Tryptophan metabolism and small fibre neuropathy: a correlation study.

Small nerve fibres located in the epidermis sense pain. Dysfunction of these fibres decreases the pain threshold known as small fibre neuropathy. Diabetes mellitus is accompanied by metabolic changes other than glucose, synergistically eliciting small fibre neuropathy. These findings suggest that various metabolic changes may be involved in small fibre neuropathy. Herein, we explored the correlation between pain sensation and changes in plasma metabolites in healthy Japanese subjects. The pain threshold evaluated from the intraepidermal electrical stimulation was used to quantify pain sensation in a total of 1021 individuals in the 2017 Iwaki Health Promotion Project. Participants with a pain threshold evaluated from the intraepidermal electrical stimulation index <0.20 mA were categorized into the pain threshold evaluated from the intraepidermal electrical stimulation index-low group (n = 751); otherwise, they were categorized into the pain threshold evaluated from the intraepidermal electrical stimulation index-high group (n = 270). Metabolome analysis of plasma was conducted using capillary electrophoresis time-of-flight mass spectrometry. The metabolite set enrichment analysis revealed that the metabolism of tryptophan was significantly correlated with the pain threshold evaluated from the intraepidermal electrical stimulation index in all participants (P < 0.05). The normalized level of tryptophan was significantly decreased in participants with a high pain threshold evaluated from the intraepidermal electrical stimulation index. In addition to univariate linear regression analyses, the correlation between tryptophan concentration and the pain threshold evaluated from the intraepidermal electrical stimulation index remained significant after adjustment for multiple factors (ß = -0.07615, P < 0.05). These findings indicate that specific metabolic changes are involved in the deterioration of pain thresholds. Here, we show that abnormal tryptophan metabolism is significantly correlated with an elevated pain threshold evaluated from the intraepidermal electrical stimulation index in the Japanese population. This correlation provides insight into the pathology and clinical application of small fibre neuropathy.

Relationship between olfactory and gustatory functions: The Iwaki health promotion project 2019.

OBJECTIVE: Olfactory and gustatory functions are important sensory aspects in humans. Although they are believed to influence each other, their interrelationship is not well understood. In this study, we aimed to investigate the relationship between the olfactory and gustatory functions based on the results of a large-scale epidemiological study (Iwaki Health Promotion Project) of the general local population. METHODS: We analyzed 565 participants who underwent taste and olfactory tests in the 2019 Iwaki Project. Gustatory function was tested for four taste qualities (sweet, sour, salty, and bitter) using whole-mouth taste tests. Olfactory function was tested using the University of Pennsylvania Smell Identification Test modified for Japanese (UPSIT-J). We evaluated sex-related differences between olfactory and gustatory functions and the effects of various factors on olfactory identification using multivariate analysis. Furthermore, we compared the percentage of accurate UPSIT-J responses between the normal and hypogeusia groups. We also analyzed the effects of taste and olfactory functions on eating. RESULTS: Olfactory and gustatory functions were lower in men than in women. Among the four taste qualities, salty taste was the most closely associated with olfactory identification ability, with lower olfactory scores of salty taste in the hypogeusia group than in the normal group. Moreover, the hyposmia group had higher daily salt intake than the normal olfaction group in women. CONCLUSION: These results suggest that olfactory identification tests may be useful in predicting elevated salt cognitive thresholds, leading to a reduction in salt intake, which may contribute to hypertension prevention.

Aggregated eosinophils and neutrophils characterize the properties of mucus in chronic rhinosinusitis.

BACKGROUND: Airway obstruction caused by viscous mucus is an important pathophysiologic characteristic of persistent inflammation, which can result in organ damage. OBJECTIVE: We investigated the hypothesis that the biophysical characteristics of accumulating granulocytes affect the clinical properties of mucus. METHODS: Surgically acquired nasal mucus samples from patients with eosinophilic chronic rhinosinusitis and neutrophil-dominant, noneosinophilic chronic rhinosinusitis were evaluated in terms of computed tomography density, viscosity, water content, wettability, and protein composition. Isolated human eosinophils and neutrophils were stimulated to induce the formation of extracellular traps, followed by the formation of aggregates. The biophysical properties of the aggregated cells were also examined. RESULTS: Mucus from patients with eosinophilic chronic rhinosinusitis had significantly higher computed tomography density, viscosity, dry weight, and hydrophobicity compared to mucus from patients with noneosinophilic chronic rhinosinusitis. The levels of eosinophil-specific proteins in mucus correlated with its physical properties. Eosinophil and neutrophil aggregates showed physical and pathologic characteristics resembling those of mucus. Cotreatment with deoxyribonuclease and heparin, which slenderizes the structure of eosinophil extracellular traps, efficiently induced reductions in the viscosity and hydrophobicity of both eosinophil aggregates and eosinophilic mucus. CONCLUSIONS: The present study elucidated the pathogenesis of mucus stasis in infiltrated granulocyte aggregates from a novel perspective. These findings may contribute to the development of treatment strategies for eosinophilic airway diseases.

