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Background: Otitis is characterised by inflammation of one or more of the structures of the ear. At present, to confirm or exclude otitis media (OM), it is most often necessary to perform a computed tomography (CT) scan or magnetic resonance imaging. Inflammation is an immune defence response found in many conditions that can be detected and tracked by measuring biological markers of inflammation as the Canine C-reactive protein (CRP)., Objectives: The objective of this study was to determine whether CRP measurement is useful as an adjunctive diagnostic tool in dogs with otitis and whether elevated concentrations correlated with disease severity/presence of OM., Animals: Twenty-four client-owned dogs were recruited over 1 year., Materials and Methods: The dogs were divided into three groups: chronic or recurrent otitis externa (CO), otitis media (OM) and H (healthy). The dogs with otitis underwent a CT scan of the head, measurement of the plasma CRP concentration and evaluation of a 0-3 Otitis Index Score 3 (OTIS3 score)., Results: No dog (0%) in group H had an increased CRP value, compared to 20% in the CO group (one of five dogs) and 23% in the OM group (3 of 13 dogs). Plasma CRP concentrations show a statistically significant positive relationship with the OTIS3 score (p = 0.04)., Conclusion and Clinical Relevance: Plasma CRP concentration is not reliable as a discriminatory tool in cases of otitis, although there is a trend for elevation in cases with more severe disease. However, a larger study may provide a statistically more reliable correlation between the severity of OM and CRP concentrations., (© 2024 ESVD and ACVD.)

Objective: The incidence of complications due to acute otitis media (AOM) in childhood has decreased significantly with the use of new antibiotics in recent years. However, acute mastoiditis (AM) is still the most common complication that can lead to further intracranial conditions with high morbidity. Our study aimed to evaluate the clinical characteristics of children with AM and identify possible indicators for further intracranial complications associated with this condition., Methods: Children hospitalized in our clinic with a diagnosis of AM were reviewed. Demographic data, disease-related symptoms, types of complications accompanied by AM, medical/surgical treatments modalities, and culture results were screened. The patients were divided into two groups as those with and without intracranial complications (ICCs). Routine complete blood count tests, biochemical analysis, and C-reactive protein (CRP) level measurement were evaluated and compared between the groups., Results: Of the 28 AM patients, five (17.9%) had isolated AM. Complications associated with AM included sub-periosteal abscess (28.6%), facial paralysis (25%), meningitis (17.9%), meningitis with sigmoid sinus thrombosis (7.1%), and meningitis with cerebellar abscess (3.6%). Eight patients developed ICCs (28.6%), of whom three had more than one complication. Ceftriaxone was found to be the first-line medical treatment (57.1%). Streptococcus pneumoniae was the most common pathogen isolated from the cultures (42.9%). Three patients (10.7%) were treated non-surgically, eight (28.6%) with myringotomy and ventilation tube (VT) insertion, eight patients (28.6%) with abscess drainage and VT insertion, and nine (32.1%) with cortical mastoidectomy and VT insertion. There was no significant difference between the patients with and without ICCs in terms of complete blood count parameters. The CRP level and the CRP-albumin ratio were significantly higher in patients with ICCs than those without these complications (p < 0.001)., Conclusion: AM remains to be the most common complication of AOM in childhood and can lead to further life-threatening conditions. Additional interventions according to the type of the complication with VT insertion is safe and effective in the management of AM. In patients with AM, it is of great importance to determine whether there is an accompanying ICC. The CRP-albumin ratio is a simple and reliable calculation to detect ICCs in patients with AM., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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&#95;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&#95;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.

Chronic otitis media (COM) is a multifactorial process, for which a clear etiology has not yet been established. The aims of the present study were to evaluate selenium (Se) and cadmium (Cd) levels in patients with COM and to analyze the correlation between Se and Cd with inflammation markers. The study population consisted of 88 participants: 45 healthy controls (group 1) and 43 patients with COM (group 2). Demographic data, Se, Cd, C-reactive protein (CRP), and white blood cell count (WBC) levels were all recorded. Se and Cd measurements were performed in a graphite furnace atomic absorption spectrophotometer (Perkin Elmer Analyst 800) using Zeeman background correction. The Se and Cd levels were compared between the groups and the correlation between Se and Cd with inflammation markers was analyzed. No statistically significant difference was determined between the groups in terms of demographic data (p > 0.05). CRP and WBC levels were significantly higher in group 2 than in group 1 (p < 0.05). Se levels were significantly lower in group 2 than in group 1, at 23.40 ± 12.08 μg/L vs. 37.31 ± 22.44 μg/L (p < 0.05). Cd levels were significantly higher in group 2 than in group 1, at 1.79 ± 1.63 μg/L vs. 0.68 ± 0.45 μg/L (p < 0.05). When all the cases were evaluated together, a statistically significant negative correlation was determined between Se and CRP (r = - 0.239, p = 0.013) and a positive correlation between Cd and CRP (r = 0.266, p = 0.006), WBC (r = 0.258, p = 0.008). Our results could propose that Se deficiency and Cd excess could play a crucial and additive role in the etiopathogenesis of COM. However, further investigations with larger numbers of patients are warranted to determine the exact role of these elements.

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., Competing Interests: None

Objectives: Chronic otitis media (COM) is caused by an infection of the middle ear, although it may also be associated with environmental pollutants. Recent reports found that cadmium exposure could be toxic to middle ear cell lines, but the role of cadmium in the development of COM in humans has not been examined to date. We hypothesised that environmental cadmium exposure was associated with an increased risk of COM in the general population., Methods: We analysed cross-sectional data for 5331 adults of 20 years of age or above, obtained from the Korea National Health and Nutrition Examination Survey 2010-2012. We examined the association between blood cadmium levels and COM diagnosed by an otolaryngologist., Results: The highest quartile group of cadmium blood concentration was associated with an OR of 3.33 (95% CI 1.78 to 7.53) for COM, after adjusting for potential confounding factors. Doubling blood cadmium concentration resulted in an OR of 1.58 (95% CI 1.19 to 2.08) for COM. These associations were robust on sensitivity analyses after excluding current smokers and former smokers and after excluding subjects with a potential history of occupational exposure to cadmium., Conclusions: The results of our study suggest that environmental cadmium exposure is associated with increased risk of COM, and further studies are warranted to understand the pathogenetic mechanism by which COM is caused by cadmium exposure., Competing Interests: Competing interests: The Korea Centers for Disease Control and Prevention provided the data from the Korea National Health and Nutrition Examination Survey used in this study., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The objectives of this study were to investigate the relationship between cerebrospinal fluid lactate and serum concentrations in dogs with clinical signs of central nervous system disease and to establish if cerebrospinal fluid lactate (CSF) concentrations are higher in dogs with structural intracranial disease (Group Pos-MRI) compared to dogs that have clinical signs of intracranial disease but no structural brain disease (Group Neg-MRI) based on magnetic resonance imaging (MRI) findings. Using a prospective study canine blood and cerebrospinal fluid were collected in 24 dogs with neurological signs after undergoing brain MRI. Dogs were divided in 2 groups. No significant difference between serum lactate (1.57 ± 0.9 mmol/L) and CSF lactate concentration (1.34 ± 0.3 mmol/L) was detected. There was a direct correlation between CSF and serum lactate concentration ( R = 0.731; P = 0.01). No significant difference was found in CSF lactate concentration between the 2 groups of dogs ( P = 0.13).

