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1.
Heliyon ; 10(3): e25190, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38333844

ABSTRACT

Background: Pulmonary infections by gram-negative organisms are important in cystic fibrosis (CF). Aminoglycosides (AG) are often part of the treatment regimen. However, they are a well-known cause of ototoxicity. Even minimal hearing impairment in children could have a future impact on functional well-being.We aimed to investigate the progression of sensorineural hearing loss (SNHL) over several years in pediatric CF patients, and to identify risk factors, such as the use of AG, including both intravenous (IV) and inhaled AG. Methods: Retrospective analyses of patient records from children and adolescents followed up at the CF clinic of the Antwerp University Hospital, Belgium, were performed. We collected data on age, sex, pure-tone audiometry, and the use of AG. Descriptive and binary logistic regression analyses, and if indicated generalized estimating equations (GEE) analyses were performed. Results: Forty pediatric patients were enrolled in the study taking part from 2013 to 2020. Pure-tone audiometry revealed an important rate of SNHL over several years, with a prevalence of 29 % for high-frequency SNHL (i.e. 8 kHz). Increasing age was identified as a significant risk factor for the development of SNHL at 8 kHz if 5 or more IV AG courses (p = 0.01) were reported or when IV AG were combined with inhaled AG (p = 0.002). Conclusions: Age combined with the use of IV AG (≥5 courses or in combination with inhaled AG) are predictive for developing high-frequency SNHL (i.e. 8 kHz). We suggest routine annual hearing screening (incl. high-frequency thresholds) in CF patients, starting from childhood.

2.
Sleep Med ; 79: 19-28, 2021 03.
Article in English | MEDLINE | ID: mdl-33465738

ABSTRACT

OBJECTIVE/BACKGROUND: Surgical interventions for obstructive sleep apnea (OSA) are less effective in obese than in normal-weight children. However, the mechanisms that underpin this relationship are not fully understood. Therefore, this study aimed to explore how body weight influences upper airway collapse and treatment outcome in children with OSA. METHODS: We conducted a retrospective analysis of prospectively collected data on polysomnography, drug-induced sleep endoscopy (DISE), and treatment outcome in otherwise healthy children with OSA. Associations between body mass index (BMI) z-score and upper airway collapse during DISE were assessed using logistic regression modelling. Treatment success was defined as obstructive apnea-hypopnea index (oAHI) < 5 events/hour and cure as oAHI < 2 events/hour with obstructive apnea index < 1 event/hour. RESULTS: A total of 139 children were included [median (Q1─Q3); age 4.5 (3.1─8.4) years; BMI z-score 0.3 (-0.8 to 1.4); oAHI 10.8 (6.8─18.0) events/hour]. Twenty-five of them were overweight and 21 were obese. After adjusting for age and history of upper airway surgery, BMI z-score was significantly correlated with circumferential upper airway collapse during DISE (odds ratio 1.67; 95% confidence interval 1.12─2.65; P = 0.011). Outcome of DISE-directed treatment was similar in normal-weight (success: 91.4%; cure: 78.5%), overweight (success: 88.0%; cure: 80.0%), and obese (success: 90.5%; cure: 76.5%) children. Children with circumferential collapse responded better to continuous positive airway pressure than to (adeno)tonsillectomy. CONCLUSION: Increasing body weight is associated with circumferential upper airway collapse during DISE and, accordingly, may require treatment strategies other than (adeno)tonsillectomy.


Subject(s)
Adenoidectomy , Sleep Apnea, Obstructive , Body Weight , Child , Child, Preschool , Endoscopy , Humans , Retrospective Studies , Sleep Apnea, Obstructive/surgery , Treatment Outcome
3.
Respir Med ; 171: 106101, 2020 09.
Article in English | MEDLINE | ID: mdl-32799061

ABSTRACT

BACKGROUND: Bronchopulmonary dysplasia (BPD) remains a common complication of preterm birth. Both historically and in current practice, radiologic evaluation of the lungs has an important role in assessing disease severity and complications. AIM: To provide an overview of imaging techniques for detecting lung abnormalities in patients with BPD in all age ranges. METHODS: A systematic literature search was conducted in PubMed, Web of Science and the Cochrane Library. Records were screened by title and abstract and then by full text. A total of 37 records were selected and included in this qualitative literature overview. RESULTS: Computed tomography (CT) was the most commonly used imaging modality, followed by chest radiography and magnetic resonance imaging (MRI). Several qualitative and quantitative scoring systems were presented and most showed good correlation with BPD severity. The association with functional and clinical outcomes was only rarely reported, showing varying correlation with spirometry results and respiratory exacerbations. MRI is an upcoming imaging technique for BPD that is technically feasible, showing clear differences in the lung parenchyma of patients with BPD. CONCLUSION: Several imaging and scoring methods indicate that lung imaging continues to play a role in BPD care. Standardization and correlation with functional and clinical outcomes will become increasingly important for further research.


