Clinical Relevance and Advantages of Intradermal Test Results in 371 Patients with Allergic Rhinitis, Asthma and/or Otitis Media with Effusion.

BACKGROUND: We evaluated the value of positive intradermal dilution testing (IDT) after negative skin prick tests (SPT) by retrospectively determining allergy immunotherapy (AIT) outcomes. METHODS: This private practice, cohort study compared the relative value of SPT vs. IDT in 371 adults and children with suspected manifestations of allergy: chronic allergic rhinitis (AR), asthma and/or chronic otitis media with effusion (OME). The primary outcome measure was symptom resolution following immunotherapy, as determined by symptom severity questionnaires completed by patients before and after AIT. RESULTS: Positive IDT identified 193 (52%) patients who would not otherwise have been diagnosed. IDT detected 3.7-fold more allergens per patient than SPT (8.56 vs. 2.3; p < 0.01). Patients positive only on IDT responded to AIT equally well as those identifiable by SPT, independent of allergen sensitivity (67% by SPT vs. 62% by IDT; p = 0.69, not significantly different). CONCLUSION: Intradermal titration can identify patients who will benefit from allergy immunotherapy more accurately than SPT. Outcomes analysis in 371 patients shows that IDT doubled their chance of successful treatment with no greater risk of therapeutic failure. Positive IDT, following negative SPT, is clinically relevant and offers superior sensitivity over SPT for detecting allergens clinically relevant to diagnosis of AIT-responsive atopic disease.

Inflammatory Mediator Profiles in Secretory Otitis Media in Relationship to Viable Bacterial Pathogens and Bacterial and Viral Nucleic Acids.

Secretory otitis media (SOM) is characterized by persistence of fluid in the middle ear, often following an episode of acute otitis media. Our hypothesis is that failure to eliminate bacterial or viral pathogens may result in persistent low-grade inflammation. In this study, we analyzed inflammatory mediators in middle ear fluids from 67 children with SOM. This was combined with determinations of viable bacteria by culture along with detection of bacterial and viral genetic material by real-time polymerase chain reaction (PCR). The inflammatory mediators found at the highest concentrations (>30 ng/mL) were stem cell growth factor-ß (median 110 ng/mL), CXCL1, IL-16, IL-8, migration inhibitory factor, CXCL10, and CXCL9. Among bacterial pathogens, Moraxella catarrhalis and Haemophilus influenzae dominated, regardless of detection methods, while rhinovirus dominated among viral pathogens. Middle ear fluid levels of interleukin (IL)-1α, IL-17, IL-1ß, fibroblast growth factor basic, and tumor necrosis factor correlated strongly with presence of bacteria detected either by culture or PCR, while IL-1RA, IL-3, IL-6, IL-8, CCL3, CCL4, and granulocyte-colony stimulating factor correlated significantly with real-time PCR values. CXCL10, CXCL9, CCL2, and TRAIL correlated significantly with viral nucleic acid levels. To conclude, persistence of viral and bacterial pathogens may fuel persistent inflammation in SOM. Bacteria caused a broad inflammatory response, while viruses chiefly elicited the interferon-induced chemokines CXCL9 and CXCL10.

The effects of adenoidectomy of serum insulin-like growth factor-1 (IGF-1) and ghrelin in hypertrophied adenoids in children with otitis media with effusion.

<b>Aim:</b> The aim of the current study was to assess the serum levels of insulin-like growth factor-1 (IGF-1) and ghrelin in hypertrophied adenoids in children suffering with or without otitis media with effusion before and after adenoidectomy. <br><b>Material and methods:</b> Serum IGF-1 and ghrelin concentrations were measured with specific enzyme-linked immunoassay (ELISA) methods. The study was carried out in 20 children with otitis media with effusion. The reference group comprised 24 children with hypertrophied adenoid, while control group included 19 children. <br><b>Results:</b> This mean values of IGF-1 in children with otitis media with effusion and children with hypertrophied adenoid before adenoidectomy were significantly lower than those found in healthy children. Serum levels of IGF-1 were higher after adenoidectomy. There was a significant difference of serum ghrelin levels between both examined groups and the control group. <br><b>Conclusion:</b> Our results suggest that adenoidectomy in children with hypertrophied adenoids and in children with otitis media with effusion significantly increases the level of IGF-1 in serum compared to before surgery through the effect of the GH-IGF-1 axis, which could contribute to children's growth.

