Occurrence Of Otitis Media Research Articles

Wildfire Seasons, Prenatal PM2.5 Exposure, and Respiratory Infections by Age 1 Year: A Population-Based Case-Control Analysis of Critical Developmental Windows.

The 2017 and 2018 wildfire seasons in British Columbia (BC), Canada were unprecedented. Among all the pollutants in wildfire smoke, fine particulate matter (PM2.5) poses the most significant risk to human health. There is limited research on prenatal wildfire smoke exposure and its impacts on infant health. We used a population-based nested case-control design to assess the association between daily PM2.5 exposures during specific developmental windows and the occurrence of otitis media or lower respiratory infections by age 1 year, including infections associated with dispensations of the antibiotic amoxicillin. We observed the strongest association between per 10 μg/m3 increase in PM2.5 exposure and otitis media during the fourth window of eustachian tube development (weeks 19-28) with an OR [95% confidence interval] of 1.31 [1.22, 1.41]. Similarly, the canalicular stage of lower respiratory tract development (weeks 18-27) was associated with the highest odds of lower respiratory infections, with an OR of 1.21 [1.15, 1.28]. Measures to reduce wildfire smoke exposure during pregnancy are warranted.

The A2ml1-Knockout mouse as an animal model for non-syndromic otitis media

BackgroundInflammation and infection of the middle ear, known as otitis media (OM), is a leading cause of hearing loss and the most frequently diagnosed disease in children worldwide. Traditionally, mouse models for OM rely on inducing acute infection through inoculation of the middle ear, e.g. with the human otopathogen non-typeable Haemophilus influenzae (NTHi), and with very few genetic models with spontaneous or chronic OM. A2ML1 variants, including loss-of-function variants, were associated with susceptibility to OM in humans, but no animal model has been reported for A2ml1-related OM. Here, we report our middle ear findings in a mouse line with a CRISPR-induced knockout (KO) of A2ml1. MethodsMice were X-rayed prior to harvest to determine if there are craniofacial or skeletal abnormalities. Tissue from mouse middle ears, as well as other upper respiratory mucosal tissues, were harvested. The harvested middle ear bullae were examined under microscope and submitted for histologic preparation to study phenotypic indications of OM. RNA samples isolated from middle ear tissue were assayed for expression of genes correlated with A2ML1 expression in humans. ResultsData from a total of 119 mice (35 wildtype, 40 heterozygous, 44 homozygous) are presented here, with each analyses being performed on subsets of these mice. There were no significant craniofacial differences by genotype (n = 22). Findings in mice with the A2ml1-KO indicated an increased incidence of OM (n=29; odds ratio = 11; CI: 1.1, 573.6; Fisher exact two-sided p = 0.02) with tympanic membrane perforations or thickening, as well as cases of middle ear effusion, inflammatory cells, or fluid from histologic sections. Dsp was upregulated in the middle ear tissues of homozygous mice (Wilcoxon test p = 0.001). ConclusionThus far, our results in this A2ml1-KO mouse line indicate spontaneous occurrence of OM and dysregulation of Dsp in the middle ear as a potential disease mechanism for A2ml1-related OM.

Using Geometric Morphometric Analysis of Magnetic Resonance Imaging to Assess the Anatomy of the Eustachian Tube in Children with and without Otitis Media.

Otitis media (OM) is among the most common of childhood illnesses. It has long been hypothesized that children under age two are predisposed to OM due to differences in the anatomy of the Eustachian tube (ET), including the angle of the ET. OM in later childhood is less common but does occur, begging the question, are there shape differences in the ET that persist underlying later occurrences of OM? To answer this question, a novel method, which applied geometric and morphometric shape analysis to landmarks obtained from MRI data, was used. MRI scans were performed on 16 children (5 control, 3 cOME, and 8 rAOM) between 2011 and 2015. Sixteen landmarks representing the shape of the ET, cranial base, and palate were analyzed. The results of a Procrustes ANOVA indicate that the shape of the ET varies significantly (p < 0.01) between the OM and control groups. The shape differences between the OM group and the control are a medial and low attachment site of the tensor veli palatini (TVP) muscle, a posterior and high torus tubarius, and an anteriorly projected palate. These results support previous findings that a relatively horizontal ET is associated with a predisposition for OM. This study used a novel approach to examine anatomical differences in children with and without OM. First, the data set is unique in that it includes MRI scans of children with a confirmed OM diagnosis. Second, the use of MRI scans in craniofacial anatomy OM research is novel and allows for the collection of soft tissue landmarks and the visualization of soft tissue structures. Third, geometric morphometric shape analysis is a statistical method that captures shape differences, offering a more universal picture of nuanced changes within the entire set of landmarks, in contrast to more traditional linear and angular measurements used in prior OM studies examining craniofacial anatomy.

