A new strategy for the treatment of middle ear infection using ciprofloxacin/amoxicillin-loaded ethyl cellulose/polyhydroxybutyrate nanofibers.

A middle ear infection occurs due to the presence of several microorganisms behind the eardrum (tympanic membrane) and is very challenging to treat due to its unique location and requires a well-designed treatment. If not treated properly, the infection can result in severe symptoms and unavoidable side effects. In this study, excellent biocompatible ethyl cellulose (EC) and biodegradable polyhydroxybutyrate (PHB) biopolymer were used to fabricate drug-loaded nanofiber scaffolds using an electrospinning technique to overcome antibiotic overdose and insufficient efficacy of drug release during treatment. PHB polymer was produced from Halomonas sp., and the purity of PHB was found to around be 90 %. Additionally, ciprofloxacin (CIP) and amoxicillin (AMX) are highly preferable since both drugs are highly effective against gram-negative and gram-positive bacteria to treat several infections. Obtained smooth nanofibers were between 116.24 and 171.82 nm in diameter and the addition of PHB polymer and antibiotics improved the morphology of the nanofiber scaffolds. Thermal properties of the nanofiber scaffolds were tested and the highest Tg temperature resulted at 229 °C. The mechanical properties of the scaffolds were tested, and the highest tensile strength resulted in 4.65 ± 6.33 MPa. Also, drug-loaded scaffolds were treated against the most common microorganisms that cause the infection, such as S.aureus, E.coli, and P.aeruginosa, and resulted in inhibition zones between 10 and 21 mm. MTT assay was performed by culturing human adipose-derived mesenchymal stem cells (hAD MSCs) on the scaffolds. The morphology of the hAD MSCs' attachment was tested with SEM analysis and hAD MSCs were able to attach, spread, and live on each scaffold even on the day of 7. The cumulative drug release kinetics of CIP and AMX from drug-loaded scaffolds were analysed in phosphate-buffered saline (pH: 7.4) within different time intervals of up to 14 days using a UV spectrophotometer. Furthermore, the drug release showed that the First-Order and Korsmeyer-Peppas models were the most suitable kinetic models. Animal testing was performed on SD rats, matrix and collagen deposition occurred on days 5 and 10, which were observed using Hematoxylin-eosin and Masson's trichrome staining. At the highest drug concentration, a better repair effect was observed. Results were promising and showed potential for novel treatment.

Changes in Otitis Media During COVID-19.

OBJECTIVES: During the COVID-19 pandemic, various non-pharmaceutical interventions such as individual hygiene practices like hand washing, social distancing, and mandates for the use of masks in public spaces were implemented to reduce the spread of the disease. Otitis media (OM) is a common infectious disease. How the changed environment due to the COVID-19 pandemic has influenced the prevalence of infectious diseases like OM is not known. This study aimed to investigate how OM prevalence and trends changed during COVID-19 in Korea. METHODS: OM patient data from 2017 to 2021 were extracted from the Health Insurance Review and Assessment Service database. Patients diagnosed with disease code H66 (suppurative and unspecified otitis media) were selected for analysis. Data on OM prevalence, gender, region, medical institution, and number of ventilating-tube prescriptions were analyzed. All age groups were included, and ages were categorized into 5-year ranges. RESULTS: The number of patients diagnosed with the OM disease code decreased continuously from 2017 to 2021 (1 598 205, 1 560 178, 1 520 948, 983 701, and 734 901). The average OM prevalence per 1000 persons decreased by 45.0% from 30.2 in 2017 to 2019 to 16.6 in 2020 to 2021. The change of OM prevalence was greater for the 0 to 5 age group than other age groups. The decrease in average prevalence per 1000 persons was greatest in the 0 to 5 age group (48.6% decrease from 358.2 in 2017-2019 to 184.1 in 2020-2021). The impact of environmental changes on ventilation-tube insertion was smaller than on OM prevalence. The average number of ventilating-tube insertions decreased by 28.1% from 27 311 in 2017 to 2019 to 19 650 in 2020 to 2021. CONCLUSIONS: OM prevalence decreased by 45.0%, and the number of ventilating-tube insertions decreased by 28.1% in Korea during COVID-19.