Diabetes can increase the prevalence of EBV infection and worsen the prognosis of nasopharyngeal carcinoma.

Epstein‒Barr virus (EBV) infection is a primary oncogenic factor of nasopharyngeal carcinoma (NPC) that elicits epithelial-mesenchymal transition (EMT). Although diabetic patients are more susceptible to various infectious diseases, the pathological association with virus-related NPC has not yet been clarified. Herein, we evaluated the influence of diabetes on the clinicopathological changes of 70 patients with NPC. Disease-specific survival (DSS) modified by viral infection was also analysed. The proportion of NPC patients with diabetes was 32.9% (23/70 cases), and 91.3% (21/23 cases) were infected with EBV detected by EBER-I in situ hybridisation. NPC with diabetes showed an effect on EMT evaluated by immunostaining for E-cadherin and vimentin, which was correlated with HbA1c levels. Receiver operating characteristic (ROC) curve analysis determined a HbA1c level of 6.5% as the cut-off value for primary disease death at 2 years [area under the curve (AUC) 0.76; sensitivity 0.64; and specificity 0.81]. High HbA1c levels (≥6.5%) significantly increased the number of lymph node metastases in NPC compared to low HbA1c levels (<6.5%, p<0.01). Diabetic NPC patients had a significantly poorer prognosis than all non-diabetic patients (DSS, 72 months vs not reached, p<0.05). Diabetic EBV-positive NPC patients had a significantly poorer prognosis than non-diabetic EBV-positive patients (DSS, 35 months vs not reached, p<0.01). Multivariate analysis using the Cox proportional hazards model also suggested that HbA1c ≥6.5% was a significant factor in poor prognosis, with a hazard ratio of 6.84 (p<0.05). Collectively, our results revealed for the first time a high prevalence of EBV infection, poor prognosis and the importance of proper glycaemic control in diabetic NPC patients.

Prevalence of perilymphatic fistula in patients with sudden-onset sensorineural hearing loss as diagnosed by Cochlin-tomoprotein (CTP) biomarker detection: its association with age, hearing severity, and treatment outcomes.

PURPOSE: To determine the prevalence of perilymphatic fistula (PLF) in sudden-onset sensorineural hearing loss (SSNHL) patients by employing the Cochlin-tomoprotein (CTP) detection test, a specific diagnostic marker for perilymph. We also analyzed the clinical characteristics associated with hearing outcomes in this cohort. METHODS: A total of 74 eligible patients were prospectively enrolled. Following myringotomy, middle ear lavage (MEL) samples underwent the CTP test to identify perilymph leakage. Intratympanic dexamethasone (IT-DEX) therapy was administered, and hearing outcomes were assessed. Control groups comprised patients with chronic otitis media (n = 40) and non-inflammatory middle ears (n = 51) with concurrent MEL sample collection. RESULTS: CTP was positive in 16 (22%) patients. No control samples showed positive results. Multiple regression analysis indicated that age and pre-treatment hearing levels significantly contributed to the CTP value. We found a positive correlation between CTP values, age, and pre-treatment pure-tone averages. Notably, CTP values in SSNHL cases aged 60 and above were significantly higher than in those below 60 years. Patients with positive CTP had significantly worse recovery rates after IT-DEX treatment. CONCLUSION: This study is the first prospective investigation demonstrating a positive relationship between CTP values, age, and hearing severity in SSNHL, indicating that PLF might be the essential cause of SSNHL, particularly in the elderly. Our findings suggest that IT-DEX may be less effective for PLF-associated SSNHL. Future research could reveal that PLF repair surgery is a viable treatment strategy for SSNHL. This study was registered under the UMIN Clinical Trials Registry (UMIN000010837) on 30/May/2013.

