Resolution Of Otitis Media Research Articles

The Impact of the Middle Ear Microbiota on Otitis Media Outcomes: A Meta-Analysis of Longitudinal Studies

Introduction: Otitis media (OM), a prevalent middle ear inflammation, often involves microbial colonization. The composition of the middle ear microbiota may influence OM outcomes, including recurrence, persistence, and treatment response. This meta-analysis investigated the relationship between the middle ear microbiota and OM outcomes. Methods: Longitudinal studies published from 2018 to 2024 that explored the middle ear microbiota and OM outcomes were systematically searched in PubMed, Embase, and Web of Science. Data on study design, participant characteristics, microbiota analysis, and OM outcomes were extracted. The risk of bias was assessed using the Newcastle-Ottawa Scale. A random-effects model was used to pool effect estimates. Results: A total of 15 studies (n = 2,540 participants) met the inclusion criteria. The middle ear microbiota diversity was significantly lower in children with recurrent OM compared to those without (standardized mean difference [SMD] = -0.45, 95% confidence interval [CI] -0.62 to -0.28, p < 0.001). The presence of specific pathogens, including Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, was associated with an increased risk of OM recurrence (odds ratio [OR] 1.75, 95% CI 1.32 to 2.31, p < 0.001). Additionally, microbial dysbiosis was associated with delayed resolution of OM and increased antibiotic treatment failure. Conclusion: The middle ear microbiota composition significantly impacts OM outcomes. Reduced diversity and specific pathogens are associated with increased OM recurrence. These findings highlight the potential for microbiota-targeted interventions in OM management.

Resolution of Otitis Media with Effusion in Adults after a Three-Day Course of Treatment with a Manosonic Nebulizer-A Pilot Study.

Background and Objectives: Aerosol drug administration is the primary treatment modality of otitis media with effusion (OME). An automatic manosonic aerosol generator (AMSA) delivers, with an acoustic overpressure, a therapeutic dosage of a drug by inhalation of the aerosol. However, available studies confirming their efficacy, especially in adults, are limited. Therefore, this pilot single-arm trial aimed to analyze changes in adults with OME following AMSA treatment. Materials and Methods: A group of 36 patients (mean age 51.4 years) with OME underwent a three-day treatment with inhaled mucolytic and steroids administered by AMSA. Tympanometry (tympanogram type, volume, compliance, pressure, and gradient) was performed to measure middle ear effusion before and after the intervention. Results: Following the intervention, partial and complete OME remission was observed in, respectively, 29 (81%) and 14 (39%) patients. The tympanogram type of the affected ears differed between baseline and after intervention measurements (p < 0.001). Tympanometry-based normalization, improvement deterioration and no change were observed in, respectively, 34 (68%), 1 (2%) 2 (4%), and 13 (26%) affected ears. Following the intervention, we observed an increase in continuously assessed middle ear volume (∆median 0.19 mL, p = 0.002) and pressure (∆median 142 daPa, p < 0.001), as well as a higher proportion of patients achieving categorical normalization of compliance (16% vs. 54%, p < 0.001) and pressure (28 vs. 64%, p < 0.001). Conclusions: Treatment efficacy was not affected by age, sex, or season of recruitment (all p > 0.05). The results of this pilot study are encouraging, however, the use of AMSA management of OME in adults needs to be verified in future studies.

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.

Insights into Otitis Media: Dissecting the interaction of C-Reactive Protein with Non-Typeable Haemophilus influenzae

Otitis Media (OM) is the inflammation of the middle ear (ME). Non-typeable Haemophilus influenzae (NTHi) is one of the leading otopathogens in causing OM. Phosphocholine (PCho) on the NTHi lipopolysaccharide influences host-pathogen interaction. C-Reactive Protein (CRP), an acute phase protein recognizes PCho, and can mediate bacterial killing. However, some strains of NTHi survive even in the presence of CRP. We aim to study the interaction of CRP with NTHi to understand its role in bacterial survival and OM. NTHi can efficiently infect the Junbo mouse, a characterised model of chronic and acute OM. CRP levels were highest 1 day post-intranasal inoculation in the ME fluid (MEF) and nasal passage (NP) washes. We show CRP is a localized response to NTHi as serum CRP levels were unaffected in NTHi inoculated and non-inoculated mice at 1, 3 and 7-day post intranasal inoculation. Further, we confirm the presence of NTHi influences CRP levels in the MEF and NP washes. We show CRP binding is influenced by the position and expression of PCho on the NTHi surface. Serum bactericidal assays indicate that the expression and position of PCho affects NTHi survival. The removal of CRP from the serum restores NTHi survival. The expression of PCho also influences opsonophagocytosis activity in macrophages, thereby confirming the importance of PCho in NTHi survival. The CRP-NTHi interaction is currently under investigation to advance our understanding of its role in the complex biological processes that influence bacterial killing and the onset, progression and resolution of OM caused by NTHi.