Actinomycosis of the Middle Ear Mimicking Cholesteatoma: A Case Report and Literature Review.

Actinomycosis is a rare infection of the middle ear. Actinomyces is an anaerobic, filamentous bacterium causing granuloma formation and suppurative infection. We present a young male with a nine-month history of unilateral, yellow-coloured otorrhoea and hearing loss. Swabs showed no growth, with the infection not responding to oral or topical antibiotics. Computed tomography of temporal bones was consistent with cholesteatoma and ossicular disruption. Surgical exploration revealed a yellow, cystic mass within the middle ear. Cortical mastoidectomy and washout were performed. Histological diagnosis confirmed Actinomyces clusters with positive gram stain. Actinomycosis of the middle ear typically presents as chronic otitis media. It likely reaches the middle ear via the eustachian tube. It is often misdiagnosed due to culture insensitivity; however, clinical suspicion can aid labs in providing an optimum culture environment. Tympanomastoidectomy allows for histopathological diagnosis. Surgical resection should be followed by a prolonged course of antibiotics.

Measuring food insecurity among a national sample of children with recurrent acute otitis media.

INTRODUCTION: Acute otitis media is one of the most common reasons for pediatric medical visits in the United States. Additionally, past studies have linked food insecurity and malnutrition with increased infections and worse health outcomes. However, there is a lack of information on the risk factors for food insecurity in specific patient populations, including the pediatric recurrent acute otitis media (RAOM) population. METHODS: The 2011 to 2018 National Health Interview Survey (NHIS) datasets were used to obtain a national estimate of the presentation of food insecurity within pediatric patients with RAOM. Relevant sociodemographic information and prevalence were identified. A multivariable logistic regression model was used to determine sociodemographic risk factors. Calculations were conducted using R with the "survey" package to account for the clustering and sampling of the NHIS. RESULTS: Of 3844 children with RAOM who responded to the food insecurity module, 20.8 % (19.0-22.6 %) were food insecure. Age, race/ethnicity, percentage of federal poverty level status, insurance status, and self-reported health status were significant and were not independent of food insecurity status. Using multivariable regression, this study found the following sociodemographic risk factors: age 6-10 and age > 10 (reference: age 0-2); Black (reference: Non-Hispanic White); 100 % to 200 % and <100 % federal poverty level (reference: >200 % federal poverty level); public insurance or uninsured status (reference: private insurance); and poor to fair self-reported health status (reference: good to excellent). DISCUSSION: Children with RAOM who were older, Black, less insured, living in lower-income households, and of poorer health had a greater association with being food insecure. Due to the frequency of RAOM pediatric visits, identifying at-risk groups as well as incorporating food insecurity screening and food referral programs within clinical practice can enable otolaryngologists to reduce disparities and improve outcomes in a targeted approach.

Role of topical antibiotic ointment in the lateral graft following underlay myringoplasty: a prospective randomised study.

OBJECTIVE: The objective of this study was to compare the graft outcome and postoperative infection of with and without the use of antibiotic ointment following myringoplasty for the treatment of chronic perforations. STUDY DESIGN: Randomized controlled trial. MATERIAL AND METHODS: 135 chronic perforations were prospectively randomized to use of antibiotic ointment group (UAO, n = 68) or no use of antibiotic ointment group (NAO, n = 67) following myringoplasty. The graft outcomes and postoperative infection were compared among two groups at 6 months. RESULTS: At postoperative 6 months, the graft infection rate was 4.4% in the UAO group and 10.4% in the NAO group, the difference was not significant (P = 0.312).The graft success rates were 92.6% in the UAO group and 91.0% in the NAO group, the difference was not significant (P = 0.979). In the UAO group, 3 patients with purulence ear discharge resulted in a residual perforation although they received ofloxacin ear drops and intravenous antibiotic therapy treatment. In the NAO group, 6 patients with purulence ear discharge resulted in a residual perforation, only one, with mild purulence discharge was successfully treated and closed. In addition, no significant between-group differences were observed pre- (P = 0.746) or post- (P = 0.521) operative air bone gap (ABG) values or mean ABG gain (P = 0.745). However, granular myringitis with minimal moistness but without infection has been noted in 3 (4.4%) patients in the UAO group and in 5 (7.5%) in the NAO group, the difference was not significant (P = 0.699). CONCLUSIONS: Use and non-use of antibiotic ointments for lateral packing of graft are both comparable methods following myringoplasty for postoperative infection and graft outcomes.

