Nocturnal oximetry in children with obstructive lung disease or sleep-disordered breathing.

OBJECTIVES: Although progress has been made in the standardized interpretation of nocturnal oximetry in children with obstructive sleep-disordered breathing (SDB), no evidence exists on oximetry abnormalities in other respiratory disorders. We aimed to compare obstructive lung disease (OLD) and SDB regarding nocturnal oximetry parameters. METHODS: We analyzed oximetry recordings from children with (i) OLD (obliterative bronchiolitis; cystic fibrosis); (ii) snoring and adenotonsillar hypertrophy (SDB); and (iii) no respiratory disorder (controls). The three groups were compared regarding: (i) oxygen desaturation of hemoglobin index (SpO2 drops ≥3%/h-ODI3) and (ii) basal SpO2 (average SpO2 between SpO2 drops). The associations of oximetry parameters (natural logarithm) with study group were tested using linear regression including age as covariate. RESULTS: Data of 16 subjects with OLD (median age: 7.3 years; Q25, Q75: 5.4, 12), 22 children with SDB (6.3 years; 4, 9) and 22 controls (6.8 years; 5.6, 10.3) were analyzed. Children with OLD or SDB had significantly lower basal SpO2 than controls (91.9% [90.8, 93.4] vs 96.3% [96, 97.4] vs 97.6% [97.1, 97.9]; P < 0.01). No subjects in the SDB or control groups had basal SpO2 < 95%. Children with SDB had significantly higher ODI3 than children with OLD or controls [8.4 episodes/h (6.2, 16.6) vs 4.4 episodes/h (3.6, 6.6) vs 2 episodes/h (1.3, 2.7); P < 0.01]. OLD had the greatest negative effect on basal SpO2 (R2 = 0.62; P < 0.001) and SDB the greatest positive effect on ODI3 (R2 = 0.34; P < 0.001). CONCLUSION: OLD is associated mostly with reduced basal SpO2 , whereas SDB is characterized by elevated ODI3.

Obstructive events in children with Prader-Willi syndrome occur predominantly during rapid eye movement sleep.

OBJECTIVE: Children with Prader-Willi syndrome (PWS) have a high prevalence of obstructive sleep apnea syndrome (OSAS). In most typically developing children with OSAS, more obstructive apneas and hypopneas occur during rapid eye movement (REM) than during non-REM (NREM) sleep. It was hypothesized that patients with PWS are even more prone to obstructive events in REM sleep than otherwise healthy subjects with OSAS. METHODS: Polysomnographic data of patients with PWS and of typically developing children (controls) with OSAS (apnea-hypopnea index [AHI] > 1 episode/h) were analyzed. The two groups were compared regarding obstructive AHI (OAHI), OAHI during NREM sleep (OAHInrem), OAHI during REM sleep (OAHIrem), and the OAHIrem/OAHI ratio (outcome measures). The association between PWS diagnosis and OAHIrem/OAHI was adjusted for confounders using a general linear model. RESULTS: Twelve children with PWS (median age 7.1 years [interquartile range 3.5, 12.4 years]) and 53 controls (6.5 years [3.9, 8.7 years]) were studied. Children with PWS and controls were similar regarding OAHI (p = 0.21) and OAHInrem (p = 0.76). However, subjects with PWS had higher OAHIrem (17.6 episodes/h [5.8, 25.8 episodes/h]) and OAHIrem/OAHI (2.3 [1.5, 3.2]) than controls (5 episodes/h [1.5, 8.1 episodes/h]; p = 0.002 and 1 [0.5, 2]; p = 0.003, respectively). The association between PWS diagnosis and higher OAHIrem/OAHI persisted after adjustment for age, gender, and obesity (p = 0.009). CONCLUSION: In children with PWS, OAHI calculated for total sleep time does not reflect OSAS severity during REM sleep, which on average can be twice as high. Mild OSAS in patients with PWS demonstrated by polygraphy without sleep staging may correspond to a moderately-to-severely increased OAHIrem.

ERS statement on obstructive sleep disordered breathing in 1- to 23-month-old children.