Niche- and Gender-Dependent Immune Reactions in Relation to the Microbiota Profile in Pediatric Patients with Otitis Media with Effusion.

Otitis media with effusion (OME) is a common inflammatory disease that primarily affects children. OME is defined as a chronic low-grade inflammation of the middle ear (ME), without any signs of infection and with effusion persisting in the ME for more than 3 months. The precise pathogenesis is, however, not fully understood. Here, we comprehensively characterized and compared the host immune responses (inflammatory cells and mediators) and the overall microbial community composition (microbiota) present in matched middle ear effusion (MEE) samples, external ear canal (EEC) lavages, and nasopharynx (NPH) samples from children with OME. Female patients had significantly increased percentages of T lymphocytes and higher levels of a wide array of inflammatory mediators in their MEE compared to that of male patients, which were unrelated to microbiota composition. The relative abundances of identified microorganisms were strongly associated with their niche of origin. Furthermore, specific inflammatory mediators were highly correlated with certain bacterial species. Interestingly, some organisms displayed a niche-driven inflammation pattern in which presence of Haemophilus spp. and Corynebacterium propinquum in MEE was accompanied by proinflammatory mediators, whereas their presence in NPH was accompanied by anti-inflammatory mediators. For Turicella and Alloiococcus, we found exactly the opposite results, i.e., an anti-inflammatory profile when present in MEE, whereas their presence in the the NPH was accompanied by a proinflammatory profile. Together, our results indicate that immune responses in children with OME are highly niche- and microbiota-driven, but gender-based differences were also observed, providing novel insight into potential pathogenic mechanisms behind OME.

Effect of probiotics in experimental otitis media with effusion.

OBJECTIVES: The article's aim was to investigate the effects of probiotics in the experimental otitis media with effusion. MATERIALS AND METHODS: Twenty-four male Wistar albino rats were used. They were divided into four groups. Experimental otitis media with effusion was created by intratympanic histamine injection. The effusion was confirmed by otomicroscopic examination 24 h after injection. Group 1; did not receive any treatment, group 2; received probiotics for 7 days after the detection of effusion, group 3; received probiotics for 7 days prior to injection of histamine, group 4; received probiotics for 7 days before injection of histamine and 7 days after detection of effusion. After detection of effusion, animals were sacrificed. Otomicroscopic evaluation was done to determine the effusion. In histopathological examination neutrophil leukocyte counts were determined in 25 areas of the sub-mucosa of the temporal bulla. RESULTS: The otomicroscopic ear effusions' healing rate in group 1 was 10%, in group 2 was 25%, in group 3 was 50%, and in group 4 was 100% (p < 0,013). The mean counts of submucosal neutrophil leukocyte from 25 areas of the temporal bulla of group 1 was 86,8 ± 24, group 2 was 66,5 ± 21, group 3 was 66,2 ± 16, and group 4 was 26,3 ± 6,5 (p < 0,001). CONCLUSION: Probiotics have a curative effect on the prevention and treatment of otitis media with effusion. This result may be related to their anti-inflammatory effects. Therefore, probiotics can be widely used in the age group at risk for otitis media with effusion as a complementary therapy by dietary supplements. LEVEL OF EVIDENCE: NA.

The Relation of Allergy to Adenoid Hypertrophy and Otitis Media with Effusion: A Cross-sectional Study.

