Annelies Van Eyck

Upper airway imaging in pediatric obstructive sleep apnea syndrome

Obstructive sleep apnea syndrome in children is a manifestation of sleep-disordered breathing and associated with a number of complications. Structural narrowing of the upper airway in combination with inadequate compensation for a decrease in neuromuscular tone is an important factor in the pathogenesis. Adenotonsillar hypertrophy is the most important predisposing factor. However, many other causes of craniofacial defects may coexist. Additionally, the pathogenesis of narrowing is more complex in certain subgroups such as children with obesity, craniofacial malformations, Down syndrome or neuromuscular disorders. The diagnosis of obstructive sleep apnea is based on an overnight polysomnography. This investigation is expensive, time consuming and not widely available. In view of the major role of structural narrowing, upper airway imaging could be a useful tool for investigating obstructive sleep apnea and in establishing the site(s) of obstruction. Several radiological techniques (lateral neck radiography, cephalometry, computerized tomography, magnetic resonance imaging and post-processing of these images using computational fluid dynamics) have been used to investigate the role of structural alterations in the pathogenesis. We reviewed the literature to examine if upper airway imaging could replace polysomnography in making the diagnosis and if imaging could predict the effect of treatment with a focus on adenotonsillectomy. There is a limited number of high quality studies of imaging predicting the effect of treatment. To avoid unnecessary risks and ineffective surgeries, it seems crucial to couple the exact individual anatomical risk factor with the most appropriate treatment. We conclude that imaging could be a non-invasive tool that could assist in selection of treatment.

Nocturnal Oximetry–based Evaluation of Habitually Snoring Children

Rationale: The vast majority of children around the world undergoing adenotonsillectomy for obstructive sleep apnea‐hypopnea syndrome (OSA) are not objectively diagnosed by nocturnal polysomnography because of access availability and cost issues. Automated analysis of nocturnal oximetry (nSpO2), which is readily and globally available, could potentially provide a reliable and convenient diagnostic approach for pediatric OSA. Methods: Deidentified nSpO2 recordings from a total of 4,191 children originating from 13 pediatric sleep laboratories around the world were prospectively evaluated after developing and validating an automated neural network algorithm using an initial set of single‐channel nSpO2 recordings from 589 patients referred for suspected OSA. Measurements and Main Results: The automatically estimated apnea‐hypopnea index (AHI) showed high agreement with AHI from conventional polysomnography (intraclass correlation coefficient, 0.785) when tested in 3,602 additional subjects. Further assessment on the widely used AHI cutoff points of 1, 5, and 10 events/h revealed an incremental diagnostic ability (75.2, 81.7, and 90.2% accuracy; 0.788, 0.854, and 0.913 area under the receiver operating characteristic curve, respectively). Conclusions: Neural network‐based automated analyses of nSpO2 recordings provide accurate identification of OSA severity among habitually snoring children with a high pretest probability of OSA. Thus, nocturnal oximetry may enable a simple and effective diagnostic alternative to nocturnal polysomnography, leading to more timely interventions and potentially improved outcomes.

Sleep-disordered breathing and C-reactive protein in obese children and adolescents

PurposeSleep-disordered breathing (SDB) is common among overweight and obese children. It is a risk factor for several health complications, including cardiovascular disease. Inflammatory processes leading to endothelial dysfunction are a possible mechanism linking SDB and cardiovascular disease. Elevated C-reactive protein (CRP) is a risk factor for cardiovascular disease and is independently correlated with obstructive sleep apnea syndrome (OSAS) in adults. Our goal is to evaluate the relationship between CRP and OSAS in overweight and obese children and adolescents.MethodsOne hundred and twenty children were prospectively studied (85 without OSAS, 20 mild OSAS, 15 moderate-to-severe OSAS). All subjects underwent polysomnography, and a blood sample was taken to determine CRP levels.ResultsNo significant differences were found in CRP between subjects with or without OSAS, and no correlations were found between CRP and OSAS severity, despite the relationship between CRP and BMI (r = 0.21, p = 0.015) and between CRP and fat mass (r = 0.31, p < 0.001).ConclusionThese results suggest that CRP levels are correlated with the level of obesity but are not influenced by SDB in obese children and adolescents; hence, this in contrast to that in adult population.