The present statement was produced by a European Respiratory Society Task Force to summarise the evidence and current practice on the diagnosis and management of obstructive sleep disordered breathing (SDB) in children aged 1-23 months. A systematic literature search was completed and 159 articles were summarised to answer clinically relevant questions. SDB is suspected when symptoms or abnormalities related to upper airway obstruction are identified. Morbidity (pulmonary hypertension, growth delay, behavioural problems) and coexisting conditions (feeding difficulties, recurrent otitis media) may be present. SDB severity is measured objectively, preferably by polysomnography, or alternatively polygraphy or nocturnal oximetry. Children with apparent upper airway obstruction during wakefulness, those with abnormal sleep study in combination with SDB symptoms (e.g. snoring) and/or conditions predisposing to SDB (e.g. mandibular hypoplasia) as well as children with SDB and complex conditions (e.g. Down syndrome, Prader-Willi syndrome) will benefit from treatment. Adenotonsillectomy and continuous positive airway pressure are the most frequently used treatment measures along with interventions targeting specific conditions (e.g. supraglottoplasty for laryngomalacia or nasopharyngeal airway for mandibular hypoplasia). Hence, obstructive SDB in children aged 1-23 months is a multifactorial disorder that requires objective assessment and treatment of all underlying abnormalities that contribute to upper airway obstruction during sleep.

When and why to treat the child who snores?

Obstructive sleep-disordered breathing (SDB) can result in cardiovascular and neurocognitive morbidity as well as adversely affect behavior, growth, quality of life, and nocturnal continence. This article summarizes the latest evidence regarding the morbidity related to obstructive SDB, commenting on the impact of severity of obstruction, that is, the difference in effects seen of moderate to severe obstructive sleep apnea syndrome (OSAS) compared to those of mild OSAS or primary snoring. The impact of therapy is discussed, focusing on which children are likely to benefit from treatment interventions; namely those with moderate or severe OSAS irrespective of the presence of morbidity, children with mild OSAS with associated morbidity or predictors of SDB persistence such as obesity, and children with complex conditions accompanied by upper airway obstruction like craniosynostosis and Prader-Willi syndrome. The co-existing conditions which may improve when treatment for obstructive SDB is offered are reviewed, while the clinical parameters associated with spontaneous improvement or resolution of obstructive SDB are discussed. The intention being to enable clinicians to make informed decisions on who should be treated, when and why. Pediatr Pulmonol. 2017;52:399-412. © 2016 Wiley Periodicals, Inc.

Obstructive sleep disordered breathing in 2- to 18-year-old children: diagnosis and management.

This document summarises the conclusions of a European Respiratory Society Task Force on the diagnosis and management of obstructive sleep disordered breathing (SDB) in childhood and refers to children aged 2-18 years. Prospective cohort studies describing the natural history of SDB or randomised, double-blind, placebo-controlled trials regarding its management are scarce. Selected evidence (362 articles) can be consolidated into seven management steps. SDB is suspected when symptoms or abnormalities related to upper airway obstruction are present (step 1). Central nervous or cardiovascular system morbidity, growth failure or enuresis and predictors of SDB persistence in the long-term are recognised (steps 2 and 3), and SDB severity is determined objectively preferably using polysomnography (step 4). Children with an apnoea-hypopnoea index (AHI) >5 episodes·h(-1), those with an AHI of 1-5 episodes·h(-1) and the presence of morbidity or factors predicting SDB persistence, and children with complex conditions (e.g. Down syndrome and Prader-Willi syndrome) all appear to benefit from treatment (step 5). Treatment interventions are usually implemented in a stepwise fashion addressing all abnormalities that predispose to SDB (step 6) with re-evaluation after each intervention to detect residual disease and to determine the need for additional treatment (step 7).

Expression of leukotriene biosynthetic enzymes in tonsillar tissue of children with obstructive sleep apnea: a prospective nonrandomized study.

