Contralateral hearing loss in children with a unilateral enlarged vestibular aqueduct.

OBJECTIVE: To evaluate the long-term ipsi- and contralateral hearing of patients with a unilateral enlarged vestibular aqueduct (EVA). STUDY DESIGN: Multicenter retrospective cohort study. SETTING: Three tertiary otology and audiology referral centers. PATIENTS AND DIAGNOSTIC INTERVENTIONS: A total of 34 children with a unilateral enlarged vestibular aqueduct as identified on CT and/or MR imaging were evaluated with pure tone and speech perception audiometry. MEAN OUTCOME MEASURES: Radiologic measurements of the vestibular aqueduct, ipsi- and contralateral hearing loss, ipsi- and contralateral hearing loss progression over time and DNA test results. RESULTS: All patients in this cohort with unilateral EVA presented with hearing loss. Hearing loss was progressive in 38% of the ipsilateral ears. In 29% of the children, hearing loss was also found in the contralateral ear without EVA. In 90%, the contralateral hearing was stable, with a mean follow up of 4.2 years. We found a significant correlation between the severity of the hearing loss and the size of the EVA. A genetic diagnosis associated with EVA and/or SNHL was found in only 7%. CONCLUSION: About a third of the children with unilateral EVA are at risk of developing hearing loss in the contralateral ear. This indicates that at least in some patients with a unilateral EVA, a bilateral pathogenic process underlies the hearing loss, in contrary to what the imaging results suggest. These findings are important for counseling of EVA patients and their parents and have implications for follow up.

Clinical relevance of Scedosporium spp. and Exophiala dermatitidis in patients with cystic fibrosis: A nationwide study.

An increased prevalence of various filamentous fungi in sputum samples of patients with cystic fibrosis (CF) has been reported. The clinical significance, however, is mostly unclear. The aim of this study was to investigate the clinical relevance of Scedosporium spp. and Exophiala dermatitidis from sputum samples of patients with CF in the Netherlands. In this cross-sectional study, all CF patients of the Dutch national CF registry who were treated at five of the seven recognized CF centers during a 3-year period were included. We linked clinical data of the national CF registry with the national Dutch filamentous fungal database. We investigated the association between clinical characteristics and a positive sputum sample for Scedosporium spp. and E. dermatitidis, using logistic regression. Positive cultures for fungi were obtained from 3787 sputum samples from 699 of the 1312 patients with CF. Scedosporium spp. was associated with severe genotype, CF-related diabetes, several microorganisms, and inhaled antibiotics. E. dermatitidis was associated with older age, female sex, and Aspergillus spp. CF patients with and without Scedosporium spp. or E. dermatitidis seemed comparable in body mass index and lung function. This study suggests that Scedosporium spp. and E. dermatitidis are probably no major pathogens in CF patients in the Netherlands. Greater understanding of epidemiologic trends, risk factors, and pathogenicity of filamentous fungi in the respiratory tracts of patients with CF is needed.

The etiological evaluation of sensorineural hearing loss in children.

This study aims to evaluate the etiology of pediatric sensorineural hearing loss (SNHL). A total of 423 children with SNHL were evaluated, with the focus on the determination of causative genetic and acquired etiologies of uni- and bilateral SNHL in relation to age at diagnosis and severity of the hearing loss. We found that a stepwise diagnostic approach comprising of imaging, genetic, and/or pediatric evaluation identified a cause for SNHL in 67% of the children. The most common causative finding in children with bilateral SNHL was causative gene variants (26%), and in children with unilateral SNHL, a structural anomaly of the temporal bone (27%). The probability of finding an etiologic diagnosis is significantly higher in children under the age of 1 year and children with profound SNHL.Conclusions: With our stepwise diagnostic approach, we found a diagnostic yield of 67%. Bilateral SNHL often has a genetic cause, whereas in unilateral SNHL structural abnormalities of the labyrinth are the dominant etiologic factor. The diagnostic yield is associated with the age at detection and severity of hearing loss: the highest proportion of causative abnormalities is found in children with a young age at detection or a profound hearing loss. What is Known: • Congenital sensorineural hearing loss is one of the most common congenital disorders • Determination of the cause is important for adequate management and prognosis and may include radiology, serology, and DNA analysis What is New: • Using a stepwise diagnostic approach, causative abnormalities are found in 67% both in uni- and bilateral SNHL, with the highest diagnostic yield in very young children and those suffering from profound hearing loss • Bilateral SNHL often has a genetic cause, whereas in unilateral SNHL structural abnormalities of the labyrinth are the dominant etiologic factor.

