Prevalence of chronic ear disease among HIV+ children in Sub-Saharan Africa.

OBJECTIVES: To determine the prevalence of chronic ear disease in HIV+, highly active anti-retroviral therapy (HAART)-treated children and compare this to the prevalence in healthy children of similar age living in a similar setting. INTRODUCTION: From previous clinical work in Ethiopia, we suspected that chronic middle ear disease was common both in the general pediatric population and especially among children with HIV/AIDS. Few studies have examined the prevalence of chronic ear disease in HIV + children, particularly in those treated with HAART. METHODS: Full examination of the head and neck was performed by otolaryngologists. This including cleaning of cerumen, otoscopy and microscopic otoscopy when needed. Patient's medical records were reviewed. Presence or absence of tympanic membrane (TM) perforation (unilateral or bilateral), tympanosclerosis, TM atrophy, otorrhea and/or cholesteatoma was documented. RESULTS: 112 HIV+ and 162 healthy (HIVU) children were included. Prevalence of TM perforations was 17% in the HIV + infected versus 3% in the HIVU (Fisher's-Exact-Test; OR: 7.2, 95% CI 2.5-20, p-value <0.0001). Presence of unilateral TM perforations was 12% in the HIV + population and 2% in the HIVU population (Fisher's-Exact-Test; OR: 6.8, 95% CI 2.0-22, p-value 0.002). The presence of bilateral perforations was 4% in the HIV + population and 1% in the HIVU population (Fisher's-Exact-Test; OR: 6.8, 95% CI 1.1-42, p-value 0.088). In the HIV + cohort, 2% were diagnosed with cholesteatoma compared to 0% in the HIVU population (95% CI HIV+ 0.002-0.06; HIVU 0.0-0.02) and 8% of HIV + subjects had active middle ear discharge, compared to 0% in the HIVU population (95% CI HIV+ 0.04-0.1; HIVU 0.0-0.02). Neither tympanosclerosis nor tympanic membrane atrophy was more frequent in the HIV + population compared to the HIVU population. Persistent or recurrent TM perforation was not more frequent in children with prior tympanoplasty in the HIV + population compared to the HIVU population. CONCLUSION: TM perforations are significantly more common in HAART-treated HIV + children than in healthy, age-matched HIVU population. Otorrhea and cholesteatoma were found only in the HIV + cohort.

Prevalence of hearing-loss among HAART-treated children in the Horn of Africa.

OBJECTIVES: The prevalence of hearing loss (HL) in children infected with HIV/AIDS is not well studied. Even fewer studies focus on stable HIV-infected children treated with high-effective antiretroviral therapy (HAART). We aim to compare the prevalence of ear disease and HL in HAART-treated, HIV + children in Addis Ababa, Ethiopia with a well, similarly-aged elementary school population with unknown HIV status (HIVU). METHODS: Children underwent standard head and neck examination and cerumen removal by board certified otolaryngologists. Next, certified audiologists performed hearing screening with pure-tone audiometry using a circumaural headset but without an ambient noise reducing environment. Children failing audiometric screening underwent full behavioral audiometry including air and bone testing. The primary outcome parameter was HL > 25 dB with the audiologist accounting for background noise. A second endpoint was PTA >40 dB (500, 1000, 2000 Hz) without assessment of background noise. RESULTS: 107 HIV+ and 147 HIVU children met inclusion criteria. In the HIV + cohort 17.8% had evidence of TM perforations and 8.4% had otorrhea. In the HIVU group 2.7% had a TM perforation and 0% had otorrhea. Hearing was significantly worse in HIV + children. (Audiologist determination: 38.3% HL HIV+, 12.2% HIVU, Fisher's-Exact-Test OR: 4.5, 95% CI 2.4-8.3, p-value <0.0001; Worse-hearing-ear PTA > 40 dB: 19.6% HL HIV+, 6.1% HIVU, OR: 3.7, 95% CI 1.7-8.4, p-value <0.001). CONCLUSIONS: Chronic OM, conductive and mixed hearing losses are significantly more common in HAART-treated HIV + children than in well, similarly-aged controls. Rates of SNHL are similar.

