Successful development of methodology for detection of hapten-specific contact hypersensitivity (CHS) memory in swine.

Hapten contact hypersensitivity (CHS) elicits a well-documented inflammation response that can be used to illustrate training of immune cells through hapten-specific CHS memory. The education of hapten-specific memory T cells has been well-established, recent research in mice has expanded the "adaptive" characteristic of a memory response from solely a function of the adaptive immune system, to innate cells as well. To test whether similar responses are seen in a non-rodent model, we used hapten-specific CHS to measure the ear inflammation response of outbred pigs to dinitrofluorobenzene (DNFB), oxazolone (OXA), or vehicle controls. We adapted mouse innate memory literature protocols to the domestic pig model. Animals were challenged up to 32 days post initial sensitization exposure to the hapten, and specific ear swelling responses to this challenge were significant for 7, 21, and 32 days post-sensitization. We established hapten-specific CHS memory exists in a non-rodent model. We also developed a successful protocol for demonstrating these CHS responses in a porcine system.

Idiopathic, Infectious and Reactive Lesions of the Ear and Temporal Bone.

A number of infectious, inflammatory and idiopathic lesions develop within otologic tissues that may share similar clinical and/or microscopic features. This review first provides a working classification for otitis externa, and then otitis media and includes two recently described entities, eosinophilic otitis media and otitis media with ANCA-associated vasculitis. Next, the microscopic findings of a spectrum of otopathologic conditions are described, including post-inflammatory conditions such as tympanosclerosis and aural polyps, an overview of animate aural foreign body as well as iatrogenic aural foreign body reactions. Finally, a review of fungal disease affecting the ear with a brief synopsis of Candida auris, a recently described and virulent organism, is presented.

Cochlear implant electrode array exposure: A delayed complication.

Exposure of the cochlear implant electrode array as a late complication has been reported rarely in the literature. A retrospective analysis revealed 4 patients presenting with exposure of their cochlear implant electrode arrays from 2 to 17 years after implantation. Data collected from these 4 patients were surgical implantation approach, type of implant, age at implant, interval between implant and complication, surgical correction of the problem, pathology at the time of correction, and length of follow-up after intervention. All 4 patients presented with otitis or mastoiditis. Each had undergone a transmastoid approach with facial recess and cochleostomy and full implant insertion. In 3 cases, the tympanic membrane had retracted to expose the electrode array. In 1 patient, the electrode array had eroded through the external canal, lateral to the facial recess. The exposed arrays were addressed surgically, including explantation/reimplantation for 1 patient. Cochlear implant electrode arrays can become exposed by relative migration of the array and the tympanic membrane. Implant surgeons and audiologists need to be aware of the possibility of this complication. Closure of the ear canal appears to be the most effective surgical intervention.

[Ototoxicity in head and neck cancers after radiotherapy and chemoradiotherapy: From primary prevention to tertiary prevention]. / Ototoxicité radio-induite et chimio-induite dans les cancers ORL : de la prévention primaire à la prévention tertiaire.

Each year, 15,000 head and neck cancer are treated in France. Prognosis is steadily improving. Consequently, limitation of late toxicities becomes essential. Ototoxicity is common, disabling and undervalued. We aimed to inventory primary, secondary and tertiary prevention measures to reduce ototoxicity induced by radiotherapy and chemotherapy, as well as its impact on quality of life of patients treated for head and neck cancer. External radiation therapy induced 30 to 40% of ototoxicity, including irreversible sensorineural hearing loss. Primary prevention of this risk is based on limiting the dose to the cochlea: 40Gy in case of radiotherapy alone, 10Gy during concomitant chemoradiotherapy with cisplatin. Dose gradients allowed by intensity-modulated radiotherapy help respecting these limits. Concurrent chemotherapy with high dose cisplatin (100mg/m2) also causes hearing loss by cochlear damages. Prescription of carboplatin-5-fluorouracil combination or cetuximab should be preferred in case of high risk of ototoxicity. This risk must be precisely evaluated before treatment. Ototoxicity monitoring during treatment allows early management, and lower long-term impact. Radiosensitivity predictive tests and research of genetic factors predisposing to chemo-induced ototoxicity should enable optimization of therapeutic choices and monitoring.

Reduction in emergency department visits for children's asthma, ear infections, and respiratory infections after the introduction of state smoke-free legislation.