Objectives: The authors' aim was to investigate whether serum neutrophil to lymphocyte ratio might be used as a predictive biomarker to help differentiate active from inactive chronic otitis media (COM)., Methods: Two hundred fifty-nine patients having inactive COM received tympanoplasty without mastoidectomy and were identified as Group 1. On the other hand, 254 patients having active COM received tympanoplasty with mastoidectomy and were identified as Group 2. Routine hemogram tests were performed preoperatively for both the groups. By performing a chart review, white blood cell count, red blood cell count, hemoglobin, hematocrit, platelet, and mean platelet volume values were compared between the groups in an age-matched and sex-matched manner., Results: A total of 513 COM patients with age range of 7 to 65 years were included in the study. Two hundred seventy-five patients (53.6%) were male, 238 were (46.4%) female. Preoperatively both serum neutrophil and lymphocyte counts were significantly higher in Group 2 (P = 0.015 and P = 0.004, respectively). However, the neutrophil-to-lymphocyte ratios between the groups were not significantly different (P = 0.511)., Conclusion: No statistically significant differences were identified from preoperative neutrophil-to-lymphocyte ratios between patients having active COM and inactive COM., Level of Evidence: Level NA.

Background: Nutrients related to serum vitamin D level were previously shown to be significantly associated with the risk of many chronic diseases. This study aimed to assess potential relationships between serum vitamin D level and otitis media (OM) risk., Methods: PubMed, EMBASE, and Cochrane Library databases were searched till Aug 18, 2015 for studies of quantitative OM risk estimates in relation to serum vitamin D level. The odds ratio and weighted mean difference, with 95% confidence intervals (CIs), were used to measure the relationship between serum vitamin D level and OM risk., Results: Of the 89 articles identified by database search, 5 studies reported data of 16,689 individuals were included in our meta-analysis. We noted participants with OM was associated with lower level of plasma vitamin D when compared with patients without OM (weighted mean difference -5.67; 95% CI -8.08 to -3.26, P < 0.001). Furthermore, as compared with control group, serum vitamin D level was not associated with the risk of OM (odds ratio 0.80, 95% CI 0.47-1.38, P = 0.425). Subgroup analyses suggested that participants with acute OM might associate with lower serum vitamin D level., Conclusions: Plasma vitamin D level might play an important role on the progression of acute OM, whereas no significant impact in patients with chronic OM., Competing Interests: The authors declare no competing interests.

Background: This study investigated genetic polymorphisms affecting the inducible nitric oxide synthase, superoxide dismutase and catalase enzymes in chronic otitis media patients with and without tympanosclerosis, and the role of genetic susceptibility in the disease aetiology., Methods: A total of 162 patients who underwent surgery for chronic otitis media were divided into two study groups: a tympanosclerosis group and a chronic otitis media group. A third, the control, group comprised 188 healthy volunteers. Venous blood samples were evaluated using reverse transcriptase polymerase chain reaction., Results: There was a significant difference in GG genotype distribution of the -277A>G polymorphism in the NOS2 gene between the tympanosclerosis and control groups (p T) polymorphism in the SOD2 gene (p > 0.05). There were significant differences in the TT genotype distribution of the -21A>T polymorphism in the CAT gene between the tympanosclerosis and control groups, and between the chronic otitis media and control groups (p < 0.05)., Conclusion: These results suggest that genetic predisposition may play a role in the aetiopathogenesis of tympanosclerosis.

Objectives: To evaluate the clinical picture and microbiological findings of children hospitalized due to acute otitis media and to analyze how it differs from acute mastoiditis., Methods: A retrospective review of the medical records of all children (0-16 years) hospitalized due to acute otitis media in the Department of Otorhinolaryngology at the Helsinki University Hospital, between 2003 and 2012. Comparison with previously published data of children with acute mastoiditis (n=56) from the same institute and period of time., Results: The most common pathogens in the children hospitalized due to acute otitis media (n=44) were Streptococcus pneumoniae (18%), Pseudomonas aeruginosa (16%), Streptococcus pyogenes (14%), and Staphylococcus aureus (14%). One of the most common pathogens of out-patient acute otitis media, Haemophilus influenzae, was absent. Otorrhea was common in infections caused by S. pyogenes and otorrhea via tympanostomy tube in infections caused by P. aeruginosa. In children under 2 years-of-age, the most common pathogens were S. pneumoniae (43%), Moraxella catarrhalis (14%), and S. aureus (7%). S. pyogenes and P. aeruginosa were only found in children over 2 years-of-age. Previous health problems, bilateral infections, and facial nerve paresis were more common in children hospitalized due to acute otitis media, compared with acute mastoiditis, but they also demonstrated lower CRP values and shorter duration of hospital stay. The number of performed tympanostomies and mastoidectomies was also comparatively smaller in the children hospitalized due to acute otitis media. S. aureus was more common and S. pneumoniae, especially its resistant strains, was less common in the children hospitalized due to acute otitis media than acute mastoiditis., Conclusions: Acute otitis media requiring hospitalization and acute mastoiditis compose a continuum of complicated acute otitis media that differs from common out-patient acute otitis media. The bacteriology of children hospitalized due to acute otitis media resembled more the bacteriology of acute mastoiditis than that of out-patient acute otitis media. The children hospitalized due to acute otitis media needed less surgical treatment and a shorter hospitalization than those hospitalized due to acute mastoiditis., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objectives: Paraoxonase-1 (PON1) prevents oxidative stress by inhibiting the oxidation of cell membrane lipids by the reactive oxygen species that form during acute and chronic inflammation. The aim of this study was to investigate serum PON1 activity and oxidative stress in patients with chronic otitis media (COM)., Methods: Fifty consecutive patients with COM and 55 controls were enrolled in the present study. The patients were divided into two groups according to the presence of cholesteatoma. The serum PON1 arylesterase activities and lipid hydroperoxide (LOOH) levels were determined., Results: Serum paraoxonase and arylesterase activities were significantly lower in the COM patients than in the controls (P < 0.001 for all comparisons), whereas the LOOH levels were significantly higher (P < 0.001)., Discussion: These results indicated that a lower level of PON1 activity was associated with an oxidant-antioxidant imbalance. In addition, decreased PON1 activity may play an important role in the pathophysiology of COM.

Objective: To investigate the relationship between Vitamin D deficiency and acute otitis media infection., Methods: The randomised, single-blind, case-control study was conducted at the Paediatric Department of Ataturk University, Erzurum, Turkey, from January to April 2010. It comprised ambulatory children diagnosed with acute otitis media and healthy controls. The subjects were divided into groups according to their serum 25-hydroxy vitamin D levels. SPSS 18 was used for statistical analysis., Results: Of the 169 subjects in the study, 88(52%) were the cases and 81(48%) were controls. The mean age of the cases was 6.21±3.4 years, and 6.18±3.12 years for the controls (p<0.951). Serum 25-hydroxy vitamin D levels in the cases and controls were 20.6±10.2 ng/mL and 23.8±10.3 ng/mL (p<0.05). There was no statistically significant difference between the groups in terms of parathormone and calcium levels (p>0.05)., Conclusion: Serum 25-hydroxy vitamin D levels being significantly lower in children diagnosed with acute otitis media compared to the controls in two otherwise similar groups suggests that Vitamin D deficiency plays a role in otitis media infection.

Objective: Immunoglobulin (Ig) G4-related disease is systemic, and it has been reported that patients with IgG4-related disease complain of symptoms involving numerous organs. However, there are few reports concerning the otologic manifestations of IgG4-related disease. The purpose of this study is to investigate the clinical features of the otologic manifestations in IgG4-related disease., Methods: We recruited 39 consecutive patients diagnosed with IgG4-related disease. Otologic symptoms, laboratory data, and audiogram findings were retrospectively examined. Mucosal tissues from the inferior turbinate were obtained from subjects before treatment. The serum IgG4 and eosinophil levels together with clinical features were analyzed., Results: Five of the 39 cases had some otologic symptoms. Otitis media with effusion was present in 2 patients. Sensorineural hearing loss was also present in I patient. Eosinophilic otitis media was present in 2 patients with bilateral rhinosinusitis and bronchial asthma, and elevated serum eosinophil levels. Oral prednisolone was effective in the treatment of IgG4-related disease., Conclusion: We revealed a new clinical entity associated with the otologic manifestations of IgG4-related disease.