Panel 7: Otitis Media: Treatment and Complications.

Objective We aimed to summarize key articles published between 2011 and 2015 on the treatment of (recurrent) acute otitis media, otitis media with effusion, tympanostomy tube otorrhea, chronic suppurative otitis media and complications of otitis media, and their implications for clinical practice. Data Sources PubMed, Ovid Medline, the Cochrane Library, and Clinical Evidence (BMJ Publishing). Review Methods All types of articles related to otitis media treatment and complications between June 2011 and March 2015 were identified. A total of 1122 potential related articles were reviewed by the panel members; 118 relevant articles were ultimately included in this summary. Conclusions Recent literature and guidelines emphasize accurate diagnosis of acute otitis media and optimal management of ear pain. Watchful waiting is optional in mild to moderate acute otitis media; antibiotics do shorten symptoms and duration of middle ear effusion. The additive benefit of adenoidectomy to tympanostomy tubes in recurrent acute otitis media and otitis media with effusion is controversial and age dependent. Topical antibiotic is the treatment of choice in acute tube otorrhea. Symptomatic hearing loss due to persistent otitis media with effusion is best treated with tympanostomy tubes. Novel molecular and biomaterial treatments as adjuvants to surgical closure of eardrum perforations seem promising. There is insufficient evidence to support the use of complementary and alternative treatments. Implications for Practice Emphasis on accurate diagnosis of otitis media, in its various forms, is important to reduce overdiagnosis, overtreatment, and antibiotic resistance. Children at risk for otitis media and its complications deserve special attention.

Otitis media.

Otitis media (OM) or middle ear inflammation is a spectrum of diseases, including acute otitis media (AOM), otitis media with effusion (OME; 'glue ear') and chronic suppurative otitis media (CSOM). OM is among the most common diseases in young children worldwide. Although OM may resolve spontaneously without complications, it can be associated with hearing loss and life-long sequelae. In developing countries, CSOM is a leading cause of hearing loss. OM can be of bacterial or viral origin; during 'colds', viruses can ascend through the Eustachian tube to the middle ear and pave the way for bacterial otopathogens that reside in the nasopharynx. Diagnosis depends on typical signs and symptoms, such as acute ear pain and bulging of the tympanic membrane (eardrum) for AOM and hearing loss for OME; diagnostic modalities include (pneumatic) otoscopy, tympanometry and audiometry. Symptomatic management of ear pain and fever is the mainstay of AOM treatment, reserving antibiotics for children with severe, persistent or recurrent infections. Management of OME largely consists of watchful waiting, with ventilation (tympanostomy) tubes primarily for children with chronic effusions and hearing loss, developmental delays or learning difficulties. The role of hearing aids to alleviate symptoms of hearing loss in the management of OME needs further study. Insertion of ventilation tubes and adenoidectomy are common operations for recurrent AOM to prevent recurrences, but their effectiveness is still debated. Despite reports of a decline in the incidence of OM over the past decade, attributed to the implementation of clinical guidelines that promote accurate diagnosis and judicious use of antibiotics and to pneumococcal conjugate vaccination, OM continues to be a leading cause for medical consultation, antibiotic prescription and surgery in high-income countries.

Information on co-morbidities collected by history is useful for assigning Otitis Media risk to children.