Association between maternal insecticide use and otitis media in one-year-old children in the Japan Environment and Children\u2019s Study

Otitis media (OM) is common among young children and is related to hearing loss. We investigated the association between maternal insecticide use, from conception to the first and second/third trimesters, and OM events in children in the first year of age. Data from Japan Environment and Children's Study were used in this prospective cohort study. Characteristics of patients with and without history of OM during the first year of age were compared. The association between history of OM in the first year and insecticide use was evaluated using logistic regression analysis. The study enrolled 98,255 infants. There was no significant difference in the frequency of insecticide use between groups. Insecticide use of more than once a week from conception to the first trimester significantly increased the occurrence of OM in children in the first year (odds ratio [OR] = 1.30, 95% confidence interval [CI] 1.01–1.67). The association between OM in the first year and insecticide use from conception to the first trimester was only significant in the group without daycare attendance (OR 1.76, 95% CI 1.30–2.38). Maternal insecticide use more than once a week from conception to the first trimester significantly increased OM risk in offspring without daycare attendance.

The Association between Iron Deficiency Anemia and Chronic Suppurative Otitis Media [Safe Type

Background: Acute otitis media is considered as one of the most frequent childhood inflammatory disorders.Aim of the work: This study aimed to investigate the possible link between iron deficiency anemia and acute episodes on top of chronic otitis media.Patient and methods: This prospective study is included pediatric patients who attend the ENT outpatient clinic in Mallawi Hospital, El Minia; El Azhar University _Assuit, from July 2019 to June 2020. A total of 100 patients of age Group up to 18 years old and both sexes suffering from recurrent otitis media divided into Group A: Included 34 children treated with iron supplementation three months, Group B: Included 33 children treated with iron supplementation and medical treatment three months.Group C: Included 33 children treated with medical treatment for three months. Results: In group A the change of hemoglobin level from [10.15 ± 0.33] to [11.41 ± 0.43] decreasing occurrence rate of CSOM from 3.47± 0.51 to 1.41± 0.49 with statistically significant difference [p <0.001].In group B, the change of Hb level from [10. ± 0.32] to [11.48 ± 0.29] decreasing occurrence rate of Chronic Suppurative Otitis Media from 33.42 ± 0.92 to 1.39± 0.56 with statistically significant difference [p <0.001].In group C, the change of Hb level from [10.03 ± 0.43] to [10.09± 0.31] decreasing occurrence rate of CSOM from 3.39±0.66 to 2.33± 0.48 with statistically significant difference [p <0.001].Conclusions: The combination of iron and medical treatment in anemic patients can improve hemoglobin level and significantly decrease otitis media's occurrence rate.

Bidirectional association between asthma and otitis media in children

BackgroundThis study explored the reciprocal association between otitis media and asthma in children.MethodsThe 2002–2013 Korean Health Insurance Review and Assessment Service-National Sample Cohort participants < 15 years old were used. In study I, 14,665 asthma patients from 2002 through 2005 were selected. The asthma patients were matched 1:1 with the control I group, and the occurrence of otitis media was followed until 2013. In study II, 27,043 otitis media patients from 2002 through 2005 were selected. The otitis media patients were matched 1:1 with the control II group, and the occurrence of asthma was followed until 2013. Stratified Cox proportional hazard models were used to analyze the hazard ratio (HRs) of asthma for otitis media (study I) and otitis media for asthma (study II).ResultsThe HR for otitis media was 1.46 in asthma patients (95% confidence interval [CI] = 1.40–1.52, P < 0.001). The HR for asthma was 1.43 in otitis media patients (95% confidence interval [CI] = 1.36–1.50, P < 0.001).ConclusionAsthma and otitis media have a bidirectional association in children.