Background: Australian indigenous infants experience the highest incidence of chronic suppurative and acute otitis media in the world with many babies developing disease in the early postnatal period. Streptococcus pneumoniae is the major cause of otitis media in this population. Infants are protected against bacterial disease in the first months of life by passive transfer of maternal antibody across the placenta during the late stages of gestation. We hypothesized that reduced passive immunity may contribute to increased disease risk in this population. We compared the concentrations and function of serotype-specific IgG in cord serum from Australian indigenous neonates and Gambian neonates, the latter experiences a similar socioeconomic status to Australian indigenous neonates., Methods: Serotype-specific IgG, IgG1 and IgG2 were measured using a modified 3rd generation enzyme linked immunosorbent assay based on World Health Organization recommendations. Antibody avidity was measured using a modified sodium thiocyanate elution method., Results: Australian indigenous neonates had significantly increased levels of serotype-specific IgG compared with Gambian populations for 6 of 12 serotypes (P < 0.02). There was no significant difference in antibody function, as measured by antibody avidity, between the 2 groups., Conclusions: An increased risk for otitis media in Australian indigenous neonates is not primarily determined by specific antibody titers against pneumococcal bacteria. Further investigation into the possible roles of the innate immune response and Eustachian tube dysfunction in the development of chronic otitis media amongst Australian indigenous infants is warranted.

The aims of this study were to evaluate serum vitamin D levels in cases of recurrent otitis media and investigate the effect of vitamin D therapy on the risk of re-occurrence of the disease. This prospective study was performed by comparing serum vitamin D levels in children with recurrent otitis media and healthy children. Eighty-four children between 1 and 5 years of age and diagnosed with recurrent otitis media were enrolled as the study group. One hundred-and-eight healthy children with similar demographic characteristics were enrolled as the control group. Patients were divided into groups according to their serum 25(OH) vitamin D levels. In patients with low initial serum vitamin D levels, vitamin D therapy was administered in addition to conventional treatment for otitis media. Mean serum 25(OH) vitamin D level in the study group was 11.4 ± 9.8 ng/mL Serum 25(OH) vitamin D levels were below 20 ng/mL in 69 % (n = 58) of cases in this group. In the control group, mean serum 25(OH) vitamin D level was 29.2 ± 13.9 ng/mL and was below 20 ng/mL in 30 % (n = 32) of cases. Comparison of serum 25(OH) vitamin D levels and PTH in the study and control groups revealed a statistically significant difference (p < 0.05). Treatment was initiated in cases diagnosed with vitamin D deficiency, and patients were followed up in due course. The only episodes detected over the course of 1-year follow-up were one attack in five patients and two attacks in two. We believe that co-administration of supplementary vitamin D together with conventional treatments is appropriate in the management of upper respiratory infections such as otitis media.

Objective: From 10 to 15% of children suffer from recurrent acute otitis media (AOM). An association between polymorphism in TLRs and their co-receptor CD14 with otitis media proneness has been described in children. Moreover, the experiments on animal models have shown that TLRs and their signaling molecules are critical for timely resolution of bacterial otitis., Aim: The aim of this study was to determine the expression of TLR1, TLR2 and TLR4 on lymphocytes, monocytes and granulocytes in peripheral blood in children with recurrent or persistent AOM., Methods: The study was performed on a group of 25 children hospitalized for recurrent AOM, failures of previous treatments and/or acute mastoiditis. The results were compared to the control group of healthy children at the same age. The expression of TLRs on peripheral blood white cells was measured by flow cytometric analysis. The results were expressed as mean fluorescence intensity (MFI). The statistical analysis was performed using the Mann-Whitney U test., Results: The highest expression of TLR was found on monocytes, the lowest on lymphocytes in both groups of children (AOM and the control one). The expression of TLR1 was the lowest and expression of TLR4 was the highest on all examined cells. The expression of all examined TLRs on monocytes was significantly higher in the AOM group., Conclusions: Peripheral blood monocytes are characterized by increased expression of TLRs in the course of recurrent AOM., (Copyright © 2013 Polish Otorhinolaryngology - Head and Neck Surgery Society. Published by Elsevier Urban & Partner Sp. z.o.o. All rights reserved.)

Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are pathogens commonly associated with infectious diseases in childhood. This study aimed to develop a fluorescent multiplexed bead-based immunoassay (FMIA) using recombinant proteins for the quantitation of serum IgG antibodies against these bacteria. Eight pneumococcal proteins (Ply, CbpA, PspA1, PspA2, PcpA, PhtD, SP1732-3 and SP2216-1), 3 proteins of H. influenzae (NTHi Protein D, NTHi0371-1, NTHi0830), and 5 proteins of M. catarrhalis (MC Omp CD, MC&#95;RH4&#95;2506, MC&#95;RH4&#95;1701, MC&#95;RH4&#95;3729-1, MC&#95;RH4&#95;4730) were used to develop the FMIA. Optimal coupling concentrations for each protein, comparison of singleplex and multiplex assays, specificity, reproducibility, and correlation to ELISA for six pneumococcal antigens were determined for validation. FMIA was then used to analyze acute and convalescent paired serum samples of 50 children with non-severe pneumonia. The coupling concentrations varied for different antigens, ranging from 1.6 to 32μg of protein/million beads. Correlation between singleplexed and multiplexed assays was excellent, with R≥0.987. The FMIA was specific, reaching >92% homologous inhibition for all specificities; heterologous inhibition ≥20% was found only in six cases. The assay was repeatable, with averages of intra-assay variation ≤10.5%, day-to-day variation ≤9.7% and variation between technicians ≤9.1%. Comparison with ELISA for pneumococcal antigens demonstrated good correlation with R ranging from 0.854 (PspA2) to 0.976 (PcpA). The samples from children showed a wide range of antibody concentrations and increases in convalescent samples. In conclusion, the FMIA was sensitive, specific, and repeatable, using small amounts of recombinant proteins and sera to detect antibodies against S. pneumoniae, H. influenzae and M. catarrhalis. The methodology would be suitable for studies investigating etiological diagnosis and in experimental vaccine studies., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: We recently found that children who experience recurrent otitis media despite individualized care (stringently-defined otitis prone [sOP]) do not develop an antibody response to several vaccine candidate protein antigens expressed by Streptococcus pneumonia (Spn) and Haemophilus influenzae. Here we sought to determine if these same children also failed to develop antibody to routine pediatric vaccinations., Study Design: One hundred forty sera collected from children age 6-24 months were analyzed. sOP (n=34) and age-matched non-sOP (n=34) children were assessed for IgG concentrations to diphtheria toxoid, tetanus toxoid, pertussis toxoid, filamentous hemagglutinin, pertactin (DTaP), polio, hepatitis B, H. influenzae type b capsule polyribosyl-ribitol-phosphate (PRP) and Spn capsular polysaccharide conjugate vaccine., Results: IgG protective titers to diphtheria toxoid (P=0.006), tetanus toxoid (P<0.0001), pertussis toxoid (P<0.0001), filamentous hemagglutinin (P=0.001), pertactin (P=0.005), hepatitis B (P<0.0001), polio 3 (P=0.03) and Spn 23F (P=0.01) but not polio 1,2, PRP or Spn 6B, and 14 were decreased in sOP versus non-sOP children using generalized estimating equations. A high percentage of sOP children had nonprotective antibody values that persisted until 24 months of age despite routine boosters., Conclusion: sOP children may fail to achieve protective antibody concentrations after several routine vaccinations.

