Otitis Media Research Research Articles

Exploring the OTITIS Research Landscape Through a Scientometric Approach.

Otitis media is a common health problem affecting people of all ages and significantly impacting public health and healthcare costs. Otitis media, a type of middle ear disease, is one of the most common types. This scientometric study aimed to provide an overview of the knowledge domain in otitis media research. Documents were retrieved from the Web of Science database. A scientometric study was then performed on a sample of 27,213 documents. This study found that research on otitis media has increased significantly in recent years, with an annual growth rate of 4.58%. The average age of the documents analyzed was 18years, with an average of 21.88 citations and an average of 4.58 authors. The United States, the United Kingdom, and Japan ranked first to third in terms of number of publications. Still, the United States, China, and Sweden were in a better position in terms of impact on the research network. Co-occurrence word analysis showed that significant attention was given to topics such as chronic inflammation in autism, acute inflammation in otitis media, and increased fluid in the middle ear. This study highlights the need to prioritize and focus attention on otitis, particularly otitis media, due to its prevalence and impact on public health. The use of scientometric software, such as Biblioshiny and CiteSpace, provides a valuable means of assessing research trends and identifying important areas for future study in the field of knowledge.

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.

Ensuring the future of otitis media research: Interest in and feasibility of a mentoring network program within the otitis media research community.

The goal of this study was to assess the feasibility of the implementation of a mentoring network program based on expressed interest and the diverse composition of the otitis media research community in order to address attrition of the scientific workforce. An online survey was sent to basic, translational, and clinical researchers with a known interest in otitis media. Of 509 eligible participants, 119 (23.4%) responded to the survey. Survey respondents had a diverse background by completed education, current job description, and membership in an underrepresented group in science. Most faculty respondents (76.4%) were willing to participate in the proposed program as mentors and faculty lecturers, or had early-career researchers or trainees in their research group who were willing to participate as mentees in the mentoring network. Scientific and non-scientific topics for inclusion in the training program were ranked, with immunology and inflammation, microbiology, science leadership and collaboration, mentoring, and grantsmanship as main foci of interest among respondents. Our survey results showed enthusiastic participation among responding otitis media researchers, indicating the feasibility of implementing a mentoring network program that will address workforce attrition, particularly among underrepresented groups in science.

Resolution of otitis media in a humanized mouse model.

Otitis media (OM) is one of the largest public health problems of children and has devastating impacts in developing countries. The substantial medical and human costs involved have led to research to understand the disease and improve treatment. Animal models of OM have yielded critical information about the immune, inflammatory and genetic mechanisms of OM. However, it is important to link animal studies to human immune and inflammatory responses. In recent years, "humanized" mice have become a valuable tool to study the human immune system in an animal model. Here we describe the first use of humanized mice to study OM. We demonstrate that humanized mice with a sufficient degree of engraftment recapitulate a normal middle ear (ME) inflammatory response to bacterial infection, including the recruitment of human immune cells, and exhibit normal recovery. Moreover, these animals exhibit regulated expression of human-specific immune and inflammatory genes in the ME. In contrast, mice with insufficient engraftment fail to resolve OM. This model has many potential uses in OM research, including using hematopoietic stem cells from patients with differing degrees of OM susceptibility, to understand the role of human immune responses in proneness to this common childhood disease.

Analysis of Inflammatory Signaling in Human Middle Ear Cell Culture Models of Pediatric Otitis Media.