The exact mechanisms of Adenoid hypertrophy (AHT) pathogenesis and otitis media with effusion (OME) are unclear but there is increasing evidence that allergies may play a role. We aimed to investigate the prevalence of atopy and the effect of anti-allergic drugs in patients with AHT and OME. In a non-randomized, prospective cross-sectional study, 122 patients younger than 18 years of age with AHT or OME were included. Atopic patients based on clinical symptoms of allergic disorders and/or elevated levels of total serum immunoglobulin E (IgE) were referred to allergists and tested for allergen sensitization by skin prick test (SPT). Atopic patients were treated with nasal corticosteroids and antihistamines. Response to treatment was evaluated by comparing symptoms score before and after the treatment. In this study 122 patients were evaluated, 116 of them had AHT and 30 patients had OME. The mean age of participants was 6.7±2.4 years old and 68 of them (55.7%) were male. Allergic symptoms were observed in 38 patients with AHT (32.7%) and nine patients with OME (30%). Among the total cases, 34 patients (28%) were considered atopic. SPT was performed on 25 (73%) cases of atopic patients, with 11 (44 %) positive results. The mean symptom score of AHT and OME decreased significantly after treatment respectively, (p=0.001, p=0.007). According to this study, atopy was relatively common in patients with AHT and OME. Treatment with nasal corticosteroid and antihistamines were effective in these patients.

High concentrations of middle ear antimicrobial peptides and proteins and proinflammatory cytokines are associated with detection of middle ear pathogens in children with recurrent acute otitis media.

Recurrent and chronic otitis media (OM) are often refractory to antibiotics due to bacterial persistence in biofilm within the middle ear. In vitro and in vivo studies have demonstrated that antimicrobial proteins and peptides (AMPs) are bactericidal against otopathogens, indicating potential therapeutic value for recalcitrant OM. We measured concentrations of 6 AMPs and 14 cytokines in middle ear effusion (MEE) from 67 children undergoing ventilation tube insertion for recurrent acute OM. Sixty one percent of children had bacterial otopathogens detected in their MEE, 39% by PCR and 22% by PCR and culture. Groups were defined as: PCR-negative/culture-negative (absence of bacterial otopathogen), n = 26; PCR-positive/culture-negative (presence of nonculturable bacterial otopathogen), n = 26; PCR-positive/culture-positive (presence of culturable bacterial otopathogen), n = 15. Age, antibiotic usage, day-care attendance, presence of respiratory viruses in MEE and number of AOM episodes were similar between groups. AMP and cytokine concentrations were higher in children with bacterial otopathogens in their MEE compared to those with no bacterial otopathogens. Median concentrations of AMPs (except HBD2) were 3 to 56-fold higher in MEE from children with bacterial otopathogens detected in their MEE (P ≤ 0.01). Similarly, median cytokine concentrations (except TGFß) were >16-fold higher in MEE with bacterial otopathogens detected (P ≤ 0.001). This is the first study to measure AMPs in MEE and together with the cytokine data, results suggest that elevated AMPs and cytokines in MEE are a marker of inflammation and bacterial persistence. AMPs may play an important role in OM pathogenesis.

Characterization of mucoid and serous middle ear effusions from patients with chronic otitis media: implication of different biological mechanisms?

BACKGROUND: Chronic otitis media with effusion (COME) is characterized by persistent middle ear effusions that are in most cases highly viscous, but some patients present with serous fluid. This study aimed at comprehensively characterizing the macromolecular composition of mucoid vs. serous middle ear effusions (MEEs). METHODS: MEEs from patients with COME were analyzed for proteins by mass spectrometry (MS) and western blot techniques, total DNA quantity, bacterial DNA (16S sequencing), and cytokine content. Proteomics datasets were studied in Ingenuity Pathway Analysis (IPA). RESULTS: Mucoid samples showed a global tendency of increased pro-inflammatory mediators. Interleukin-1ß (IL-1ß) and IL-10 were significantly more abundant in serous samples (p < 0.01). Mucoid samples had higher DNA quantity (p = 0.04), more likely to be positive in MUC5B protein (p = 0.008) and higher peptide counts (12,786 vs. 2225), as well as an overall larger number of identified proteins (331 vs. 177), compared to serous. IPA found the mucoid sample dataset to be related to immune cell function and epithelial remodeling, whereas the serous sample dataset showed acute responses and blood-related proteins. Interestingly, serous samples showed more bacterial DNA than mucoid ones, with less bacterial genera variability. CONCLUSION: This study demonstrates divergent immune responses in children with COME by effusion quality.