Otitis media (OM) is well known as a common feature of proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA)-related Wegener granulomatosis, but is a very rare condition in myeloperoxidase ANCA (MPO-ANCA)-related vasculitis. In addition, there have been a few reports showing an association of MPO-ANCA-positive OM with cranial polyneuropathy. In this report, we describe 2 patients with bilateral facial nerve palsy due to MPO-ANCA-related OM. One patient also had bilateral trigeminal neuropathy, pachymeningitis and MPO-ANCA-related glomerulonephritis, whereas the other showed isolated bilateral facial nerve palsy with OM. In both the patients, treatment with prednisolone and immune-suppressant drugs resulted in an improvement of OM and cranial polyneuropathy. Physicians should be aware that MPO-ANCA-positive OM can cause bilateral facial nerve palsy.

MYH9-related disease (MYH9-RD) is one of the most frequent autosomal-dominant forms of inherited macrothrombocytopenias and is caused by mutations in MYH9 (nonmuscle myosin IIA), the gene coding for the heavy chain of the nonmuscle myosin IIA. Affected individuals can present with isolated thrombocytopenia, and whereas only some will have bleeding events requiring intervention, nearly all will require the use of prophylactic platelet transfusions before surgery. Here we report the first prophylactic use of eltrombopag before surgery in a child with MYH9-RD. Our patient was a 13-year-old girl with an MYH9 S96L missense mutation who required a tympanoplasty due to chronic otitis media. Pretreatment microscopic platelet count was 10 × 10(9)/L. The child was treated with eltrombopag starting 4 weeks before her planned surgery. On the day of surgery her platelet count was 70 × 10(9)/L. She required no platelet transfusions and no abnormal bleeding was reported either during surgery or postoperatively. Given these results, the first reported in a child, we suggest that the use of this thrombopoietic agent should be further evaluated as a useful presurgical prophylactic option in this hereditary thrombocytopenia, thus avoiding the use of platelet transfusions and their associated risks, which include alloimmunization and the transmission of infectious agents.

It has been suggested that oxidative stress may play an important role in the pathogenesis of chronic otitis media (COM), but the role of oxidative stress in the pathogenesis of COM has not yet been fully explored. Therefore, the aim of this study was to investigate serum myeloperoxidase (MPO) activity, 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), total antioxidant capacity (TAC) and nitric oxide (NO) in patients with COM. Sixty-one patients with COM and 30 controls were enrolled in the present study. Patients were divided into two groups according to the presence (n = 21) or absence (n = 40) of cholesteatoma. Serum MPO activity and 4-HNE, MDA and NO levels were significantly higher in patients with COM than controls (for all, p < 0.001), while TAC levels were significantly lower (for all, p < 0.001). Serum MPO activity and MDA, 4-HNE and NO levels were significantly higher in patients with cholesteatoma than in those without cholesteatoma, while TAC levels were significantly lower; but the difference between groups was not statistically significant (p > 0.05). Increased oxidative stress seems to be associated with decreased antioxidant levels in patients with COM. Thus, increased oxidative stress may play a role in the pathogenesis of COM. It is believed that the administration of antioxidant vitamins such as A, C and E may be useful in preventing and treating COM.

Objectives/hypothesis: Acute otitis media (AOM) involves an inflammatory response to microbes in the middle ear that facilitates clearance of otopathogens. Clinically, Streptococcus pneumoniae (Spn) infections of the respiratory tract are characterized by greater inflammatory responses than nontypeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat). Interleukin 10 (IL-10) plays an important role in down-regulating the inflammatory response. We compared serum IL-10 levels in children before onset, at onset, and after recovery from AOM caused by Spn, NTHi, and Mcat. We sought to determine if IL-10 could serve as a biomarker to distinguish AOM caused by Spn versus NTHi and Mcat., Study Design: Prospective, longitudinal study in a primary care pediatric practice in Rochester, NY., Methods: Participants were 54 children, 6 to 30 months of age. Outcomes measured were serum IL-10 levels when healthy, at onset of AOM, and after recovery from AOM., Results: Serum IL-10 was elevated when children developed AOM (P=0.013) due to infections caused by Spn (P=0.011) but not AOM caused by NTHi or Mcat. Middle ear fluid levels of IL-10 mirrored those seen in serum but were 10-fold higher (P=0.02). Other effector cytokines in serum: IL-4, IFN-γ, and TNF-alpha, did not show the same increases as IL-10 at onset of AOM., Conclusion: Our study indicates that AOM caused by Spn elicits a significantly higher IL-10 response compared to NTHi and Mcat and may prove to be a biomarker of AOM infections by Spn., (Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.)

Introduction: Infection markers are appreciated supplements in the clinical diagnosis of ear, nose and throat (ENT) infections. We aimed to examine the differential diagnostic usefulness of C-reactive protein (CRP), white blood cell count (WBC) and absolute neutrophil count (ANC) according to severity of middle ear and tonsillar infections., Material and Methods: This was a retrospective study including all patients admitted to the ENT Department, Aarhus University Hospital, from January 2001 to December 2008 and diagnosed with acute otitis media, mastoidismus, acute mastoiditis, acute tonsillitis, peritonsillar abscess, parapharyngeal abscess and necrotizing fasciitis., Results: A total of 1,773 patients were included. Between the tonsil subgroups, significant differences were found in CRP (p < 0.001), WBC (p < 0.001) and ANC (p < 0.001) levels. However, sensitivities and specificities related to differential diagnostics were low. In the middle ear group, no differences in CRP (p = 0.84), WBC (p = 0.46), and ANC (p = 0.72) levels were found. The number of CRP levels above the reference value was significantly higher than the corresponding number of WBC and ANC levels. A trend (non-significant) was found towards lower parameter levels in acute tonsillitis and peritonsillar abscess patients who grew Staphylococcus aureus compared with patients infected with other bacteria., Conclusion: CRP and ANC levels were related to severity of tonsillar-derived infections, but no such relation was found in infections with middle ear origin. None of the infection markers studied were useful for differential diagnostics., Funding: not relevant., Trial Registration: not relevant.

Background: Otitis media (OM) is the most common childhood bacterial infection and also the leading cause of conductive hearing loss in children. Currently, there is an urgent need for developing novel therapeutic agents for treating OM based on full understanding of molecular pathogenesis in the areas of molecular biology, biochemistry, genetics, and animal model studies in OM., Objective: To provide a state-of-the-art review concerning recent advances in OM in the areas of molecular biology, biochemistry, genetics, and animal model studies and to discuss the future directions of OM studies in these areas., Data Sources and Review Methods: A structured search of the current literature (since June 2007). The authors searched PubMed for published literature in the areas of molecular biology, biochemistry, genetics, and animal model studies in OM., Results: Over the past 4 years, significant progress has been made in the areas of molecular biology, biochemistry, genetics, and animal model studies in OM. These studies brought new insights into our understanding of the molecular and biochemical mechanisms underlying the molecular pathogenesis of OM and helped identify novel therapeutic targets for OM., Conclusions and Implications for Practice: Our understanding of the molecular pathogenesis of OM has been significantly advanced, particularly in the areas of inflammation, innate immunity, mucus overproduction, mucosal hyperplasia, middle ear and inner ear interaction, genetics, genome sequencing, and animal model studies. Although these studies are still in their experimental stages, they help identify new potential therapeutic targets. Future preclinical and clinical studies will help to translate these exciting experimental research findings into clinical applications.