Cell culture models are valuable tools for investigation of the molecular pathogenesis of diseases including otitis media (OM). Previous study indicates that age-, sex-, and race-associated differences in molecular signaling may impact disease pathophysiology. Currently, a singular immortalized middle ear epithelial (MEE) cell line exists, HMEEC-1, derived from an adult without known middle ear disease. In this study, HMEEC-1 and primary MEE cultures from pediatric patients with and without OM were stimulated with inflammatory cytokines or OM-pathogenic bacterial lysates to examine differences in the response of molecules associated with OM pathogenesis. Case-control series. MEE cultures were established from patients aged <6 years: two with recurrent OM (ROM), two with OM with effusion (OME), and one patient without OM who was undergoing cochlear implant surgery control undergoing cochlear implantation (Peds CI). Primary MEE cultures and HMEEC-1 cells were stimulated with tumor necrosis factor-α, interleukin (IL)-1β, or nontypeable Haemophilus influenzae lysate. TNFA, IL1B, IL6, IL8, IL10, and MUC5B were assayed via quantitative polymerase chain reaction. IL-8 was assayed by enzyme-linked immunosorbent assay. Gene/protein target expressions were frequently higher in pediatric OM lines than in HMEEC-1 and Peds CI. HMEEC-1 cells were frequently less responsive to stimuli than all pediatric lines. OME lines were often more responsive than ROM lines. OM may be associated with specific molecular phenotypes that are retained in primary cell culture. Adult-derived HMEEC-1 cells differ significantly in baseline expression and response of OM-associated molecules relative to pediatric MEE cells. Work is underway to immortalize pediatric OM MEE cultures as improved tools for the OM research community. 4 Laryngoscope, 131:410-416, 2021.

Middle ear disease in CF? It's not just about the sinuses anymore!

IntroductionHistorically cystic fibrosis (CF), in contrast to primary ciliary dyskinesia (PCD), has been considered protective of the middle ear from otitis media and rarely were such patients “severely affected” to require tympanostomy tube placement (BMT). Previously the Pittsburgh Otitis Media Research group reported a 10% prevalence of otitis media in the pediatric CF population which is significantly lower than age matched non-CF children. We studied the prevalence of OM in pediatric CF patients to assess if the otologic phenotype has changed in parallel with changes in the diagnosis itself. MethodsThe medical records of 133 CF patients seen either inpatient or outpatient from one of the largest tertiary pediatric CF centers in the world from 2010 to 2019 were reviewed for demographics, acute otitis media (AOM) episodes, risk factors for AOM, placement of myringotomy tubes, genotype, BMI, pancreatic status, respiratory culture results, and pulmonary exacerbations. ResultsJust over half (52.6%) the patients were male. A median age for CF diagnosis was 11 days old (range 0 days–16 years). The most common genotype (49.6%) was homozygous for ΔF508 mutation. Fifty-five (41.4%) patients had 1-2 episodes of AOM, and 15 (11.3%) were severely affected (i.e. ≥3 episodes/6 months or ≥4 episodes/year). COME was diagnosed in 4 (3.0%) of the patients. Twelve (9.0%) patients had tympanostomy tubes at least once, including 3 patients with multiple sets of tubes. Having at least one AOM episode was not predicted by genetic mutation groups, BMI, age at diagnosis, or comorbidities, p > .05. ConclusionsThe time-honored adage of CF protecting against otitis media is no longer true and pediatric otolaryngologists must now prioritize the management of middle ear disease as highly as sino-nasal and pulmonary disease. Future study into mechanisms explaining the change is needed.

Moraxella catarrhalis Promotes Stable Polymicrobial Biofilms With the Major Otopathogens.

Otitis media (OM) is a prevalent pediatric infection characterized by painful inflammation of the middle ear. The Gram-negative diplococcus Moraxella catarrhalis is a commensal of the nasopharynx and one of three leading causative agents of OM. The most recent work on this multifaceted disease indicates that biofilms and polymicrobial infections play a pivotal role in recurrent and chronic OM, which are difficult to eradicate using standard antibiotic protocols. Although there have been significant advances in OM research, the actual bacterial and viral interactions leading to pathogenesis remain largely uncharacterized. However, colonization and persistence in the nasopharynx is clearly an essential first step. In this study, we assessed the role M. catarrhalis plays in the co-colonization and persistence of the other major otopathogens, Streptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi). We characterized both monomicrobial and polymicrobial biofilms using an in vitro nasopharyngeal colonization model. Biofilm assays were designed to mimic the nasopharynx and bacterial persistence was quantified over time. NTHi showed a steady and significant decline in viability over 20–48 h when this organism was in a dual species biofilm with S. pneumoniae. However, when M. catarrhalis was present in the polymicrobial biofilm NTHi survived for 48 h at 107 CFU per mL. In addition, an isogenic M. catarrhalis catalase-deficient mutant was also fully capable of protecting NTHi from the bactericidal activity of S. pneumoniae in a polymicrobial biofilm. Our results show that M. catarrhalis promotes a favorable environment for stable polymicrobial biofilms by enhancing the survival of NTHi in the presence of S. pneumoniae. These data suggest that colonization with M. catarrhalis promotes stable co-colonization with other otopathogens.