A case promoting use of ultrasound-guided sampling techniques to correctly diagnose MDR-TB in children.

A paediatric case of multidrug-resistant tuberculosis in which endo-oesophageal ultrasound-guided fine-needle aspiration using an endobronchial ultrasound-guided bronchoscope was used to collect a sample for microbial analyses is presented. In our experience, ultrasound-guided sampling techniques, both endo-oesophageal and endobronchial, can be safely used for the diagnosis of paediatric intrathoracic tuberculous lymphadenopathy in children aged 3 years. Interventional pulmonologists with experience in using these techniques should be part of the multidisciplinary team treating these patients.

Evaluation of the outcome of CT and MR imaging in pediatric patients with bilateral sensorineural hearing loss.

OBJECTIVE: To evaluate the clinically relevant abnormalities as visualized on CT and MR imaging in children with symmetric and asymmetric bilateral sensorineural hearing loss (SNHL), in relation to age and the severity of hearing loss. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary referral otology and audiology center. PATIENTS AND DIAGNOSTIC INTERVENTIONS: From January 2006 until January 2016, a total of 207 children diagnosed with symmetric and asymmetric bilateral SNHL were included. They underwent CT and/or MR imaging for the evaluation of the etiology of their hearing loss. MAIN OUTCOME MEASURES: Radiologic abnormalities associated with SNHL. RESULTS: 302 scans were performed in 207 children (median age of 0.8 years old) with bilateral SNHL. The most frequently identified cause of bilateral SNHL was a malformation of the labyrinth. The combined diagnostic yield of CT and MR imaging was 32%. The diagnostic yield of MR (34%) was considerably higher than that of CT (20%). We found a higher rate of abnormalities in children with profound hearing loss (41%) compared to milder hearing loss (8-29%), and in asymmetric SNHL (52%) compared to symmetric SNHL (30%). CONCLUSION: Imaging is essential in the etiologic evaluation of children with bilateral SNHL. The highest diagnostic yield is found in children with bilateral asymmetric SNHL or profound SNHL. Based on our findings, MR is the primary imaging modality of choice in the etiological evaluation of children with bilateral SNHL because of its high diagnostic yield.

The Otology Questionnaire Amsterdam: a generic patient reported outcome measure about the severity and impact of ear complaints. A cross-sectional study on the development of this questionnaire.

OBJECTIVE: Development of the 'Otology Questionnaire Amsterdam' (OQUA), a patient reported outcome measure (PROM), measuring the severity and impact of ear complaints of patients visiting an ENT surgeon. DESIGN: Multicenter, cross-sectional study. Phase 1: qualitative research. In-depth interviews (N = 16) to identify relevant types of ear complaints and to formulate items. Pilot study of the first and second draft of the OQUA (N = 32, N = 39). Phase 2: quantitative research. Field-testing of the OQUA (N = 352). Item reduction based on inter-item correlation, factor analysis and expert opinion. SETTING: Two secondary and two tertiary ENT clinics. PARTICIPANTS: Patients over the age of sixteen visiting an ENT surgeon with an ear complaint. MAIN OUTCOME MEASURES: Phase 1: meaning units and frequency of selected descriptions. Phase 2: inter-item correlation, factor loading and Cronbach's Alpha (α). RESULTS: Phase 1: eight relevant types of ear complaints were identified: earache, pressure in ear, hearing loss, tinnitus, otorrhoea, itch, dizziness and loss of taste. Phase 2: factor analysis generated a factor 'impact' (α = 0.913). The current version of the OQUA consists of 34 items, covers eight types of ear complaints and consists of two constructs: complaints and impact. CONCLUSION: The OQUA is a generic, otologic PROM designed to evaluate the severity of ear complaints and their impact on patients lives.