Despite the benefits of smoke-free legislation on adult health, little is known about its impact on children's health. We examined the effects of tobacco control policies on the rate of emergency department (ED) visits for childhood asthma (N=128,807), ear infections (N=288,697), and respiratory infections (N=410,686) using outpatient ED visit data in Massachusetts (2001-2010), New Hampshire (2001-2009), and Vermont (2002-2010). We used negative binomial regression models to analyze the effect of state and local smoke-free legislation on ED visits for each health condition, controlling for cigarette taxes and health care reform legislation. We found no changes in the overall rate of ED visits for asthma, ear infections, and upper respiratory infections after the implementation of state or local smoke-free legislation or cigarette tax increases. However, an interaction with children's age revealed that among 10-17-year-olds state smoke-free legislation was associated with a 12% reduction in ED visits for asthma (adjusted incidence rate ratios (aIRR) 0.88; 95% CI 0.83, 0.95), an 8% reduction for ear infections (0.92; 0.88, 0.97), and a 9% reduction for upper respiratory infections (0.91; 0.87, 0.95). We found an overall 8% reduction in ED visits for lower respiratory infections after the implementation of state smoke-free legislation (0.92; 0.87, 0.96). The implementation of health care reform in Massachusetts was also associated with a 6-9% reduction in all children's ED visits for ear and upper respiratory infections. Our results suggest that state smoke-free legislation and health care reform may be effective interventions to improve children's health by reducing ED visits for asthma, ear infections, and respiratory infections.

Clinical and Genotypic Spectrum of Chronic Granulomatous Disease in 71 Latin American Patients: First Report from the LASID Registry.

AIM: We analyzed data from 71 patients with chronic granulomatous disease (CGD) with a confirmed genetic diagnosis, registered in the online Latin American Society of Primary Immunodeficiencies (LASID) database. RESULTS: Latin American CGD patients presented with recurrent and severe infections caused by several organisms. The mean age at disease onset was 23.9 months, and the mean age at CGD diagnosis was 52.7 months. Recurrent pneumonia was the most frequent clinical condition (76.8%), followed by lymphadenopathy (59.4%), granulomata (49.3%), skin infections (42%), chronic diarrhea (41.9%), otitis (29%), sepsis (23.2%), abscesses (21.7%), recurrent urinary tract infection (20.3%), and osteomyelitis (15.9%). Adverse reactions to bacillus Calmette-Guérin (BCG) vaccination were identified in 30% of the studied Latin American CGD cases. The genetic diagnoses of the 71 patients revealed 53 patients from 47 families with heterogeneous mutations in the CYBB gene (five novel mutations: p.W361G, p.C282X, p.W483R, p.R226X, and p.Q93X), 16 patients with the common deletion c.75_76 del.GT in exon 2 of NCF1 gene, and two patients with mutations in the CYBA gene. CONCLUSION: The majority of Latin American CGD patients carry a hemizygous mutation in the CYBB gene. They also presented a wide range of clinical manifestations most frequently bacterial and fungal infections of the respiratory tract, skin, and lymph nodes. Thirty percent of the Latin American CGD patients presented adverse reactions to BCG, indicating that this vaccine should be avoided in these patients.

Domestic use of bleach and infections in children: a multicentre cross-sectional study.

OBJECTIVE: To report the effects of bleach use at home on the frequency of infections in 9102 school-age children participating in the HITEA project. METHODS: Parents of pupils aged 6-12 years from schools in Barcelona province (Spain), Utrecht province (the Netherlands) and Eastern and Central Finland were administered a questionnaire including questions on the frequency of infections (influenza, tonsillitis, sinusitis, otitis, bronchitis and pneumonia) in the past 12 months and bleach use at home. We developed multivariable mixed-effects multilogistic regression models to obtain relative risk ratios (RRR) and their 95% CI per country, and combined the RRR using random-effects meta-analyses. RESULTS: Bleach use was common in Spain (72%, n=1945) and uncommon in Finland (7%, n=279). Overall, the prevalence of infections (recurrent or once) was higher among children of bleach users. Significant combined associations were shown for influenza only once (RRR=1.20, 95% CI 1.04 to 1.38), recurrent tonsillitis (RRR=1.35, 95% CI 1.07 to 1.71) and any infection (RRR=1.18, 95% CI 1.01 to 1.38). CONCLUSIONS: Passive exposure to cleaning bleach in the home may have adverse effects on school-age children's health by increasing the risk of respiratory and other infections. The high frequency of use of disinfecting irritant cleaning products may be of public health concern, also when exposure occurs during childhood.