Clostridium paraputrificum Bacteremia in a Patient with Rectal Cancer after Receiving Antibiotic Therapy for Acute Pharyngolaryngitis.

Clostridium paraputrificum bacteremia is very rare, and its clinical importance is poorly understood. An 86-year-old man was receiving lascufloxacin therapy for acute pharyngolaryngitis before presenting to our emergency department with a recurrent fever. Two sets of blood cultures on admission revealed C. paraputrificum. A stool culture showed a reduced presence of intestinal commensal bacteria. After admission, the patient's fever resolved without antibiotics. Colonoscopy revealed a rectal tumor. Rectal tumor and microbial substitutions caused by antibiotics may have led to bacteremia. When treating C. paraputrificum bacteremia, physicians should be mindful of coexisting gastrointestinal disorders and a history of antibiotic administration.

Effect of gut microbial composition and diversity on major inhaled allergen sensitization and onset of allergic rhinitis.

BACKGROUND: Decreased gut microbiota diversity is associated with gut dysbiosis and causes various diseases, including allergic diseases. We investigated the relationship between gut microbial diversity and sensitization to major inhaled allergens. Furthermore, the relationship of allergic symptom onset with bacterial composition in sensitized individuals was investigated. METHODS: This study included 1092 local residents who had participated in the Iwaki Health Promotion Project in 2016. Blood samples were analyzed to ascertain specific IgE levels against major inhaled allergens (JCP, HD1, Grass-mix, Weed-mix). Nasal symptoms were estimated by questionnaires. Fecal samples were analyzed for bacterial 16S rRNA using next generation sequencing. The diversity index (α-diversity, ß-diversity) and the composition of gut microbes in phylum/order levels were compared between patients sensitized or unsensitized to allergen, and symptomatic and asymptomatic groups. RESULTS: Some α-diversity metrics were significantly decreased in patients who were sensitized to any/all four allergens compared with the unsensitized group. ß-diversity differed significantly between those unsensitized and sensitized to all allergens (aged 20-49 years), and between those unsensitized and sensitized to any/all four allergens (aged ≥50 years). The relative abundance of Bacteroidales was significantly lower in the unsensitized than in the sensitized group. The composition and diversity of gut microbiota were similar between the symptomatic and asymptomatic groups. CONCLUSIONS: Our results suggest that lack of diversity in gut microbiota has an effect on sensitization to allergens. Bacteroidales in order level may affect sensitization; however, the onset of allergy symptoms was not significantly associated with bacterial composition and diversity.

Executive summary: Japanese guidelines for allergic rhinitis 2020.

The Practical Guideline for the Management of Allergic Rhinitis, the fist guideline for allergic rhinitis in Japan, was prepared after a symposium held by the Japanese Society of Allergology in 1993. The current 9th edition was published in 2020 and is widely used today. The most recent collection of evidence from the literature was supplemented to the revised guideline to incorporate evidence-based medicine. The revised guideline includes updated epidemiology of allergic rhinitis in Japan, a figure representing the mechanisms of allergic rhinitis in both the onset and sensitization phases with the introduction of regulatory T cells and type 2 innate lymphoid cells, practical assessment for diagnosis, new pharmacotherapy agents such as anti-IgE mAb and a new drug delivery system for antihistamines, sublingual immunotherapy for children, dual sublingual immunotherapy for house dust mites and Japanese cedar pollen extract, new classification for surgery for allergic rhinitis, and treatment and prescriptions for older adults. An evidence-based step-by-step strategy for treatment is also described.

Major basic protein deposited at intra mucosal epithelium with probable eosinophilic chronic rhinosinusitis.