[The role of Th1/Th2 cells imbalance in the pathogenesis of secretory otitis media].

Objective:The aim of this study is to explore the role of Th1/Th2 cells imbalance in the pathogenesis of secretory otitis media. Method:Ninety secretory otitis media patients were enrolled in observation group. According to medical history, they were divided into acute and chronic group. In addition, 90 healthy volunteers during the same period were selected as the control group. The levels of Th1-type cytokines IFN-γ, Th2-type cytokines interleukin-4 (IL-4) and IFN-γ/IL-4 in peripheral blood were compared between observation group and control group. Compare with acute and chronic secretory otitis media patients IFN-γ, IL-4, IFN-γ/IL-4 levels as well as the compare with middle ear effusion and peripheral blood sIFN-γ, IL-4, IFN-γ/IL-4 levels in observation group. Result:The level of IFN-γ, IL-4 and IFN-γ/IL-4 in the peripheral blood in the observation group were higher than those of the control group (P<0.05). The levels of IFN-γ, IL-4 and IFN-γ/IL-4 in the peripheral blood of patients in the chronic group were higher than those in the acute group. There was no significant difference in IL4, IFN-γ/IL-4 levels between the observation group and the middle ear effusion (P>0.05), IFN-γ levels in peripheral blood were lower than those of the middle ear effusion IFN-γ (P<0.05). Conclusion:Abnormal IFN-γ, IL-4 levels of the peripheral blood and the middle ear effusion have some relationship with secretory otitis media, and Th1/Th2 imbalance may be a risk factor for secretory otitis media.

Eosinophilic Otitis Media Treated with Anti-IgE Monoclonal Antibodies and A Bone Conduction Implant.

Eosinophilic otitis media (EOM) are intractable otitis media characterized by highly viscous secretions containing eosinophils in the middle ear. They are resistant to conventional medication and surgery. This condition occurs primarily in patients with bronchial asthma or allergic rhinitis and is often complicated by rhinosinusitis. Systemic and topical steroid therapies are effective treatments. However, long-term steroid therapy is often limited by a high risk of serious adverse effects. The use of topical steroids and otorrhea are bothersome when wearing hearing aids. Here, we report a case of intractable otitis media due to EOM. Otorrhea was controlled with topical steroids. Bone conduction hearing was stable for an extended period with anti-IgE monoclonal antibodies (omalizumab). An implantable bone conduction hearing aid was used for rehabilitation of conductive hearing loss.

Roles of T follicular helper cells in the pathogenesis of adenoidal hypertrophy combined with secretory otitis media.

The aim of this study was to investigate the roles of T follicular helper (Tfh) cells in secretory otitis media (SOM) combined with adenoidal hypertrophy (AH).Patients with AH or AH combined with SOM admitted to the Yancheng No. 1 People's Hospital from December 2012 to December 2014 were included. Fourteen age-matched healthy individuals received physical examinations in the hospital served as control. The venous Tfh was determined using flow cytometry, and CD3 + CD4 + CXCR5 + T lymphocytes were defined as Tfh cells. Serum inflammatory factors including IL-8, IL-1b, IL-6, IL-10, TNF, IL-12p70, IL-21, and IgE were determined using commercial kits.Compared with the AH group, the number of CD4 + CXCR5 + T cells in peripheral blood of the AH combined with SOM group showed significant increase. Statistical differences were noticed in the number of the number of CD4 + CXCR5 + T cells in moderate and severe AH groups compared with that of the control group. Statistical differences were identified in the proportion of CD4 + CXCR5 + T cells in the adenoidal tissues between the AH combined with SOM group and AH group (P < .05). For the CD4 + CXCR5 + T cells in adenoidal tissues, no statistical differences were noticed between the moderate and severe AH groups (P > .05). The number of CD4 + CXCR5 + T cells was positively correlated to the serum IL-21. Nevertheless, no correlation was noticed between CD4 + CXCR5 + T cell and serum IL-8, IL-6, IL-10, and IgE.Tfh is involved in the AH combined with SOM in children. Besides, serum IL-21, IL-8, IL-6, IL-10, and IgE may be involved in the onset of SOM in children.