Concurrent chemoradiotherapy was associated with a higher severe late toxicity rate in nasopharyngeal carcinoma patients compared with radiotherapy alone: a meta-analysis based on randomized controlled trials.

BACKGROUND: To investigate the incidence and risk of severe late toxicity with concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma patients. METHODS: Eligible studies included prospective randomized controlled trials (RCTs) evaluating CCRT versus radiotherapy alone in patients with nasopharyngeal carcinoma and in which data on severe late toxicities were available. Random effects or fixed effect models were applied to obtain the summary incidence, relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: Five RCTs with 1102 patients with NPC were included in this analysis. The summary incidence of overall severe late toxicities in patients receiving CCRT was 30.7% (95% CI, 18-47.2%) and the incidence of radiotherapy alone group was 21.7% (95% CI, 13.3-33.4%). The use of concurrent chemotherapy was associated with an increased risk of severe late toxicities, with a RR of 1.349 (95% CI, 1.108-1.643; P = 0.005). As for specific late toxicity, CCRT significantly increased the risk of ear deafness/otitis (RR = 1.567; 95% CI, 1.192-2.052), but other late toxicities were not significantly different. Patients receiving concurrent chemotherapy regimens with 3-week high-dose cisplatin (HC) have a higher risk of ear deafness/otitis (RR = 1.672; 95% CI, 1.174-2.382; P = 0.026). However, there was no significant increase in the RR of severe ear complication with the addition of non-3-week high-dose cisplatin (nonHC) regimens (RR = 1.433; 95% CI, 0.946-2.171; P = 0.095). CONCLUSION: With the present evidence, the addition of concurrent chemotherapy seems to increase the risk of severe late toxicities in patients with NPC, especially when using HC regimen for the occurrence of severe ototoxicity.

First branchial cleft anomalies: otologic manifestations and treatment outcomes.

OBJECTIVE: This study describes the presentation of first branchial cleft anomalies and compares outcomes of first branchial cleft with other branchial cleft anomalies with attention to otologic findings. STUDY DESIGN: Case series with chart review. SETTING: Pediatric tertiary care facility. METHODS: Surgical databases were queried to identify children with branchial cleft anomalies. Descriptive analysis defined sample characteristics. Risk estimates were calculated using Fisher's exact test. RESULTS: Queries identified 126 subjects: 27 (21.4%) had first branchial cleft anomalies, 80 (63.4%) had second, and 19 (15.1%) had third or fourth. Children with first anomalies often presented with otologic complications, including otorrhea (22.2%), otitis media (25.9%), and cholesteatoma (14.8%). Of 80 children with second branchial cleft anomalies, only 3 (3.8%) had otitis. Compared with children with second anomalies, children with first anomalies had a greater risk of requiring primary incision and drainage: 16 (59.3%) vs 2 (2.5%) (relative risk [RR], 3.5; 95% confidence interval [CI], 2.4-5; P<.0001). They were more likely to have persistent disease after primary excision: 7 (25.9%) vs 2 (2.5%) (RR, 3; 95% CI, 1.9-5; P=.0025). They were more likely to undergo additional surgery: 8 (29.6%) vs 3 (11.1%) (RR, 2.9; 95% CI, 1.8-4.7; P=.0025). Of 7 persistent first anomalies, 6 (85.7%) were medial to the facial nerve, and 4 (57.1%) required ear-specific surgery for management. CONCLUSIONS: Children with first branchial cleft anomalies often present with otologic complaints. They are at increased risk of persistent disease, particularly if anomalies lie medial to the facial nerve. They may require ear-specific surgery such as tympanoplasty.

Cochlear implant complications in 403 patients: comparative study of adults and children and review of the literature.

