Clinical significance of T helper-1/T helper-2 cytokines in peripheral blood of children with otitis media with effusion and allergic rhinitis.

OBJECTIVE: Otitis media with effusion (OME) is a prevalent and costly disease, especially in children. This article analyzed the expression patterns and clinical significance of T helper-1 (Th1)/Th2 cytokines in the peripheral blood of children with OME and allergic rhinitis (AR). METHODS: Subjects were assigned to the OME + AR group and the Control group (children with OME), with their clinical baseline data documented. The correlations between Th1/Th2 cytokines and between the total nasal symptom score (TNSS) and Th1/Th2 cytokines were analyzed. The risk factors and the predictive value of Th1/Th2 cytokines for OME + AR were analyzed using logistics multivariate regression analysis and receiver operating characteristic curve. RESULTS: Significant differences were observed in tympanic pressure/speech frequency/air conduction valve/TNSS score/immunoglobulin E (IgE) level between both groups. The OME + AR children exhibited evidently elevated interleukin-2 (IL-2)/tumor necrosis factor-α (TNF-α)/IL-4/IL-10/IL-6 levels and no significant difference in interferon-γ (IFN-γ) level. Th1/Th2 cytokines were remarkably positively-correlated with the TNSS score. IL-2/TNF-α/IL-4/IL-6 were risk factors for OME with AR. The area under the curves (AUCs) of IL-6/IL-2/IL-4/TNF-α levels in predicting the occurrence of OME + AR were 0.805/0.806/0.775/0.781, with sensitivities of 75.76 %/89.39 %/72.21 %/72.73 % and specificities of 74.29 %/61.34 %/72.86 %/70.00 %, and the cut-off values were 239.600/20.300/29.880/34.800 (pg/mL). The AUC of their combination in predicting OME + AR was 0.955 (93.94 % sensitivity, 85.71 % specificity). CONCLUSION: Th1/Th2 cytokine levels were imbalanced and obviously positively-correlated with the TNSS score in OME + AR children. IL-2, TNF-α, IL-4, and IL-6 levels had auxiliary predictive value in the occurrence of OME + AR.

Effects of Qing Qiao Capsule in the treatment of chronic secretory otitis media and the levels of serum inflammatory factors.

To explore the effects of Qing Qiao Capsule in the treatment of chronic secretory otitis media and the levels of serum inflammatory factors, a total of 50 chronic secretory otitis media patients in the control group were subjected to caefaclor capsule, while the total of 50 cases in the observation group were treated with Qing Qiao Capsule. The traditional Chinese medicine (TCM) syndrome scores, therapeutic effects, and the levels of inflammatory factors were evaluated. After treatment, the scores of deafness, hearing loss, dizziness, soreness and weakness of the waist and knees, and fever is hens in palms and soles were significantly decreased in both groups (all P value <0.05). However, each score in the observation group was markedly less than that of the control group (all P value <0.05). Moreover, the C-reactive protein (CRP), procalcitonin (PCT) and tumor necrosis factor-α (TNF-α) levels measured after treatment were significantly lowered than those before treatment (all P value <0.05). Also, the levels of CRP, PCT and TNF-α in the observation group were obviously less than that of the control group (all P value <0.05). And the total therapeutic efficacy of the observation group was significantly higher than that of the control group (P<0.05). But no significant difference was observed in the rates of adverse reactions between both groups (P>0.05). Application of Qing Qiao Capsule in the treatment of chronic secretory otitis media yields better results, lowers TCM syndrome scores, and alleviates the body's inflammatory response, which is a safe drug in clinical use.

ABO Genotype and Blood Type Are Associated with Otitis Media.

Aim: To determine if there is an association between ABO variants or blood types and otitis media. Methods: DNA samples from 214 probands from Finnish families with recurrent acute (RAOM) and/or chronic otitis media with effusion (COME) were submitted for exome sequencing. Fisher exact tests were performed when (a) comparing frequencies of ABO genotypes in the Finnish probands with otitis media vs. counts in gnomAD Finnish, and (b) within the Finnish family cohort, comparing occurrence of RAOM vs. COME according to ABO genotype/haplotype and predicted blood type. Results: Female sex is protective against having both RAOM and COME. The wildtype genotype for the ABO c.260insG (p.Val87_Thr88fs*) variant resulting in blood type O was protective against RAOM. On the other hand, type A was associated with increased risk for COME. These findings remained significant after adjustment for age and sex. Conclusions: Within the Finnish family cohort, the wildtype genotype for the ABO c.260insG (p.Val87_Thr88fs*) variant and type O are protective against RAOM while type A increases risk for COME. This suggests that the association between the ABO locus and otitis media is specific to blood type, otitis media type and cohort.

