Non-protective immunity after standard pneumococcal vaccination series identified as a potential contributing risk factor for refractory otolaryngologic conditions in children.

OBJECTIVE: To examine the relationship between conferred immunity after standard pneumococcal series and refractory otolaryngologic infections in pediatric patients using post-vaccination antibody titers, and to identify contributory underlying conditions revealed when vaccination/re-vaccination fails to confer protective immunity. STUDY DESIGN: IRB-reviewed and "exempt" retrospective case series with chart review using the Epic® Electronic Medical Record system from 2013 to 2021. SETTING: Dedicated tertiary referral children's hospital. METHODS: Pneumococcal antibody titer results were assessed for children ages 0 to 21 years and: (1) at least 1 of 7 otolaryngologic disease diagnoses and (2) having received the 4-dose schedule of pneumococcal conjugate vaccine (PCV 7 or 13). RESULTS: A total of 241 subjects met inclusion criteria with 356 laboratory tests. Recurrent acute otitis media, chronic rhinitis, and chronic otitis media with effusion were the 3 most frequent diagnoses. At presentation, only 27.0% of subjects had titers conferring immunity from their prior vaccinations with PCV. About 85 subjects had been subsequently revaccinated with Pneumococcal Polysaccharide Vaccine (PPSV), and antibody responses conferring immunity reached 91.8%. Seven subjects never developed adequate responses; 5 of these had recurrent acute otitis media as the primary otolaryngologic diagnosis. Secondary "revealed" diagnoses included Juvenile Rheumatoid Arthritis (n = 1), unresolved specific antibody deficiency (n = 2), and Hypogammaglobulinemia (n = 1). CONCLUSION: In pediatric patients with recurrent infectious otolaryngologic disease refractory to traditional medical and surgical therapy, inadequate responses to pneumococcal vaccination may be revealed. This correlation represents a potential pathway for diagnosis and therapy.

Clinical and molecular analysis of Guangxi patients with Kabuki syndrome and KMT2D mutations.

Kabuki syndrome (KS) is a multiple congenital anomaly syndrome that is characterized by postnatal growth deficiency, hypotonia, short stature, mild-to-moderate intellectual disability, skeletal abnormalities, persistence of fetal fingertip pads, and distinct facial appearance. It is mainly caused by pathogenic/likely pathogenic variants in the KMT2D or KDM6A genes. Here, we described the clinical features of nine sporadic KS patients with considerable phenotypic heterogeneity. In addition to intellectual disability and short stature, our patients presented with a high prevalence of motor retardation and recurrent otitis media. We recommended that KS should be strongly considered in patients with motor delay, short stature, intellectual disability, language disorder and facial deformities. Nine KMT2D variants, four of which were novel, were identified by whole-exome sequencing. The variants included five nonsense variants, two frameshift variants, one missense variant, and one non-canonical splice site variant. In addition, we reviewed the mutation types of the pathogenic KMT2D variants in the ClinVar database. We also indicated that effective mRNA analysis, using biological materials from patients, is helpful in classifying the pathogenicity of atypical splice site variants. Pedigree segregation analysis may also provide valuable information for pathogenicity classification of novel missense variants. These findings extended the mutation spectrum of KMT2D and provided new insights into the understanding of genotype-phenotype correlations, which are helpful for accurate genetic counseling and treatment optimization.

The effect of pneumococcal conjugated vaccines on occurrence of recurrent acute otitis media among infants diagnosed with acute otitis media at an age younger than 2 months.

