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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.

Chronic otitis media with effusion (COME) is the most common cause of hearing loss in children, and known to have high heritability. Mutant mouse models have identified Fbxo11, Evi1, Tgif1, and Nisch as potential risk loci. We recruited children aged 10 and under undergoing surgical treatment for COME from 35 hospitals in the UK, and their nuclear family. We performed association testing with the loci FBXO11, EVI1, TGIF1 and NISCH and sought to replicate significant results in a case-control cohort from Finland. We tested 1296 families (3828 individuals), and found strength of association with the T allele at rs881835 (p = 0.006, OR 1.39) and the G allele at rs1962914 (p = 0.007, OR 1.58) at TGIF1, and the A allele at rs10490302 (p = 0.016, OR 1.17) and the G allele at rs2537742 (p = 0.038, OR 1.16) at FBXO11. Results were not replicated. This study supports smaller studies that have also suggested association of otitis media with polymorphism at FBX011, but this is the first study to report association with the locus TGIF1. Both FBX011 and TGIF1 are involved in TGF-β signalling, suggesting this pathway may be important in the transition from acute to chronic middle ear inflammation, and a potential molecular target.

To identify genetic risk factors of childhood otitis media (OM), a genome-wide association study was performed on Finnish subjects, 829 affected children, and 2118 randomly selected controls. The most significant and validated finding was an association with an 80 kb region on chromosome 19. It includes the variants rs16974263 (P = 1.77 × 10(-7), OR = 1.59), rs268662 (P = 1.564 × 10(-6), OR = 1.54), and rs4150992 (P = 3.37 × 10(-6), OR = 1.52), and harbors the genes PLD3, SERTAD1, SERTAD3, HIPK4, PRX, and BLVRB, all in strong linkage disequilibrium. In a sub-phenotype analysis of the 512 patients with chronic otitis media with effusion, one marker reached genome-wide significance (rs16974263, P = 2.92 × 10(-8)). The association to this locus was confirmed but with an association signal in the opposite direction, in a UK family cohort of 4860 subjects (rs16974263, P = 3.21 × 10(-4), OR = 0.72; rs4150992, P = 1.62 × 10(-4), OR = 0.71). Thus we hypothesize that this region is important for COME risk in both the Finnish and UK populations, although the precise risk variants or haplotype background remain unclear. Our study suggests that the identified region on chromosome 19 includes a novel and previously uncharacterized risk locus for OM.

Objective: Otitis media is a multifactorial disease where genetic background may have an important role. For genome-wide association studies, it is important to understand the degree of heritability. The objective of this study was to estimate the heritability of recurrent acute otitis media and chronic otitis media with effusion., Methods: Children operated because of recurrent or chronic otitis media at the Helsinki University Central Hospital, Finland, as well as their families were recruited during 2008-2009. A cohort of 2436 subjects was enrolled consisting of 1279 children and their parents. The study subjects answered a questionnaire concerning their otitis media history and treatment, as well as tobacco exposure, allergy and asthma history. Heritability estimates were calculated for recurrent acute, chronic and any episodes of otitis media using software especially designed for estimating heritability in family cohorts., Results: Altogether 901 subjects suffered from recurrent otitis media and 559 from chronic otitis media with effusion. The heritability estimates in our cohort were 38.5% for recurrent (P=7.3 × 10(-9)), 22.1% for chronic (P=4.6 × 10(-3)) and 47.8% for any otitis media (P=1.5 × 10(-11))., Conclusions: Our results demonstrate a moderately strong and statistically significant genetic component for both recurrent acute otitis media and chronic otitis media with effusion. These results highlight the importance of unraveling the genetic factors for otitis media that are still poorly known., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Adenoidectomy is among the most frequent surgical procedures performed on children. The rationale for adenoidectomy is to remove a chronically infected or enlarged and obstructing adenoid. Adenoidectomies are performed on children who have recurrent or chronic otitis media with effusion, on children with chronic rhinosinusitis, and on children with nasopharyngeal obstruction causing sleep disturbances and continuous mouth breathing. Various underlying factors that lead to adenoidectomy are also associated with asthma. Asthma is associated with recurrent respiratory tract infections predisposing individuals to recurrent or chronic otitis media and chronic rhinosinusitis. Children with asthma also have an increased risk of sleep-disordered breathing that is treated with adenoidectomy in the presence of nasopharyngeal obstruction. In nonasthmatic children, adenoidectomy does not influence the development of IgE-mediated allergy, bronchial hyperreactivity, or exhaled nitric oxide concentrations, all of which are surrogate asthma markers. Adenoidectomy in selected asthmatic children may relieve comorbidities associated with asthma.