Subject(s)
Bronchopulmonary Dysplasia/diagnostic imaging , Lung/diagnostic imaging , Disease Progression , Female , Humans , Infant , Infant, Newborn , Magnetic Resonance Imaging , Male , Premature Birth , Radiography, Thoracic , Severity of Illness Index , Tomography, X-Ray Computed
4.
Sleep Med ; 44: 1-3, 2018 04.
Article in English | MEDLINE | ID: mdl-29530362

ABSTRACT

Continuous positive airway pressure (CPAP) is being increasingly used in children of all age ranges. The limited number of commercially available masks especially in infants and young children may complicate its use and compliance. In this report, we describe our experience with the use of the Optiflow™ (Fisher and Paykel Healthcare) Nasal Cannula attached to a regular CPAP device in the setting of chronic CPAP use. This interface consists of a nasal cannula and was originally designed for the delivery of high-flow oxygen therapy. We could show an objective improvement in breathing parameters in several children selected for CPAP mainly because of obstructive sleep apnea syndrome (OSAS). However, this interface cannot be used for bilevel non-invasive ventilation due to insufficient triggering.


Subject(s)
Continuous Positive Airway Pressure/instrumentation , Masks , Sleep Apnea, Obstructive/therapy , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Noninvasive Ventilation/methods , Respiration
5.
Eur J Pediatr ; 177(5): 641-648, 2018 May.
Article in English | MEDLINE | ID: mdl-29502303

ABSTRACT

Sleep disorders are a common problem during childhood. The consequences are variable, and sleep disorders can influence medical, psychological and developmental aspects of the growing child. It is important to recognize sleep disorders and to treat them correctly. We discuss common sleep disorders during childhood using the 3rd edition of the International Classification of Sleep Disorders. We analyze the different sleep disorders from a clinical approach and provide an overview of adequate treatment options.Conlusion: This review discusses common sleep disorders during childhood using the 3rd edition of the International Classification of Sleep Disorders. We analyze the different sleep disorders from a clinical approach and provide an overview of adequate treatment options. What is known: • Sleep disorders are a common problem during childhood. • The consequences are variable, and sleep disorders can influence medical, psychological, and developmental aspects of the growing child. What is new: • Pediatricians should routinely screen for sleep and sleep disorders. • It is important to recognize sleep disorders and to treat them correctly.


Subject(s)
Sleep Wake Disorders/diagnosis , Sleep/physiology , Adolescent , Behavior Therapy/methods , Central Nervous System Depressants/therapeutic use , Child , Child, Preschool , Humans , Infant , Melatonin/therapeutic use , Sleep Wake Disorders/therapy
6.
Sleep Med ; 15(8): 929-33, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24985758

ABSTRACT

OBJECTIVE: Obese children have an increased risk of developing obstructive sleep apnea syndrome (OSAS) compared to normal-weight children. In obese children, OSAS is more frequently associated with oxygen desaturations, which might be caused by pulmonary function abnormalities. Our goal was to investigate the association between OSAS and pulmonary function in obese children and adolescents. METHODS: There were 185 children included and distributed in groups based on their obstructive apnea-hypopnea index (151 controls, 20 mild OSAS, and 14 moderate-to-severe OSAS). All subjects underwent polysomnography and pulmonary function testing. RESULTS: Several differences in pulmonary function were observed between groups. Vital capacity (VC) and forced expired volume in 1s (FEV1) were significantly decreased in patients with moderate-to-severe OSAS, as were expiratory reserve volume (ERV), total lung capacity, and functional residual capacity (FRC). Correlations between FEV1, FRC, and ERV with OSAS severity remained significant independent of the degree of adiposity. Correlations between FEV1/VC and sleep-related respiratory parameters did not persist after correction for adiposity. CONCLUSION: An association between awake pulmonary function and sleep-related respiratory parameters could be observed in our population of obese children. These results suggest that OSAS severity is correlated with a diminished lung function. However, the level of obesity remains an important confounding factor in both OSAS severity and pulmonary function.