High prevalence of abnormalities on CT and MR imaging in children with unilateral sensorineural hearing loss irrespective of age or degree of hearing loss.

OBJECTIVE: Evaluation of causal abnormalities identified on CT and MR imaging in children with unilateral sensorineural hearing loss (USNHL), and the association with age and severity of hearing loss. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary referral otology/audiology center. PATIENTS AND DIAGNOSTIC INTERVENTIONS: 102 children diagnosed with USNHL between 2006 and 2016 were included. They underwent CT and/or MR imaging for the evaluation of the etiology of their hearing loss. MAIN OUTCOME MEASURES: Radiologic abnormalities of the inner ear and brain associated with USNHL. RESULTS: Using CT and/or MR imaging, causal abnormalities were identified in 49%, which is higher than previously reported (25-40%). The most frequently affected site was the labyrinth (29%), followed by the cochlear nerve (9%) and brain (7%). No significant difference in the number or type of abnormalities was found for the degree of hearing loss or age categories. CONCLUSIONS: Imaging is essential in the etiologic analysis of USNHL because of the high prevalence of causative abnormalities that can be identified with radiology, irrespective of the patients' age or degree of hearing loss. CT and MR imaging are complementary imaging options. The ideal imaging algorithm is controversial. Based on our findings, we conclude that there is limited additional diagnostic value of simultaneous dual modality imaging over sequential diagnostics. We therefore perform a stepwise radiological workup in order to maximize the diagnostic yield while minimizing impact and costs. If the primary imaging modality does not identify a cause for USNHL, performing the alternative imaging modality should be considered. LEVEL OF EVIDENCE: Retrospective cohort study 2b.

Detection of Staphylococcus aureus in cystic fibrosis patients using breath VOC profiles.

Staphylococcus aureus (S. aureus) is a common bacterium infecting children with cystic fibrosis (CF). Since current detection methods are difficult to perform in children, there is need for an alternative. This proof of concept study investigates whether breath profiles can discriminate between S. aureus infected and non-infected CF patients based on volatile organic compounds (VOCs). We collected exhaled breath of CF patients with and without S. aureus airways infections in which VOCs were identified using gas chromatography-mass spectrometry. We classified these VOC profiles with sparse partial least squares discriminant analysis. Multivariate breath VOC profiles discriminated infected from non-infected CF patients with high sensitivity (100%) and specificity (80%). We identified the nine compounds most important for this discrimination. We successfully detected S. aureus infection in CF patients, using breath VOC profiles. Nine highlighted compounds can be used as a focus point in further biomarker identification research. The results show considerable potential for non-invasive diagnosis of airway infections.

Evaluation of monitoring strategies for childhood asthma.

INTRODUCTION: The goal of monitoring pediatric asthma is to obtain and maintain asthma control, which is defined as minimizing asthma symptoms, restrictions to daily activities and the use of rescue medication. Long term goals include reducing the risk of fixed airflow limitation, and preventing asthma exacerbations and side effects of treatment. Several monitoring tools are available but no consensus exists on how to monitor patients in the most optimal way. Areas covered: In this review, we provide an overview of different tools and address general considerations on monitoring childhood asthma. Asthma care should be tailored to the individual patient. The health care professional should decide which monitoring strategy and frequency is optimal for the individual patient. Expert commentary: Personalized medicine should be the key issue in monitoring asthma in children. It is crucial to monitor disease activity and deterioration but there is no monitoring strategy that is clearly superior compared to others: The optimal strategy and frequency will vary between patients. Actually, both treatment and monitoring of pediatric asthma probably benefit from a personalized approach.

Identification of Pseudomonas aeruginosa and Aspergillus fumigatus mono- and co-cultures based on volatile biomarker combinations.