Objectives: To evaluate the cytokine response pattern in Inuit in Greenland in relation to age, gender, body mass index (BMI), Mycobacterium tuberculosis infection (MTI), and otitis media (OM) to assess whether Inuit may have signs of impaired immune responsiveness to infection., Methods: A cross-sectional health assessment was conducted among inhabitants of Maniitsoq, West Greenland, in 2009, and several health outcomes were measured. The prevalence of MTI, overweight, and obesity was assessed among 263 school children and 137 adults, and OM was assessed among the children. Cytokine responses were measured in whole blood cultures after stimulation with phytohemagglutinin or purified protein derivative (PPD). Associations between cytokine concentrations, age, gender, BMI, MTI, and OM were estimated by linear regression., Results: Adults had generally higher cytokine concentrations than children. Children with MTI had 2.7 times higher interleukin (IL)-10 concentrations than those without (P = 0.01), and girls had 80% higher IL-10 than boys (P < 0.01) after phytohemagglutinin stimulation. Interferon (IFN)γ and tumor necrosis factor (TNF) concentrations were strongly elevated among children (P(IFNγ) < 0.001 and P(TNF) < 0.001) and adults (P(IFNγ) < 0.001 and P(TNF) <0.01) with MTI compared to those without after PPD stimulation. Adult women had significantly lower IFNγ (P = 0.03) and TNF (P = 0.04) concentrations than men. TNF was positively correlated with BMI in children (P = 0.01), and IL-10 was positively correlated with BMI in adults (P = 0.0004) after PPD stimulation., Conclusion: We found cytokine patterns similar to those reported from other immune competent study populations. Therefore, the study does not support the suggestion that Inuit may have impaired immune reactivity to infection., (Copyright © 2012 Wiley Periodicals, Inc.)

Introduction: Respiratory syncytial virus (RSV) infection is the most common cause of hospitalization in infants and small children. The aim was to present a 13-months old boy diagnosed with acute airway infection, acute otitis media (AOM) and hepatitis during the RSV-infection., Material and Methods: Serum catalytic activities of alkaline phosphatase (ALP), aspartate aminotranspherase (AST), alanine aminotranspherase (ALT), gamma glutamyl transpherase (GGT), lactate dehydrogenase (LD), and concentrations of bilirubin were monitored during hospitalization and at control examination., Results: The child had clinical signs and symptoms of respiratory failure, AOM, and laboratory findings of virus infection and liver disease. On admission, catalytic activities of enzymes were markedly increased, especially the activity of ALP (10333 U/L, i.e. 24-fold increase in comparison with the upper reference limit). The highest increased in AST (339 U/L, 4.5-fold), ALT (475 U/L, 10.3-fold) and LD (545 U/L, 1.5-fold) were registered on the 3rd day, and the highest increase in GGT (68 U/L, 3.1-fold) occurred on the 11th day. Seven weeks after discharge AST, ALT, GGT and LD decreased into reference range, and ALP remain mildly increased (478 U/L, 1.1 fold increase). RSV was confirmed in nasal lavage fluid., Conclusion: Laboratory results in patient with RSV infection needs to be interpreted in the light of both, respiratory and extrapulmonary manifestations of the infection, respectively.

Genetic predisposition is recognized as an important pathogenetic factor in otitis media (OM) and associated diseases. Mutant Lmna mice heterozygous for the disheveled hair and ears allele (Lmna(Dhe/+)) exhibit early-onset, profound hearing deficits and other pathological features mimicking human laminopathy associated with the LMNA mutation. We assessed the effects of the Lmna(Dhe/+) mutation on development of OM and pathological abnormalities characteristic of laminopathy. Malformation and abnormal positioning of the eustachian tube, accompanied by OM, were observed in all of the Lmna(Dhe/+) mice (100% penetrance) as early as postnatal day P12. Scanning electronic microscopy revealed ultrastructural damage to the cilia in middle ears that exhibited OM. Hearing assessment revealed significant hearing loss, paralleling that in human OM. Expression of NF-κB, TNF-α, and TGF-β, which correlated with inflammation and/or bony development, was up-regulated in the ears or in the peritoneal macrophages of Lmna(Dhe/+) mice. Rugous, disintegrative, and enlarged nuclear morphology of peritoneal macrophages and hyperphosphatemia were found in Lmna(Dhe/+) mutant mice. Taken together, these features resemble the pathology of human laminopathies, possibly revealing some profound pathology, beyond OM, associated with the mutation. The Lmna(Dhe/+) mutant mouse provides a novel model of human OM and laminopathy., (Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

The bactericidal antibody response to three nontypeable Haemophilus influenzae (NTHi) outer membrane proteins (D, P6, and OMP26) was studied in 24 otitis-prone children (aged 7-28 months) after an acute otitis media (AOM) caused by NTHi. The study was carried out to understand the contribution of antigen-specific bactericidal antibody responses in the class of children who are most vulnerable to recurrent otitis media infections. Levels of protein D (P = 0.005) and P6 (P = 0.026) but not OMP26 antibodies were higher in bactericidal sera compared with nonbactericidal sera. For five (24%) and 16 (76%) of 21 bactericidal sera tested, removal of anti-protein D and P6 antibody, respectively, resulted in a two- to fourfold drop in bactericidal antibody. Antibodies to OMP26 did not make any contribution to the overall bactericidal activity in any serum samples. Eleven of 21 sera (52%) had bactericidal activity against a heterologous NTHi (86-028 NP) strain but the titers were significantly lower (P < 0.05) as compared to the homologous strains. Future studies of protein D, P6, OMP26, and other potential NTHi vaccine antigens should include studies of bactericidal antibody in children who are otitis prone as a possible correlate of protection., (© 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.)

Background: Mannose-binding lectin (MBL) is a collagen-like serum protein that plays an important role in first-line host defense, especially in infants and young children. The objective of this study was to explore the genetic polymorphisms and serum protein levels of MBL in Chinese pediatric patients with common infectious diseases, including recurrent respiratory infection (RRI), acute respiratory infection (ARI), active cytomegalovirus (CMV) infection, localized abscess, and otitis media., Methods: MBL genetic polymorphisms of 151 pediatric patients with infectious diseases and 105 healthy controls were detected by PCR and sequencing. Serum MBL levels of all the patients and controls were measured using a Human MBL ELISA Kit. Differences in MBL genetic polymorphisms and serum levels between patients and controls were analyzed by statistical methods., Results: The frequencies of allele H/L at position -550 of the promoter and three haplotypes - HYPA, HYPB, and LYPB - were statistically different between patients and controls (p<0.05). The frequencies of genotypes 'YA' and 'XB', relevant to serum protein levels, were also significantly different between patients and controls (p<0.05). Serum MBL levels of patients with active CMV infection were significantly lower than those of controls (p<0.05). Conversely, serum MBL levels of patients with ARI and localized abscess were significantly higher than those of controls (p<0.05)., Conclusions: Genetic polymorphisms attributable to mutations in the promoter and exon 1 of the MBL2 gene appear to be relatively common in pediatric patients with infectious diseases. Low serum MBL levels may play a role in the high sensitivity of pediatric CMV infections., (Copyright © 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Lateral sinus thrombosis (LST) is an uncommon, but life-threatening complication of both acute and chronic otitis media. There is some evidence that acquired or hereditary prothrombotic disorders are risk factors for LST. The aim of this work was to evaluate the role of thrombotic screening, anticoagulant therapy or prophylaxis in patients with either acute or chronic otitis media and LST. The medical records of five children hospitalized at Pediatric Hospital Bambino Gesù of Rome because of acute or chronic otitis media complicated by mastoiditis and LST were reviewed. All children underwent laboratory workup for hypercoagulability. All the five children were found to be heterozygote for the C677T MTHFR mutation and a child presented also heterozygosity for factor V Leiden mutation. They have been successfully treated with anticoagulant therapy without sequels. Children with acute or chronic otitis media may have a prothrombotic tendency that becomes clinically evident because of the inflammatory state. Patients with a family and/or personal history of thrombosis and/or thrombophilic conditions need anticoagulant prophylaxis also in the absence of clear signs of LST. Treatment with low molecular weight is successful in patients with LST.