Subject(s)
Lung/physiopathology , Pediatric Obesity/physiopathology , Sleep Apnea, Obstructive/physiopathology , Adolescent , Child , Child, Preschool , Expiratory Reserve Volume , Female , Forced Expiratory Volume , Functional Residual Capacity , Humans , Male , Pediatric Obesity/complications , Polysomnography , Prospective Studies , Severity of Illness Index , Sleep Apnea, Obstructive/etiology , Total Lung Capacity , Vital Capacity
7.
Pediatr Obes ; 9(1): 36-42, 2014 Feb.
Article in English | MEDLINE | ID: mdl-23325614

ABSTRACT

UNLABELLED: What is already known about this subject BDNF is involved in the regulation of food intake and body weight. BDNF deficient animal models are obese. Chromosomal abnormalities cause obesity in humans. What this study adds Evaluation of point mutations in BDNF. Identification of BDNF mutations in obese children. Point mutations in BDNF are not a common cause of childhood obesity. INTRODUCTION: There is ample evidence that BDNF has a role in the regulation of food intake and body weight. Study of various mouse models gave a clear indication that BDNF deficiency leads to the development of obesity. Functional loss of one copy of the BDNF gene, due to chromosomal rearrangements or microdeletions, can cause an obesity phenotype in humans. Therefore, we wanted to investigate whether point mutations in the gene also result in a comparable phenotype. METHODS: We screened 554 severely overweight and obese children and adolescents and 565 lean adults for mutations in the coding region of BDNF. Mutation screening was performed by high-resolution melting curve analysis and direct sequencing. RESULTS: Screening of obese patients led to the identification of two synonymous variations (V37V and H65H) and two non-synonymous coding mutations (T2I and V46M) in the BDNF gene. When we subsequently screened our control population, we found T2I with comparable frequency and confirmed that this is a rare and non-pathogenic variant. In addition, we found another non-synonymous mutation (N187S) in the control population. CONCLUSIONS: In silico analysis of the V46M variant did not support a clear disease-causing effect and no family data were available in order to determine whether the mutation segregates with obesity. However, we cannot rule out a possible pathogenic effect for this variant. In general, we tend to conclude that mutations in the coding region of BDNF are uncommon in obese patients and are therefore not likely to play an essential role in the pathogenesis of childhood obesity.


Subject(s)
Brain-Derived Neurotrophic Factor/genetics , Genetic Testing , Pediatric Obesity/genetics , Point Mutation , Adolescent , Adult , Child , Child, Preschool , Female , Genetic Variation , Humans , Male , Pediatric Obesity/diagnosis , Phenotype
8.
Int J Obes (Lond) ; 38(7): 1000-4, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24097297

ABSTRACT

BACKGROUND: The transcription factor SIM1 (Single-minded 1) is involved in the control of food intake and in the pathogenesis of obesity. In mice, Sim1 is involved in the development of the paraventricular nucleus, and Sim1 deficiency leads to severe obesity and hyperphagia. In humans, chromosomal abnormalities in the SIM1 gene region have been reported in obese individuals. Furthermore, recent data also suggest that loss-of-function point mutations in SIM1 are responsible for SIM1 haplo-insufficiency that is involved in causing human obesity. In this study, we therefore wanted to expand the evidence regarding the involvement of SIM1 mutations in the pathogenesis of severe early-onset obesity. METHODS: We screened 561 severely overweight and obese children and adolescents and 453 lean adults for mutations in the coding region of the SIM1 gene. Mutation screening in all patients and lean individuals was performed by high-resolution melting curve analysis combined with direct sequencing. To evaluate the effect of the mutations on SIM1 transcriptional activity, luciferase reporter assays were performed. RESULTS: Mutation analysis identified four novel nonsynonymous coding variants in SIM1 in four unrelated obese individuals: p.L242V, p.T481K, p.A517V and p.D590E. Five synonymous variants, p.P57P, p.F93F, p.I183I, p.V208V and p.T653T, were also identified. Screening of the lean control population revealed the occurrence of four other rare SIM1 variants: p.G408R, p.R471P, p.S492P and p.S622F. For variants p.T481K and p.A517V, which were found in obese individuals, a decrease in SIM1 transcriptional activity was observed, whereas the transcriptional activity of all variants found in lean individuals resembled wild type. CONCLUSIONS: In this study, we have demonstrated the presence of rare SIM1 variants in both an obese pediatric population and a population of lean adult controls. Further, we have shown that functional in vitro analysis of SIM1 variants may help in distinguishing benign variants of no pathogenic significance from variants which contribute to the obesity phenotype.