To examine the impact of pneumococcal conjugate vaccines (PCV) on the occurrence of recurrent acute otitis media (rAOM) among infants diagnosed with an early acute otitis media (AOM) episode. Retrospective cohort study of pediatric patients with a first episode of AOM at an age < 2 months. Data included clinical, demographic, and microbiological findings at the first AOM episode. In addition, a 5-year follow-up after the patient's first episode was completed from the medical records. This information included documentation of rAOM episodes and complications of AOM (hearing loss, speech disturbance, mastoiditis, and tympanic membrane perforation) and of ear-related surgical procedures (ventilation tube placement, adenoidectomies, and mastoid surgery). Two groups were studied: patients diagnosed between 2005 and 2009 (representing the unvaccinated group, group 1) and those diagnosed in 2010-2014 (the vaccinated group, group 2). A total of 170 infants were diagnosed with a first AOM episode at an age < 2 months; 81 of them belonged to group 1 and 89 to group 2. Streptococcus pneumoniae was isolated in the middle-ear fluid in the first AOM episode in 48.1% of the patients in group 1 and in 30.3% in group 2 (P = 0.0316). 49/81 (60.5%) infants in group 1 were diagnosed with rAOM versus 39/80 (43.8%) in group 2 (P = 0.0298). No statistical differences were found between the groups with respect to long-term complications or need for surgery later in life.   Conclusion: Our study showed a significant decrease in the occurrence of rAOM in infants diagnosed with AOM during the first 2 months of life and timely immunized with PCVs following this initial AOM episode. What is Known: • 30% of children experience recurrent AOM (rAOM) at the first year of life. The earlier the age of the first AOM, the greater the risk for future complications. • After the introduction of PCVs, the overall pneumococcal AOM incidence declined. We investigated the future effect of PCVs on rAOM occurrence, when administered after the first AOM episode. What is New: • A retrospective cohort of 170 infants with a first AOM episode at an age <2 months and followed for 5 years, showed a significant decrease (28.0%) of rAOM in immunized infants following the initial AOM episode. • Our findings supplement previous data suggesting that the widespread PCVs use prevents rAOM by preventing early AOM and emphasize the importance of timely administration of the PCVs.

Characterization of a DRC1 null variant associated with primary ciliary dyskinesia and female infertility.

PROPOSE: We here present a female case with primary ciliary dyskinesia (PCD) and infertility. In this report, we also present the evaluation of the patient family, including her twin sister, also with PCD and infertility. METHODS: Confirmation of the PCD clinical diagnosis was performed through assessment of cilia motility, by high-speed video microscopy (HSVM), axoneme ultrastructure, by transmission electron microscopy (TEM), and genetic characterization, by whole-exome sequence (WES). Gene expression studies used qPCR for mRNA expression and immunofluorescence to determine cell protein localization. RESULTS: We identified a homozygous nonsense variant in the DRC1 gene (NM 145038.5:c.352C>T (p.Gln118Ter)) in the female patient with PCD and infertility that fit the model of autosomal recessive genetic transmission. This variant eventually results in a dyskinetic ciliary beat with a lower frequency and a partial lack of both dynein arms as revealed by TEM analysis. Moreover, this variant implies a decrease in the expression of DRC1 mRNA and protein. Additionally, expression analysis suggested that DRC1 may interact with other DRC elements. CONCLUSIONS: Our findings suggest that the DRC1 null variant leads to PCD associated with infertility, likely caused by defects in axoneme from Fallopian tube cilia. Overall, our outcomes contribute to a better understanding of the genetic factors involved in the pathophysiology of PCD and infertility, and they highlight the interaction of different genes in the patient phenotype, which should be investigated further because it may explain the high heterogeneity observed in PCD patients.

Genome sequencing identifies three molecular diagnoses including a mosaic variant in the COL2A1 gene in an individual with Pol III-related leukodystrophy and Feingold syndrome.

Undiagnosed genetic disease imposes a significant burden on families and health-care resources, especially in cases with a complex phenotype. Here we present a child with suspected leukodystrophy in the context of additional features, including hearing loss, clinodactyly, rotated thumbs, tapered fingers, and simplified palmar crease. Trio genome sequencing (GS) identified three molecular diagnoses in this individual: compound heterozygous missense variants associated with polymerase III (Pol III)-related leukodystrophy, a 4-Mb de novo copy-number loss including the MYCN gene associated with Feingold syndrome, and a mosaic single-nucleotide variant associated with COL2A1-related disorders. These variants fully account for the individual's features, but also illustrate the potential for superimposed and unclear contributions of multiple diagnoses to an individual's overall presentation. This report demonstrates the advantage of GS in detection of multiple variant types, including low-level mosaic variants, and emphasizes the need for comprehensive genetic analysis and detailed clinical phenotyping to provide individuals and their families with the maximum benefit for clinical care and genetic counseling.

Middle ear effusion prevalence at time of tympanostomy before and during COVID-19 pandemic.