Cerebellar Abscess Induced by Cochlear Fistula due to Chronic Suppurative Otitis Media.

Cochlear fistulas with cholesteatoma as the primary disease have been reported frequently in the relevant literature. However, there are no reports of cochlear fistula without cholesteatoma due to chronic suppurative otitis media with intracranial complications. We report a case of cochlear fistula due to chronic otitis media that was diagnosed after the onset of a cerebellar abscess. The patient was a 25-year-old man with severe autism. He was admitted to our hospital with otorrhea from his left ear, emesis, and impaired consciousness. Computed tomography (CT) of the head showed left suppurative otitis media, left cerebellar abscess, and brainstem compression due to hydrocephalus. Right extra-ventricular drainage and brain abscess drainage were urgently performed. The next day, foramen magnum decompression and abscess drainage with partial resection of the swollen cerebellum were performed for decompression purposes. He was subsequently treated with antimicrobial therapy, but magnetic resonance imaging of the head showed an increase in the size of the cerebellar abscess. Re-examination of the temporal bone CT scans revealed a bony defect in the left cochlear promontory angle. We assumed that the cochlear fistula was responsible for the otogenic brain abscess. Thus, the patient underwent surgical closure of the cochlear fistula. After the operation, the cerebellar abscess lesion gradually shrank, and his general condition stabilized. Cochlear fistula should be considered in the management of patients with inflammatory middle ear disease associated with otogenic intracranial complications in the middle ear.

Benefit of Educational Video on Parental Knowledge, Attitude and Practice About Middle Ear Infection in Children.

The aim of the study was to determine the benefit of educational video on parental knowledge, attitude and practice about risk factors of middle ear infection in children. An educational video was developed in English with information on anatomy of the ear, signs and symptoms, risk factors, consequences, prevention, and management related to ear infections. A KAP (Knowledge, attitude and practice) questionnaire was also developed comprising of 33 questions. Parents were requested to fill the questionnaire online and after watching the educational video they were asked to fill the same questionnaire after 1 month. 61 parents responded to both pre questionnaire and post questionnaire. In knowledge domain, thirty five parents gave correct answers to more than sixty percent of questions in the pre questionnaire and fifty six parents gave correct answers to more than sixty percent of the question in the post questionnaire. In attitude domain, all sixty one parents gave correct answers to more than sixty percent of questions in the pre questionnaire. In practice domain, twenty six parents gave correct answers to more than sixty percent of questions in the pre questionnaire and forty nine parents gave correct answers to more than sixty percent of the question in the post questionnaire after watching the educational video. Using the test of proportion, there was statistically significant difference in scores in pre questionnaire and post questionnaire in knowledge and practice domain. In the present study, there was statistically significant improvement in parents overall knowledge and practice about middle ear infection after watching the educational video.

The ECRG4 cleavage product augurin binds the endotoxin receptor and influences the innate immune response during otitis media.

Otitis media (OM), the most common disease of childhood, is typically characterized by bacterial infection of the middle ear (ME). Prominent features of OM include hyperplasia of the ME mucosa, which transforms from a monolayer of simple squamous epithelium with minimal stroma into a full-thickness respiratory epithelium in 2-3 days after infection. Analysis of the murine ME transcriptome during OM showed down-regulation of the tumor suppressor gene Ecrg4 that was temporally related to mucosal hyperplasia and identified stromal cells as the primary ECRG4 source. The reduction in Ecrg4 gene expression coincided with the cleavage of ECRG4 protein to release an extracellular fragment, augurin. The duration of mucosal hyperplasia during OM was greater in Ecrg4 -/- mice, the number of infiltrating macrophages was enhanced, and ME infection cleared more rapidly. ECRG4-null macrophages showed increased bacterial phagocytosis. Co-immunoprecipitation identified an association of augurin with TLR4, CD14 and MD2, the components of the lipopolysaccharide (LPS) receptor. The results suggest that full-length ECRG4 is a sentinel molecule that potentially inhibits growth of the ME stroma. Processing of ECRG4 protein during inflammation, coupled with a decline in Ecrg4 gene expression, also influences the behavior of cells that do not express the gene, limiting the production of growth factors by epithelial and endothelial cells, as well as the activity of macrophages.