OBJECTIVES: Determine if a 2-Step multivariate analysis of historical symptom/sign data for comorbid diseases can abstract high-level constructs useful in assigning a child's "risk" for different Otitis Media expressions. METHODS: Seventeen items related to the symptom/sign expression of hypothesized Otitis Media comorbidities were collected by history on 141 3-year-old children. Using established criteria, the children were assigned to 1 of 3 groups: Control (no significant past Otitis Media, n=45), Chronic Otitis Media with Effusion (n=45) and Recurrent Acute Otitis Media (n=51). Principal Component Analysis was used to identify factors representing the non-redundant shared information among related items and Discriminant Analysis operating on those factors was used to estimate the best predictor equation for pairwise group assignments. RESULTS: Six multivariate factors representing the assignable comorbidities of frequent colds, nasal allergy, gastroesophageal disease (specific and general), nasal congestion and asthma were identified and explained 81% of the variance in the 17 items. Discriminant Analysis showed that, for the Control-Chronic Otitis Media with Effusion comparison, a combination of 3 factors and, for the Control-Recurrent Acute Otitis Media comparison, a combination of 2 factors had assignment accuracies of 74% and 68%, respectively. For the contrast between the two disease expressions, a 2-factor combination had an assignment accuracy of 61%. CONCLUSION: These results show that this analytic methodology can abstract high-level constructs, comorbidities, from low-level data, symptom/sign scores, support a linkage between certain comorbidities and Otitis Media risk and suggest that specific comorbidity combinations contain information relevant to assigning the risk for different Otitis Media expressions.

Meniere's disease.

Meniere's disease (MD) is a disorder of the inner ear that causes vertigo attacks, fluctuating hearing loss, tinnitus and aural fullness. The aetiology of MD is multifactorial. A characteristic sign of MD is endolymphatic hydrops (EH), a disorder in which excessive endolymph accumulates in the inner ear and causes damage to the ganglion cells. In most patients, the clinical symptoms of MD present after considerable accumulation of endolymph has occurred. However, some patients develop symptoms in the early stages of EH. The reason for the variability in the symptomatology is unknown and the relationship between EH and the clinical symptoms of MD requires further study. The diagnosis of MD is based on clinical symptoms but can be complemented with functional inner ear tests, including audiometry, vestibular-evoked myogenic potential testing, caloric testing, electrocochleography or head impulse tests. MRI has been optimized to directly visualize EH in the cochlea, vestibule and semicircular canals, and its use is shifting from the research setting to the clinic. The management of MD is mainly aimed at the relief of acute attacks of vertigo and the prevention of recurrent attacks. Therapeutic options are based on empirical evidence and include the management of risk factors and a conservative approach as the first line of treatment. When medical treatment is unable to suppress vertigo attacks, intratympanic gentamicin therapy or endolymphatic sac decompression surgery is usually considered. This Primer covers the pathophysiology, symptomatology, diagnosis, management, quality of life and prevention of MD.

Craniofacial shape in children with and without a positive otitis media history.

OBJECTIVES: Past studies using traditional morphometric approaches have reported a handful of differences in craniofacial dimensions between individuals with and without otitis media (OM). In this study, a geometric morphometry (GM) approach was used to determine if craniofacial shape is different among children with no history of OM and a history of recurrent acute OM (RAOM) at two different ages. METHODS: Nineteen standard landmarks were identified on lateral cephalometric radiographs from 79 children (41 Control, 38 RAOM) at 4 years and 52 children (27 Control, 25 RAOM) at 6 years of age. Following Procrustes superimposition of the landmark coordinate data, comparisons of group differences in overall size and shape were performed. Discriminant function analysis and principal component analysis were used to determine which, if any, aspects of shape variation distinguished RAOM from Control groups. RESULTS: At 4 years of age, craniofacial size and shape were significantly different between RAOM and Control groups (p<0.05). Shape differences were evident in the relative positions of the mandible, cranial base, external acoustic meatus, sphenoid and palate. Those shape differences were not found in the 6-year old group. CONCLUSIONS: At 4 years of age, the RAOM and Control groups have distinct craniofacial morphologies, but by 6 years of age these differences have largely disappeared. This is consistent with the clinical observation that excess RAOM risk resolves around 6 years of age and the hypothesis that this resolution is partially a result of age-related craniofacial changes.

Eustachian Tube Function in 6-Year-Old Children with and without a History of Middle Ear Disease.