THE ROLE OF N-ACETYLCYSTEINE IN THE TREATMENT OF OTITIS MEDIA WITH EFFUSION

Otitis media with effusion (OME) is a chronic accumulation of fluid within the middle ear cleft and sometimes the mastoid air cells system. The disease is more common among children. Surgical management is cost effective and carry complications from anaesthesia and surgical intervention. The condition can be resolved with high percentage by using mucopeptide breaking agent N-acetylcysteine The aim of this study is to evaluate the effect of N-acetylcysteine on the resolution of otitis media with effusion in children. Fifty seven children (107 ears) aged between 4-15 years with OME were included in this study. Patients underwent a thorough otorhinolaryngological examination and were divided into two groups; in the study group of 30 patients, N-acetylcysteine was administered, and the control group of 27 patients did not receive this treatment. Patient were followed-up at attendance, one month, two months and three months later with microscopical ear examination, tympanometric and pure tone audiometric examination. Patients were 39 males (68.4%) and 18 females(31.6%), 50 of them were with bilateral and 7 with unilateral disease. Following the treatment, there was improvement in the hearing loss as air bone gap was decreased. This improvement was statically significant in comparing the study and control groups (P value= 0.022). Number of ears with type A tympanogram increased to a rate of 74%, 71% in the right and left ears respectively in the study group. This rate was statically significant in comparing with the control group (P value=0.014). In conclusion, N-acetylcysteine is effective in the treatment of children with OME as well as that N-acetylcysteine has minimal side effect and can be used safely in patients who are medically unfit for general anaesthesia

Antibiotic modulation of mucins in otitis media; should this change our approach to watchful waiting?

BackgroundGel-forming mucins (GFMs) play important roles in otitis media (OM) pathogenesis. Increased mucin expression is activated by pathogens and proinflammatory cytokines. Bacterial biofilms influence inflammation and resolution of OM and may contribute to prolonged mucin production. The influence of specific pathogens on mucin expression and development of chronic OM with effusion (OME) remains an area of significant knowledge deficit. ObjectivesTo assess the relationship between GFM expression, specific pathogens, middle ear mucosal (MEM) changes, biofilm formation, and antibiotic utilization. MethodsMixed gender chinchillas were inoculated with nontypeable Haemophilus influenzae (NTHi) strain 86028NP or Streptococcus pneumoniae (SP) strain TIGR4 via transbulla injection. Antibiotic was administered on day 3–5 post inoculation. GFM expression was measured by quantitative PCR. Biofilm formation was identified and middle ear histologic changes were measured. ResultsSP infection resulted in higher incidence of biofilm and ME effusion compared with NTHi infection. However, NTHi persisted in the ME longer than SP with no substantive bacterial clearance detected on day 10 compared with complete bacterial clearance on day 10 for 50–60% of the SP-infected chinchillas. Both infections increased MEM inflammatory cell infiltration and thickening. NTHi upregulated the Muc5AC, Muc5B and Muc19 expression on day 10 (p = 0.0004, 0.003, and 0.002 respectively). SP-induced GFM upregulations were trended toward significant. In both NTHi and SP infections, the degree of GFM upregulation had a direct relationship to increased MEM hypertrophy, inflammatory cell infiltration and biofilm formation. Antibiotic treatment reduced the incidence of ME effusion and biofilm, limited the MEM changes and reversed the GFM upregulation. In NTHi infection, the rate of returning to baseline level of GFMs in treated chinchillas was quicker than those without treatment. ConclusionsIn an animal model of OM, GFM genes are upregulated in conjunction with MEM hypertrophy and biofilm formation. This upregulation is less robust and more quickly ameliorated to a significant degree in the NTHi infection with appropriate antibiotic therapy. These findings contribute to the understanding of pathogen specific influences on mucin expression during OM pathogenesis and provide new data which may have implications in clinical approach for OM treatment.