Otitis media and biofilm: An overview

Otitis media (OM) is a group of complex infective and inflammatory conditions affecting the middle ear, with a variety of subtypes differing in presentation and associated complications. It is the highest cause of pediatric health-care visits and antibiotic prescriptions internationally. It has been stated that approximately 75% of children under age three suffer from middle-ear infections. OM complications are the essential cause of preventable hearing loss, particularly in low-resource settings. Currently, scientists have confirmed that bacteria form colonies in the middle ear and are responsible for chronic infections. While bacteria are often thought of as independently free-floating living microorganisms, most of the bacteria and fungus forms organize complex communities and attach to surfaces called biofilm. Biofilm formation is considered as a survival strategy by bacteria to counteract traditional approaches (such as antibiotics) which are effective against bacteria. Biofilms are almost impossible to grow in the laboratory media and are incredibly resistant to antimicrobials which mean that the diagnosis of chronic OM is one of the most challenging in the management of middle-ear infection. This article aims to provide an appraisal of current scientific successes within the field of OM research and clinical management.

Panel 2: Anatomy (Eustachian Tube, Middle Ear, and Mastoid-Anatomy, Physiology, Pathophysiology, and Pathogenesis).

Objective In this report, we review the recent literature (ie, past 4 years) to identify advances in our understanding of the middle ear-mastoid-eustachian tube system. We use this review to determine whether the short-term goals elaborated in the last report were achieved, and we propose updated goals to guide future otitis media research. Data Sources PubMed, Web of Science, Medline. Review Methods The panel topic was subdivided, and each contributor performed a literature search within the given time frame. The keywords searched included middle ear, eustachian tube, and mastoid for their intersection with anatomy, physiology, pathophysiology, and pathology. Preliminary reports from each panel member were consolidated and discussed when the panel met on June 11, 2015. At that meeting, the progress was evaluated and new short-term goals proposed. Conclusions Progress was made on 13 of the 20 short-term goals proposed in 2011. Significant advances were made in the characterization of middle ear gas exchange pathways, modeling eustachian tube function, and preliminary testing of treatments for eustachian tube dysfunction. Implications for Practice In the future, imaging technologies should be developed to noninvasively assess middle ear/eustachian tube structure and physiology with respect to their role in otitis media pathogenesis. The new data derived from these structure/function experiments should be integrated into computational models that can then be used to develop specific hypotheses concerning otitis media pathogenesis and persistence. Finally, rigorous studies on medical or surgical treatments for eustachian tube dysfunction should be undertaken.

Aboriginal and non-Aboriginal children in Western Australia carry different serotypes of pneumococci with different antimicrobial susceptibility profiles.