Eosinophilic otitis media diagnosis using flow cytometric immunophenotyping.

OBJECTIVES: (1) To assess the ability of flow cytometric immunophenotyping to detect and quantitate eosinophils in patients with eosinophilic otitis media (EOM). (2) to evaluate the association of EOM to bronchial asthma. METHODS: Twenty-one patients with chronic otorrhea or middle ear effusion (MEE) were included in this prospective cohort study. Group I composed of 10 patients (14 ears) and associated to bronchial asthma. Group II included 11 patients (11 ears) without bronchial asthma. Samples of MEE were sent for flow cytometric analysis at initial presentation. Patients with positive eosinophils on flow cytometric immunophenotyping were analyzed after one-month course of dexamethasone eardrops. RESULTS: EOM was diagnosed in all patients of group I and in three patients of group II. The mean eosinophils percentage was 43.5% and 14.2% for group I and group II, respectively (p = .006). Those patients showed a significant response to dexamethasone eardrops, both on clinical examination and on flow cytometric analysis with a decrease in eosinophil levels post-treatment. However, this improvement was temporary and symptoms recurred after treatment cessation. Bronchial asthma was not associated to all patients with EOM. CONCLUSION: Diagnosis of EOM remained mostly clinical; flow cytometry immunophenotyping of MEE may be helpful as an additional tool in diagnosis and monitoring the response to treatment, particularly in non-asthmatic patients.

The Predictive Value of Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratio for the Effusion Viscosity in Otitis Media With Chronic Effusion.

OBJECTIVE: The objective of the authors' study was to investigate the predictive value of the neutrophil-lymphocyte rate (NLR) and platelet-lymphocyte rate (PLR) in otitis media with effusion and the correlation of the effusion type with these ratios. STUDY DESIGN: Retrospective case-control study. METHODS: One hundred twenty-six pediatric patients diagnosed otitis media with chronic effusion and had ventilation tube inserted between October 2015 and July 2016 were included in the study group and 124 healthy children, who applied for the routine examination and had blood count analysis, were included in the control group. The patients in the study group were divided into 2 groups regarding the effusion viscosity, which was obtained from the patients' operation files. Seventy-one patients were included in the serous group and 55 patients in the mucous group. The NLR and PLR rates of the groups were compared and statistically evaluated. RESULTS: The average NLR and PLR rates were significantly higher in the study group than in the control group (P = 0.000, P = 0.004 respectively). Comparison of the serous and mucous groups with the control group revealed a significant difference between the control group and the serous group regarding the NLR and PLR (P = 0.000; P = 0.000 respectively), but not between the control group and mucous group (P = 0.694; P = 0.691 respectively). CONCLUSION: Neutrophil-lymphocyte rate and PLR had a predictive value for otitis media with effusion and additionally it was a laboratory indicator supporting the typing of the viscosity of the fluid accumulated in the middle ear.

[Current in eosinophilic otitis media].

Eosinophilic otitis media(EOM) is a kind of intractable disease. It has drawn much attention since it being recognitized first time in 1995. The pathogenesis of EOM remains unknown, and clinical manifestation varies. Early diagnosis and treatment is of great importance for improving the prognosis and avoiding severe hearing loss. This article reviewed current analysis of EOM for better understanding of this disease, and help to establish a standard procedure for the diagnosis and treatment of EOM.

Increased IL-17 and 22 mRNA expression in pediatric patients with otitis media with effusion.