OBJECTIVES: The purpose of this study was to assess the postoperative complications related to cochlear implants and to discuss the differences observed between adult and paediatric populations. Cochlear implant complications were defined as any pathological events observed during the postoperative period, whether or not they were directly related to the surgical technique. We therefore recorded all complications, in the broad sense of the term, ranging from acute otitis media to cochlear explantation. STUDY DESIGN: Retrospective analysis of cochlear implant patients. MATERIAL AND METHODS: All surgical procedures (unilateral or bilateral cochlear implantation, revision surgery) performed in our institution between March 1993 and January 2013 were reviewed. This population comprised 168 adults (median age at the time of implantation: 51.9 years), and 235 children (median age at the time of implantation: 4.5 years). All postoperative complications were classified as either major (requiring surgical revision or hospital management) or minor (requiring conservative management). RESULTS: The global complication rate was 19.9% (80/403 cases), comprising 5% of major complications (20 cases) and 14.9% of minor complications (60 cases). This complication rate was significantly higher in the adult population (P=0.004). CONCLUSION: Cochlear implantation is a safe hearing rehabilitation surgical technique associated with a low complication rate. However, surgeons must be familiar with these complications in order to ensure optimal prevention. Minor complications were mainly infectious in children (acute otitis media) and cochleovestibular in adults (tinnitus and vertigo). Major complications were mostly reimplantation following revision surgery or device failure. Only the minor complication rate was significantly higher in the adult population.

Effect of an injectable trace mineral supplement containing selenium, copper, zinc, and manganese on immunity, health, and growth of dairy calves.

The objective of this study was to evaluate the effect of 2 subcutaneous injections of a multimineral preparation, each containing 60 mg of zinc, 10mg of manganese, 5mg of selenium, and 15 mg of copper at 3 and 30 d after birth on immunity, health, and growth of dairy calves during the preweaning period. The study was conducted in upstate New York in 2 commercial dairy farms. A total of 790 Holstein heifer calves were randomly allocated at birth into 1 of 2 treatments: trace mineral supplement (TMS) treated or control. Blood samples were collected at 3, 14, and 35 d after birth to evaluate glutathione peroxidase (GPx) activity, superoxide dismutase (SOD) activity, haptoglobin, and neutrophil and monocyte function. Incidence of diseases and average daily gain was evaluated in the first 50 d of life. At 14 d of life, TMS-treated calves had increased neutrophil activity compared with control calves. Moreover, TMS-treated calves had greater GPx activity on d 14 after birth than control calves. The TMS treatment reduced the incidence of diarrhea (TMS=41.7% vs. control=49.7%) and combined incidence of pneumonia or otitis or both (TMS=41.7% vs. control=49.1%). Additionally, GPx was greater for calves diagnosed with otitis at d 35 after birth. However, calves diagnosed with pneumonia had decreased GPx activity at d 35 after birth. Serum SOD and haptoglobin concentrations were not affected by treatment or disease. Moreover, no effects were observed on average daily gain and survivability between TMS-treated and control calves during the preweaning period. Supplementation with trace minerals at 3 and 30 d of life increased neutrophil function and GPx activity and reduced the incidence of health disorders.

Exposure to air pollution and respiratory symptoms during the first 7 years of life in an Italian birth cohort.

BACKGROUND: Ambient air pollution has been consistently associated with exacerbation of respiratory diseases in schoolchildren, but the role of early exposure to traffic-related air pollution in the first occurrence of respiratory symptoms and asthma is not yet clear. METHODS: We assessed the association between indexes of exposure to traffic-related air pollution during different periods of life and respiratory outcomes in a birth cohort of 672 newborns (Rome, Italy). Direct interviews of the mother were conducted at birth and at 6, 15 months, 4 and 7 years. Exposure to traffic-related air pollution was assessed for each residential address during the follow-up period using a Land-Use Regression model (LUR) for nitrogen dioxide (NO2) and a Geographic Information System (GIS) variable of proximity to high-traffic roads (HTR) (>10 000vehicles/day). We used age-specific NO2 levels to develop indices of exposure at birth, current, and lifetime time-weighted average. The association of NO2 and traffic proximity with respiratory disorders were evaluated using logistic regression in a longitudinal approach (Generalised Estimating Equation). The exposure indexes were used as continuous and categorical variables (cut-off points based on the 75th percentile for NO2 and the 25th percentile for distance from HTRs). RESULTS: The average NO2 exposure level at birth was 37.2 µg/m(3) (SD 7.2, 10-90th range 29.2-46.1). There were no statistical significant associations between the exposure indices and the respiratory outcomes in the longitudinal model. The odds ratios for a 10-µg/m(3) increase in time-weighted average NO2 exposure were: asthma incidence OR=1.09; 95 CI% 0.78 to 1.52, wheezing OR=1.07; 95 CI% 0.90 to 1.28, shortness of breath with wheezing OR=1.16; 95 CI% 0.94 to 1.43, cough or phlegm apart from cold OR=1.11; 95 CI% 0.92 to 1.33, and otitis OR=1.08; 95 CI% 0.89 to 1.32. Stronger but not significant associations were found considering the 75th percentile of the NO2 distribution as a cut-off, especially for incidence of asthma and prevalence of wheeze (OR=1.41; 95 CI% 0.88 to 2.28 and OR=1.27; 95 CI% 0.95 to 1.70, respectively); the highest OR was found for wheezing (OR=2.29; 95 CI% 1.15 to 4.56) at the 7-year follow-up. No association was found with distance from HTRs. CONCLUSIONS: Exposure to traffic-related air pollution is only weakly associated with respiratory symptoms in young children in the first 7 years of life.