Background: Vaccines including conserved antigens from Streptococcus pneumoniae and nontypeable Haemophilus influenzae (NTHi) have the potential to reduce the burden of acute otitis media. Little is known about the antibody response to such antigens in young children with recurrent acute otitis media, however, it has been suggested antibody production may be impaired in these children., Methods: We measured serum IgG levels against 4 pneumococcal (PspA1, PspA 2, CbpA and Ply) and 3 NTHi (P4, P6 and PD) proteins in a cross-sectional study of 172 children under 3 years of age with a history of recurrent acute otitis media (median 7 episodes, requiring ventilation tube insertion) and 63 healthy age-matched controls, using a newly developed multiplex bead assay., Results: Children with a history of recurrent acute otitis media had significantly higher geometric mean serum IgG levels against NTHi proteins P4, P6 and PD compared with healthy controls, whereas there was no difference in antibody levels against pneumococcal protein antigens. In both children with and without a history of acute otitis media, antibody levels increased with age and were significantly higher in children colonised with S. pneumoniae or NTHi compared with children that were not colonised., Conclusions: Proteins from S. pneumoniae and NTHi induce serum IgG in children with a history of acute otitis media. The mechanisms in which proteins induce immunity and potential protection requires further investigation but the dogma of impaired antibody responses in children with recurrent acute otitis media should be reconsidered.

Oxidative stress is involved in the development and progression of otitis media (OM). In this study, we investigated the effect of Ginkgo leaf parenteral solution on blood and cochlea antioxidant and immunity indexs in OM rats. In OM model rats, blood and cochlea malondialdehyde (MDA), nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-10 (IL-10) levels were significantly increased, whereas antioxidant enzymes activities (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione reductase (GR)) were significantly decreased compared with normal rats. Treatment with Ginkgo leaf parenteral solution restored the altered parameters in a dose-dependent manner. We conclude that Ginkgo leaf parenteral solution confers protection against oxidative injuries in OM rats by increasing activities of antioxidants and immunity, suggesting a potential drug for the prevention and therapy of OM.

Aim: To investigate levels of matrix metalloproteinases 2 and 9, and of their tissue inhibitor (i.e. tissue inhibitor matrix metalloproteinase 1), in the serum of patients with tympanosclerosis., Materials and Method: We included 40 patients (age range 13-63 years) who had undergone surgery in the ENT department of Izmir Atatürk Training and Research Hospital between 2002 and 2007. Twenty had uncomplicated chronic otitis media and 20 had tympanosclerosis. We also included as the control group 20 individuals with no history of previous otic complaints or systemic or infectious disease. Serum levels of serum matrix metalloproteinases 2 and 9 and of tissue inhibitor matrix metalloproteinase 1 were measured in all subjects and compared., Result: Significantly higher levels of serum matrix metalloproteinases 2 and 9 were found in the tympanosclerosis group, compared with the chronic otitis media and control groups. There was no statistically significant difference in tissue inhibitor matrix metalloproteinase 1 level between the three groups., Conclusion: Tympanosclerosis surgery has poor success rates, since the pathological process is still active. We suggest that high levels of matrix metalloproteinases may play a role in the continuation of the disease process.

Background: The International Union of Immunological Societies defined transient hypogammaglobulinemia of infancy as decreased IgG and IgA levels. Some others, however, include decreased IgA level alone. We compared infants with decreased levels of IgG and IgA, all isotypes, and IgA alone., Objective: To determine whether infants presenting with diminished IgA only differ clinically and in time of immunoglobulin recovery, from those with decreased levels of IgG and IgA, or of all major isotypes., Methods: Eighty-seven term infants found to have immunoglobulin isotype(s) 2 or more SDs below mean, normal antibody response, intact cellular immunity, and absence of other immunodeficiency syndrome features were evaluated between January 1, 1977 and December 31, 2008. Infants had decreased IgA level (group 1, n = 43), decreased IgA and IgG levels (group 2, n = 39), or low IgA, IgG, and IgM levels (group 3, n = 5)., Results: Groups had similar histories. Immunoglobulins normalized in a similar percentage of all groups during infancy but earlier for group 1 (P = .005)., Conclusion: Little reason exists to separate infants with isolated decreased IgA levels from those with decreased levels of IgA and IgG or all isotypes., (Copyright © 2010 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Aim: Assessment of specific IgG levels in children with recurrent respiratory infections after immunization with Pneumo 23 and Act-HIB vaccines., Materials and Methods: Concentrations of IgG to polysaccharide capsular antigens and cell wall antigens of Streptococcus pneumoniae and Haemophilus influenzae were measured by solid-phase ELISA in sera of 256 immunized children., Results: Increase of levels of IgG to cell wall antigens and certain polysaccharide antigens was observed in patients with low or intermediate antibody levels at baseline., Conclusion: Obtained results allow to conclude that vaccination of children with recurrent respiratory and middle ear infections results in induction of IgG production that proves immunological effect of performed vaccination.

Objective: To determine the differences in the outcome of treatment, the middle ear immune response, and micronutrient status between patients with purulent (POM) and mucoid (MOM) otitis media., Design: Children with acute otitis media were recruited, treated, and followed up for between 6 and 10 months. The sera and middle ear secretion (MES) were analyzed for immunoglobulins and zinc using enzyme-linked immunoassay and flame atomic absorption spectrophotometry, respectively. The parameters were compared with selected healthy controls., Subjects: There were 399 participants: 228 children with acute otitis media selected using the American Academy of Otolaryngology-Head and Neck Surgery criteria and 171 healthy controls, with ages ranging between 6 months and 9 years (mean 7 years; SD 2.32 years)., Result: POM accounted for 126 of 228 patients, and MOM accounted for 102. The chronicity of otitis media (using the 3-month duration cutoff) was seen in 87 subjects (46%): 31 of 126 POM subjects and 56 of 102 MOM subjects (p = .002). The serum IgA to IgG ratios were 0.03 and 0.07 among POM and MOM, respectively; however, the MES IgA to IgG ratios were higher, 0.3 and 0.2, for POM and MOM, respectively. This gives a MES to serum ratio of IgA to IgG value of 0.3 to 0.03 (10) for POM and 0.2 to 0.07 (2.67) for MOM, which showed a significant statistical difference (p = .001). The MES to serum ratios of IgE were 0.89 and 1.3 among POM and MOM, respectively (p = .03). There was a significant difference in the serum IgG (p = .019), serum zinc (p = .009), and MES IgA (p = .028) and IgG (p = .01)., Conclusion: Chronicity was greater in MOM than in POM; POM had a higher middle ear immune response (measured by the MES to serum ratio of IgA to IgG) and serum zinc than MOM but a lower MES IgE.

Background: Despite the recent advances in methods for culturing bacteria, at least 24 hours are needed for most pathogens to be recognized. This period may be critical for the differentiation of a true bacteremia from a contaminated culture. We studied the value of CRP compared to total leukocytes (WBC) and absolute neutrophil count (ANC) in differentiating positive, contaminated and negative blood cultures in various pediatric infectious diseases (pneumonia, acute gastroenteritis (AGE), urinary tract infection (UTI) and acute otitis media (AOM))., Material/methods: Data was collected retrospectively from patients who were admitted or discharged from to the pediatric ward with one of the above diagnoses. Children with chronic diseases or with immunodeficiency were excluded from the study., Results: CRP levels were significantly higher in the positive culture group versus contaminated and negative groups (101 mg/L, 30.9 mg/L, 34.3 mg/L, respectively). The total leukocytes and ANC were not of value. When divided into diagnostic subgroups, CRP levels were significantly higher in the positive blood culture groups in patients with pneumonia and AGE. The sensitivity of a CRP value above 85 mg/L for pneumonia and UTI and above 30 mg/L for AGE and AOM in discriminating true positive versus contaminated culture was 70% with a specificity of 67.6% and a positive predictive value of 60.3%., Conclusions: CRP may be used for differentiation between positive and contaminated blood cultures in children and have been shown to be a better predictor than WBC or ANC for this purpose.