Peripheral blood immunological parameters of children with adenoid hypertrophy with otitis media with effusion: propensity score matching.

PURPOSE: To evaluate peripheral blood immunological parameters and the possible correlation with age, gender and adenoid size in children with adenoid hypertrophy with OME. METHODS: A total of 664 children with adenoid hypertrophy were initially enrolled in our study, of which 83 had concomitant OME. To minimize selection bias, we performed one to two propensity score matching (PSM) between children with and without OME. After PSM, 80 children with OME (OME group) and 157 children without OME (adenoid hypertrophy [AH] group) were selected. The patients' peripheral blood samples were prepared prior to surgery and their immunological parameters were compared between groups. RESULTS: Compared to the AH group, the serum level of C3 was significantly higher in the OME group (0.88 ± 0.01 g/L vs. 0.94 ± 0.02 g/L; p = 0.014), which was the only independent risk factor for OME (odds ratio 13.58, 95% confidence interval 1.25-147.99; p = 0.032). However, no such difference was seen for serum immunoglobulin (IgG, IgA, IgM, IgE), T cell subsets (CD3+, CD4+ and CD8+ T cells), or lymphocytes and monocytes. Further subgroup analyses showed that in children ≤ 5 years old, the C3 level was significantly higher in OME patients (p = 0.023). A subgroup analysis based on sex indicated that there was a significantly higher level of serum C3 (p = 0.009) and lower CD3+ and CD4+ T cells (p = 0.010 and p = 0.021, respectively) in girls with OME compared to those without OME. No association between immunological parameters and adenoid size was found. CONCLUSIONS: There were no significant differences in cellular immunology and humoral immune indicators in children with adenoid hypertrophy with or without OME. In children ≤ 5 years old, significantly higher serum C3 levels in patients with OME demonstrate excessively activated C3 in comparison to patients without OME. For girls, a higher serum level of C3 with a lower amount of CD3+ and CD4+ T cells may be associated with OME.

Relationship of T lymphocytes, cytokines, immunoglobulin E and nitric oxide with otitis media with effusion in children and their clinical significances.

OBJECTIVE: To investigate the relations of T lymphocytes, cytokines, immunoglobulin E, and nitric oxide with otitis media with effusion (OME) in children and their clinical significances. METHODS: Fifty children with OME treated in our hospital were enrolled in the study (observation group). Fifty healthy children were selected as control. The percentages of CD4+ and CD8+ T lymphocyte and CD4+/CD8+ ratio in peripheral blood, and the levels of cytokine (IL)-2, IL-4, IL-6, immunoglobulin E (IgE) and nitric oxide (NO) in peripheral blood and middle ear effusion (MEE) in both groups were detected. The correlations of these indexes with OME were analyzed. RESULTS: The percentage of peripheral blood CD4+ and CD8+ levels, CD4+/CD8 ratio, IgE, and NO levels in the observation group were significantly higher than those in the control group (P < 0.01). In the observation group, the IL-2 and IL-6 levels, and IgE and NO levels in the MEE were significantly higher than those in peripheral blood (P < 0.01). In addition, in the observation group, the MEE IL-2 and IL-6 levels were positively correlated with peripheral blood CD4+/CD8+ ratio, respectively r = 0.366, P = 0.009; r = 0.334, P = 0.018. CONCLUSIONS: The levels of peripheral blood CD4+ and CD8+ lymphocytes and MEE IL-2, IL-6, IgE, and NO levels are increased in children with OME. These indexes have provided significant clues for the diagnosis of OME in children.

Relationship of T lymphocytes, cytokines, immunoglobulin E and nitric oxide with otitis media with effusion in children and their clinical significances