Effects of allergic rhinitis on the progression and recovery of acute otitis media in a mouse model

ObjectivesThe objective of this study was to evaluate the effects of allergic rhinitis (AR) on the development, progression, and recovery of acute otitis media (OM) in an animal model and investigate the secondary effects of bacterial infection. MethodsBALB/c mice were divided into four groups: AR + OM, AR, OM, and control groups. AR + OM and AR groups were sensitized with ovalbumin (OVA) and alum and then challenged intranasally with OVA. Phosphate-buffered saline (PBS) was administered to the OM and control groups the same number of times. After AR induction, OM was induced by surgical inoculation of non-typeable Haemophilus influenza (NTHi) into the middle ear (ME) cavity of the mice in the AR + OM and OM groups. PBS was injected into the bulla in the AR and control groups. Each group was subdivided into sets of six mice, one for each of the four time points (0, 2, 7, and 10 days post-bacterial inoculation), at which point the mice were euthanized and ME and nasal cavity mucosa were obtained and evaluated. The occurrence of OM and the ME mucosa thickness were evaluated and compared among the four groups. Tissue expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) in infected ME mucosa was assessed by immunohistochemical staining. We also investigated IgE, IL-4, and IL-5 in the nasal mucosa. ResultsMost of the ears showed OM on post-inoculation day 2 in both AR + OM and OM groups. In the AR + OM group, 58.3% of ears still had OM on post-inoculation day 10, while only 16.7% of the OM group had OM. The ME mucosa of all groups increased, and the AR + OM group exhibited the thickest mucosa. The OM group showed peak thickness on post-inoculation day 2 and then decreased, whereas the ME mucosa thickness of the AR + OM group continued to increase to day 7. In the OM group, the expression of IL-1β, IL-6, and TNF-α in the ME also increased significantly, peaking on post-inoculation day 2, and then gradually decreased. In the AR + OM group, the expression of these proteins increased until day 7 and then decreased. The IgE and Th2 response (IL-4 and IL-5) cytokines were expressed at higher levels in the AR + OM and AR groups than in the OM and control groups. ConclusionThe inflammatory reaction to NTHi was more intense and lasted longer in the allergic group, which indicates that AR affects the progression and subsequent recovery of acute bacterial OM.

Childhood otitis media: Relationship with daycare attendance, harsh parenting, and maternal mental health.

Psychological stress has been linked to developmental problems and poor health in children, but it is unclear whether it is also related to otitis media (OM). As part of a long-term study surveying the characteristics of childcare and development in Taiwan, we analyzed the relationship between OM and sources of psychological stress in children, such as poor maternal mental health and harsh parental discipline. We analyzed the data of 1998 children from the “Kids in Taiwan: National Longitudinal Study of Child Development & Care (KIT) Project” at the age of 3 years. Using bivariate and multivariate logistic regression models, we tested several risk factors as potential independent predictors of two outcomes: parent-reported incidence of OM and child health. The proportion of children who had developed OM in the first 3 years of their life was 12.5%. Daycare attendance (odds ratio [OR]: 1.475; 95% confidence interval [CI]: 1.063–2.046), poor maternal mental health (OR: 1.913; 95% CI: 1.315–2.784), and harsh parental discipline (OR: 1.091; 95% CI: 1.025–1.161) correlated with parent-reported occurrence of OM. These findings suggest that providing psychosocial support to both parents and children might be a novel strategy for preventing OM.

Risk Factors for Acute Otitis Mediain Children at Dr.Soedono Hospital

Acute otitis media (OMA) was the most common ear infection in children. Because of Tuba Eustachius was not developed yet, shorter and flatter / horizontal in children so the secretions of nasopharynx were easier to enter the middle ear. OMA can cause many complications such as subperiosteal abscess to severe complications like meningitis and brain abscess. Epidemiological studies of OMA in developing countries were still rare. The prevalence of OMA was different in many country, ranging from 2.3 - 20%. The result of study showed that the prevalence of OMA in children in East Jakarta was 5.38%, and the highest prevalence was on group among 2-5 years old. 179 patients analyzed were 50.8% male and 49.2% female. The mean age of this study subjects was 4.75 years (SD 4.54). 31.3% were diagnosed with OMA. There was no difference in the location of the OMA occurrence between the right and left ear. There was a significant correlation between age factor and the incidence of OMA (p = 0.014) and subjects which under 5 years of old became a risk factor for OMA. The results also showed that there was a correlation between treatment and the incidence of OMA (p = 0.000), ARI patients without treatment was being a risk factor for the incidence of OMA in children. There was no correlation between sex, type factor and health insurance against the occurrence of OMA.

Notch signaling is active in normal mouse middle ear epithelial cells.