Background: Pneumococcal surface protein A (PspA) is a highly variable yet cross-reactive protein that exists as 2 major families. We assessed the development of human serum and salivary antibodies against the PspA families 1 (PspA1) and 2 (PspA2) in early childhood and their role in the prevention of pneumococcal acute otitis media (AOM)., Methods: Serum levels of IgG and salivary levels of IgA antibodies to PspA1 and PspA2 were measured by use of enzyme immunoassay from the samples from the Finnish Otitis Media Cohort Study obtained at the ages of 12 months (287 and 160 samples, respectively) and 18 months (258 and 131 samples, respectively). The Cox proportional hazard model was used to evaluate the relative risk (RR) of pneumococcal AOM during the 6 months after sampling relative to concentration of serum or presence of salivary anti-PspA in the samples., Results: Anti-PspA1 and anti-PspA2 concentrations at 12 and 18 months were related to prior culture-confirmed pneumococcal exposure. The concentrations of serum anti-PspA were not significantly associated with the risk of pneumococcal AOM. At 18 months, the presence of salivary anti-PspA was significantly associated with a lower risk of pneumococcal AOM during the 6 months after sampling (RR, 0.27 [95% confidence interval, 0.11-0.69])., Conclusions: The lowered risk of pneumococcal AOM associated with the presence of salivary anti-PspA at 18 months suggests that mucosal anti-PspA antibodies have a role in the prevention of pneumococcal AOM.

Pneumococcal neuraminidase, NanA, is a pneumococcal vaccine candidate. Prior culture-confirmed pneumococcal contacts were shown to induce serum anti-NanA antibodies during the first 2 years of life. The antibody concentrations at neither 12 nor 18 months were significantly associated with the risk of subsequent pneumococcal carriage or acute otitis media.

Objective: Recurrent episodes of acute otitis media (AOM) and acute tonsillitis (AT) are a common problem in infectious disorders during childhood and are major cause of morbidity in children. The organism maintains defense systems including nonenzymatic antioxidants such as Vitamins A, E and C and reduced glutathione (GSH) against reactive oxygen species (ROS). In the present study, lipid peroxidation status and nonenzymatic antioxidant capacity were investigated in children with AOM and AT. Our aim was to compare the lipid peroxidation and responses of the body's antioxidant status in the closely associated infections such as AOM and acute tonsillitis., Methods: The study included 23 (14 males, 9 females) children with AOM, 27 (14 males, 13 females) with AT and 29 (16 males, 13 females) healthy control subjects. The ages of the study and control subjects were between 2 and 7 years. Serum beta-carotene, retinol, Vitamin E, Vitamin C, and whole blood malondialdehyde (MDA) (as an indicator of lipid peroxidation) and GSH levels were studied in all subjects., Results: There was a statistically significant difference between the groups for all parameters (P<0.05). All of the antioxidant vitamins such as beta-carotene, retinol, Vitamin E, and Vitamin C levels were observed to be significantly decreased in the both patient groups. Nevertheless, GSH levels were also decreased in the patient groups. MDA levels were found to be higher in children with AOM and AT than in the healthy control subjects. When compared the AOM and AT groups, there was statistically significant difference between the groups for whole blood MDA (P<0.05)., Conclusion: Even though they seem to react in a similar way against ROS, in the cases of AOM and AT, it is possible to see the different approaches in these tissues for the oxidative stress.

Respiratory tract infections, allergies and otitis media are common problems in early childhood. Our aim was to evaluate in a longitudinal community-based cohort study the association between maturation of immunoglobulin (Ig) and mannan-binding lectin (MBL) responses and disease manifestations in the first 4 years of life. Sustained low levels of IgA proved the strongest single indicator of susceptibility for recurrent otitis media (P = 0.008) and respiratory tract infections (P = 0.02), and this condition was also associated with low production of IgG subclasses. About 7% of the cohort had sustained low levels of MBL (<0.4 mg/l). Low MBL did not predispose to any ailments studied, but children with low IgA and recurrent otitis media had relatively low MBL at birth, which failed to increase during the study period and was significantly reduced at the age of 4 years (P = 0.04). MBL levels increased from birth to 2 years (P < 0.0001) and were higher in children than in adults (P = 0.001). The increase was 1.9-fold in children with no recorded clinical events and 1.7-fold in children with asthma or infections, but significantly lower, 1.2-fold, in children with recurrent otitis media. Low levels of IgA within the normal range may reveal disease susceptibility not detected by conventional criteria. Slow maturation of Ig appears to be the main factor of susceptibility during childhood, but a strong corollary role for MBL is indicated by the high levels produced during childhood as well as the precipitation of disease in children with low levels of MBL and Ig.

Objectives: To analyze the peripheral leukocyte counts of children with acute otitis media (AOM) in relation to etiology, age, clinical symptoms and signs, prior antibiotic treatment, previous AOM history and pathogen eradication during antibiotic therapy., Patients and Methods: Leukocyte counts were determined at diagnosis and on days 4 to 6 of therapy in patients age 3 to 36 months with AOM enrolled in double tympanocentesis studies. Clinical status was determined by a clinical score evaluating severity of fever, irritability and tympanic membrane redness and bulging., Results: Of 771 enrolled patients, culture-positive middle ear fluid was reported in 590 (77%): 294 (50%) Haemophilus influenzae; 150 (25%) Streptococcus pneumoniae; 127 (21%) H. influenzae and S. pneumoniae together; 9 (2%) Moraxella catarrhalis; and 10 (2%) others. Mean leukocyte count +/- sd in patients with AOM caused by S. pneumoniae (15.7 +/- 6.7 cells x 10/mm) was significantly higher than those of patients with AOM caused by H. influenzae (13.7 +/- 5.8 cells x 10/mm) and patients with culture-negative AOM (13.8 +/- 5.6 cells x 10/mm), P < 0.01 for each comparison. Mean absolute neutrophil count (ANC) +/- sd was higher in patients with AOM caused by S. pneumoniae (8.6 +/- 5.1 cells x 10/mm) than in patients with AOM caused by H. influenzae (6.5 +/- 4.0 cells x 10/mm) or culture-negative patients (6.5 +/- 4.4 cells x 10/mm), P < 0.05 for each comparison. When multivariant regression analysis was used, S. pneumoniae etiology and fever (body temperature > or = 38 degrees Celsius) were independent factors, each significantly associated with leukocyte and ANCs. A significant correlation was found between leukocyte and ANCs and higher clinical scores in patients with pneumococcal AOM (P = 0.01, r = 0.21 and P < 0.01, r = 0.27, respectively). The mean leukocyte count on Days 4 to 6 was lower than on Day 1 (11.5 +/- 4.1 compared with 14.2 +/- 6.0 cells x 10/mm, P < 0.01). When paired (Day 1 and Days 4 to 6) examinations were analyzed, the leukocyte counts were lower on Days 4 to 6 irrespective of bacterial eradication or persistence., Conclusions: Significantly higher leukocyte counts and ANCs were found in pneumococcal AOM than in AOM caused by H. influenzae or in culture-negative AOM. A significant decrease in leukocyte counts was found during antibiotic therapy for AOM, regardless of etiology and bacteriologic outcome. Isolation of S. pneumoniae and fever were each significantly associated with increased peripheral leukocyte and ANCs.