BACKGROUND: Management of pediatric otitis media with effusion (OME) and recurrent otitis media typically includes observation up to 3 months. Bilateral myringotomy and tube (BMT) placement is performed due to persistent effusion with associated symptoms such as decreased hearing. With the COVID-19 pandemic and mandatory stay at home orders (MSHO), children were quarantined at home and many remained home after MSHO. We reviewed the prevalence of middle ear effusion (MEE) at the time of BMT during similar time periods in the year before, during and after MSHO in this pandemic year. STUDY DESIGN: Retrospective summary of BMT cases at a single tertiary children's hospital. METHODS: All children <18 years who underwent BMT between March 1, 2020 and July 1, 2020 and between March 1, 2019 and July 1, 2019 were included. Statistical analysis included chi-squared and Mann-Whitney U tests. RESULTS: A total of 778 cases were reviewed; 551 (71%) were performed pre-pandemic and 227 (29%) during onset of pandemic (N = 778). There were no significant differences in gender, age, and BMI between groups, but significantly fewer Caucasians (58% vs. 45%, p < 0.05) and more Hispanics (20% vs. 33%, p < 0.05) during-COVID. The prevalence of intraoperative effusion during-COVID was significantly lower compared to pre-COVID (65% vs. 83%, p < 0.001). CONCLUSION: Pandemic and COVID-19 MSHO were associated with significantly lower intraoperative OME prevalence. Further research may elucidate the impact of face covering, social distancing, and virtual schooling on the incidence of pediatric ROM, OME, and ENT symptoms.

Analysis of Inflammatory Signaling in Human Middle Ear Cell Culture Models of Pediatric Otitis Media.

OBJECTIVES/HYPOTHESIS: Cell culture models are valuable tools for investigation of the molecular pathogenesis of diseases including otitis media (OM). Previous study indicates that age-, sex-, and race-associated differences in molecular signaling may impact disease pathophysiology. Currently, a singular immortalized middle ear epithelial (MEE) cell line exists, HMEEC-1, derived from an adult without known middle ear disease. In this study, HMEEC-1 and primary MEE cultures from pediatric patients with and without OM were stimulated with inflammatory cytokines or OM-pathogenic bacterial lysates to examine differences in the response of molecules associated with OM pathogenesis. STUDY DESIGN: Case-control series. METHODS: MEE cultures were established from patients aged <6 years: two with recurrent OM (ROM), two with OM with effusion (OME), and one patient without OM who was undergoing cochlear implant surgery control undergoing cochlear implantation (Peds CI). Primary MEE cultures and HMEEC-1 cells were stimulated with tumor necrosis factor-α, interleukin (IL)-1ß, or nontypeable Haemophilus influenzae lysate. TNFA, IL1B, IL6, IL8, IL10, and MUC5B were assayed via quantitative polymerase chain reaction. IL-8 was assayed by enzyme-linked immunosorbent assay. RESULTS: Gene/protein target expressions were frequently higher in pediatric OM lines than in HMEEC-1 and Peds CI. HMEEC-1 cells were frequently less responsive to stimuli than all pediatric lines. OME lines were often more responsive than ROM lines. CONCLUSIONS: OM may be associated with specific molecular phenotypes that are retained in primary cell culture. Adult-derived HMEEC-1 cells differ significantly in baseline expression and response of OM-associated molecules relative to pediatric MEE cells. Work is underway to immortalize pediatric OM MEE cultures as improved tools for the OM research community. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:410-416, 2021.

Assessing the Educational Quality of Facebook Videos as an Informative Resource on Otitis Media.

OBJECTIVE: This study analyzes the quality and reliability of otitis media (OM) videos on Facebook and investigates whether the videos shared within the Facebook community are considered to be a valuable educational tool. The results of this study are important for providing clinicians with the necessary understanding about the video content that their patients may be exposed to. STUDY DESIGN: Cross-sectional analysis of video content. SETTING: A new Facebook account was created to carry out a search for videos on OM. METHODS: Inclusion criteria were as follows: videos intended for educating patients or guardians on OM, videos in the English language, and videos with at least 1 share. RESULTS: A total of 364 videos were screened, and 62 fit our inclusion criteria for analysis. The majority (56%) of OM videos on Facebook focused on complementary and alternative medication without mentioning any current guidelines. A limited amount of videos (29%) made any mention to surgical treatment options for OM. There was a strong positive correlation (rho = 0.8419, P < .001) between a video's content and its reliability. There was no correlation seen between a video's content and its shares (rho = -0.142, P = .1359). CONCLUSIONS: The majority of OM videos on Facebook are inadequate for educational value. Clinicians should know about the existence of videos on OM and the quality of information that parents are exposed to.

In vitro Inhibition of Clinical Isolates of Otitis Media Pathogens by the Probiotic Streptococcus salivarius BLIS K12.