Microevolution in response to transient heme-iron restriction enhances intracellular bacterial community development and persistence.

Bacterial pathogens must sense, respond and adapt to a myriad of dynamic microenvironmental stressors to survive. Adaptation is key for colonization and long-term ability to endure fluctuations in nutrient availability and inflammatory processes. We hypothesize that strains adapted to survive nutrient deprivation are more adept for colonization and establishment of chronic infection. In this study, we detected microevolution in response to transient nutrient limitation through mutation of icc. The mutation results in decreased 3',5'-cyclic adenosine monophosphate phosphodiesterase activity in nontypeable Haemophilus influenzae (NTHI). In a preclinical model of NTHI-induced otitis media (OM), we observed a significant decrease in the recovery of effusion from ears infected with the icc mutant strain. Clinically, resolution of OM coincides with the clearance of middle ear fluid. In contrast to this clinical paradigm, we observed that the icc mutant strain formed significantly more intracellular bacterial communities (IBCs) than the parental strain early during experimental OM. Although the number of IBCs formed by the parental strain was low at early stages of OM, we observed a significant increase at later stages that coincided with absence of recoverable effusion, suggesting the presence of a mucosal reservoir following resolution of clinical disease. These data provide the first insight into NTHI microevolution during nutritional limitation and provide the first demonstration of IBCs in a preclinical model of chronic OM.

Myringotomy as a Diagnostic and Therapeutic Tool in a Case of Otitis Media in a Guinea Pig (Cavia porcellus)

A 1.5 year old male adult guinea pig (Cavia porcellus) presented with acute vestibular disease, consisting of a right head tilt, circling, and ataxia. The head tilt was non-responsive to initial empirical antimicrobial therapy for presumptive otitis media. Video otoscopy and a myringotomy were performed under general anesthesia. A large amount of purulent debris was flushed from the middle ear and submitted for culture. Treatment with appropriate systemic and topical antibiotics was pursued for 4 weeks. Near complete resolution of clinical signs was achieved by the end of treatment with only a minor residual head tilt. This is the first described use of a diagnostic and therapeutic myringotomy for the treatment and resolution of otitis media in a guinea pig. Based on the clinical success seen in this case and the relative ease of the procedure, myringotomies should be considered for diagnosis and treatment of otitis media in guinea pigs.

Resolution of Otitis Media With Effusion in Children With Cleft Palate Followed Through Five Years of Age.

To describe the temporal pattern of otitis media with effusion (OME) resolution for a cohort of nonsyndromic cleft palate children enrolled before palatoplasty and followed through 5 years of age. This is a prospective, longitudinal study of the time course for OME resolution in infants and children with palatal clefts. Cleft Palate Craniofacial Center of a tertiary care pediatric hospital. This study included 52 children with cleft palate (29 boys, 45 white, Veau 1 through 4) who had a Furlow-type palatoplasty between 10 and 24 months of age performed by one of six surgeons. Standard cleft palate management was supplemented with study visits to the research clinic pre- and postpalatoplasty and then yearly to 6 years of age for assessments of middle ear status by interval history, otoscopy, and tympanometry. The main outcome measure was age at otitis media resolution defined as the age in years at the first in a sequence of "disease-free" diagnoses not interrupted or followed by any other diagnosis. The cumulative percent OME resolution for ears/children at ages <1, 1, 2, 3, 4, 5 years was 4.1/4.4, 14.3/10.9, 31.6/21.7, 45.9/37.0, 56.1/50.0, and 70.4/60.9%. OME resolution followed a simple linear time curve with slopes of 13.5% (confidence interval [CI] = 12.2% to 14.8%, r(2) = .99) and 11.9% (CI = 10.1% to 13.6%, r(2) = .99) resolutions per year for ears and children, respectively. There is a natural, age-related pattern of resolution for persistent OME that affects most infants and young children with cleft palate that is not affected by palatoplasty.

Innate Immunity: Orchestrating Inflammation and Resolution of Otitis Media.

Otitis media (OM) is a common disease in young children, accounting for more office visits and surgeries than any other pediatric condition. It is associated with an estimated cost of five billion dollars annually in the USA. Moreover, chronic and recurrent middle ear (ME) disease leads to hearing loss during critical periods of language acquisition and learning leading to delays in reaching developmental milestones and risking permanent damage to the ME and inner ear in severe cases. Therefore, research to understand the disease pathogenesis and identify new therapeutics is important. Although OM is a multifactorial disease, targeting the molecular mechanisms that drive inflammation and OM resolution is critical. In this review, we discuss the current evidence suggesting that innate immune receptors and effectors play key roles in OM by mediating both the ME inflammatory responses and recovery.