Background: Eosinophilic chronic rhinosinusitis (ECRS) is diagnosed by Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) scoring system and histopathological eosinophil counts of dissected nasal polyps. Patients with low JESREC score and small number of tissue eosinophils are diagnosed with non-ECRS (NECRS). Due to the 2 parameters of this diagnostic system, chronic rhinosinusitis is to be divided to 4 groups and some patients fall into the 2 groups other than ECRS and NECRS: probable ECRS (pECRS) and probable non-ECRS (pNECRS). We attempted to clarify clinical and histopathological similarities and differences, especially concerning major basic protein (MBP), among those groups. Methods: One hundred twenty-eight patients treated by endoscopic sinus surgery was included. Clinical characteristics were compared among each group, and immunohistological analysis for MBP was performed to 35 randomly selected patients. MBP deposition at intra mucosal epithelium was evaluated by semiquantificational approach. Results: ECRS patients showed significantly higher comorbidity rate with allergic rhinitis (36 patients, 78.3%), asthma (36 patients, 78.3%) compared with other groups. Also, percentage of the patients complaining olfactory dysfunction (42 patients, 91.3%) was significantly higher (p < 0.001). Lund-Mackay score (mean, 14.5; 6-24) and recurrence rate (27 patients, 61.4%) was the highest in ECRS patients. Regarding pECRS, the number of patients with olfactory dysfunction (5 patients, 55.6%) was higher than pNECRS and NECRS groups. Also, comorbidity of asthma and percentage of blood eosinophils tended to be higher than those 2 groups. MBP score of pECRS group was significantly higher than NECRS (p < 0.05), despite of smaller tissue eosinophil counts. Conclusion: pECRS might share some characteristics with ECRS although tissue eosinophil count was significantly smaller compared with ECRS. The results of this study have shown that MBP score in pECRS nasal polyps was significantly higher than NECRS patients and close to ECRS. That might suggest that eosinophils have existed in the nasal polyps of pPECRS patients at some point before surgery.

Association of mitochondrial DNA haplogroup and hearing impairment with aging in Japanese general population of the Iwaki Health Promotion Project.

Age-related hearing loss (ARHL) is a complex multifactorial disorder. Studies in animals, including mitochondria-mutator mice, and in human suggest that oxidative stress and mitochondrial disturbance play an important role in the pathoetiology of ARHL. Mitochondrial DNA (mtDNA) haplogroups are populations with genetically similar traits, and they have been reported to affect the mitochondrial function of oxidative phosphorylation. To gain further insights into the relationships between mitochondrial haplotypes and the susceptibility to cochlear aging, in this study, we aimed to elucidate how the differences in mtDNA haplogroups may affect ARHL development in Japanese general population. We focused on early onset ARHL, as the same mtDNA haplogroup can show either a negative or positive effect on systemic co-morbidities of ARHL that appear later in life. A total of 1167 participants of the Iwaki Health Promotion Project were surveyed in 2014, and 12 major haplotype groups (D4a, D4b, D5, G1, G2, M7a, M7b, A, B4, B5, N9, and F) were selected for the analysis. A total of 698 subjects aged 30 to 65 years were included in the statistical analysis, and the hearing loss group consisted of 112 males (40.3%) and 111 females (26.4%). Multiple logistic regression analysis showed that the male subjects belonging to haplogroup A had a significantly increased risk of hearing loss, whereas the female subjects belonging to haplogroup N9 had a significantly decreased risk of hearing loss. These results suggested that the mtDNA haplogroup may be an indicator for future risk of morbidity associated with ARHL.

Survey of nebulizer therapy for nasal inflammatory diseases in Japan before and during the COVID-19 pandemic.

OBJECTIVE: Nebulizer therapy is an effective and safe topical treatment for rhinosinusitis and is frequently used by otolaryngologists in Japan. However, treatment methods used vary among regions and according to doctors' preferences. In this study, we aimed to investigate the use of nebulizer therapy for rhinosinusitis. Administration of nebulizer therapy has been affected by the coronavirus disease 2019 (COVID-19) pandemic. Thus, we also investigated the difference in the prevalence of nebulizer use before and during the pandemic. METHODS: Between February and September 2016 and in January 2021, we administered questionnaire surveys on nebulizer treatment for rhinosinusitis to otorhinolaryngologists, who were members of the Oto-Rhino-Laryngological Society of Japan, in Aomori, Saitama, Mie, Fukui, Shiga, Okayama, and Kagoshima prefectures. RESULTS: More than 90% of the otorhinolaryngologists performed nebulizer treatment for rhinosinusitis in 2016. In April 2020 (the first wave of the COVID-19 pandemic), the use rate decreased to 20%, but in January 2021, the use rate increased to 60%. Jet nebulizers were the most frequently used type. One-third of the otolaryngologists enlarged the natural opening of the paranasal sinuses in more than half of their patients by using vasoconstrictors. Cefmenoxime and betamethasone were the most commonly used antibiotics and steroids, respectively. CONCLUSION: Because it is important to perform nasal pretreatment and strict disinfection of nebulizer equipment, it is clear that education of otorhinolaryngologists as well as paramedical personnel is required to ensure safe and effective use of nebulizer therapy in Japan.