SUMMARY OBJECTIVE To investigate the relations of T lymphocytes, cytokines, immunoglobulin E, and nitric oxide with otitis media with effusion (OME) in children and their clinical significances. METHODS Fifty children with OME treated in our hospital were enrolled in the study (observation group). Fifty healthy children were selected as control. The percentages of CD4+ and CD8+ T lymphocyte and CD4+/CD8+ ratio in peripheral blood, and the levels of cytokine (IL)-2, IL-4, IL-6, immunoglobulin E (IgE) and nitric oxide (NO) in peripheral blood and middle ear effusion (MEE) in both groups were detected. The correlations of these indexes with OME were analyzed. RESULTS The percentage of peripheral blood CD4+ and CD8+ levels, CD4+/CD8 ratio, IgE, and NO levels in the observation group were significantly higher than those in the control group (P < 0.01). In the observation group, the IL-2 and IL-6 levels, and IgE and NO levels in the MEE were significantly higher than those in peripheral blood (P < 0.01). In addition, in the observation group, the MEE IL-2 and IL-6 levels were positively correlated with peripheral blood CD4+/CD8+ ratio, respectively r = 0.366, P = 0.009; r = 0.334, P = 0.018. CONCLUSIONS The levels of peripheral blood CD4+ and CD8+ lymphocytes and MEE IL-2, IL-6, IgE, and NO levels are increased in children with OME. These indexes have provided significant clues for the diagnosis of OME in children.

RESUMO OBJETIVO Investigar as relações entre linfócitos T, citocinas, imunoglobulina E e óxido nítrico e a otite média com efusão (OME) em crianças e sua significância clínica. MÉTODOS Cinquenta crianças com OME tratadas em nosso hospital foram incluídas no estudo (grupo de observação). Selecionamos também 50 crianças saudáveis como controle. As porcentagens de linfócitos T CD4 + e CD8 + e a razão CD4+/CD8+ no sangue periférico, além dos níveis das citocinas IL-2, IL-4, IL-6, imunoglobulina E (IgE) e óxido nítrico (NO) no sangue periférico e de efusão no ouvido médio (MEE) de ambos os grupos foram medidos. A correlação desses índices com a OME foi analisada. RESULTADOS A porcentagem dos níveis de CD4+ e CD8 +, da razão CD4+/CD8+, de IgE e NO no sangue periférico do grupo de observação foram significativamente maiores do que no grupo controle (P < 0,01). No grupo de observação, os níveis de IL-2 e IL-6, IgE e NO em MEE foram significativamente maiores do que no sangue periférico (P < 0,01). Além disso, no grupo de observação, foi encontrada uma correlação positiva entre os níveis de IL-2 e IL-6 em MEE e a razão de CD4+/CD8+no sangue periférico, respectivamente, r = 0,366, P = 0,009; r = 0,334, P = 0,018. CONCLUSÃO Os níveis de linfócitos CD4 + e CD8 + no sangue periférico e IL-2, IL-6, IgE e NO em MEE são mais altos em crianças com OME. Esses índices forneceram evidências valiosas para o diagnóstico de OME em crianças.

Evaluation of oxidative stress and antioxidants effect on turning process acute otitis media to chronic otitis media with effusion.

OBJECTIVE: The aim of this study was to investigate the effect of oxidative stress and antioxidant situation on chronic otitis media with effusions (COME) and acute otitis media (AOM) in children. METHODS: A total of 107 children aged 2 to 13 years were examined. The study included 31 patients with AOM, 39 with COME, and 37 as control subjects. Venous blood samples were collected from all patients and control group. Myeloperoxidase (MPO), glutathione peroxidase (GPx), catalase (CAT), nitric oxide (NO), malondialdehyde (MDA), and superoxide dismutase (SOD) activities were investigated in the blood samples. RESULTS: The mean age was found as 7.3 ± 3.3 in the AOM group, 6.2 ± 3.0 in the COME group, and 6 ± 2.4 in the control group. MPO, NO, and CAT were found to be significantly higher in the AOM and COME groups than the control groups (P = 0.040, P = 0.001, and P = 0.044). CONCLUSION: In this study, we observed activity of antioxidant and oxidative stress in children with COME and AOM. These results may be important in the diagnosis of these diseases and may affect the theurapeutic approach to the patients with COME and AOM.

Clinical role of vitamin D in prognosis of otitis media with effusion.