Otitis media is a common childhood infection, frequently requiring antibiotics. With high rates of antibiotic prescribing and increasing antibiotic resistance, new strategies in otitis media prevention and treatment are needed. The aim of this study was to assess the in vitro inhibitory activity Streptococcus salivarius BLIS K12 against otitis media pathogens. Efficacy of the bacteriocin activity of S. salivarius BLIS K12 against the otitis media isolates was assessed using the deferred antagonism test. Overall, 48% of pathogenic isolates exhibited some growth inhibition by S. salivarius BLIS K12. S. salivarius BLIS K12 can inhibit the in vitro growth of the most common pathogens.

Factors associated with retained tympanostomy tubes a case-controlled study.

OBJECTIVE: To determine factors associated with retained tympanostomy tubes in order to improve parent counseling on procedure risks and outcomes. METHODS: This is a case-control study; we conducted a retrospective chart review from 2012 to 2019 of cases of retained tympanostomy tubes compared to controls with confirmed tympanostomy tube extrusion. The study was conducted at a single tertiary care center, Boston Medical Center. A retained tympanostomy tube was defined as in place for more than two years requiring removal in the operating room. Cases were matched to two controls and assessed for the following factors: indication for tympanostomy tube insertion, frequency of otitis media and otorrhea after tympanostomy tube insertion, duration tympanostomy tubes were in place, numbered set of tympanostomy tubes, sinopulmonary conditions, and adenoidectomy status prior to tympanostomy tube removal or extrusion. RESULTS: 46 cases were identified and matched to 92 controls. Cases had a significantly longer tympanostomy tube duration (3.273, IQR 1.099 vs 1.611, IQR 0.894 years, p < 0.001). The indication for tympanostomy tube placement for cases compared to controls was significantly more likely to be recurrent otitis media only (odds ratio 2.36, CI 1.121 to 5.003). A multiple logistic regression model was performed with the indication for tympanostomy tube placement (chronic or recurrent otitis media) and a history of more than two sets of tympanostomy tubes. The model had a low sensitivity, 9.09%, and high specificity, 98.91%. CONCLUSION: Patients whose only indication for surgery is recurrent otitis media are possibly at higher risk for retained tympanostomy tubes that require removal in the operating room.

A child with recurrent otitis media due to Bacteroides thetaiotaomicron.

Brain abscess remains a life-threatening condition. Here, we are reporting a case of brain abscess due to Bacteroides thetaiotaomicron in a previously known case of recurrent otitis media. A 15 years old boy with a history of recurrent otitis media presented with the complaints of right otalgia, headache and fever. Computed Tomography (CT) brain and neck revealed fluid filled right middle ear cavity with bony destruction along the inner cortex of right temporal bone. The abscess was drained and culture showed growth of Bacteroides thetaiotaomicron. This report illustrates the importance of MALDI-TOF MS in the species level identification of anaerobes thereby facilitating the selection of appropriate and prompt adjuvant antibiotic therapy. This timely identification thus led to a favourable outcome in an era of increasing antimicrobial resistance.

Immunoglobulin G4-Related Disease Presented as Recurrent Otitis Media and Mixed Hearing Loss Treated With Cyclophosphamide and Rituximab: A Case Report.

Immunoglobulin G4-related disease (IgG4-RD) is a systemic autoimmune disease; however, it rarely presents as recurrent otitis media and mixed hearing loss. In this article, we present a 43-year-old male patient who presented with recurrent otitis media and mixed hearing loss that is the 12th case of IgG4-RD with middle and inner ear involvement. We also report the clinical response of cyclophosphamide and rituximab therapy in IgG4- RD. These two drugs have never been used to treat otologic symptoms, but were used to treat other organs affected by IgG4-RD. One year later, the patient underwent mastoidectomy of the right ear and the pathological reports revealed IgG4-related disease. A rheumatologist administered immunosuppressive therapy comprising cyclophosphamide and rituximab. After therapy, patient's right-sided mixed hearing loss partially improved. We recorded all pure tone audiometry data to evaluate the clinical course and treatment effect. Finally, we concluded that pathological confirmation and further immunosuppressive therapy should be considered in a timely manner to prevent hearing impairment. We recommend cyclophosphamide and rituximab for the treatment of diseases involving the middle and inner ear.

Epidemiology and antimicrobial susceptibility of non-typeable Haemophilus influenzae in otitis media in Taiwanese children.