BackgroundCarriage of Streptococcus pneumoniae is considered a precursor to pneumococcal diseases including pneumonia. As part of the Kalgoorlie Otitis Media Research Project, we characterised pneumococci isolated from the nasopharynx of Western Australian Aboriginal and non-Aboriginal children.MethodsBetween 1999 and 2005, 100 Aboriginal and 180 non-Aboriginal children were followed from birth to two years, with nasopharyngeal aspirates collected at ages 1–3 and 6–8 weeks, then at 4, 6, 12, 18 and 24 months. Introduction of 7-valent pneumococcal conjugate vaccine (7vPCV) in 2001 enabled evaluation of its impact on carriage in study participants according to vaccines doses received. Pneumococcal serotyping was performed by Quellung and antimicrobial susceptibility by disk diffusion and Etest®. Molecular epidemiology of pneumococcal isolates was investigated by pulse-field gel electrophoresis and multilocus sequence typing.ResultsOverall, the prevalence of 7vPCV serotypes was similar for Aboriginal and non-Aboriginal children (19 % vs. 16 %), but the prevalence of non-vaccine serotypes was higher in Aboriginal children (22 % vs. 7 %). A multi-resistant 6B clone (ST90) was found only in non-Aboriginal children. Aboriginal children who received three doses of 7vPCV had lower odds of carrying 7vPCV serotypes (odds ratio [OR] 0.19, 95 % CI 0.08–0.44) and higher odds of carrying non-vaccine serotypes (OR 2.37, 95 % CI 1.13–4.99) than unvaccinated Aboriginal children; this finding was not observed in non-Aboriginal children.ConclusionsThis unique study shows important differences in pneumococcal serotypes, genotypes, and antimicrobial susceptibility between Aboriginal and non-Aboriginal children living in the same geographic area before widespread 7vPCV use, and highlights the need for ongoing post-vaccination surveillance in outback Australia.Electronic supplementary materialThe online version of this article (doi:10.1186/s41479-016-0015-9) contains supplementary material, which is available to authorized users.

Otitis media induced by peptidoglycan-polysaccharide (PGPS) in TLR2-deficient (Tlr2−/−) mice for developing drug therapy

BackgroundToll like receptor 2 (TLR2) signaling can regulate the pathogenesis of otitis media (OM). However, the precise role of TLR2 signaling in OM has not been clarified due to the lack of an optimal animal model. Peptidoglycan–polysaccharide (PGPS) of the bacterial cell wall can induce inflammation by activating the TLR2 signaling. This study aimed at examining the pathogenic characteristics of OM induced by PGPS in Tlr2−/− mice, and the potential therapeutic effect of sodium aescinate (SA) in this model. MethodsWild-type (WT) and Tlr2−/− mice were inoculated with streptococcal PGPS into their middle ears (MEs) and treated intravenously with vehicle or SA daily beginning at 3days prior to PGPS for 6 consecutive days. The pathologic changes of individual mice were evaluated longitudinally. ResultsIn comparison with WT mice, Tlr2−/− mice were susceptible to PGPS-induced OM. Tlr2−/− mice displayed greater hearing loss, tympanic membrane damage, ME mucosal thickening, longer inflammation state, cilia and goblet cell loss. SA-treatment decreased neutrophil infiltration, modulated TLR2-related gene expression and improved ciliary organization. ConclusionsPGPS induced a relatively stable OM in Tlr2−/− mice, providing a new model for OM research. Treatment with SA mitigated the pathogenic damage in the ME and may be valuable for intervention of OM.

Update on otitis media &amp;ndash; prevention and treatment

Acute otitis media and otitis media with effusion are common childhood disorders, a source of significant morbidity, and a leading cause of antibiotic prescription in primary health care. Although effective treatments are available, some shortcomings remain, and thus better treatments would be welcome. Recent discoveries within the field of otitis media research relating to its etiology and pathogenesis have led to further investigation aimed at developing novel treatments. This article provides a review of the latest evidence relating to the understanding of acute otitis media and otitis media with effusion, current treatment strategies, their limitations, new areas of research, and novel strategies for treatment.

Mouse Models of Otitis Media

There has been a rapid rise in the use of the mouse to investigate pathobiology of otitis media. This is for good reason, including easy husbandry, but also capacity for genetic manipulation of the mouse. Insights into human disease have been gleaned from mouse models, but there are limitations of the mouse-to-man approach. First, important differences exist between mouse and man, particularly in immune function. Second, functional equivalence of genes in the 2 species is not ensured. Third, laboratory mice of a uniform genetic background and environment are an inadequate model of the plethora of factors affecting complex disease in humans. Finally, gene function in mouse models is often obliterated using gene knockout technology, but this is a poor mimic of normal gene variation in man. These drawbacks of the mouse may in the future limit its usefulness in otitis media research.