OBJECTIVE: To investigate the clinical role of Vitamin D in prognosis of Otitis media with effusion. METHODS: This prospective-controlled study was conducted at otolaryngology department in Duzce University, Turkey. The study group comprised children who were diagnosed with Otitis media with effusion between September 2016 and February 2017. Control group was conducted with children underwent circumcision or inguinal hernia repair operations that confirmed with ENT examination they do not have any sign of otitis media. After 3 months of follow-up without any treatment, unresolved cases who were accepted as chronic otitis media with effusion were operated under general anesthesia for ventilation tube application. Study and control groups were assessed depending on the serum 25(OH)Vitamin D levels at the end of 3 months; < 15 ng/mL was accepted as vitamin D deficiency. The results were compared with the control group in terms of vitamin D levels. Also, subgroup analysis was performed addressing to the complete recovery otitis media with effusion and chronic otitis media with effusion. RESULTS: One-hundred-seventy-four children with otitis media with effusion and 80 control patients were included to the study. One-hundred-eight (62%) out of 174 patients with otitis media with effusion was completely recovered after a 3-months follow up. Of those 66 out of 174 children, they had persistent diseases, underwent ventilation tube insertion after a 3-months follow-up. The mean 25(OH)Vitamin D level was 18.98 ± 10.60 in otitis media with effusion group and 28.07 ± 14.10 in control group and the difference was statistically significant between the study and control group (p < 0.001). Vitamin D deficiency was observed in 33 out of 66 patients (50.0%) in chronic otitis media with effusion group whilst 35 out of 108 patients (32.4%) in complete recovery otitis media with effusion group (p = 0.021). The rate of 25(OH)Vitamin D deficiency was 25% in control group which was statistically different from chronic otitis media with effusion and recovery chronic otitis media with effusion groups (p = 0.006). CONCLUSIONS: This study not only shows the relationship between Vitamin D and otitis media with effusion development, but also demonstrates the effects of Vitamin D on otitis media with effusion prognosis. There is a significant association between 25(OH)Vitamin D deficiency and follow-up outcomes of otitis media with effusion.

Compound shuanghua tablets combined with Western medicine on serum and secretion inflammatory factors in patients with acute secretory otitis media caused by swimming.

To observe and analyze the effect of compound shuanghua tablets combined with western medicine on serum and secretion inflammatory factors in patients with acute secretory otitis media caused by swimming. The 140 patients who had been treated in our hospital for acute secretory otitis media were selected as research objects, all of which were caused by swimming. The patients were divided into two groups, namely the control group accepting routine western drug therapy and the research group accepting compound shuanghua tablets combined with western drug therapy, each group contains 70 patients. The therapeutic effect of patients in two groups were observed and compared. Through observation, the levels of tumor necrosis factor, interleukin-6 and interleukin-10 were found to be significantly improved in the research group compared with the control group, and the intergroup difference was of statistical significance, p<0.05; The overall treatment efficiency of the research group was significantly higher than that of the control group, with statistical significance, p<0.05. For patients with acute secretory otitis media caused by swimming, the compound shuanghua tablets combined with Western medicine treatment can not only actively reduce various inflammatory factors in middle ear effusion, but also significantly improve the overall treatment efficiency.

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.

Higher serum 25(OH)D concentration is associated with lower risk of chronic otitis media with effusion: a case-control study.

AIM: Vitamin D supplementation and higher 25(OH)-vitamin D concentration are associated with reduced risk of acute respiratory infection. This study examined whether there is a similar association between higher serum 25(OH)D concentration and lower risk of chronic otitis media with effusion (COME). METHODS: In a case-control study, serum 25(OH)D concentration in children referred for tympanostomy tube placement for COME (n = 178) was compared to that of healthy children randomly sampled from primary care practices (n = 179). Subjects aged three and four years were recruited in Auckland, New Zealand between May 2011 and November 2013. Blood samples were collected from the children, and their guardians were interviewed. Odds ratios were calculated using logistic regression. RESULTS: In a multivariable analysis, higher serum 25(OH)D concentration was associated with a lower risk of COME (OR: 0.86 per 10 nmol/L; 95% CI 0.77-0.97) after adjusting for age, sex, deprivation index, ethnicity, tobacco smoke exposure, duration of breastfeeding and season of blood sampling. Further adjustment for eight additional risk factors did not change the result. CONCLUSION: This finding supports further investigation into whether the risk of COME could be reduced by increasing serum 25(OH)D concentration through increased sun exposure, higher dietary intake or vitamin D supplementation.

Studying the Serum as Well as Serous Level of IL-17 and IL-23 in Patients with Serous Otitis Media.

Serous otitis media with effusion (OME) is a middle ear inflammatory response to allergens and microbes which stimulate leukocytes to produce different inflammatory mediators after obstruction of Eustachian tube. Here, we investigated the levels of these mediators, IL-17 and IL-23, in serum and middle ear fluids of children with OME. 75 patients with otitis media and 75 age and sex-matched healthy controls were enrolled in this study. IL-17 and IL-23 levels in serous secretion of the patients and their serum levels were measured in both groups by ELISA. Serum IL-17 levels were significantly higher in the patients than controls (p=0.001). There was no significant difference between serum IL-23 levels in patients and controls. Patients' serous levels of both cytokines of IL-17 and IL-23 were higher than those in serum according to different parameters of sex, age, and duration of the disease. This study shows an elevated presence of IL-17 and IL-23, as pro inflammatory cytokines, in OME. These finding may represent the contribution of such cytokines in the pathogenesis of OME. Blocking such molecules may yield new non-surgical therapeutics.