Sleep-disordered breathing, systemic adipokine secretion, and metabolic dysregulation in overweight and obese children and adolescents

OBJECTIVE Obstructive sleep apnea (OSA) is common among overweight and obese children, and it is an independent risk factor for developing metabolic syndrome. However, the mechanisms linking OSA and metabolic syndrome are still unclear, but a role for adipose tissue dysfunction caused by intermittent hypoxia has been suggested. Therefore, the goal of this study was to investigate the relationship between OSA and systemic adipokine concentrations in overweight and obese children. METHODS We included 164 overweight and obese children in a tertiary center and distributed them in groups based on their obstructive apnea-hypopnea index (111 controls, 28 mild OSA, 25 moderate-to-severe OSA). All subjects underwent polysomnography and a blood sample was taken to determine leptin, adiponectin, tumor necrosis factor alpha, and interleukin-6 levels. RESULTS No significant differences were found in adipokine levels between subjects with or without OSA. Leptin correlated with oxygen desaturation index (r = -0.17, p = 0.03), adiponectin correlated with mean oxygen saturation (r = 0.24, p = 0.002) and with the percentage of sleep time with an oxygen saturation >95% (r = 0.25, p = 0.001). However, these associations did not persist after correction for adiposity. No correlations between interleukin-6 and tumor necrosis factor alpha, and OSA severity were found. CONCLUSION These results suggest that serum adipokine levels are mostly dependent on central obesity, while they are not influenced by OSA in an obese pediatric population.

Sleep disordered breathing and autonomic function in overweight and obese children and adolescents

Obstructive sleep apnoea (OSA), common in children with obesity, is associated with cardiovascular morbidity. Autonomic dysfunction has been suggested to be a key player in the development of these complications. We investigated the relationship between obesity, OSA and sympathetic activity in children. 191 children with obesity were included and distributed into two groups: 131 controls and 60 with OSA. Beat-to-beat RR interval data were extracted from polysomnography for heart rate variability analysis. Urinary free cortisol levels were determined. Urinary free cortisol did not differ between groups and was not associated with OSA, independent of the level of obesity. Differences in heart rate variability measures were found: mean RR interval decreased with OSA, while low/high-frequency band ratio and mean heart rate increased with OSA. Heart rate variability measures correlated with OSA, independent of obesity parameters and age: oxygen desaturation index correlated with mean heart rate (r=0.19, p=0.009) and mean RR interval (r= −0.18, p=0.02), while high-frequency bands and low/high-frequency band ratio correlated with arterial oxygen saturation measured by pulse oximetry (SpO2) (r= −0.20, p=0.008 and r= −0.16, p=0.04) and SpO2 nadir (r=0.23, p=0.003 and r= −0.19, p=0.02). These results suggest that sympathetic heart activity is increased in children with obesity and OSA. Measures of hypoxia were related to increased sympathetic tone, suggesting that intermittent hypoxia is involved in autonomic dysfunction. Sympathetic heart activity is increased in children with obstructive sleep apnoea and obesity http://ow.ly/iSVc305AZRv

Clinical Predictors of Residual Sleep Apnea after Weight Loss Therapy in Obese Adolescents

Objective To investigate clinical factors that could predict residual sleep‐disordered breathing (SDB) after weight loss. Study design Obese subjects between 10 and 19 years of age were recruited while entering an in‐patient weight loss treatment program. All subjects underwent anthropometry and sleep screening using a portable device at baseline and after 4‐6 months of therapy. Sleep and International Study of Asthma and Allergies in Childhood questionnaires were completed at baseline. Results A total of 339 patients were included. Median age was 15.4 years (10.1‐19.1). Body mass index z score at baseline was 2.75 ± 0.42, and 35% of subjects were boys. SDB was present in 32%. After a mean decrease in body mass index z score of 32%, residual SDB was found in 20% of subjects with SDB at baseline. Subjects with more severe SDB (OR 1.18; CI 1.01‐1.34; P = .02) and respiratory allergies (OR 7.85; CI 1.20‐51.39; P = .03) were at higher risk of developing residual SDB, unlike age, sex, and anthropometric variables. Conclusions Weight loss was successful for treating SDB in 80% of patients. More severe SDB and the presence of respiratory allergies at baseline were associated with a higher risk of residual SDB after weight loss.

Longitudinal Study of the Role of Epidermal Growth Factor on the Fractional Excretion of Magnesium in Children: Effect of Calcineurin Inhibitors

Background: It was shown in animal models and adults that the epidermal growth factor (EGF) is involved in the pathophysiology of calcineurin inhibitor (CNI) induced renal magnesium loss. In children, however, the exact mechanism remains unclear, which was set as the purpose of the present study. Methods: Children with nephrotic syndrome and renal transplant children treated with CNI (n = 50) and non-CNI treated children (n = 46) were included in this study. Urine and serum samples were collected at three time points to determine magnesium, creatinine, and EGF. The magnesium intake was calculated from a food frequency questionnaire. Results: Serum Mg2+ and urinary EGF/creatinine were significantly lower in the CNI treated children, with significantly more CNI-treated children developing hypomagnesaemia. In the latter patients, the fractional excretion of magnesium (FE Mg2+) was significantly higher. Urinary EGF, age, renal function, and serum magnesium were independent predictors of the FE Mg2+. Only 29% of the children reached the recommended daily intake of magnesium. The magnesium intake did not differ between hypomagnesemic and normomagnesemic patients and was not a predictor of the FE Mg2+. Conclusions: In CNI-treated children who developed hypomagnesemia, the FE Mg2+ was increased. The urinary EGF concentration, age, and renal function are independent predictors of the FE Mg2+.