OBJECTIVE: To test the hypothesis that eustachian tube opening efficiency, measured as the fractional gradient equilibrated (FGE), is lower in 6-year-old children with no middle ear disease but a well-documented history of recurrent acute otitis media, as compared with children with a negative disease history (control). STUDY DESIGN: Cross-sectional study. SETTING: Tertiary care pediatric hospital. SUBJECTS AND METHODS: Bilateral eustachian tube function was evaluated in 44 healthy 6-year-old children (19 boys, 29 white). None had middle ear disease at the time of testing, but 23 had a history of recurrent acute otitis media. Twenty-one had no significant past otitis media. Eustachian tube function was measured with a pressure chamber protocol that established negative middle ear gauge pressures (referenced to the chamber pressure) and recorded that pressure before and after a swallow. FGE was calculated as the change in middle ear gauge pressure with swallowing divided by the preswallow pressure. Between-group comparisons of the preswallow pressures and FGEs were made with a 2-tailed Student's t test. RESULTS: FGE was independent of the preswallow middle ear gauge pressure. For the 39 and 44 evaluable ears in the control and recurrent acute otitis media groups, the mean preswallow pressures were -194 daPa (95% confidence interval [95% CI] = -211 to -177) versus -203 (95% CI = -216 to -190; P > .40), and FGEs were 0.32 (95% CI = 0.21-0.43) vs 0.16 (95% CI = 0.08-0.24; P = .016), respectively. CONCLUSION: In children with past recurrent acute otitis media, residual eustachian tube opening inefficiency is maintained after they have "outgrown" their middle ear disease.

Predisposition to Childhood Otitis Media and Genetic Polymorphisms within the Toll-Like Receptor 4 (TLR4) Locus.

BACKGROUND: Predisposition to childhood otitis media (OM) has a strong genetic component, with polymorphisms in innate immunity genes suspected to contribute to risk. Studies on several genes have been conducted, but most associations have failed to replicate in independent cohorts. METHODS: We investigated 53 gene polymorphisms in a Finnish cohort of 624 cases and 778 controls. A positive association signal was followed up in a tagging approach and tested in an independent Finnish cohort of 205 cases, in a British cohort of 1269 trios, as well as in two cohorts from the United States (US); one with 403 families and the other with 100 cases and 104 controls. RESULTS: In the initial Finnish cohort, the SNP rs5030717 in the TLR4 gene region showed significant association (OR 1.33, P = .003) to OM. Tagging SNP analysis of the gene found rs1329060 (OR 1.33, P = .002) and rs1329057 (OR 1.29, P = .003) also to be associated. In the more severe phenotype the association was stronger. This finding was supported by an independent Finnish case cohort, but the associations failed to replicate in the British and US cohorts. In studies on TLR4 signaling in 20 study subjects, the three-marker risk haplotype correlated with a decreased TNFα secretion in myeloid dendritic cells. CONCLUSIONS: The TLR4 gene locus, regulating the innate immune response, influences the genetic predisposition to childhood OM in a subpopulation of patients. Environmental factors likely modulate the genetic components contributing to the risk of OM.

Intratemporal and intracranial complications of acute otitis media in a pediatric population.