Volatile organic compound (VOC) analysis in exhaled breath is proposed as a non-invasive method to detect respiratory infections in cystic fibrosis patients. Since polymicrobial infections are common, we assessed whether we could distinguish Pseudomonas aeruginosa and Aspergillus fumigatus mono- and co-cultures using the VOC emissions. We took headspace samples of P. aeruginosa, A. fumigatus and co-cultures at 16, 24 and 48 h after inoculation, in which VOCs were identified by thermal desorption combined with gas chromatography - mass spectrometry. Using multivariate analysis by Partial Least Squares Discriminant Analysis we found distinct VOC biomarker combinations for mono- and co-cultures at each sampling time point, showing that there is an interaction between the two pathogens, with P. aeruginosa dominating the co-culture at 48 h. Furthermore, time-independent VOC biomarker combinations were also obtained to predict correct identification of P. aeruginosa and A. fumigatus in mono-culture and in co-culture. This study shows that the VOC combinations in P. aeruginosa and A. fumigatus co-microbial environment are different from those released by these pathogens in mono-culture. Using advanced data analysis techniques such as PLS-DA, time-independent pathogen specific biomarker combinations can be generated that may help to detect mixed respiratory infections in exhaled breath of cystic fibrosis patients.

Rare cause of bilateral sudden deafness.

In this paper, we describe the case of a 62-year-old female with recurring episodes of sudden deafness with vertigo and facial paresis. Within a month's time, this resulted in bilateral deafness and vestibular areflexia. Erroneously, the patient was diagnosed with sudden deafness of unknown origin and subsequently with neuroborreliosis (Lyme disease). The true diagnosis of relapsing polychondritis (RP) was revealed 9 months after initial presentation. The diagnostic delay is in part explained by the fact that, by definition, the disease has to relapse before the diagnosis can be made, but also by its pluriform clinical presentation. Timely identification of RP as the cause of this profound sensorineural hearing loss proved to be important. It was key in instigating adequate follow-up, and allowed for cochlear implantation before total cochlear obliteration, which might have hampered optimal hearing rehabilitation.

Extended nitric oxide analysis may improve personalized anti-inflammatory treatment in asthmatic children with intermediate F(E)NO50.

Exhaled nitric oxide (F(E)NO) is elevated in asthma, and a clinical practice guideline has been published with recommendations for anti-inflammatory treatment. It summarizes that a F(E)NO at an expiratory flow rate of 50 ml s(-1) (F(E)NO50) above 35 ppb in children indicates eosinophilic inflammation, and the most likely response is to use inhaled corticosteroids. Intermediate F(E)NO50 between 20-35 ppb should be interpreted cautiously. The aim of the study was to investigate this guideline in a small group of asthmatic children. Thirty-seven asthmatic children; 23 boys and 14 girls, visited the outpatient clinic, and provided exhaled breath samples for offline NO measurement. These samples were analysed with chemiluminescence techniques. Three flow rates, namely 16, 90 and 230 ml s(-1) were used for the extended NO analysis (Högman-Meriläinen algorithm, HMA) to estimate the alveolar concentration (C(A)NO), diffusion rate of the airway wall (D(aw)NO) and airway wall content (C(aw)NO). For accuracy of the HMA, the estimated value of F(E)NO at 50 ml s(-1) (F(E)NO50) was compared with measured F(E)NO50. In nine children the difference was more than 5 ppb and the data were therefore excluded. Five children with F(E)NO50 <20 ppb had no known allergy and their F(E)NO50 geometrical mean (25th; 75th percentile) was 11 (10;14) and CawNO was 32 (20;43) ppb. Ten children with F(E)NO50 > 35 ppb had an allergy and had F(E)NO50 of 56 (47;60) ppb and C(aw)NO of 140 (121;172) ppb. Thirteen children with allergies, with intermediate F(E)NO50, had F(E)NO50 of 27 (25;30) ppb with a wide range of C(aw)NO. In five of these children, values were comparable to healthy children, 44 (43;50) ppb while eight children had elevated C(aw)NO values of 108 (95;129) ppb. Our data indicate the clinical potential use of extended NO analysis to determine the personal target value of F(E)NO50 for monitoring the treatment outcome. Furthermore, for children with intermediate F(E)NO50 more than half of them could possibly benefit from an adjustment of inhaled corticosteroids if the C(aw)NO value was considered.