OBJECTIVES: Middle ear effusion has been reported to be associated with immune responses in patients with otitis media with effusion (OME). Although various cytokines are involved in immunologic responses in patients with OME, no study to date has assessed the involvement of the pro-inflammatory cytokines interleukin (IL)-17 and IL-22. This study analyzed the levels of expression of IL-17 and IL-22 in the middle ear effusion of patients with OME. METHODS: Patients aged <11 years who were diagnosed with chronic OME and underwent ventilation tube insertion from May 2013 to August 2015 were enrolled. Effusion fluid samples were obtained during surgery and levels of IL-17 and IL-22 mRNAs assessed by real-time PCR. IL-17 and IL-22 mRNA levels were compared in patients with effusion fluid positive and negative for bacteria; in patients with and without accompanying diseases, recurrent disease, and re-operation; and relative to fluid characteristics. RESULTS: The study cohort included 70 pediatric patients, 46 boys and 24 girls, of mean age 4.31 ± 2.11 years. The levels of IL-17 and IL-22 mRNA were higher in patients with than without sinusitis, but only IL-22 mRNA levels differed significantly (p < 0.05). The level of IL-17 mRNA was significantly higher in patients who did than did not undergo T&A (p < 0.05). The level of IL-22 expression was significantly higher in mucoid and purulent middle ear fluid samples than in serous fluid samples (p < 0.05). CONCLUSION: IL-17 and IL-22 mRNAs are involved in the pathophysiology of OME and are significantly higher in subjects with than without accompanying diseases.

Association of microRNA 146 with middle ear hyperplasia in pediatric otitis media.

OBJECTIVE: Toll-like receptor signaling activated by bacterial otitis media pathogens in the middle ear has been shown to play a key role in OM susceptibility, pathogenesis and recovery. Recent studies implicate microRNA 146 (miR-146) in regulation of inflammation via negative feedback of toll-like receptor signaling (TLR) in a wide variety of tissues, however its involvement in otitis media is unknown. METHODS: Human middle ear epithelial cells were stimulated with proinflammatory cytokines, interleukin 1 beta or tumor necrosis factor alpha, for two to twenty-four hours. Middle ear biopsies were collected from children with otitis media with effusion (n = 20), recurrent otitis media (n = 9), and control subjects undergoing cochlear implantation (n = 10). miR-146a, miR-146b expression was assayed by quantitative PCR (qPCR). Expression of miR-146 targets involved in TLR signaling, IRAK1 and TRAF6, was assayed by qPCR in middle ear biopsies. Middle ear biopsies were cryosectioned and epithelial thickness measured by a certified pathologist. RESULTS: Proinflammatory cytokines induced expression of miR-146 in middle ear epithelial cells in vitro. Middle ear miR-146a and miR-146b expression was elevated in otitis media patients relative to control subjects and correlated with middle ear epithelial thickness. A trend towards inverse correlation was observed between miR-146 and TRAF6 expression in the clinical population. CONCLUSIONS: This report is the first to assess miRNA expression in a clinical population with OM. Findings herein suggest miR-146 may play a role in OM.

Proteomic Characterization of Middle Ear Fluid Confirms Neutrophil Extracellular Traps as a Predominant Innate Immune Response in Chronic Otitis Media.

BACKGROUND: Chronic Otitis Media (COM) is characterized by middle ear effusion (MEE) and conductive hearing loss. MEE reflect mucus hypersecretion, but global proteomic profiling of the mucosal components are limited. OBJECTIVE: This study aimed at characterizing the proteome of MEEs from children with COM with the goal of elucidating important innate immune responses. METHOD: MEEs were collected from children (n = 49) with COM undergoing myringotomy. Mass spectrometry was employed for proteomic profiling in nine samples. Independent samples were further analyzed by cytokine multiplex assay, immunoblotting, neutrophil elastase activity, next generation DNA sequencing, and/or immunofluorescence analysis. RESULTS: 109 unique and common proteins were identified by MS. A majority were innate immune molecules, along with typically intracellular proteins such as histones and actin. 19.5% percent of all mapped peptide counts were from proteins known to be released by neutrophils. Immunofluorescence and immunoblotting demonstrated the presence of neutrophil extracellular traps (NETs) in every MEE, along with MUC5B colocalization. DNA found in effusions revealed unfragmented DNA of human origin. CONCLUSION: Proteomic analysis of MEEs revealed a predominantly neutrophilic innate mucosal response in which MUC5B is associated with NET DNA. NETs are a primary macromolecular constituent of human COM middle ear effusions.