OBJECTIVE: To review all cases intratemporal and intracranial complications of acute otitis media (AOM) in infants and children from 1998 to 2013. METHODS: Retrospective chart review of 109 consecutive patients admitted for complications of AOM during a 15-year period at a tertiary-care children's hospital. The main outcomes are: (1) complications of AOM, (2) bacteriology, (3) management strategies. RESULTS: In our population, complications included mastoiditis (86.1%), subperiosteal abscess (38%), facial nerve palsy (16.7%), sigmoid sinus thrombosis (8.3%) and epidural abscess (7.4%). Other complications included post-auricular cellulitis, otic hydrocephalus and elevated intracranial pressure, internal jugular thrombosis, cranial nerve VI palsy and Gradenigo's syndrome, labyrinthine fistula, sensorineural hearing loss, and cerebellar infarct. Sixty-one patients (56%) received antibiotics prior to presentation. Cultures revealed Streptococcus pneumoniae in 36 patients (33.3%), other bacteria in 30 patients (27.8%), and "no growth" in 33 patients (30.5%). Nine patients (8.3%) did not undergo culture. Of the patients with S. pneumoniae, 20 cultures (55%) were found to be multidrug-resistant. Eleven patients (10.2%) were treated non-surgically, 31 (31%) were treated with myringotomy and intravenous antibiotics. Forty patients (97.5%) presenting with subperiosteal abscess required mastoid surgery. Thirteen of 18 (72.2%) patients with facial paralysis had full recovery. Eight of 10 (80%) patients with epidural abscess empyema required mastoid surgery and incision and drainage of the abscess. CONCLUSION: Complications of AOM are uncommon, yet continue to have potentially serious consequences. The bacteriology in this population reveals an increasing trend of multi-drug resistant S. pneumoniae as the causative organism.

Eustachian tube function in young children without a history of otitis media evaluated using a pressure chamber protocol.

CONCLUSIONS: Protocol limitations were identified and accounted for in the analysis. Percent gradient equilibrated (PGE) was affected by driving gradient direction in a similar manner to other efficiency measures. A finer resolution of possible age-related changes in eustachian tube opening efficiency is expected with the application of more sophisticated statistical models to the complete dataset at study end. OBJECTIVE: To report the results of an interim analysis for an ongoing study designed to characterize the age-related changes in eustachian tube opening efficiency measured using a pressure chamber protocol in children without a history of middle ear disease. METHODS: To date, 41 children aged 3 years without a history of otitis media have been enrolled in a longitudinal study of the age-related changes in eustachian tube function and evaluated at yearly intervals between 3 and 7 years of age. Eustachian tube opening efficiency, the percent of the applied pressure gradient equilibrated by swallowing, was measured by repeat tympanometry during a pressure chamber protocol. Data (120 tests) were analyzed using an ANOVA with variance partitioned by age (3 through 6 years), gradient direction (positive/negative), and ear (left/right). RESULTS: PGE was higher for left ears and positive driving gradients, but was not different among age groups.

The forced-response test does not discriminate ears with different otitis media expressions.

OBJECTIVES/HYPOTHESIS: Test the hypothesis that the eustachian tube (ET) function measured using standard manometric test methods is different between groups of ears with tympanostomy tubes inserted for recurrent acute otitis media (RAOM) and for chronic otitis media with effusion (COME). STUDY DESIGN: A cross-sectional study of ET function in populations of young children with different otitis media expressions. METHODS: The results for forced-response testing of ET function were compared using a general linear model between 37 ears of 26 children and 34 ears of 26 children, aged 3 and 4 years, with ventilation tubes inserted for COME and RAOM, respectively. RESULTS: There were no significant between-group differences in either the active measure of ET opening function, dilatory efficiency, or in the passive measures reflecting the magnitude of the forces that tend to hold the ET lumen closed, the opening and closing pressures, and passive trans-ET conductance. CONCLUSIONS: The results do not support the hypothesis that ET closing forces are less in ears with RAOM when compared to ears with COME, and from the results of earlier studies, ears without disease. Both groups were characterized by a low ET opening efficiency (referenced to ears of adults with no disease history). Because both disease expressions present the same pattern of ET dysfunction, other factors are required to explain why a subset of ears with that type of dysfunction develop RAOM, as opposed to the default expression of COME. LEVEL OF EVIDENCE: 2b

A genome-wide association study of chronic otitis media with effusion and recurrent otitis media identifies a novel susceptibility locus on chromosome 2.