Validity, reliability and discriminative capacity of an electronic quality of life instrument (Pelican) for childhood asthma in the Netherlands.

PURPOSE: To assess psychometric properties of the Pelican instrument, an online Dutch self-administered Quality of Life instrument for childhood asthma for scientific and clinical use. METHODS: A cohort study was done in two asthma populations and healthy children. One asthma population had assessment at start, 4 and 8 weeks. The other asthma population and healthy children had one assessment. All children were aged 6-12 years. Children completed the Pelican instrument, Paediatric Asthma Quality of Life Questionnaire, feeling thermometer and Childhood Asthma Control Test. Lung function and fraction exhaled nitric oxide were measured. Parents completed Functional Status II, Asthma Control Questionnaire, Childhood Asthma Control Test questionnaires and symptom diaries. We assessed interpretability, structural validity, internal consistency, reliability, construct and discriminative validity of the Pelican instrument. RESULTS: Eighty-five asthmatic (mean age 8.5 years) and 49 healthy children (mean age 8.4 years) participated. The Pelican instrument has 5 domains with 21 items after factor analysis. Internal consistency was 0.89 (CI 0.85-0.92), domain reliability showed Cronbach's α's from 0.64 to 0.76 and item-to-scale correlations from 0.61 to 0.81. Test-retest reliability was confirmed ICC = 0.88 (CI 0.79-0.93). Construct validity was demonstrated by significant moderate correlations with other relevant asthma outcomes like PAQLQ (r = -0.59, p < 0.01). Discriminative capacity between controlled or uncontrolled asthma (t = 3.20, p < 0.01, Δ = 0.64) and asthma versus healthy subjects (t = 6.31, p < 0.01, Δ = 0.94) was found. CONCLUSIONS: The psychometric properties of the Pelican instrument were acceptable in Dutch paediatric asthma patients between 6 and 12 years old.

Improved treatment response to dornase alfa in cystic fibrosis patients using controlled inhalation.

Better treatment of obstructed small airways is needed in cystic fibrosis. This study investigated whether efficient deposition of dornase alfa in the small airways improves small airway obstruction. In a multicentre, double-blind, randomised controlled clinical trial, cystic fibrosis patients on maintenance treatment with 2.5 mL dornase alfa once daily were switched to a smart nebuliser and randomised to small airway deposition (n = 24) or large airway deposition (n = 25) for 4 weeks. The primary outcome parameter was forced expiratory flow at 75% of forced vital capacity (FEF(75%)). FEF(75%) increased significantly by 0.7 sd (5.2% predicted) in the large airways group and 1.2 sd (8.8% pred) in the small airways group. Intention-to-treat analysis did not show a significant difference in treatment effect between groups. Per-protocol analysis, excluding patients not completing the trial or with adherence <70%, showed a trend (p = 0.06) in FEF(75%) Z-score and a significant difference (p = 0.04) between groups in absolute FEF(75%) (L · s(-1)) favouring small airway deposition. Improved delivery of dornase alfa using a smart nebuliser that aids patients in correct inhalation technique resulted in significant improvement of FEF(75%) in children with stable cystic fibrosis. Adherent children showed a larger treatment response for small airway deposition.

Validation of a web-based version of the asthma control test and childhood asthma control test.