Otitis media is one of the most common childhood infections and the most frequent cause for antibiotic prescriptions in children. As respiratory infections are also associated with childhood asthma, children with recurrent otitis media or with persistent middle-ear effusion are also at an increased risk for developing asthma, which should be appreciated when a child with middle-ear disease is evaluated. The first choice of surgery in chronic middle-ear inflammatory disease is the insertion of tympanostomy tubes. It is warranted when the middle-ear effusion has lasted for 3 or more months. When chronic adenoid infection is suspected, adenoidectomy may be beneficial in treating otitis media in children who are older than 4 years of age and who have previously undergone tympanostomy-tube insertion.

Objective: To evaluate the efficacy of adenoidectomy in reducing the incidence of otitis media among children who are younger than 4 years and receive tympanostomy tubes., Methods: A randomized trial was conducted at a tertiary center clinic. A total of 217 children who were aged 12 to 48 months and had recurrent acute otitis media (>3 episodes during the past 6 months) or chronic otitis media with effusion, no obstructive symptoms as a result of adenoid enlargement, and no previous surgical intervention were enrolled in the study. Adenoidectomy in conjunction with the insertion of tympanostomy tubes or insertion of tympanostomy tubes without adenoidectomy was studied. The number of otitis media episodes during the follow-up period of 12 months was measured., Results: During the follow-up, the mean number of otitis media episodes was 1.7 among children who underwent adenoidectomy with concurrent insertion of tympanostomy tubes and 1.4 among children who received tympanostomy tubes only. The risk for recurrent otitis media (>or=3 episodes) could not be reduced by adenoidectomy (odds ratio: 1.66; 95% confidence interval: 0.80-3.46)., Conclusion: Adenoidectomy does not significantly reduce the incidence of acute otitis media in otitis prone children who are younger than 4 years and receive tympanostomy tubes.

Adenoidectomy in children with otitis media with effusion reduces inflammation in the middle ear by an unknown mechanism. Potentially, the adenoids of these children may serve as a site for the differentiation of lymphocytes, which after entering blood circulation eventually extravasate in the middle ear mucosa and thereby contribute to excessive inflammation. During lymphocyte extravasation various adhesion molecules and chemokines play a crucial role. To evaluate possible connections between the adenoids and middle ear inflammation, the expression of the chemokine receptors CXCR4 and CCR5 and the lymphocyte homing receptor L-selectin were analyzed in adenoidal and middle ear lymphocytes. It was found that most CD4+ T lymphocytes in the middle ear effusion express the memory phenotype marker CD45RO and the chemokine receptors CXCR4 and CCR5, but are negative for the lymphocyte homing receptor L-selectin. This cell phenotype was rare in peripheral blood but was found much more frequently in the adenoids. The results suggest that the adenoids provide a microenvironment for the generation for CD4+, CD45RO+, L-selectin–, CXCR4+ and CCR5+ T lymphocytes. Further, these cells may include cells that have the capacity to home to the middle ear mucosa. As the adenoidal CD4+ memory phenotype CD45RO+ T cells expressed the activation antigen CD69 and included cells expressing the HIV co-receptors CXCR4 and CCR5 at a high level, they may be permissive for HIV infection. [ABSTRACT FROM PUBLISHER]