Chronic otitis media with effusion (COME) and recurrent otitis media (ROM) have been shown to be heritable, but candidate gene and linkage studies to date have been equivocal. Our aim was to identify genetic susceptibility factors using a genome-wide association study (GWAS). We genotyped 602 subjects from 143 families with 373 COME/ROM subjects using the Illumina Human CNV370-Duo DNA Bead Chip (324,748 SNPs). We carried out the GWAS scan and imputed SNPs at the regions with the most significant associations. Replication genotyping in an independent family-based sample was conducted for 53 SNPs: the 41 most significant SNPs with P < 10(-4) and 12 imputed SNPs with P < 10(-4) on chromosome 15 (near the strongest signal). We replicated the association of rs10497394 (GWAS discovery P = 1.30 × 10(-5)) on chromosome 2 in the independent otitis media population (P = 4.7 × 10(-5); meta-analysis P = 1.52 × 10(-8)). Three additional SNPs had replication P values < 0.10. Two were on chromosome 15q26.1 including rs1110060, the strongest association with COME/ROM in the primary GWAS (P = 3.4 ×10(-7)) in KIF7 intron 7 (P = 0.072), and rs10775247, a non-synonymous SNP in TICRR exon 2 (P = 0.075). The third SNP rs386057 was on chromosome 5 in TPPP intron 1 (P = 0.045). We have performed the first GWAS of COME/ROM and have identified a SNP rs10497394 on chromosome 2 is significantly associated with COME/ROM susceptibility. This SNP is within a 537 kb intergenic region, bordered by CDCA7 and SP3. The genomic and functional significance of this newly identified locus in COME/ROM pathogenesis requires additional investigation.

Sensitivity and specificity of eustachian tube function tests in adults.

IMPORTANCE: The study demonstrates the utility of eustachian tube (ET) function (ETF) test results for accurately assigning ears to disease state. OBJECTIVES: To determine if ETF tests can identify ears with physician-diagnosed ET dysfunction (ETD) in a mixed population at high sensitivity and specificity and to define the interrelatedness of ETF test parameters. DESIGN, SETTING, AND PARTICIPANTS: Through use of the forced-response, inflation-deflation, Valsalva, and sniffing tests, ETF was evaluated in 15 control ears of adult subjects after unilateral myringotomy (group 1) and in 23 ears of 19 adult subjects with ventilation tubes inserted for ETD (group 2). Data were analyzed using logistic regression including each parameter independently and then a step-down discriminant analysis including all ETF test parameters to predict group assignment. Factor analysis operating over all parameters was used to explore relatedness. EXPOSURES: ETF testing. MAIN OUTCOMES AND MEASURES: ETF parameters for the forced response, inflation-deflation, Valsalva, and sniffing tests measured in 15 control ears of adult subjects after unilateral myringotomy (group 1) and in 23 ears of 19 adult subjects with ventilation tubes inserted for ETD (group 2). RESULTS: The discriminant analysis identified 4 ETF test parameters (Valsalva, ET opening pressure, dilatory efficiency, and percentage of positive pressure equilibrated) that together correctly assigned ears to group 2 at a sensitivity of 95% and a specificity of 83%. Individual parameters representing the efficiency of ET opening during swallowing showed moderately accurate assignments of ears to their respective groups. Three factors captured approximately 98% of the variance among parameters: the first had negative loadings of the ETF structural parameters; the second had positive loadings of the muscle-assisted ET opening parameters; and the third had negative loadings of the muscle-assisted ET opening parameters and positive loadings of the structural parameters. CONCLUSIONS AND RELEVANCE: These results show that ETF tests can correctly assign individual ears to physician-diagnosed ETD with high sensitivity and specificity and that ETF test parameters can be grouped into structural-functional categories.

Childhood socioeconomic status, telomere length, and susceptibility to upper respiratory infection.