Distribution and Antimicrobial Resistance Profiles of Bacterial Aetiologies of Childhood Otitis Media in Accra, Ghana.

Background: Otitis media (OM), also known as middle ear infection, is a clinically significant childhood disease. In sub-Saharan Africa, there is a paucity of contemporary reports on it is bacterial aetiologies and antimicrobial resistance among them. Aim: To investigate the OM bacterial aetiologies and their antimicrobial resistance patterns among children visiting the Ear, Nose, and Throat clinics of 3 healthcare facilities in Accra, Ghana - Princess Marie Louise Children's Hospital, 37 Military Hospital, and Mamprobi Hospital. Methods: This cross-sectional study involved 100 children below 13 years old with suppurative otitis media. Following standard bacteriological methods, sterile ear swabs were used to take middle ear discharges from the study participants for culture and antimicrobial susceptibility testing. A standard questionnaire was also used to collect data on socio-demographic and clinical characteristics. Results: The major OM bacterial aetiologies were Pseudomonas aeruginosa (38.5%), Klebsiella pneumoniae (19.8%), Proteus mirabilis (11.5%), and Staphylococcus aureus (10.4%). The majority of the bacteria demonstrated low to moderate resistance (0%-33.3%) to most of the antibiotics. Eight of the bacteria (4 each of Klebsiella pneumoniae and Escherichia coli) were extended-spectrum beta-lactamase (ESBL) producers; 6 ampicillinase (Amp C)-producing organisms (4 Citrobacter spp. and one each of Morganella morganii and Serratia marcescens) were also identified, and they showed high antibiotic resistance. Conclusions: The predominant OM aetiologies were Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus mirabilis, and Staphylococcus aureus, and they were generally susceptible to most of the antibiotics tested. Amikacin, cefepime, ciprofloxacin, and meropenem could be valuable in the empirical management of childhood OM.

Frequency of hearing impairment in children between the ages of 2 and 10 years with middle ear infection.

This study was conducted on children between 2 and 10 years age to determine the frequency of hearing impairment in middle ear infection. It was a cross-sectional survey, done at Riphah International University from August 2018 to January 2019. Data was collected from the ENT Department of Children's Hospital Lahore through convenience sampling technique and included 52 patients with middle ear infection. Measurements for the level of hearing impairment were taken, and data was analysed using statistical package for social sciences, SPSS 20.0. Of the total 52 patients, 15 (28.8%) had ear infection once a month and 37 (71.2%) had it off and on. Mild hearing loss was determined in 35 (67.3%) patients,13 (25%) had moderate, 2 (3.8%) severe and 2 (3.8%) had normal hearing. It was concluded that most of the children with middle ear infections developed hearing loss.

The Nontypeable Haemophilus influenzae Major Adhesin Hia Is a Dual-Function Lectin That Binds to Human-Specific Respiratory Tract Sialic Acid Glycan Receptors.