Improving the diagnosis of obstructive sleep apnea in children with nocturnal oximetry-based evaluations

Sleep-disordered breathing (SDB) includes a spectrum of clinical entities that can be defined as a clinically relevant disturbance of nocturnal breathing patterns, and includes primary snoring, upper airway resistance syndrome, and obstructive sleep apnea (OSA). OSA is considered the end of the spectrum of SDB [1], and is characterized by intermittent cycles of upper airway collapse usually associated with intermittent desaturations and arousal during sleep. It is a prevalent disorder in childhood, affecting 2–3% of children [2]. Several factors can predispose children to OSA, including adenotonsillar hypertrophy, neuromuscular disorders, craniofacial abnormalities, and obesity. Consequently, certain subgroups of children for example children with obesity and Down syndrome exhibit a higher prevalence of OSA [1]. Several complications are associated with OSA in childhood, including cardiovascular, metabolic, and neurocognitive complications. Ultimately, these complications can diminish the general health and quality of life of these children. Therefore, a timely diagnosis of OSA is important for appropriate treatment. Furthermore, it is also of clinical importance to determine the severity of the disease since moderate-to severe OSA is less likely to resolve on its own, and treatment is essential [3]. Polysomnography (PSG) is the current gold standard for the diagnosis of OSA in children. During this investigation, sleep architecture, gas exchange, respiratory events, arousals, heart rate, and body position are measured. Although PSG is an indispensable diagnostic tool in sleep medicine, it is associated with several disadvantages. First, it is an expensive investigation that is time consuming and labor intensive. Furthermore, it is not universally available, especially in resource-constrained environments. The limited availability of sleep centers may also result in long waiting lists. As a result, a timely diagnosis of OSA is not always possible. Nocturnal pulse oximetry has been proposed as an abbreviated and low-cost screening method for SDB both in adults and children. Brouillette et al. [4] were the first to investigate the feasibility of nocturnal pulse oximetry as a diagnostic tool for OSA. Since then, several studies around this topic have been initiated. In a recent systematic review by Kaditis et al., these studies on the use of nocturnal pulse oximetry for diagnosing OSA in children were discussed [5]. They concluded that overnight oximetry is useful for the diagnosis of OSA, as most studies in otherwise healthy children referred to a pediatric sleep clinic for suspected OSA had a good positive predictive value (range: 84–98%) and specificity (range: 60–99%). Moreover, it was concluded that oximetry can facilitate treatment decisions and help predict postadenotonsillectomy complications in children. Overall, it was concluded that a desaturation index of more than two episodes per hour can predict both mild and moderate-to-severe OSA, while criteria based on clusters of desaturations as described by Brouillette et al. [4], and the McGill oximetry score can predict moderate-to-severe OSA. However, not all reports are in agreement and it seems that overnight oximetry is less reliable in certain subgroups of children. It remains essential to study the role of pulse oximetry in subgroups of children, as different abnormalities in nocturnal oximetry could occur in different subgroups. For example, a study in obese children showed that nocturnal oximetry alone is insufficient for a diagnosis of OSA [6]. Oximetry seems less reliable in predicting the presence of OSA in obese children compared to normal-weight children. This could be attributed to the fact that overweight and obesity can be associated with the presence of sleep-related hypoxia even in the absence of OSA [7]. Also in patients with Down syndrome, oximetry seems to be less reliable as it has a higher night-to-night variability compared to other children [8]. In the paper by Pavone and colleagues, a good night-to-night consistency of nocturnal oximetry was described in otherwise normal children referred for suspected SDB [9]. The discrepancy between these papers again demonstrates that nocturnal oximetry can have a different outcome in specific subgroups of children. There have been attempts to determine normative data for oximetry across the pediatric age spectrum. Scholle et al. [10] described that the 90th percentile for the oxygen desaturation index ≥3% was 2.2 events/hour during the second year of life; less than 1.2 events/hour for ages 2–10 years; and less than 0.5 events/hour for children ages 11–18 years. An important