Prostate Cancer Metastasis to Facial Nerve

*Department of Sensory Medicine, Division of Otorhinolaryngology & Head and Neck Surgery, Akita University School of Medicine, Akita, Japan; †Department of Otolaryngology, Otitis Media Research Center, University of Minnesota; and ‡Paparella Ear, Head and Neck Institute, Minneapolis, Minnesota, U.S.A. Address correspondence and reprint requests to Michael M. Paparella, M.D., 701 25th Avenue South, Suite 200, Minneapolis, MN 55454-1449; E-mail: [email protected] This work was supported by the International Hearing Foundation, the Starkey Foundation, and the Society for Promotion of International Oto-Rhino-Laryngology Foundation.

Vestibular Schwannoma

*International Hearing Foundation; †Department of Otolaryngology, University of Minnesota; and ‡Paparella Ear Head and Neck Institute, Minneapolis, Minnesota, U.S.A. Address correspondence and reprint requests to Sebahattin Cureoglu, M.D., Department of Otolaryngology, Otitis Media Research Center, University of Minnesota, Room 21, Lions Research Building, 2001 6th Street SE, Minneapolis, MN, U.S.A.; E-mail: [email protected] Supported by the International Hearing Foundation and Starkey Hearing Foundation.

Antimicrobial susceptibility of Moraxella catarrhalis isolated from children in Kalgoorlie–Boulder, Western Australia

To investigate antimicrobial susceptibility of Moraxella catarrhalis isolated from a cohort of children being followed in a study of the natural history of otitis media in a semi-arid region of Western Australia. In the Kalgoorlie Otitis Media Research Project nasopharyngeal aspirates were collected from children up to seven times between the age of 1 week and 2 years. A total of 261 M. catarrhalis strains from 50 Aboriginal and 50 non-Aboriginal children were tested against 14 antibiotics using the Clinical and Laboratory Standards Institute (CLSI) agar dilution method. All strains were susceptible to amoxicillin/clavulanate, cefuroxime, azithromycin, ciprofloxacin, moxifloxacin, levofloxacin, erythromycin and minocycline. While no criteria exist for assessment of susceptibility to roxithromycin, minimum inhibitory concentrations (MICs) were low. Approximately 46% of strains from Aboriginal children and 27% from non-Aboriginal children appeared susceptible to ampicillin. A small number of strains was intermediately resistant to cefaclor (9/261, 3.4%), while the bulk of strains was intermediately resistant to co-trimoxazole. A low prevalence of tetracycline resistance (3/261, 1.1%) was noted. beta-lactamase production was observed in 97.7% of strains. While M. catarrhalis strains from children of the Kalgoorlie region were susceptible to many of the antibiotics used to treat respiratory tract infections, a large proportion of strains were resistant to ampicillin and/or co-trimoxazole. Current therapeutic guidelines, which recommend amoxicillin for treatment of otitis media, may need to be revised.

New horizons: otitis media research in Australia

Otitis media affects nearly all children worldwide. Despite an enormous amount of research, our understanding of this common condition continues to be challenged. New pathogens involved in otitis media are still being identified. The importance of interactions between viral and bacterial infection and the role of new vaccines need to be clarified. The proposal that bacteria can become more resistant to therapy through biofilm formation and intracellular infection could have important implications for treatment. The most important clinical research findings have been summarised in systematic reviews. In developed countries, research supporting "watchful waiting" of otitis media with effusion and acute otitis media have had most impact on evidence-based clinical practice guidelines. Indigenous Australian children remain at risk of more severe otitis media. Research programs targeting this population have been well supported. Unfortunately, interventions that can dramatically improve outcomes have remained elusive. For children at high risk of otitis media, health care services should concentrate on accurate diagnosis, antibiotic treatment of suppurative infections, and scheduled follow-up of affected children. Despite the lack of recent studies, strategies to minimise the impact the hearing loss associated with otitis media are important. Improvements in education, hygiene practices, and living conditions are likely to reduce the incidence and severity of otitis media. Studies of these types of interventions are needed.