BACKGROUND: Concerns about non-typeable Haemophilus influenzae (NTHi) in otitis media (OM) have grown after the introduction of pneumococcal conjugate vaccine (PCV). We aim to better understand the clinical role of NTHi in pediatric OM. METHODS: Middle ear fluid samples from children <18 years with OM were obtained from 2010 to 2015. For culture-positive episodes (Streptococcus pneumoniae, H. influenzae, Moraxella catarrhalis, and Streptococcus pyogenes), patients' demographic and clinical information were reviewed and analyzed. RESULTS: A total of 783 episodes were included with 31.8% of isolates as positive. S. pneumoniae was recovered in 69.4%, NTHi in 24.6%, M. catarrhalis in 5.6%, and S. pyogenes in 4.0% of culture-positive episodes. The proportion of pneumococcal OM has declined since 2012 (P for trend <0.005), but NTHi OM rose simultaneously (P for trend = 0.009). Factors associated with increased risk of NTHi infection included less spontaneous otorrhea (OR 0.15, 95% CI 0.06-0.39, P < 0.001), absence of fever (OR 0.30, 95% CI 0.14-0.66, P = 0.003), concurrent sinusitis (OR 2.91, 95% CI 1.36-6.20, P = 0.006), previous ventilation tube insertion (OR 12.02, 95% CI 3.15-45.92, P < 0.001) and recurrent OM (OR 3.43, 95% CI 1.01-11.71, P = 0.049). The susceptibility of NTHi to amoxicillin/clavulanate was 82.0%. CONCLUSIONS: NTHi OM has trended upward in the post-PCV era. Concurrent sinusitis, previous ventilation tube insertion, and recurrent OM were associated with NTHi OM implicated a correlation between NTHi and complex OM. In consideration of NTHi infection, we suggest amoxicillin/clavulanate as the first-line therapy for OM among Taiwanese children.

Does Acute Otitis Media in the First Month of Life Increase the Risk for Recurrent Otitis?

Acute otitis media (AOM) is a common childhood illness. The aim of this study was to assess whether AOM in the first month of life predicts recurrent AOM (rAOM) in early childhood. The medical records of all neonates with AOM and isolation of bacterial pathogen from middle-ear fluid during 2005-2010 were reviewed. Neonates without AOM admitted during the same period for neonatal fever workup were included as controls. Information regarding rAOM and possible risk factors were collected through a phone interview with the parents. A total of 84 neonates with AOM were enrolled; 25 (30%) had rAOM compared with 8/79 (10%) in the control group. Neonatal AOM increases 4-fold the odds of rAOM later in childhood (odds ratio = 4; 95% CI = 1.44-11.42; P = .008), independent of smoke exposure, numbers of siblings, AOM in siblings, breastfeeding, day care attendance, or use of pacifier. Neonatal AOM is a significant risk factor for rAOM during infancy.

Salivary cotinine levels in children with otolaryngological disorders.

OBJECTIVE: To determine if salivary cotinine, a biomarker for tobacco smoke exposure, is elevated more often or to a higher degree in children meeting criteria for tonsillectomy or tympanostomy tube insertion. METHODS: Saliva samples were obtained from 3 groups of children for salivary cotinine measurement. Group 1 served as healthy controls. Group 2 consisted of subjects meeting tympanostomy tube criteria. Group 3 consisted of patients meeting tonsillectomy criteria. Environmental tobacco smoke (ETS) exposure was defined as a salivary cotinine concentration ≥1.0 ng/mL. Demographic data, smoke exposure history, and co-morbidities were also determined. RESULTS: 331 patients were included, with 112 in Group 1, 111 in Group 2, and 108 in Group 3. No differences were encountered for smoke exposure by history or smoker's identity, salivary cotinine level, or frequency of positive cotinine results. 42.6% of Group 1 had positive salivary cotinine compared to 51.8% of Group 2 and 47.7% of Group 3. Group 1 had a mean salivary cotinine level of 2.42 ng/mL compared to 2.54 ng/mL in Group 2 and 2.60 ng/mL in Group 3. The frequency of positive cotinine levels was higher than expected based on parental history. Among subjects with positive cotinine levels, 93 had no ETS exposure, and 64 had ETS exposure by history. CONCLUSION: Approximately 50% of children who undergo tonsillectomy and tympanostomy tube insertion have objective evidence of ETS exposure. Parental history underestimates passive smoke exposure, which can impact perioperative care.