Recruitment to oral steroids for the resolution of otitis media with effusion in children (OSTRICH) study: challenges of a randomised controlled trial in secondary care sites across Wales and England

OSTRICH is a randomised controlled trial for otitis media with effusion (OME) in children, to determine the clinical and cost effectiveness of a short course of oral steroids. The aim is to describe and evaluate factors that have contributed to lower than expected recruitment rates.

The inflammasome adaptor ASC contributes to multiple innate immune processes in the resolution of otitis media

This study was designed to understand the contribution of the inflammasome and IL-1β activation in otitis media (OM). We examined the middle ear (ME) response to non-typeable Haemophilus influenzae (NTHi) in wild type (WT) mice using gene microarrays and a murine model of acute OM. Expression of members of the NOD domain-like receptor family of inflammasome genes was significantly up-regulated early in NTHi infection of the ME, potentially activating specific downstream regulatory cascades that contribute to the proliferative inflammatory response observed during OM. Expression of the pro-forms of the inflammasome targets IL-1β and IL-18 were also up-regulated. To evaluate the role of inflammasome-mediated cytokine maturation, NTHi-induced OM was examined in Asc(-/-)-deficient mice and compared with that seen in WT mice. Mice lacking the Asc gene showed near absence of IL-1β maturation in the ME and a reduction in leukocyte recruitment and infiltration to the cavity, and their macrophages exhibited reduced phagocytosis of NTHi. These inflammatory defects were linked to an increase in the degree and duration of mucosal epithelial hyperplasia in the ME of Asc(-/-) mice, as well as a delay in bacterial clearance from their MEs. These data demonstrate an important role for the inflammasome and cytokine processing in the course and resolution of OM.

TLR4-mediated induction of TLR2 signaling is critical in the pathogenesis and resolution of otitis media

TLR4-mediated induction of TLR2 signaling is critical in the pathogenesis and resolution of otitis media

Effectiveness of corticosteroids in otitis media with effusion: an experimental study

The aim of the present study was to investigate the dose-related effectiveness of corticosteroids in the management of otitis media with effusion, by using the objective assessment techniques of tympanometry and cytokine measurement. The eustachian tubes of 42 male rats were obstructed. Thirty-six subjects with effusion were randomly divided into three equal groups: controls; 0.5 mg/kg/day corticosteroid; and 1 mg/kg/day corticosteroid. Concentrations of interleukin-1beta and tumour necrosis factor alpha in the middle-ear effusions were analysed using enzyme-linked immunosorbent assay. An effusion occurred on the 14th post-operative day and was present on the 30th post-operative day in the control group. Otomicroscopic examination and tympanometric measurement showed an improvement in the intervention groups. There was a significant difference between both intervention groups and the control group for both interleukin-1beta and tumour necrosis factor alpha concentrations (p 0.05). The study confirmed a short term beneficial effect of systemic steroids on resolution of otitis media with effusion in a rat model. Our results support the theory that corticosteroids significantly decrease concentrations of both interleukin-1beta and tumour necrosis factor alpha. In our model, the 0.5 mg/kg corticosteroid dose was as effective as the 1 mg/kg corticosteroid dose. Further studies should be carried out to determine the optimal dose and duration of corticosteroids in the treatment of otitis media with effusion.

Effectiveness of adenoidectomy and laser tympanic membrane fenestration.