Mucous cell metaplasia/hyperplasia in the middle ear epithelium is associated with the occurrence of otitis media with effusion during infections. However, the mechanism by which Notch signaling regulates cell fate in the middle ear epithelium is unclear. The aim of the present study was to elucidate this mechanism by investigating the localization of Notch receptors, such as Notch1 and Notch2, and Notch ligands, such as Jagged1, in the normal mouse middle ear epithelium (NMMEE) using immunofluorescence. Furthermore, the mRNA expression levels of Notch receptors and ligands were evaluated using reverse transcription polymerase chain reaction (PCR). The effects of the γ-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine tert-butyl ester (DAPT) on epithelial cell proliferation were determined using 5-ethynyl-2′-deoxyuridine (EdU) staining and immunofluorescence staining of the apoptosis marker caspase-3 and the epithelial proliferation marker pan-cytokeratine. In addition, the differentiation of the NMMEE cells was characterized by evaluating the mRNA expression levels of the mucous cell-associated genes Arg2, Muc2, Spdef, Spink4 and Tff1 using quantitative PCR. Notch1, Notch2 and Jagged1 were observed to be co-localized throughout the mouse middle ear epithelium. Furthermore, Notch1-4, Jagged1, Jagged2, Dll1 and Dll4 mRNAs were expressed in the NMMEE cells. The inhibition of Notch by DAPT resulted in fewer EdU-positive cells and the upregulation of the expression levels of various mucous cell-associated genes. The results indicate that DAPT suppresses the proliferation of NMMEE cells while promoting their differentiation into mucous cells. Therefore, DAPT may provide a specific therapeutic strategy for the reversal of multiple pathological processes that are associated with epithelium thickening in the middle ear.

Lack of Impact of Body Mass Index at Young Age on Otitis Media Occurrence During Preschool Years

Using data on weight and height at 6 and 11 months of age and primary care electronic health records data from 1960 children participating in the Wheezing Illnesses Study Leidsche Rijn birth cohort study, we found that body mass index at 6 and 11 months of age was not associated with otitis media occurrence during the first 4 years of life.

Prenatal pesticide exposure and otitis media during early childhood in the PELAGIE mother–child cohort

ObjectiveContemporary pesticides, such as triazines or organophosphates, possess immunotoxic properties. We aimed to determine whether prenatal environmental exposure to these current-use pesticides was associated with otitis media (OM) during the...

Factors influencing the development of otitis media among Sicilian children affected by upper respiratory tract infections

IntroductionUpper respiratory tract infection is a nonspecific term used to describe an acute infection involving the nose, paranasal sinuses, pharynx and larynx. Upper respiratory tract infections in children are often associated with Eustachian tube dysfunction and complicated by otitis media, an inflammatory process within the middle ear. Environmental, epidemiologic and familial risk factors for otitis media (such as sex, socioeconomic and educational factors, smoke exposure, allergy or duration of breastfeeding) have been previously reported, but actually no data about their diffusion among Sicilian children with upper respiratory tract infections are available. ObjectiveTo investigate the main risk factors for otitis media and their prevalence in Sicilian children with and without upper respiratory tract infections. MethodsA case–control study of 204 children with upper respiratory tract infections who developed otitis media during a 3 weeks monitoring period and 204 age and sex-matched healthy controls. Seventeen epidemiologically relevant features were inventoried by means of standardized questionnaires and skin tests were performed. Univariate analysis and multivariate logistic regression analysis were used to examine the association between risk factors and occurrence of otitis media. ResultsOtitis media resulted strongly associated to large families, low parental educational attainment, schooling within the third years of life (p<0.05); children were more susceptible to develop otitis media in the presence of asthma, cough, laryngopharyngeal reflux disease, snoring and apnea (p<0.05). Allergy and urban localization increased the risk of otitis media in children exposed to smoke respectively of 166% and 277% (p<0.05); the joint effect of asthma and presence of pets in allergic population increased the risk of recurrence of 11%, while allergy, cough and runny nose together increased this risk of 74%. ConclusionsUpper respiratory tract infections and otitis media are common childhood diseases strongly associated with low parental educational attainment (p=0.0001), exposure to smoke (p=0.0001), indoor exposure to mold (p=0.0001), laryngopharyngeal reflux disease (p=0.0002) and the lack of breast-feeding (p=0.0014); an increased risk of otitis media recurrences was observed in the presence of allergy, persistent cough and runny nose (p=0.0001). The modification of the identified risk factors for otitis media should be recommended to realize a correct primary care intervention.