IMPORTANCE: Cysteinyl leukotrienes (CysLTs) potentially promote adenotonsillar hypertrophy in children with obstructive sleep apnea (OSA). Previous studies have identified CysLTs and their receptors in tonsillar tissue from children with OSA. OBJECTIVE: To demonstrate expression of the leukotriene biosynthetic enzymes 5-lipoxygenase (5-LO), 5-lipoxygenase activating protein (FLAP), leukotriene A(4) hydrolase (LTA(4)H), and leukotriene C(4) synthase (LTC(4)S) in T and B tonsillar lymphocytes from pediatric patients with OSA. It was hypothesized that children with OSA have greater expression of biosynthetic enzymes for CysLTs (5-LO, FLAP, and LTC(4)S) in their tonsillar tissue than do children with recurrent tonsillitis (RT), who were enrolled as controls. DESIGN, SETTING, AND PARTICIPANTS: This prospective, nonrandomized study was performed at a tertiary care university hospital on 13 children with OSA and adenotonsillar hypertrophy undergoing adenotonsillectomy and 12 children without OSA also undergoing tonsillectomy for RT. Tonsillar tissue from children with OSA or RT was examined for 5-LO, FLAP, LTA(4)H, and LTC(4)S expression under real time-quantitative polymerase chain reaction (RT-qPCR), flow cytometry (FC), and confocal laser scanning microscopy (CM). MAIN OUTCOMES AND MEASURES: Expression of biosynthetic enzymes for CysLTs (5-LO, FLAP, and LTC(4)S) was the main outcome measure. Patients with OSA and control patients with RT were compared for numbers of copies of 5-LO, FLAP, and LTC(4)S messenger RNA (by RT-qPCR) in T or B tonsillar lymphocytes and proportions of CD3(+) or CD19(+) tonsillar lymphocytes that expressed 5-LO, FLAP, and LTC(4)S (by FC). RESULTS: Messenger RNA for all 4 enzymes was detected in T and B lymphocytes from both study groups, and expression of all biosynthetic enzymes was demonstrated in participants with OSA and RT by FC. Patients with OSA differed from controls in the proportions (median [10th-90th percentile]) of LTC(4)S(+) CD3(+) T lymphocytes (23.31% [8.64%-50.07%] vs 10.81% [3.48%-23.32%], respectively) (P = .01) and LTC(4)S(+) CD19(+) B lymphocytes (20.66% [14.62%-65.77%] vs 12.53% [2.87%-36.64%], respectively) (P = .01) detected by FC. Immunoreactivity for the 4 enzymes was detected by CM in B lymphocytes of mantle zones and T lymphocytes of extrafollicular areas. CONCLUSIONS AND RELEVANCE: Leukotriene biosynthetic enzymes are expressed in tonsillar lymphocytes, and the previously reported detection of CysLTs in tonsillar tissue from children with OSA may be attributed to endogenous synthesis. Enhanced expression of LTC(4)S is a potential target for pharmacologic interventions in OSA.

Poincaré plot width, morning urine norepinephrine levels, and autonomic imbalance in children with obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) in childhood is accompanied by sympathetic overflow unopposed by the parasympathetic tone. Complex methods like power spectral analysis of heart rate variability have been applied to study this imbalance. In this report, width of Poincaré scattergram of the R-R interval (parasympathetic tone) and morning urine norepinephrine concentration (sympathetic activity) were used to assess autonomic imbalance. METHODS: Poincaré plot was obtained from the electrocardiographic channel of nocturnal polysomnography and its width was measured, and norepinephrine-to-creatinine concentration ratio was calculated in morning urine specimen. RESULTS: Twenty children with obstructive sleep apnea and moderate-to-severe nocturnal hypoxemia (oxygen saturation of hemoglobin [SpO(2)] nadir <90%), 24 subjects with mild hypoxemia (SpO(2) nadir ≥90%), and 11 control subjects were recruited. Children with obstructive sleep apnea and moderate-to-severe hypoxemia had significantly narrower Poincaré plot width (318.7 ± 139.3 ms) and higher ln-transformed urine norepinephrine-to-creatinine ratio (4.5 ± 0.6) than control subjects (484.2 ± 104.4 ms and 3.8 ± 0.4, respectively; P < 0.05). Ln-transformed urine norepinephrine levels were inversely related to Poincaré plot width (P = 0.02). CONCLUSIONS: Subjects with obstructive sleep apnea and moderate-to-severe nocturnal hypoxemia have enhanced sympathetic activity and reduced parasympathetic drive. Poincaré plot width and urine norepinephrine levels are simple measures of autonomic imbalance in pediatric obstructive sleep apnea.

Insomnia symptoms, objective sleep duration and hypothalamic-pituitary-adrenal activity in children.