NTHi is a human-adapted pathogen that colonizes the human respiratory tract. Strains of NTHi express multiple adhesins; however, there is a unique, mutually exclusive relationship between the major adhesins Hia and HMW1 and HMW2 (HMW1/2). Approximately 25% of NTHi strains express Hia, a phase-variable autotransporter protein that has a critical role in colonization of the host nasopharynx. The remaining 75% of strains express HMW1/2. Previous work has shown that the HMW1 and HMW2 proteins mediate binding to 2-3- and 2-6-linked sialic acid glycans found in the human respiratory tract. Here, we show that the high-affinity binding domain of Hia, binding domain 1 (BD1), is responsible for binding to α2-6-sialyllactosamine (2-6 SLN) glycans. BD1 is highly specific for glycans that incorporate the form of sialic acid expressed by humans, N-acetylneuraminic acid (Neu5Ac). We further show that Hia has lower-affinity binding activity for 2-3-linked sialic acid and that this binding activity is mediated via a distinct domain. Thus, Hia with its dual binding activities functionally mimics the combined activities of the HMW1 and HMW2 adhesins. In addition, we show that Hia has a role in biofilm formation by strains of NTHi that express the adhesin. Knowledge of the binding affinity of this major NTHi adhesin and putative vaccine candidate will direct and inform development of future vaccines and therapeutic strategies for this important pathogen.IMPORTANCE Host-adapted bacterial pathogens like NTHi have evolved specific mechanisms to colonize their restricted host niche. Relatively few of the adhesins expressed by NTHi have been characterized as regards their binding affinity at the molecular level. In this work, we show that the major NTHi adhesin Hia preferentially binds to Neu5Ac-α2-6-sialyllactosamine, the form of sialic acid expressed in humans. The receptors targeted by Hia in the human airway mirror those targeted by influenza A virus and indicates the broad importance of sialic acid glycans as receptors for microbes that colonize the human airway.

Phase-based Eulerian motion magnification reveals eardrum mobility from pneumatic otoscopy without sealing the ear canal.

Pneumatic otoscopy is the recommended diagnostic method for middle ear infections. Physicians use a pneumatic otoscope to assess the position of the eardrum (bulging or retraction) as well as the eardrum mobility while an insufflation bulb is squeezed to generate air pressure changes in a sealed ear canal. While pneumatic otoscopy provides increased sensitivity and specificity by detecting decreased eardrum mobility, there exist many challenges to correctly perform and interpret results. For example, the ear canal must be sealed using a specialized ear speculum to deliver sufficiently large pressure changes that can induce visible movements of an eardrum. To overcome this challenge, video motion magnification is proposed to amplify pneumatic-induced motions of the eardrum without sealing of the ear canal. Pneumatic otoscopy is performed on adult subjects using a smartphone camera with an otoscope attachment at 60 frames per second, with pressure inputs at 5 Hz. Phase-based Eulerian motion magnification is applied to magnify spatiotemporal dependent motions in the video. As a result, the motion magnification of unsealed pneumatic otoscopy reveals comparable eardrum motions as in standard pneumatic otoscopy with a sealed ear canal. Furthermore, the estimated motions (in pixels) are quantified to examine the spatial and the temporal variations of the eardrum motions. The motion magnification may avoid the need for sealing the ear canal as well as decrease patient discomfort in pneumatic otoscopy, improving the capability and the usability as a point-of-care diagnostic tool in primary care and otology.

MUC5B induces in vitro neutrophil extracellular trap formation: Implication in otitis media.

BACKGROUND: Chronic otitis media (COM) is characterized by middle ear fluid predominantly containing cytokines, Nontypeable haemophilus influenzae (NTHi), the mucin MUC5B, and neutrophil extracellular traps (NETs). NETs consist of extracellular DNA coated with antibacterial proteins such as myeloperoxidase (MPO) and citrullinated histone 3 (CitH3). NETs can damage tissues and sustain inflammation. Our study aimed to develop an in vitro model of NETosis, testing COM inductors. METHODS: NETosis was evaluated in fresh blood human neutrophils attached to collagen-coated plates and in suspension exposed to phorbol myristate acetate (PMA) as a control, and COM relevant mediators. Confocal microscopy, DNA fluorescence assay and flow cytometry were used to quantify NETosis. RESULTS: PMA exposure induced DNA, MPO, and CitH3 by immunofluorescence (IF) most significantly at 3 hours (3.8-fold for DAPI, 7.6-fold for MPO, and 6.9-fold for CitH3, all P < .05). IL-8 and TNF-α cytokines showed milder increases of DAPI, MPO, and CitH3 positive cells. NTHi had no effect on these NETs markers. Purified salivary MUC5B (10 to 40 µg/mL) produced potent increases, comparable to PMA. A composite NET score summing the fold-increases for DAPI, MPO, and CitH3 demonstrated PMA at 13.6 to 19 relative to control set at 1; and MUC5B at 8.6 to 16.3 (all P < .05). IL-8 and TNF-α showed scores of 5.4 and 3, respectively, but these were not statistically significant. CONCLUSION: We developed a reliable in vitro assay for NETosis which demonstrated that salivary MUC5B is a potent inductor of NETs whereas IL-8, TNF-α, live and lyzed NTHi demonstrated minimal to no NETosis. LEVEL OF EVIDENCE: NA.