Polymorphisms of Immunity Genes and Susceptibility to Otitis Media in Children

BackgroundAcute otitis media (OM) is a common disease which often develops through complex interactions between the host, the pathogen and environmental factors. We studied single nucleotide polymorphisms (SNPs) of genes involved in innate and adaptive immunity, and other host and environmental factors for their role in OM.MethodsUsing Sequenom Massarray platform, 21 SNPs were studied in 653 children from prospective (n = 202) and retrospective (n = 451) cohorts. Data were analyzed for the relationship between SNPs and upper respiratory infection (URI) frequency, risk of acute OM during URI episodes, and proneness to recurrent OM.ResultsIncreased risk for OM proneness was associated with CX3CR1 (Thr280Met) SNP and with a jointly interactive group of IL-10 (−1082) SNP, IL-1β (−511) wild type genotype and white race. Family history of OM proneness independently increased the risk for frequent URIs, OM occurrence during URI, and OM proneness. Additionally, IL-1β (−31) SNP was associated with increased risk for frequent URIs, but IL-10 (−592), IL-1β (−511), IL-5 (−746) and IL-8 (−251) SNPs were associated with decreased risk of URI.ConclusionIL-1β (−31), CX3CR1 (Thr280Met), IL-10 (−1082) and IL-1β (−511) SNPs were associated with increased risk for frequent URIs or OM proneness.

Diet as a Risk Factor for Pneumococcal Carriage and Otitis Media: A Cross-Sectional Study among Children in Day Care Centers

BackgroundPharyngeal bacteria are exposed to different sugar conditions depending on the diet of the child. We hypothesized that dietary factors such as daily intake of carbohydrates could be associated with pneumococcal carriage and the occurrence of otitis media in children.MethodsOur study design was a cross-sectional study among 1006 children attending child day care centers. Parents filled in a food frequency questionnaire. Oropharyngeal swabs were collected from each child. The primary outcome was the occurrence of pneumococcal carriage and the secondary outcome the number of acute otitis media episodes during life. Principal component analysis was used to group dietary intake into nine factors. The models were adjusted for age, gender of the child and educational level of the mother.ResultsThe dietary factor which included high consumption of sweet pastries and jam was associated with an increased risk of pneumococcal carriage (OR 1.17, 95% CI 1.01 to 1.36, P-value 0.04). The factor including frequent consumption of fruit and berries was associated with a decreased risk of acute otitis (regression coefficient −0.51, 95% CI −0.98 to −0.03, P = 0.04). A high intake of consumption of sweets and snacks (OR 1.36, 95% CI 1.03 to 1.80, P = 0.03) was associated with an increased risk of caries.ConclusionsDiet was associated with a risk of pneumococcal carriage and the occurrence of otitis media. Diet may thus be a modifiable risk factor for the occurrence of acute otitis media.

Antimicrobial susceptibility pattern of clinical isolates from cases of ear infection using amoxicillin and cefepime

The aim of the present study was to determine the sensitivity pattern of clinical isolates of otitis media. During the last few decades, the occurrence of otitis media seems to have been rising probably because of prevalence of multidrug-resistant Pseudomonas aeruginosa and β-lactamase producing Staphylococcus aureus in the pathogenesis of otitis media. Pseudomonas aeruginosa and Staphylococcus aureus were the most common causative microorganisms of ear infection. Keeping in view the importance of these pathogens, the present study had been designed to determine the sensitivity pattern of clinical isolates of otitis media. These isolates were collected from different hospitals and pathological laboratories of Karachi and their sensitivity against cefepime and amoxicillin were determined by using disk diffusion method. The results have shown that Pseudomonas aeruginosa was the most common causative microorganism of ear infection. Cefepime, a fourth generation cephalosporin appeared to be an effective antibiotic against Pseudomonas aeruginosa and Staphylococcus aureus.

Tensor tenopexy: A clinical study to assess its effectiveness in improving Eustachian tube function and preventing hearing loss in patients with cleft palate