BACKGROUND: Insomnia symptoms are the most common parent-reported sleep complaints in children; however, little is known about the pathophysiology of childhood insomnia symptoms, including their association with hypothalamic-pituitary-adrenal (HPA) axis activation. The objective of this study is to examine the association between parent-reported insomnia symptoms, objective short sleep duration and cortisol levels in a population-based sample of school-aged children. DESIGN: A sample of 327 children from the Penn State Child Cohort (5-12 years old) underwent 9-h overnight polysomnography and provided evening and morning saliva samples to assay for cortisol. Objective short sleep duration was defined based on the median total sleep time (i.e., <7·7 h). Parent-reported insomnia symptoms of difficulty initiating and/or maintaining sleep were ascertained with the Pediatric Behavior Scale. RESULTS: Children with parent-reported insomnia symptoms and objective short sleep duration showed significantly increased evening (0·33±0·03 µg/dL) and morning (1·38±0·08 µg/dL) cortisol levels. In contrast, children with parent-reported insomnia symptoms and 'normal' sleep duration showed similar evening and morning cortisol levels (0·23±0·03 µg/dL and 1·13±0·08 µg/dL) compared with controls with 'normal' (0·28±0·02 µg/dL and 1·10±0·04 µg/dL) or short (0·28±0·02 µg/dL and 1·13±0·04 µg/dL) sleep duration. CONCLUSIONS: Our findings suggest that insomnia symptoms with short sleep duration in children may be related to 24-h basal or responsive physiological hyperarousal. Future studies should explore the association of insomnia symptoms with short sleep duration with physical and mental health morbidity.

Sleep apnoea, sleepiness, inflammation and insulin resistance in middle-aged males and females.

In obese males obstructive sleep apnoea (OSA) is associated with inflammation and insulin resistance; however, findings are confounded by adipose tissue, a hormone- and cytokine-secreting organ. Our goal was to examine whether in a relatively nonobese population, OSA is associated with sleepiness and inflammation/insulin resistance, and to assess the effects of a 2-month placebo-controlled continuous positive airway pressure (CPAP) use. 77 subjects, 38 middle-aged males and post-menopausal females with OSA and 39 male and female controls, were studied in the sleep laboratory for 4 nights. Measures of sleepiness (objective and subjective), performance, serial 24-h blood samples for interleukin (IL)-6, tumour necrosis factor receptor (TNFR)-1, leptin and adiponectin, and single samples for high-sensitivity C-reactive protein (hsCRP), fasting glucose and insulin levels were obtained. Apnoeic males were significantly sleepier and had significantly higher hsCRP, IL-6, leptin and insulin resistance than controls. Apnoeic females had significantly higher hsCRP; however, objective sleepiness, IL-6, TNFR-1, insulin resistance (Homeostatic Model Assessment index), leptin and adiponectin were similar to controls. CPAP improved subjective sleepiness, but no changes were observed in any of the biomarkers. In conclusion, OSA is associated with sleepiness, inflammation and insulin resistance, even in nonobese males, and this association is stronger in males than in females. Short-term CPAP does not improve the inflammatory/metabolic aberrations in OSA.

Effects of recovery sleep after one work week of mild sleep restriction on interleukin-6 and cortisol secretion and daytime sleepiness and performance.

One workweek of mild sleep restriction adversely impacts sleepiness, performance, and proinflammatory cytokines. Many individuals try to overcome these adverse effects by extending their sleep on weekends. To assess whether extended recovery sleep reverses the effects of mild sleep restriction on sleepiness/alertness, inflammation, and stress hormones, 30 healthy young men and women (mean age ± SD, 24.7 ± 3.5 yr; mean body mass index ± SD, 23.6 ± 2.4 kg/m(2)) participated in a sleep laboratory experiment of 13 nights [4 baseline nights (8 h/night), followed by 6 sleep restriction nights (6 h/night) and 3 recovery nights (10 h/night)]. Twenty-four-hour profiles of circulating IL-6 and cortisol, objective and subjective daytime sleepiness (Multiple Sleep Latency Test and Stanford Sleepiness Scale), and performance (Psychomotor Vigilance Task) were assessed on days 4 (baseline), 10 (after 1 wk of sleep restriction), and 13 (after 2 nights of recovery sleep). Serial 24-h IL-6 plasma levels increased significantly during sleep restriction and returned to baseline after recovery sleep. Serial 24-h cortisol levels during restriction did not change compared with baseline, but after recovery they were significantly lower. Subjective and objective sleepiness increased significantly after restriction and returned to baseline after recovery. In contrast, performance deteriorated significantly after restriction and did not improve after recovery. Extended recovery sleep over the weekend reverses the impact of one work week of mild sleep restriction on daytime sleepiness, fatigue, and IL-6 levels, reduces cortisol levels, but does not correct performance deficits. The long-term effects of a repeated sleep restriction/sleep recovery weekly cycle in humans remain unknown.