Optical Identification of Middle Ear Infection.

Ear infection is one of the most commonly occurring inflammation diseases in the world, especially for children. Almost every child encounters at least one episode of ear infection before he/she reaches the age of seven. The typical treatment currently followed by physicians is visual inspection and antibiotic prescription. In most cases, a lack of improper treatment results in severe bacterial infection. Therefore, it is necessary to design and explore advanced practices for effective diagnosis. In this review paper, we present the various types of ear infection and the related pathogens responsible for middle ear infection. We outline the conventional techniques along with clinical trials using those techniques to detect ear infections. Further, we highlight the need for emerging techniques to reduce ear infection complications. Finally, we emphasize the utility of Raman spectroscopy as a prospective non-invasive technique for the identification of middle ear infection.

Middle ear infection in children and its association with dental caries.

INTRODUCTION: Middle ear infection affects mostly infants and children, associated with elevated level of S. mutans, which increases the chances of developing caries. AIM: To evaluate the difference in level of Streptococcus mutans between normal children & children affected by middle ear infection. METHOD: This descriptive study was carried out on 120 children aged 5 years and younger. They were selected randomly from schools and medical hospitals. S. mutans was counted from saliva sample and a questionnaire was given to be filled by their parents about the feeding method, pattern and specific childhood illness. RESULT: Out of 120 children examined, 62 were boys and 58 were girls. Mean CFU in middle ear infection group was 5.60+9.53, whereas in children with no middle ear infection it was 1.70+3.34. Unpaired 't' test revealed statistically significant difference among the two groups (p value = 0.001). CONCLUSION: S. mutans count was comparatively higher in children having middle ear infection rather than non-infected children, which may cause dental caries in the future.

Associations between Otitis media, taste sensitivity and adiposity: Two studies across childhood.

BACKGROUND: Otitis media (OM), or middle ear infections, are one of the most common diseases during early childhood. OM has been linked to changes in food preferences through potential effects on taste signalling, and thereby, to increased weight. OBJECTIVES: We investigated the associations between OM, taste sensitivity and adiposity across two studies in early childhood and conducted exploratory post-hoc analyses of sex differences. METHODS: Study I assessed 101 children between 2 and 3 years old (59.0% boys). Children were weighed and their height was measured to estimate BMI centiles. Waist measurements were taken to calculate Waist-to-Height Ratio (WHtR). Child's taste sensitivity was assessed using Short Sensory Profile questionnaire. Study II included 95 children between 5 and 9 years old (52.9% boys). Children were weighed and their height was measured to calculate their BMI. Children took part in a Sucrose Detection Threshold (SDT) assessment to establish their taste sensitivity. In both studies parents reported child's history of OM. RESULTS: In Study I OM was associated with higher WHtR (p=0.047), though this was observed among girls (p=0.011), but not boys (p=0.53). OM was not linked to BMI centiles or taste sensitivity (all p>0.05). In Study II children with OM history had higher BMI centiles (p=0.010), and this effect was stronger in boys (p=0.037) than girls (p=0.17). Multiple OM exposure increased the odds of overweight by 6.2 times (95%CI [1.46, 26.50]). Boys with multiple OM exposure had higher SDT (p=0.022) compared to boys not exposed to OM, akin to lower taste sensitivity. This was not observed in girls (p=0.67). CONCLUSIONS: OM history was associated with higher BMI among 5-9 year old children and this may be linked to taste impairments. This association was not observed in 2-3 year old children. Potential sex differences in these associations require further investigation.

FUT2 Variants Confer Susceptibility to Familial Otitis Media.