RATIONALE: Recent guidelines focus on adjusting asthma treatment to the level of asthma control. The availability of a web-based asthma control questionnaire offers the possibility to assess asthma control without the need of outpatient clinic visits. The aim of this study was to evaluate the agreement between web-based and paper-based versions of the Asthma Control Test (ACT) and Childhood Asthma Control Test (C-ACT), short-term reproducibility and satisfaction with both versions. METHODS: One hundred seventy-three children with stable asthma and a normal lung function were randomized to fill in a web-based or paper-based version of the C-ACT (4-11 years) or ACT (12-18 years). According to a cross-over design, they completed the opposite version after 1 week. Reproducibility was evaluated by repeating the 2nd version (web- or paper-based) 7 days later. RESULTS: Eighty-eight children filled in the C-ACT, 68 children filled in the ACT. Intraclass Correlation Coefficient (ICC) for web-based versus paper-based C-ACT was 0.81 (95% confidence interval [95% CI] 0.72-0.87). For ACT this was 0.84 (95% CI 0.76-0.90). For web-based and paper-based C-ACT the reproducibility ICC was 0.82 (95% CI 0.67-0.90) and 0.75 (95% CI 0.59-0.85), respectively. The reproducibility ICC of the ACT for web- and paper-based versions was 0.93 (95% CI 0.87-0.97) and 0.77 (95% CI 0.59-0.88), respectively. Eighty-six percent of patients preferred the web-based version. CONCLUSION: The web-based version of the C-ACT and ACT is reproducible and comparable with the paper-based version in assessing asthma control. Most children and their parents prefer the web-based version.

Comparing Global Initiative for Asthma (GINA) criteria with the Childhood Asthma Control Test (C-ACT) and Asthma Control Test (ACT).

Several tools are useful in detecting uncontrolled asthma in children. The aim of this study was to compare Global Initiative for Asthma (GINA) guidelines with the Childhood Asthma Control Test (C-ACT) and the Asthma Control Test (ACT) in detecting uncontrolled asthma in children. 145 children with asthma filled in a web-based daily diary card for 4 weeks on symptoms, use of rescue medication and limitations of activities, followed by either the C-ACT or ACT. For predicting uncontrolled asthma, score cut-off points of 19 were used for C-ACT and ACT. According to GINA guidelines, asthma was uncontrolled in 71 (51%) children and completely controlled in 19 (14%) children. The area under the curve in the receiver operating characteristic curves for C-ACT and ACT versus GINA guidelines were 0.89 and 0.92, respectively. Cut-off points of 19 for C-ACT and ACT resulted in a sensitivity of 33% and 66% in predicting uncontrolled asthma, respectively. C-ACT and ACT correlate well with GINA criteria in predicting uncontrolled asthma, but commonly used cut-off points for C-ACT and ACT seem to underestimate the proportion of children with uncontrolled asthma as defined by GINA.

Cochlear implantation after bacterial meningitis in infants younger than 9 months.

Objective. To describe the audiological, anesthesiological, and surgical key points of cochlear implantation after bacterial meningitis in very young infants. Material and Methods. Between 2005 and 2010, 4 patients received 7 cochlear implants before the age of 9 months (range 4-8 months) because of profound hearing loss after pneumococcal meningitis. Results. Full electrode insertions were achieved in all operated ears. The audiological and linguistic outcome varied considerably, with categories of auditory performance (CAP) scores between 3 and 6, and speech intelligibility rating (SIR) scores between 0 and 5. The audiological, anesthesiological, and surgical issues that apply in this patient group are discussed. Conclusion. Cochlear implantation in very young postmeningitic infants is challenging due to their young age, sequelae of meningitis, and the risk of cochlear obliteration. A swift diagnostic workup is essential, specific audiological, anesthesiological, and surgical considerations apply, and the outcome is variable even in successful implantations.

Effect of enzyme therapy in juvenile patients with Pompe disease: a three-year open-label study.

Pompe disease is a rare neuromuscular disorder caused by deficiency of acid α-glucosidase. Treatment with recombinant human α-glucosidase recently received marketing approval based on prolonged survival of affected infants. The current open-label study was performed to evaluate the response in older children (age 5.9-15.2 years). The five patients that we studied had limb-girdle muscle weakness and three of them also had decreased pulmonary function in upright and supine position. They received 20-mg/kg recombinant human α-glucosidase every two weeks over a 3-year period. No infusion-associated reactions were observed. Pulmonary function remained stable (n = 4) or improved slightly (n = 1). Muscle strength increased. Only one patient approached the normal range. Patients obtained higher scores on the Quick Motor Function Test. None of the patients deteriorated. Follow-up data of two unmatched historical cohorts of adults and children with Pompe disease were used for comparison. They showed an average decline in pulmonary function of 1.6% and 5% per year. Data on muscle strength and function of untreated children were not available. Further studies are required.