The role of subtotal petrosectomy in cochlear implant recipients.

Describe the indications and outcome of subtotal petrosectomy for cochlear implant recipients. Tertiary care referral center. This is a retrospective study of all subtotal petrosectomies and cochlear implants performed between January 2012 and December 2014. We review the charts of these patients collecting the following data: age, gender, otologic history, audiologic tests, indication of subtotal petrosectomy, data of surgery, surgical and immediate complications, late complications and follow-up of for at least 2.5 years. 12 cases of subtotal petrosectomies with cochlear implantation in 11 patients were performed during this period; 2 children and 10 adults. The indication for a cochlear implant was in 10 cases bilateral severe to profound sensorineural hearing loss and in the remaining 2 cases was asymmetric hearing loss or unilateral hearing loss. The reason for performing a subtotal petrosectomy was chronic otitis media with or without cholesteatoma, radical cavities from previous surgeries or electrode extrusion of previously implanted devices. All cases were performed in one stage. One patient had an infectious complication that required revision surgery and finally an explantation. No other complications are described. Subtotal petrosectomy combined with cochlear implantation is a procedure required in certain situations. It is an effective and safe procedure for managing middle ear problems and creating a safe cavity to receive a cochlear implant either in adults and children.

Frequency of Sensorineural hearing loss in chronic suppurative otitis media.

Chronic suppurative otitis media (CSOM) is defined as chronic otorrhea (i.e., lasting > 6-12 weeks) through a perforated tympanic membrane. It is generally associated with some degree of conductive hearing loss. However, recurrent ear infections due to perforated eardrum result in absorption of toxins and macromolecules into the cochlea leading to sensorineural hearing loss (SNHL). We planned to determine the frequency of sensorineural hearing loss in chronic suppurative otitis media. A descriptive cross-sectional study was conducted at Aga Kgan University Hospital, Karachi, from October 2013 to March 2014. Average threshold of speech frequencies was calculated via pure tone audiogram for both diseased and normal contralateral ear.A mean of >25db in diseased ear was labelled as positive case for SNHL. SNHL was reported in 64(52%) patients and the frequency was found to increase with increasing duration. Patients with CSOM should be counselled regarding the risk of developing SNHL if left untreated.

The Effect of Age and History of Recurrent Otitis Media on Dichotic Listening and Verbal Memory in Children.

OBJECTIVES: To explore the possible effects of recurrent otitis media (ROM) in early childhood on binaural processing and verbal memory in school-aged children. METHODS: Two hundred eleven children, including 31 children with and 180 children without a history of ROM, were examined. A dichotic digit test (DDT) and a forward and backward digit memory span test (DMST) were administered. RESULTS: A significant difference was observed between age groups among ROM-free children. The ROM-positive group earned significantly poorer results than the ROM-free group in all measurements, except for the right DDT (rDDT) score. Furthermore, a significant correlation was found between the DDT and EA scores with both DMST scores in the ROM-free group. The correlation between the rDDT and forward DMST scores was not significant in the ROM-positive group, and no significant correlation was observed between the EA score and either DMST score. CONCLUSIONS: Our findings support that a history of OM in early childhood based on a parental survey of children is associated with differences in DDT and DMST outcomes.

Peripheral blood antigen presenting cell responses in otitis-prone and non-otitis-prone infants.

Stringently defined otitis-prone (sOP) children represent a new classification of the otitis-prone condition. Previous studies showed dysfunction in Ab, B-cell memory and T-cell memory responses. We sought to determine whether there are defects in numbers, phenotype and/or function of professional APC in the peripheral blood of sOP infants. APC phenotypic counts, MHC II expression and intracellular cytokine levels were determined in response to TLR7/8 (R848) stimulation by flow cytometry. Innate immune mRNA expression was measured using RT-PCR and cytokines were measured using Luminex technology. Significant (P < 0.05) increases in the phenotypic counts of monocytes and conventional dendritic cells but not plasmacytoid DCs were observed in sOP compared with non-otitis-prone (NOP) age-matched infants. No significant differences in APC activation or function were observed. Expression of various TLRs, intracellular signaling molecules and downstream cytokines was also not found to be significantly different between sOP and NOP infants. Higher numbers of APCs in sOP infants suggest the possibility of a persistent mucosal inflammatory status. Transcriptional and cytokine profiles of PBMCs among sOP infants suggest their systemic innate responses are not different compared to NOP infants.