Low socioeconomic status (SES) during childhood and adolescence has been found to predict greater susceptibility to common cold viruses in adults. Here, we test whether low childhood SES is associated with shorter leukocyte telomere length in adulthood, and whether telomere length mediates the association between childhood SES and susceptibility to acute upper respiratory disease in adulthood. At baseline, 196 healthy volunteers reported whether they currently owned their home and, for each year of their childhood, whether their parents owned the family home. Volunteers also had blood drawn for assessment of specific antibody to the challenge virus, and for CD8+ CD28- T-lymphocyte telomere length (in a subset, n=135). They were subsequently quarantined in a hotel, exposed to a virus (rhinovirus [RV] 39) that causes a common cold and followed for infection and illness (clinical cold) over five post-exposure days. Lower childhood SES as measured by fewer years of parental home ownership was associated with shorter adult CD8+ CD28- telomere length and with an increased probability of developing infection and clinical illness when exposed to a common cold virus in adulthood. These associations were independent of adult SES, age, sex, race, body mass, neuroticism, and childhood family characteristics. Associations with infections and colds were also independent of pre-challenge viral-specific antibody and season. Further analyses do not support mediating roles for smoking, alcohol consumption or physical activity but suggest that CD8+ CD28- cell telomere length may act as a partial mediator of the associations between childhood SES and infection and childhood SES and colds.

Eustachian tube function as a predictor of the recurrence of middle ear effusion in children.

OBJECTIVES/HYPOTHESIS: In children with ventilation tubes (VTs) inserted for chronic otitis media with effusion (COME), the authors sought to determine whether any parameter of Eustachian tube (ET) function measured by the forced response test (FRT) predicts disease recurrence after the VT becomes nonfunctional. STUDY DESIGN: Prospective study of those factors that predict disease recurrence in children with VTs inserted for COME. METHODS: Forty-nine subjects (73 ears; 28 male, 34 white, aged 5.3 ± 1.2 years) with COME had VTs inserted and were evaluable for disease status after the VT(s) became nonfunctional. The FRT was done when the VTs were patent, and results for the last test before the VT became nonfunctional were used in the analysis. After each VT became nonfunctional, the children were followed for disease recurrence over a 12-month period. Logistic regression was used to determine whether the ET opening pressure, closing pressure, and/or dilatory efficiency predicted disease recurrence. That model was expanded to include age, sex, race, history of adenoidectomy, previous VTs, and duration of VT patency as potential predictive factors. RESULTS: Twenty-nine (40%) ears had recurrence of significant disease within 12 months after the VT became nonfunctional. For the complete logistic regression model, male gender (P = .03), nonwhite race (P = .02), shorter period of VT patency (P = .01), and low dilatory efficiency (P = .01) were significant predictors of disease recurrence. CONCLUSIONS: A measure of active ET function, dilatory efficiency, but not measures of passive function predicted disease recurrence within the 12 months after the VT became nonfunctional in children with COME.

Panel 1: Epidemiology, natural history, and risk factors.

BACKGROUND: The First International Symposium on Recent Advances in Otitis Media (OM) with Effusion was held in Columbus, Ohio, in 1975. The symposium has been organized in the United States every 4 years since, followed by a research conference to (a) assess major research accomplishments, (b) identify important research questions and opportunities, (c) develop consensus on definitions and terminology, and (d) establish priorities with short- and long-term research goals. One of the principal areas reviewed quadrennially is Epidemiology, Natural History, and Risk Factors. OBJECTIVE: To provide a review of recent literature on the epidemiology, natural history, and risk factors for OM. DATA SOURCES AND REVIEW METHODS: A search of OM articles in English published July 2007 to June 2011 was conducted using PubMed and related databases. Those with findings judged of importance for epidemiology, public health, and/or statistical methods were reviewed. RESULTS: The literature has continued to expand, increasing understanding of the worldwide burden of OM in childhood, complications from treatment failures, and comorbidities. Novel risk factors, including genetic factors, have been examined for OM susceptibility. Population-based studies in Canada, the United States, and other countries confirmed reductions in OM prevalence. Although most studies concentrated on acute OM (AOM) or OM with effusion (OME), a few examined severe chronic suppurative OM (CSOM), a major public health problem in developing countries and for certain indigenous populations around the world. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Recent publications have reinforced earlier epidemiological findings, while extending our knowledge in human population groups with high burden of OM.

Panel 8: Complications and sequelae.