Mucormycosis of the Temporal Bone

Department of Otolaryngology, Otitis Media Research Center, University of Minnesota; and International Hearing Foundation, Minneapolis, Minnesota, U.S.A. Address correspondence and reprint requests to Michael M. Paparella, M.D., 701 25th Avenue South, Suite 200, Minneapolis, MN 55454-1449; E-mail: [email protected] This study was supported by Grant RO1 DC006452 from the National Institute on Deafness and Other Communication Disorders, the International Hearing Foundation, the Hubbard Foundation, and the Starkey Foundation.

The Kalgoorlie Otitis Media Research Project: rationale, methods, population characteristics and ethical considerations

SummaryOtitis media (OM) is one of the most common paediatric illnesses for which medical advice is sought in developed countries. Australian Aboriginal children suffer high rates of OM from early infancy. The resultant hearing loss can affect education and quality of life. As numerous factors contribute to the burden of OM, interventions aimed at reducing the impact of single risk factors are likely to fail. To identify key risk factors and understand how they interact in complex causal pathways, we followed 100 Aboriginal and 180 non‐Aboriginal children from birth to age 2 years in a semi‐arid zone of Western Australia. We collected demographic, obstetric, socio‐economic and environmental data, breast milk once, and nasopharyngeal samples and saliva on seven occasions. Ear health was assessed by clinical examination, tympanometry, transient evoked otoacoustic emissions and audiometry. We considered the conduct of our study in relation to national ethical guidelines for research in Aboriginal and Torres Strait Islander health. After 1 year of community consultation, the study was endorsed by local committees and ethical approval granted. Fieldwork was tailored to minimise disruption to people's lives and we provided regular feedback to the community.We saw 81% of non‐Aboriginal and 65% of Aboriginal children at age 12 months. OM was diagnosed on 55% and 26% of routine clinical examinations in Aboriginal and non‐Aboriginal children respectively. Aboriginal mothers were younger and less educated, fewer were employed and they lived in more crowded conditions than non‐Aboriginal mothers. Sixty‐four per cent of Aboriginal and 40% of non‐Aboriginal babies were exposed to environmental tobacco smoke. Early consultation, provision of a service while undertaking research, inclusion of Aboriginal people as active members of a research team and appropriate acknowledgement will assist in ensuring successful completion of the research.

Choosing the Best Practice: Evidence to Support Fluoroquinolone Drops for Acute Otitis Media Through Tympanostomy Tubes

To the Editor .— In his commentary, “Why Don't Those Ear Drops Work for My Patients?”1 Isaacson presented his argument against the use of ototopical fluoroquinolones alone or in combination with a steroid as the first line of defense for the treatment of acute tube otorrhea in infants. He made several points to discount the use of these agents in pediatric patients with acute otitis media with tympanostomy tubes. However, rooted in the first sentence of the commentary was the fact that seems to lie at the epicenter of his concerns: “‘Topical Ciprofloxacin/Dexamethasone Is Superior to Oral Amoxicillin/Clavulanic Acid in Acute Otitis Media With Otorrhea Through Tympanostomy Tubes,’ [is] the latest in a series of pharmaceutical industry–funded articles… .” Isaacson's first critique of this article2 pertains to the study population. He stated that “[i]f one were trying to design a study to demonstrate the superiority of ototopical drops over oral antibiotics, the ideal population would be older children.” This statement directly contradicted his other criticism that “more than half of their subjects were >22 months of age.” In fact, 58% of the subjects in the study were <23 months of age, and the remaining patients were 2 to 11 years of age. These age distributions reflect …