Adenoidectomy alone or with tonsillectomy (A+/-T) is an effective surgical intervention in the management of otitis media in children, especially when it is performed in conjunction with insertion of pressure equalization tubes (PETs). Otorrhea and persistent tympanic membrane (TM) perforation are frequent complications. This study evaluates the effectiveness of intermediate duration middle ear ventilation using laser tympanic membrane fenestration (LTMF) without tube insertion and as an adjunct to adenoidectomy in resolving middle ear disease within the first 90 days after surgery. This pilot study was a multicenter, prospective clinical cohort trial. Institutional review board approval and informed consent were obtained. The study involved four tertiary care pediatric otolaryngology departments. Fifty children (96 ears) were treated with LTMF in conjunction with A+/-T from June 1, 1998, through March 30, 1999. Ages ranged from 9 months to 12 years. Patients undergoing A+/-T who would have been recommended for PET insertion instead underwent middle ear ventilation with LTMF using the Oto-LAM device (ESC/Sharplan, Yokneam, Israel). Patients were seen at 30, 60, and 90 days postoperatively. Resolution of otitis media with effusion was determined by clinical examination, which included pneumatic otoscopy, audiometry, and tympanometry. Of the treated ears, 88%, 86%, and 83% had clinical resolution of middle ear disease at 30, 60, and 90 days, respectively. Preoperatively, 45% (n = 85) of ears had normal hearing; 92% (n = 49) had normal hearing at 90 days. Eighty-nine percent (n = 92) had type C2 or B tympanograms preoperatively, and 12% (n = 60) had type C2 or B at 90 days. Laser tympanic membrane fenestration in conjunction with adenoidectomy was effective in restoring normal middle ear function at 90 days post-treatment in greater than 80% of children who otherwise may have had placement of PETs.

Meta-analysis of antibiotics for the treatment of otitis media with effusion.

To reconcile conflicting reports of antibiotic efficacy for otitis media with effusion in children. English-language MEDLINE search ("antibiotics" and "otitis" media with effusion") from January 1980 through December 1990. Current Contents 1990, consultation with experts, and references from review articles, textbook chapters, and retrieved reports. Randomized clinical trials with concurrent controls (placebo or no drug), and children with at least one ear not violated by tympanocentesis. Ten of the initial 82 articles were selected after blind review of the methods sections. We independently evaluated each trial using 20 measures of internal and external validity, then extracted treatment and control responses for an end point of all affected ears free of effusion at the first posttreatment assessment. Pooled analysis of 1325 children yielded a rate difference of 22.8% (95% Cl, 10.5 to 35.1) that was minimally affected by interstudy quality differences, and was unlikely to represent publication bias. Variations in trial outcomes were not attributable to chance, study design, or choice of drug, but were inversely related to the control group natural cure rate. Children with chronic bilateral effusions not related to a recent episode of acute otitis media tended to have lower natural cure rates, and a more favorable response to therapy. Antibiotics have a clinically and statistically significant impact on the resolution of otitis media with effusion. The association between outcome and natural cure rate has important implications for the design and interpretation of future trials.

Resolution of otitis media with effusion with the use of a stepped treatment regimen of trimethoprim-sulfamethoxazole and prednisone

This double blind, placebo-controlled trial was designed to determine whether intervention with a stepped regimen of trimethoprim-sulfamethoxazole (TMP-SMX) and prednisone would prevent high risk children from developing chronic otitis media with effusion (OME) and recurrent acute otitis media. Forty-two children were enrolled, assigned to treatment with active drug or placebo and then examined at 2-week intervals. They received TMP-SMX (or placebo) during the first 2 weeks, TMP-SMX and prednisone (or placebo) during Weeks 3 and 4 for persistent OME and TMP-SMX (or placebo) for Weeks 5 and 6 if OME was still unresolved. After treatment 48% of active drug and 14% of placebo subjects resolved OME bilaterally (P less than 0.05). Active drug subjects also had fewer acute otitis media episodes than placebo subjects while receiving study treatment (P less than 0.01). Although this treatment regimen produced short term OME resolution, long term benefits were not demonstrated.

Rhinomanometry in the selection for adenoidectomy and its relation to preoperative radiology

Recent work has shown that resolution of otitis media with effusion (OME) following adenoidectomy may be related to certain preoperative radiographic parameters. This study was performed to investigate the relationship between the total nasal resistance (TNR), adenoid volume and the radiographic palatal airway and adenoid depth in children with OME. Fifty-six children underwent anterior active rhinomanometry and 40 completed the investigation. There was a significant association between the Palatal Airway and the TNR, and in the 27 who subsequently underwent adenoidectomy this was nearly so with respect to adenoid volume and TNR. The relationship demonstrated was not strong enough for TNR to be of use in selection of children for adenoidectomy based on radiographic parameters. Rhinomanometry can be difficult and time-consuming to perform in children. In its present form it is unlikely to be of routine clinical use in this context.

Bromhexine Slows the Resolution of Otitis Media with Effusion

Bromhexine Slows the Resolution of Otitis Media with Effusion