphangiogenesis in a mouse model of acute otitis media.

Altered secretome by diesel exhaust particles and lipopolysaccharide in primary human nasal epithelium.

BACKGROUND: Airway epithelial cells can actively participate in the defense against environmental pathogens to elicit local or systemic inflammation. Diesel exhaust particles (DEP), a main component of urban air pollution with particulate matter, are associated with the occurrence of acute and chronic upper airway inflammatory diseases. OBJECTIVES: We sought to investigate the effect of DEP alone or in combination with lipopolysaccharide on the secretome in the primary human nasal epithelium (PHNE) and to find potential biomarkers to relate DEP exposure to upper airway inflammatory diseases. METHODS: PHNE was cultured at an air-liquid interface to create a differentiated in vivo-like model. Secreted proteins (secretome) on the bottom media of the PHNE were analyzed by mass spectrometry-based label-free quantitative proteomics and ELISA. RESULTS: Considerably more differentially expressed secreted proteins were identified in response to DEP plus lipopolysaccharide than to DEP alone. Some canonical pathways related to inflammation and cancer such as the p53, ß-catenin, and extracellular signal-regulated kinase 1/2 pathways were involved. Among differentially expressed secreted proteins, leukemia inhibitory factor was also detected at a high level in the middle ear effusions of otitis media patients, and the leukemia inhibitory factor level was significantly correlated with daily mean mass concentrations of atmospheric particulate matter averaged over 8 days before sample collection. CONCLUSIONS: Apical stimulation with DEP and lipopolysaccharide can significantly alter the basal secretome in PHNE, and this alteration can be reflected by surrounding inflammation with effusion of fluids in vivo such as middle ear effusions in otitis media patients.