Granulomatosis de Wegener causante de parálisis facial y cofosis bilaterales / Wegener’s granulomatosis causing bilateral facial paralysis and deafness

La parálisis facial bilateral (PFB) es una entidad infrecuente, que habitualmente se presenta como manifestación de una enfermedad sistémica. Presentamos el caso de una mujer afecta de granulomatosis de Wegener (GW), con especial afectación de las vías respiratorias altas y ótica, que desarrolló hipoacusia y PFB resistente a tratamientos inmunosupresores y bolos de corticoides, con pruebas de imagen que no muestran afectación del nervio facial en las estructuras óticas. Finalmente, la paciente mejoró de la PFB, pero la cofosis es permanente y se ha realizado un implante coclear. Las series publicadas sobre PFB son escasas, y no hacen referencia a la GW como posible etiología (AU)

Bilateral facial paralysis (BFP) is an uncommon condition that typically occurs as a manifestation of systemic disease. We present a female patient with Wegener's granulomatosis (WG), particularly upper respiratory and ear impairment who develops hypoacusis and BFP, resistant to immunosuppressive therapy and steroid boluses. Her imaging tests showed no involvement of the facial nerve as it passed through the ear structures. The patient finally improved the BFP; however, deafness is permanent and she has entered into a cochlear implant program. Published papers on BFP are rare and they make no reference to WG as a possible aetiology (AU)

Early-life exposure to outdoor air pollution and respiratory health, ear infections, and eczema in infants from the INMA study.

BACKGROUND: Prenatal and early-life periods may be critical windows for harmful effects of air pollution on infant health. OBJECTIVES: We studied the association of air pollution exposure during pregnancy and the first year of life with respiratory illnesses, ear infections, and eczema during the first 12-18 months of age in a Spanish birth cohort of 2,199 infants. METHODS: We obtained parentally reported information on doctor-diagnosed lower respiratory tract infections (LRTI) and parental reports of wheezing, eczema, and ear infections. We estimated individual exposures to nitrogen dioxide (NO(2)) and benzene with temporally adjusted land use regression models. We used log-binomial regression models and a combined random-effects meta-analysis to estimate the effects of air pollution exposure on health outcomes across the four study locations. RESULTS: A 10-µg/m(3) increase in average NO(2) during pregnancy was associated with LRTI [relative risk (RR) = 1.05; 95% CI: 0.98, 1.12] and ear infections (RR = 1.18; 95% CI: 0.98, 1.41). The RRs for an interquartile range (IQR) increase in NO(2) were 1.08 (95% CI: 0.97, 1.21) for LRTI and 1.31 (95% CI: 0.97, 1.76) for ear infections. Compared with NO(2), the association for an IQR increase in average benzene exposure was similar for LRTI (RR = 1.06; 95% CI: 0.94, 1.19) and slightly lower for ear infections (RR = 1.17; 95% CI: 0.93, 1.46). Associations were slightly stronger among infants whose mothers spent more time at home during pregnancy. Air pollution exposure during the first year was highly correlated with prenatal exposure, so we were unable to discern the relative importance of each exposure period. CONCLUSIONS: Our findings support the hypothesis that early-life exposure to ambient air pollution may increase the risk of upper and lower respiratory tract infections in infants.