IgG4 Expression in Patients with Eosinophilic Otitis Media.

OBJECTIVE: Eosinophilic otitis media (EOM) is an intractable middle ear disease recognized by an eosinophil enriched middle ear effusion and mucosa. Although precise pathogenesis of EOM remains unclear, it is characterized by type 2 inflammation. Since IgG4 is an IgG subclass induced by type 2 cytokines such as IL-4 and IL-13, we sought to characterize and compare local IgG4 expression in patients with and without EOM. METHODS: Twelve patients with bilateral profound hearing loss, 9 of which underwent a cochlear implant surgery, were enrolled in this study (6 with EOM and 6 without EOM). The surgical specimens were harvested during surgery and were subjected to IgG4 immunostaining. RESULT: The middle ear mucosa showed the presence of a large number of IgG4-positive cells in patients with EOM, which was significantly higher than that in patients without EOM. CONCLUSION: Local IgG4 expression was observed in patients with EOM in comparison to those without EOM, suggesting that IgG4 contributes to EOM pathogenesis.

Correction to: Prevalence of the mitochondrial 1555 A>G and 1494 C>T mutations in a community-dwelling population in Japan.

[This corrects the article DOI: 10.1038/s41439-020-00115-9.].

CD11c(+) dendritic cells coexpressing thymic stromal lymphopoietin receptor in animal model of eosinophilic otitis media.

BACKGROUND: Eosinophilic otitis media (EOM) is an intractable middle ear disease often associated with eosinophilic inflammatory airway conditions. Recently, dendritic cells (DCs) have been indicated as an essential component of Th2 allergic inflammation, such as bronchial asthma. DCs are activated by thymic stromal lymphopoietin (TSLP), an epithelial cell-derived cytokine. However, the relationship between TSLP and DCs in EOM remains unknown. OBJECTIVE: This study aimed to investigate the relationship between DCs and TSLP and to determine the involvement of DCs in EOM in an animal model. METHODS: Hartley guinea pigs were used as the animal model. Daily ovalbumin (OVA) stimulation of the middle ear was performed for 7 or 14 days. The temporal bone was dissected on the last day of stimulation, and paraffin-embedded sections were prepared. Immunostaining and immunofluorostaining for TSLP receptor (TSLPR) and CD11c, a surface marker of DCs, were performed. RESULTS: We found CD11c-immunopositive cells in the submucosal area of the middle ear epithelium, particularly around the eustachian tube. TSLPR-immunopositive cells exhibited a similar distribution as CD11c-positive cells. CONCLUSION: CD11c positive DCs coexpressing TSLPR were recruited after OVA challenge which might activate Th2 allergic reaction.

Prevalence of the mitochondrial 1555 A>G and 1494 C>T mutations in a community-dwelling population in Japan.

Single nucleotide polymorphisms in mitochondrial DNA, such as mitochondrial 1555 A>G (m.1555 A>G) and mitochondrial 1494 C>T (m.1494 C>T), are known to be causative mutations of nonsyndromic hearing loss following exposure to aminoglycoside antibiotics. The prevalence of the m.1555 A>G and m.1494 C>T mutations has not been reported for the general population in Japan. The purpose of this study was to investigate the prevalence of m.1555 A>G and m.1494 C>T mutations in a community-dwelling population in Japan in order to prevent aminoglycoside-induced hearing loss. We recruited participants older than 20 years of age to the Iwaki Health Promotion Project in 2014, 2015, and 2016, resulting in the recruitment of 1,683 participants. For each participant, we performed a hearing test and a genetic test for the m.1555 A>G and m.1494 C>T mutations using the TaqMan genotyping method. The m.1555 A>G mutation was detected in only 1 of the 1,683 participants (0.06%). This carrier of the m.1555 A>G mutation was a 69-year-old male with bilateral, symmetric, and high-frequency hearing loss. We provided genetic counseling and distributed a drug card advising him to avoid the administration of aminoglycoside antibiotics. In contrast, the m.1494 C>T mutation was not detected in this study population.