Objective: Venous sinus thrombosis (VST) is the second most common intracranial complication of acute otitis media (AOM). There is some evidence that hereditary and acquired prothrombotic disorders are risk factors for VST. The aim of the present study was to evaluate whether children with AOM complicated VST have a prothrombotic tendency, which might have important therapeutic and preventive implications., Study Design: Retrospective., Methods: The files of children hospitalized at Schneider Children's Medical Center of Israel, a tertiary referral center, from 1999 to 2002, because of AOM complicated by acute mastoiditis and VST were reviewed. All children underwent laboratory work-up for hypercoagulability., Results: Seven children met the study criteria. Of these, five had prothrombotic disorders, namely elevated levels of lipoprotein apolipoprotein (Lp[a]) (n = 4), antibodies to beta 2-glycoprotein and to cardiolipin (markers of antiphospholipid syndrome) (n = 4), and heterozygosity for factor V Leiden mutation (n = 1). One child had three abnormalities, two children had two abnormalities, and two children had one abnormality., Conclusions: A prothrombotic tendency may exist in children with AOM complicated by mastoiditis and VST. Further studies are needed to evaluate its extent.

Using two different animal models of Streptococcus pneumoniae infection, we have demonstrated that this organism is able to spread to the central nervous system and cause meningitis by bypassing the bloodstream. Following respiratory tract infection induced via intranasal inoculation, bacteria were rapidly found in the bloodstream and brains in the majority of infected mice. A similar pattern of dissemination occurred following otitis media infection via transbullar injection of gerbils. However, a small percentage of animals infected by either route showed no bacteria in the blood and yet did have significant numbers of bacteria in brain tissue. Subsequent experiments using a galU mutant of S. pneumoniae, which is impaired in its ability to disseminate to the bloodstream following infection, showed that this organism is able to spread to the brain and cerebrospinal fluid. These results demonstrate that, unlike many bacterial pathogens that cause meningitis, S. pneumoniae is able to do so independent of bloodstream involvement upon different routes of infection. This may address the difficulty in treating human infections caused by this organism.

Objective: To investigate the role of fibrinolysis in pathogenesis of middle ears adhesions., Methods: The amount of Tissue-type Plasminogen Activator (tPA) of 28 sections from 6 ears with adhesive otitis media (AOM) and of 22 sections from 6 normal ears was examined by Super Sensitive Biotin-Streptavidin (SSBSA) method. Amount of Fibrin of 11 sections from 3 ears with significant adhesions was compared with that of 12 sections from 3 normal ears. Qualitative analysis of light microscopy with computer-assisted image system was employed., Results: In adhesive ears, tPA stains were negative in 11 of 28 sections and faint positive were 10 of 28 sections, while Fibrin stains were positive in 6 of 11 sections and strong positive were in 3 of 11 sections. In normal ears, tPA stains positive were in 8 of 22 sections and strong positive were 10 of 22 sections, meanwhile, fibrin stains were negative in 8 of 12 sections and faint positive were in 3 of 12 sections. Quantitative analysis showed that the amount of tPA was 16.70 +/- 5.11 and 39.84 +/- 6.26 in ears with AOM and normal ones respectively (P < 0.05)., Conclusion: In adhesive ears the amount of tPA was less than that in the normal ears, whereas, the amount of Fibrin was greater in ears with AOM than that in normal ears. It indicates that fibrinolysis involved in the process of adhesion formation of AOM, which may acts as a key factor.

With the recent emergence and increases of multiple-drugs-resistant Streptococcus pneumoniae, we have been seeing an increasing number of infants with intractable recurrent otitis media which is resistant to the general conservative out-patient treatments such as oral administration of medicines or tympanotomy. In this study, we investigated the inflammation-causing bacteria in the infants with otitis media which were treated in our hospital from January to December in 1997, and in six serious cases among them, we measured IgG subclass and specific IgG2 antibody to S. pneumoniae to examine them. As a result, S. pneumoniae was found to be the cause in 45% of the cases of initial development of otitis media, and in 88% of them the S. pneumoniae was penicillin-resistant. The level of specific IgG2 antibody to S. pneumoniae was low in all the cases, whereas IgG2 subclass was deficient only in one out of the six cases; from these findings, the selectively low level of immune status was thought to be the cause of the recurrences of otitis media. In two cases, clinical condition was markedly improved by immunoglobulin substitute therapy, which demonstrates that immunoglobulin is effective for the intractable recurrent otitis media in infants.

Pneumococcal surface protein A (PspA), pneumococcal surface adhesin A (PsaA), and pneumolysin (Ply) are common to virtually all Streptococcus pneumoniae isolates. They are immunogenic and protective against pneumococcal challenge in animals and are the major candidates for a protein-based pneumococcal vaccine for humans. However, little is known of the natural development of antibodies to these proteins in humans. The objective of this study was to evaluate the natural development of antibodies to PspA, PsaA, and Ply in relation to pneumococcal infection and carriage in young children. Serum antibodies to these proteins were measured by EIA in children at ages 6, 12, 18, and 24 months and in their mothers. All age groups were capable of producing antibodies to the 3 proteins. The antibody concentrations increased with age and were strongly associated with pneumococcal exposure, whether by carriage or infection (acute otitis media).

The immune response was evaluated in 11 children with Streptococcus pneumoniae and in 9 children with Moraxella catarrhalis otitis media. The age of the children had a range of 4-32 months. The mean IgG, IgM, and IgA antibody responses to surface protein A (PspA) of S. pneumoniae in sera from children at the acute and convalescent stages were 4864 versus 5831 ng/mL, P<.05, 1075 versus 3752 ng/mL, P<.05, and 67 versus 93 ng/mL, nonsignificant (NS), respectively. The mean IgG, IgM, and IgA antibody responses to the high-molecular-weight outer membrane protein (UspA) of M. catarrhalis in sera from children at acute and convalescent stages were 710 versus 935 mg/mL, NS; 1895 versus 2646 ng/mL, NS; and 121 versus 204 ng/mL, P<.05, respectively. These data show that PspA and UspA are immunogenic in children after otitis media.

We investigated whether organochlorine exposure is associated with the incidence of infectious diseases in Inuit infants from Nunavik (Arctic Quebec, Canada). We compiled the number of infectious disease episodes during the first year of life for 98 breast-fed and 73 bottle-fed infants. Concentrations of organochlorines were measured in early breast milk samples and used as surrogates to prenatal exposure levels. Immune system parameters were determined in venous blood samples collected from infants at 3, 7, and 12 months of age. Otitis media was the most frequent disease, with 80. 0% of breast-fed and 81.3% of bottle-fed infants experiencing at least one episode during the first year of life. During the second follow-up period, the risk of otitis media increased with prenatal exposure to p,p'-DDE, hexachlorobenzene, and dieldrin. The relative risk (RR) for 4- to 7-month-old infants in the highest tertile of p, p'-DDE exposure as compared to infants in the lowest tertile was 1. 87 [95% confidence interval (CI), 1.07-3.26]. The RR of otitis media over the entire first year of life also increased with prenatal exposure to p,p'-DDE (RR, 1.52; CI, 1.05-2.22) and hexachlorobenzene (RR, 1.49; CI, 1.10-2.03). Furthermore, the RR of recurrent otitis media ( [Greater/equal to] 3 episodes) increased with prenatal exposure to these compounds. No clinically relevant differences were noted between breast-fed and bottle-fed infants with regard to immunologic parameters, and prenatal organochlorine exposure was not associated with immunologic parameters. We conclude that prenatal organochlorine exposure could be a risk factor for acute otitis media in Inuit infants.