Pepsinogen identification in the middle ear fluid of children with otitis media with effusion.

OBJECTIVES: This study aims to investigate the presence and concentration of pepsin/pepsinogen in middle ear fluid and to discuss the potential mechanisms involved in the pathogenesis of this condition. PATIENTS AND METHODS: A total of 33 children (21 boys, 12 girls; mean age 5.7±2.4 years; range 3 to 13 years) diagnosed with otitis media with effusion and scheduled for operation were enrolled into the study. Fluids aspirated from the middle ear were assessed for the presence of pepsinogen and albumin and blood samples were drawn simultaneously for comparison. RESULTS: Mean pepsinogen concentration was statistically significantly higher in middle ear fluids compared with serum samples (262.4 ng/mL [range: 211.7 ng/mL - 301.1 ng/mL] versus 102.6 ng/mL [range: 80.7 ng/mL - 134.5 ng/mL], respectively) (p<0.001). On the other hand, mean albumin concentration was significantly lower (1.1 g/dL [range: 0.01 g/dL - 9.5 g/dL] versus 5.8 g/dL [range: 0.9 - 9.5 g/dL], respectively) (p<0.001). The highest pepsinogen concentration was detected in patients with purulent effusion (275.3 ng/mL). CONCLUSION: Our findings support the theory of gastro-esophageal reflux related pepsinogen transition to the middle ear and indicate that pepsinogen may a reliable biochemical marker for the assessment of gastro-esophageal reflux.

A novel predictive marker for the viscosity of otitis media with effusion.

OBJECTIVES: To evaluate the significance of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio for the prediction of the viscosity of otitis media with effusion. METHODS: This retrospective study was performed on 81 patients who were admitted to the otolaryngology clinic.The patients were divided into two groups according to their effusion type, as serous or mucoid, which was defined intraoperatively after myringotomy. The NLR and PLR were calculated as a simple ratio between the absolute neutrophil/platelet and absolute lymphocyte counts.Tympanostomy tube insertion was performed for all cases.Under direct visualization, the effusion was aspirated and classified as serous or mucous. RESULTS: We postulated that an NLR value of less than 1.38 may show mucoid effusion and if the PLR value is less than 97.96, the effusion is mucoid. CONCLUSIONS: We speculate that a useful predictor of viscosity for a middle ear effusion could prevent unnecessary surgeries and additional costs in the treatment of EMO. Additional studies are needed to confirm our results.

Do orally administered antibiotics reach concentrations in the middle ear sufficient to eradicate planktonic and biofilm bacteria? A review.

INTRODUCTION: Infectious conditions of the middle ear are a common and significant cause of morbidity and mortality worldwide. Systemic antibiotics are frequently used, but their effectiveness will depend on whether an adequate antibiotic concentration is achieved in the middle ear; this is especially important in biofilm infections such as otitis media with effusion (OME), where high antibiotic concentrations are typically required for effective treatment. OBJECTIVE: This review examines what antibiotic levels can be reached in the middle ear with oral administration, as a means of guiding rational antibiotic choice in the clinic and future research, and to determine whether levels high enough for biofilm eradication are reached. METHODS: A literature search of studies measuring levels of antibiotics in the plasma and in the middle ear after oral administration was conducted. These levels were compared to the minimum inhibitory concentrations (MIC) provided by the European Committee for Antimicrobial Susceptibility Testing (EUCAST) to determine if antibiotic doses were reaching sufficient levels to inhibit planktonic bacteria. The middle ear concentrations were then calculated as a multiple of the MIC to determine if the concentrations were reaching biofilm eradication concentrations (typically up to 1000×MIC). RESULTS: The highest antibiotic levels against Staphylococcus aureus reach 8.3×MIC, against Moraxella catarrhalis 33.2×MIC, against Haemophilus influenzae 31.2×MIC, and against Streptococcus pneumoniae 46.2×MIC. The macrolide antibiotics reach higher levels in the middle ear than in plasma. CONCLUSIONS: Orally administered antibiotics reach levels above the MIC in the middle ear. However, they do not reach levels that would be likely to eradicate biofilms.