Do Staphylococcus aureus superantigens play a role in the pathogenesis of otitis media with effusion in children?

OBJECTIVES: Staphylococcal enterotoxins (SEs), acting as superantigens, have been reported to be involved in the pathogenesis of chronic inflammatory diseases of the upper and lower airway. There has been no previous study investigating the role of SEs in otitis media with effusion (OME). Therefore, this study was designed to analyze middle ear aspirates from children with and without OME for the presence of SEs. METHODS: Middle ear aspirates were obtained from 24 patients and 24 controls. All samples were processed for bacterial culture and detection of five staphylococcal SEs (SEA, SEB, SEC and SED) and toxic shock syndrome toxin-1 using the Rapid Latex Agglutination Test. RESULTS: In bacterial culture assays, six samples (25%) of the study group and five samples (20.8%) of the control group showed bacterial growth. At least one SE was demonstrated in 6 of 24 patients and in 3 of 24 controls. There was no statistically significant difference between the two groups with respect to the presence of SEs. CONCLUSION: Although there is evidence that SEs have a potential role in the pathogenesis of chronic inflammatory diseases, there is no evidence that the inflammation process is initiated by SEs in patients with OME.

Aetiology and pathology of otitis media with effusion in adult life.

OBJECTIVES: To gather and analyse information concerning the aetiology and pathology of otitis media with effusion in adults. METHOD: A review of the English language literature from 1970 to the present was conducted. RESULTS: The available evidence suggests that otitis media with effusion in adult life is best viewed as a syndrome with a number of causes, including: infiltration of the eustachian tube by nasopharyngeal carcinoma and other local malignancies; changes in the middle ear and eustachian tube induced by radiotherapy; and systemic disease. CONCLUSION: There is now a body of evidence specifically related to the aetiology and pathology of otitis media with effusion in adult life. However, further research is required to fill in the gaps in our knowledge and understanding of this condition.

Accumulation of Regulatory T Cells and Chronic Inflammation in the Middle Ear in a Mouse Model of Chronic Otitis Media with Effusion Induced by Combined Eustachian Tube Blockage and Nontypeable Haemophilus influenzae Infection.

Nontypeable Haemophilus influenzae (NTHi) is associated with chronic otitis media (COM). In this study, we generated a murine model of COM by using eustachian tube (ET) obstruction and NTHi (10(7) CFU) inoculation into the tympanic bulla, and we investigated the relationship between regulatory T cells (Treg) and chronic inflammation in the middle ear. Middle ear effusions (MEEs) and middle ear mucosae (MEM) were collected at days 3 and 14 and at 1 and 2 months after inoculation. Untreated mice served as controls. MEEs were used for bacterial counts and to measure the concentrations of cytokines. MEM were collected for histological evaluation and flow cytometric analysis. Inflammation of the MEM was prolonged throughout this study, and the incidence of NTHi culture-positive MEE was 38% at 2 months after inoculation. The levels of interleukin-1ß (IL-ß), tumor necrosis factor alpha, IL-10, and transforming growth factor ß were increased in the middle ear for up to 2 months after inoculation. CD4(+) CD25(+) FoxP3(+) Treg accumulated in the middle ear, and the percentage of Treg in the MEM increased for up to 2 months after inoculation. Treg depletion induced a 99.9% reduction of bacterial counts in MEEs and also significantly reduced the ratio of NTHi culture-positive MEE. The levels of these cytokines were also reduced in MEEs. In summary, we developed a murine model of COM, and our findings indicate that Treg confer infectious tolerance to NTHi in the middle ear.