Non-secretor status due to homozygosity for the common FUT2 variant c.461G>A (p.Trp154∗) is associated with either risk for autoimmune diseases or protection against viral diarrhea and HIV. We determined the role of FUT2 in otitis media susceptibility by obtaining DNA samples from 609 multi-ethnic families and simplex case subjects with otitis media. Exome and Sanger sequencing, linkage analysis, and Fisher exact and transmission disequilibrium tests (TDT) were performed. The common FUT2 c.604C>T (p.Arg202∗) variant co-segregates with otitis media in a Filipino pedigree (LOD = 4.0). Additionally, a rare variant, c.412C>T (p.Arg138Cys), is associated with recurrent/chronic otitis media in European-American children (p = 1.2 × 10-5) and US trios (TDT p = 0.01). The c.461G>A (p.Trp154∗) variant was also over-transmitted in US trios (TDT p = 0.01) and was associated with shifts in middle ear microbiota composition (PERMANOVA p < 10-7) and increased biodiversity. When all missense and nonsense variants identified in multi-ethnic US trios with CADD > 20 were combined, FUT2 variants were over-transmitted in trios (TDT p = 0.001). Fut2 is transiently upregulated in mouse middle ear after inoculation with non-typeable Haemophilus influenzae. Four FUT2 variants-namely p.Ala104Val, p.Arg138Cys, p.Trp154∗, and p.Arg202∗-reduced A antigen in mutant-transfected COS-7 cells, while the nonsense variants also reduced FUT2 protein levels. Common and rare FUT2 variants confer susceptibility to otitis media, likely by modifying the middle ear microbiome through regulation of A antigen levels in epithelial cells. Our families demonstrate marked intra-familial genetic heterogeneity, suggesting that multiple combinations of common and rare variants plus environmental factors influence the individual otitis media phenotype as a complex trait.

Air Pollution and Otitis Media in Children: A Systematic Review of Literature.

Young children are particularly vulnerable to otitis media (OM) which globally affects over 80% of children below the age of 3 years. Although there is convincing evidence for an association between environmental tobacco smoke exposure and OM in children, the relationship with ambient air pollution is not clear. We aimed to systematically review the literature on the relationship between ambient air pollution exposure and OM in children. A systematic search was performed in PubMed and EMBASE databases. Of 934 references identified, 24 articles were included. There is an increasing body of evidence supporting an association between higher ambient air pollution exposure and a higher risk of OM in children. While NO2 showed the most consistent association with OM, other specific pollutants showed inconsistent associations. Studies were mainly conducted in high/middle income countries with limited evidence from low-income countries. Although there was a general consensus that higher air pollution exposure is associated with a greater prevalence of OM, the evidence for associations with specific pollutants is inconsistent. More well-designed studies on associations between specific air pollutants as risk factors for OM are warranted, especially in low income countries with high air pollution levels.

Otogenic Meningitis: A Comparison of Diagnostic Performance of Surgery and Radiology.

Development of intracranial complications from middle ear infections might be difficult to diagnose. We compared radiological and surgical findings of 26 patients affected by otogenic meningitis. Results of our analysis showed that surgery is more reliable than imaging in revealing bone defects. Therefore, suggest that surgery be performed for diagnosis and eventual management of all cases of suspected otogenic meningitis.

Non-Typeable Haemophilus influenzae Infection of the Junbo Mouse.

Acute otitis media, inflammation of the middle ear bulla, is the most common bacterial infection in children. For one of the principal otopathogens, non-typeable Haemophilus influenzae (NTHi), animal models allow us to investigate host-microbial interactions relevant to the onset and progression of infection and to study treatment of middle ear disease. We have established a robust model of NTHi middle ear infection in the Junbo mouse. Intranasal inoculation with NTHi produces high rates of bulla infection and high bacterial titers in bulla fluids; bacteria can also spread down the respiratory tract to the mouse lung. An innate immune response is detected in the bulla of Junbo mice following NTHi infection, and bacteria are maintained in some ears at least up to day 56 post-inoculation. The Junbo/NTHi infection model facilitates studies on bacterial pathogenesis and antimicrobial intervention regimens and vaccines for better treatment and prevention of NTHi middle ear infection. © 2017 by John Wiley & Sons, Inc.