BACKGROUND AND OBJECTIVES: Although serious complications of otitis media (OM) such as brain abscess are rare, sequelae of OM such as tympanic membrane perforation and atelectatic tympanic membrane are quite common. Inner ear sequelae can cause hearing loss and speech and language problems. The objectives of this article are to provide a state-of-the-art review on recent articles on complications and sequelae of OM in different anatomic locations, from the tympanic membrane to intracranial sites, as well as hearing loss and speech and language development. DATA SOURCES: Primarily PubMed supplemented by Ovid MEDLINE and the Cochrane Database. REVIEW METHODS: All types of articles related to OM complications and sequelae published in English between January 2007 and June 2011 were identified. A total of 127 relevant quality articles are summarized and included in this report. RESULTS: Key findings are summarized based on the following major anatomic locations and categories: tympanic membrane; cholesteatoma; ossicular problems; mucosal sequelae; inner ear sequelae; speech and language development; extracranial areas, including mastoiditis and facial nerve paralysis; intracranial complications; and future research goals. New information and insights were gained to prevent complications and sequelae. CONCLUSION AND IMPLICATIONS FOR PRACTICE: Over the past 4 years, progress has been made in advancing the knowledge on the complications and sequelae of OM, which can be used to prevent and treat them effectively. Areas of potential future research have been identified and outlined.

Association between telomere length and experimentally induced upper respiratory viral infection in healthy adults.

IMPORTANCE: Although leukocyte telomere length is associated with mortality and many chronic diseases thought to be manifestations of age-related functional decline, it is not known whether it relates to acute disease in younger healthy populations. OBJECTIVE: To determine whether shorter telomeres in leukocytes, especially CD8CD28- T cells, are associated with decreased resistance to upper respiratory infection and clinical illness in young to midlife adults. DESIGN, SETTING, AND PARTICIPANTS: Between 2008 and 2011, telomere length was assessed in peripheral blood mononuclear cells (PBMCs) and T-cell subsets (CD4, CD8CD28+, CD8CD28-) from 152 healthy 18- to 55-year-old residents of Pittsburgh, Pennsylvania. Participants were subsequently quarantined (single rooms), administered nasal drops containing a common cold virus (rhinovirus 39), and monitored for 5 days for development of infection and clinical illness. MAIN OUTCOME MEASURES: Infection (virus shedding or 4-fold increase in virus-specific antibody titer) and clinical illness (verified infection plus objective signs of illness). RESULTS: Rates of infections and clinical illness were 69% (n = 105) and 22% (n = 33), respectively. Shorter telomeres were associated with greater odds of infection, independent of prechallenge virus-specific antibody, demographics, contraceptive use, season, and body mass index (PBMC: odds ratio [OR] per 1-SD decrease in telomere length, 1.71 [95% CI, 1.08-2.72]; n = 128 [shortest tertile 77% infected; middle, 66%; longest, 57%]; CD4: OR, 1.76 [95% CI, 1.15-2.70]; n = 146 [shortest tertile 80% infected; middle, 71%; longest, 54%]; CD8CD28+: OR, 1.93 [95% CI, 1.21-3.09], n = 132 [shortest tertile 84% infected; middle, 64%; longest, 58%]; CD8CD28-: OR, 2.02 [95% CI, 1.29-3.16]; n = 144 [shortest tertile 77% infected; middle, 75%; longest, 50%]). CD8CD28- was the only cell population in which shorter telomeres were associated with greater risk of clinical illness (OR, 1.69 [95% CI, 1.01-2.84]; n = 144 [shortest tertile, 26%; middle, 22%; longest, 13%]). The association between CD8CD28- telomere length and infection increased with age (CD8CD28- telomere length × age interaction, b = 0.09 [95% CI, 0.02-0.16], P = .01, n = 144). CONCLUSION AND RELEVANCE: In this preliminary study among a cohort of healthy 18- to 55-year-olds, shorter CD8CD28- T-cell telomere length was associated with increased risk for experimentally induced acute upper respiratory infection and clinical illness.