Relationship between gut microbiota composition and sensitization to inhaled allergens.

BACKGROUND: An imbalance in gut microbiota is implicated in several pathological conditions, including allergic diseases. This study investigates the association between gut microbiota composition and sensitization to two inhaled antigens. METHODS: The study comprised 1109 local residents who had participated in the Iwaki Health Promotion Project in 2016. Blood samples were analyzed for levels of antigen-specific IgE against Japanese cedar pollen (JCP) and house dust (HD1). Fecal samples were analyzed for bacterial 16S rRNA (ribosomal ribonucleic acid) using next generation sequencing. The percent composition of gut microbes was compared between patients sensitized and unsensitized group for JCP and HD1 to determine whether the rate of sensitization to inhaled antigens associates with specific bacterial orders composing the gut microbiota. RESULTS: In participants aged 20-49 years, the percent composition of Bacteroidales was significantly higher among participants sensitized to JCP than in those unsensitized. The percent composition of Lactobacillales was significantly higher in participants unsensitized to HD group than in those sensitized to that antigen. In addition, participants with low Bacteroidales and high Bifidobacteriales or Lactobacillales has low sensitization rates to HD compared with high Bacteroidales and low Bifidobacteriales or Lactobacillales. CONCLUSIONS: The presence of bacteria of order Lactobacillales, Bifidobacteriales, and Bacteroidales in the gut microbiota may affect sensitization to inhaled allergens.

Treatment strategy for a penetrating stab wound to the vertebral artery: a case report.

CASE: Vertebral artery injury is a low-frequency but high-mortality injury. The surgical approach to a bleeding vertebral artery injury is one of the most difficult procedures in trauma surgery.A 64-year-old woman was transported to our emergency department after being stabbed in the middle side of the right neck with a large kitchen knife. Her initial hospital examination indicated a shock state, and computed tomography images revealed a right vertebral artery injury. We undertook angiography and transcatheter arterial embolization before the surgical operation. OUTCOME: The patient suffered right upper extremity paralysis due to brachial plexus injury and was transferred to another hospital for rehabilitation on the 24th hospital day. CONCLUSION: Computed tomography angiography for diagnosis and interventional radiology treatment are useful for the management of penetrating neck trauma. Transcatheter arterial embolization for vertebral artery injury is safe and allows for easy control of bleeding compared to a surgical procedure.

Brain Computer Interface Using Modulation of Auditory Steady-State Response with Help of Stochastic Resonance.

This paper proposes an eye-movement independent brain computer interface based on the modulations of auditory steady-state response (ASSR-BCI) to amplitude-modulated (AM) tones elicited by paying selective attention to one of the two AM tones. Moreover, the proposed ASSR-BCI exploits a stochastic resonance effect to improve the signal separation and attained the mean classification accuracy of 77 % across nine normal subjects under a noise-added condition with sound pressures 60 dB for the two tones and 30 dB for the noise added to the two AM tones. Results from information transfer rate and its inter-individual difference suggest that it may be adequate to set an inter-trial interval at 2∽3 s for a trial time length. It is consequently feasible to develop a practical eye-movement-independent BCI available in eyes-closed state by optimizing the parameters such as the trial time length and electrode sites each user.

The expression of thymic stromal lymphopoietin in patients and animal models with eosinophilic otitis media.

OBJECTIVE: In the present study, we aimed to clarify the expression of thymic stromal lymphopoietin (TSLP), a key trigger of Th2-type allergic disease, in the middle ear mucosa of eosinophilic otitis media (EOM). METHODS: An immunohistological study of TSLP was conducted in patients with EOM and in animal models of EOM constructed by intraperitoneal and intratympanic injection of ovalbumin for 7 and 14 days. In addition, the messenger RNA (mRNA) expression of TSLP in the middle ear mucosa of the animal models was analyzed using real-time PCR, and was compared with that of the control animals. RESULTS: Immunoreactivities for TSLP were observed in the middle ear mucosa around the tympanic ostium of the eustachian tube of patients with EOM. In the animal model, strong immunoreactivity for TSLP was also observed in the eustachian tube epithelium, and mRNA expression of TSLP in the seven-day stimulated animals was significantly higher than that in the controls. CONCLUSION: The present study indicates that the presence of epithelium-derived TSLP in the eustachian tubes plays an important role in the onset of EOM.