Subject(s)
Basic Helix-Loop-Helix Transcription Factors , Genetic Predisposition to Disease , Mutation, Missense , Obesity, Morbid/genetics , Repressor Proteins , Adolescent , Adult , Animals , Basic Helix-Loop-Helix Transcription Factors/genetics , Child , DNA Mutational Analysis , Genes, Reporter , Genetic Association Studies , Humans , Mice , Phenotype , Repressor Proteins/genetics , Transcriptional Activation
9.
Sleep Med ; 14(5): 433-9, 2013 May.
Article in English | MEDLINE | ID: mdl-23474060

ABSTRACT

OBJECTIVE: We aim to investigate if anatomical and functional properties of the upper airway using computerized 3D models derived from computed tomography (CT) scans better predict obstructive sleep apnea (OSA) severity than standard clinical markers. METHODS: Consecutive children with suspected OSA underwent polysomnography, clinical assessment of upper airway patency, and a CT scan while awake. A three-dimensional (3D) reconstruction of the pharyngeal airway was built from these images, and computational fluid dynamics modeling of low inspiratory flow was performed using open-source software. RESULTS: Thirty-three children were included (23 boys; mean age, was 6.0±3.2y). OSA was diagnosed in 23 patients. Children with OSA had a significantly lower volume of the overlap region between tonsils and the adenoids (median volume, 1408 mm compared to 2173 mm; p=0.04), a lower mean cross-sectional area at this location (median volume, 69.3mm(2) compared to 114.3mm2; p=0.04), and a lower minimal cross-sectional area (median volume, 17.9 mm2 compared to 25.9 mm2; p=0.05). Various significant correlations were found between several imaging parameters and the severity of OSA, most pronounced for upper airway conductance (r=-0.46) (p<0.01) for correlation between upper airway conductance and the apnea-hypopnea index. No differences or significant correlations were observed with clinical parameters of upper airway patency. Preliminary data after treatment showed that none of the patients with residual OSA had their smallest cross-sectional area located in segment 3, and this frequency was significantly lower than in their peers whose sleep study normalized (64%; p=0.05). CONCLUSION: Functional imaging parameters are highly correlated with OSA severity and are a more powerful correlate than clinical scores of upper airway patency. Preliminary data also showed that we could identify differences in the upper airway of those subjects who did not benefit from a local upper airway treatment.


Subject(s)
Nasal Cavity/diagnostic imaging , Nasal Obstruction/diagnostic imaging , Sleep Apnea, Obstructive/diagnostic imaging , Tomography, X-Ray Computed/methods , Algorithms , Child , Child, Preschool , Female , Humans , Hypertrophy , Imaging, Three-Dimensional/methods , Male , Nasal Cavity/pathology , Nasal Obstruction/pathology , Palatine Tonsil/diagnostic imaging , Palatine Tonsil/pathology , Polysomnography , Severity of Illness Index , Sleep Apnea, Obstructive/pathology
10.
Obesity (Silver Spring) ; 21(7): 1446-50, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23408643

ABSTRACT

OBJECTIVE: Sleep-disordered breathing (SDB) is prevalent in obesity. Weight loss is one of the most effective treatment options. The aim was to assess the association of SDB and metabolic disruption before and after weight loss. DESIGN AND METHODS: Obese adolescents were included when entering an in-patient weight loss program. Fasting blood analysis was performed at baseline and after 4-6 months. Sleep screening was done at baseline and at follow-up in case of baseline SDB. RESULTS: 224 obese adolescents were included. Median age was 15.5 years (10.1-18.0) and mean BMI z-score was 2.74 ± 0.42. About 30% had SDB at baseline (N = 68). High-density lipoprotein (HDL)-cholesterol was associated with mean nocturnal oxygen saturation () (partial r = 0.21; P = 0.002). Aspartate aminotransferase (ASAT) and alanine aminotransferase were related with oxygen desaturation index (partial r = -0.15; P = 0.03 and partial r = -0.15; P = 0.02), but this became insignificant after correction for sex. After weight loss, 24% had residual SDB. Linear regression showed an association between ASAT and (partial r = -0.34; P = 0.002). There were no significant correlations between improvements in laboratory measurements and sleep parameters. HDL-cholesterol improved in relation with the decrease in BMI z-score. CONCLUSION: SDB at baseline was associated with higher levels of liver enzymes and lower HDL-cholesterol concentration. Improvements in sleep parameters were not associated with improvements in laboratory measurements.


Subject(s)
Obesity/physiopathology , Sleep Apnea Syndromes/physiopathology , Weight Loss , Adolescent , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Body Mass Index , Body Weight , Child , Cholesterol, HDL/blood , Humans , Linear Models , Obesity/therapy , Prevalence , Sleep Apnea Syndromes/therapy
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