There is a consensus about the occurrence of otitis media in children with cleft palate before repair. However, controversy continues regarding the recovery of Eustachian tube function and level of hearing loss in the patients after cleft palate repair. Levator sling palatoplasty is an important component of the cleft repair. Most surgeons would routinely transect the tensor tendon (tensor tenotomy) during the course of palatoplasty. However, this procedure may pose a risk to Eustachian tube function. Some authorities feel that addition of tensor tenopexy during palatoplasty would maintain the Eustachian tube in an open conformation, thereby improving middle ear ventilation. The present study assesses the effectiveness of tensor tenopexy in improving Eustachian tube function and preventing hearing loss in cleft palate patients treated with palatoplasty. A prospective randomised controlled trial was conducted in the Department of Plastic Surgery at a tertiary care institute in India. A total of 17 children in the age group of 9-24 months were assigned to one of two groups: palatoplasty with either tensor tenotomy (n=8) or tensor tenotomy with tensor tenopexy (n=9). All patients were subjected to tympanometry, otoscopy and brainstem evoked response audiometry before surgery and at 3, 6, 9 and 12 months after surgery. Of these, 52.9% of patients already had hearing loss at the time of presentation. Hearing loss and middle ear effusion persisted even after palatoplasty. There was no significant difference in hearing loss and middle ear effusion between the two groups of patients. Thus, tensor tenopexy was not found to be helpful in maintaining Eustachian tube function or preventing hearing loss in cleft palate patients. However, further long-term studies are needed to confirm this study.

Tobacco smoke increases the risk of otitis media among Greenlandic Inuit children while exposure to organochlorines remain insignificant

BackgroundPrenatal exposure to environmental levels of organochlorines (OCs) has been demonstrated to have immunotoxic effects in humans. We investigated the relationship between prenatal exposure to OCs and the occurrence of otitis media (OM) among Inuit children in Greenland. MethodsWe estimated the concentration of 14 PCB congeners and 11 pesticides in maternal and cord blood samples and in breast milk in a population-based cohort of 400 mother–child pairs. At follow-up, we examined the children's ears and used their medical records to assess the OM occurrence and severity. Multivariate regression analyses were used with adjustments for passive smoking, crowding, dietary habits, parent's educational level, breast feeding and the use of child-care. ResultsThe children were 4–10years of age at follow-up and 223 (85%) participated. We found no association between prenatal OC exposure and the development of OM. Factors associated with the child's hazard of OM during the first 4years of life were: mother's history of OM (HR 1.70, 95% CI 1.11–2.59, p=0.01); mother's smoking habits: current (HR 2.47, 95% CI 1.45–4.21, p<0.01) and previous (HR 2.00, 95% CI 1.19–3.36, p<0.01); number of smokers in the home (HR 1.17, 95% CI 1.05–1.31, p<0.01). After adjustment mothers' smoking habits remained significant. ConclusionWe found no relationship between high levels of prenatal exposure of OCs and occurrence of OM. Passive smoking was found as the strongest environmental risk factor for the development of OM.Interventions to reduce passive smoke in children's environment are needed.

42 Antibiotic Use in Infants in the First Year of Life in Five European Countries

Background and aimsIn view of antibiotic resistance problems and development of atopic diseases there is a need to improve the appropriateness of antibiotic use, especially in young children. Antibiotics are...

Mutation in Phex Gene Predisposes BALB/c-PhexHyp-Duk/Y Mice to Otitis Media

Genetic susceptibility underlying otitis media (OM) remains to be understood. We show in this study that mutation in Phex gene predisposes the BALB/c-PhexHyp-Duk/Y (abbreviated Hyp-Duk/Y) mice to OM, which occurs at post-natal day 21 (P21) with an average penetrance of 73%. The OM was identified by effusion in the middle ear cavity and/or thickening of middle ear mucosae, and was characterised by increase in goblet cells, deformity of epithelial cilia and higher expression of proliferating cell nuclear antigen (PCNA) in cells of the middle ear mucosae. Moreover, the transcription levels of Tlr2, Tlr4, Nfkb1, Ccl4, Il1b and Tnfα in the ears of the Hyp-Duk/Y mice at P35 were significantly upregulated, compared to those of the controls. Higher expression levels of TLR2, TLR4, NF-κB and TNF-α in the middle ears were demonstrated by immunohistochemistry (IHC). However, the OM in the mice was not prevented by azithromycin administration from gestational day 18 to P35. Further study showed that, in contrast to the low mRNA levels of Phex gene in the ears of the Hyp-Duk/Y mice, the mRNA level of Fgf23 was significantly elevated at P9, P14, P21 and P35. Meanwhile, mRNA levels of EP2 (PGE2 receptor), which expressed in the middle ear epithelia as demonstrated by IHC, were already increased at P14 even before the occurrence of OM, indicating that PGE2, an inflammatory mediator, is involved in the OM development in the mutants. Taking together, Phex mutation primarily up-regulates gene expression levels in FGF23 mediated pathways in the middle ears, resulting in cell proliferation and defence impairment at the mucosae and subsequently bacterial infection. The Hyp-Duk/Y mouse is a new genetic mouse model of OM.