Age-dependent changes in the size of adenotonsillar tissue in childhood: implications for sleep-disordered breathing.

OBJECTIVE: To analyze age-associated changes in linear and cross-sectional area (CSA) measurements of adenoid, tonsils, and pharyngeal lumen. STUDY DESIGN: Measurements were completed in head magnetic resonance imaging examinations performed for diagnostic purposes. Linear and nonlinear regression models were applied to describe the effect of age on the size of soft tissues and upper airway. RESULTS: Magnetic resonance imaging data were analyzed in 149 children without snoring (aged 0-15.9 years) and in 33 children with snoring (aged 1.6-15 years). In the children without snoring, adenoid size increased during the first 7-8 years of life and then decreased gradually [% (adenoid oblique width/mental spine-clivus length) = 11.38 + 1.52 (age) - 0.11 (age)(2), R(2) = 0.22, P < .01; adenoid CSA = 90.75 + 41.93 (age) - 2.47 (age)(2); R(2) = 0.50; P < .01]. Nasopharyngeal airway CSA increased slowly up to age 8 years and rapidly thereafter. Similar patterns were noted for the tonsils and oropharyngeal airway. In contrast, in children with snoring, adenoid and tonsils were large irrespective of age, and nasopharyngeal airway size increased slowly with age. CONCLUSIONS: In children without snoring, growing adenotonsillar tissue narrows the upper airway lumen to variable degrees only during the first 8 years of life. In contrast, in children with snoring, appreciable pharyngeal lymphoid tissue enlargement is present during the preschool years and persists beyond the eighth birthday.

Cysteinyl leukotriene receptors in tonsillar B- and T-lymphocytes from children with obstructive sleep apnea.

OBJECTIVES: Cysteinyl leukotrienes have been implicated in the pathogenesis of adenotonsillar hypertrophy in children with obstructive sleep apnea (OSA). This study aimed to quantify the expression of cysteinyl leukotriene receptors (CysLT(1), CysLT(2)) by tonsillar lymphocyte subpopulations from children with OSA and to make comparisons to lymphocyte subpopulations from control subjects with recurrent tonsillitis (RT). METHODS: Tonsillar tissue from children with OSA or RT was studied for CysLT(1) and CysLT(2) expression by RT-PCR, flow cytometry (FC), and immunofluorescence. RESULTS: Ten children with OSA and 10 control subjects were recruited. In OSA participants, CysLT(1)+ fraction of small-size CD19+ B-lymphocytes was similar to the CysLT(1)+ CD3+ T-lymphocytes fraction (FC: 36.5 [16.5-55.4] vs. 14 [2.8-22.1]) (p>0.05) and higher than the CysLT(1)+ moderate/large-size CD19+ B-lymphocytes fraction (6.6 [1.5-14.4]) (p<0.01). Similar trends were recognized for CysLT(2). CysLT(1) and CysLT(2) immunoreactivity was detected by immunofluorescence in the tonsillar mantle zones (small B-lymphocytes) and the extrafollicular areas (T-lymphocytes). Compared to subjects with RT, children with OSA had significantly higher expression of CysLT(1) in small-size CD19+ B-lymphocytes (FC) and in CD3+ T-lymphocytes (RT-PCR and FC) (p<0.05). CONCLUSIONS: Increased expression of leukotriene receptors by immunologically active tonsillar areas in children with OSA is a potential therapeutic target for pediatric sleep apnea.

Learning, attention/hyperactivity, and conduct problems as sequelae of excessive daytime sleepiness in a general population study of young children.

STUDY OBJECTIVES: Although excessive daytime sleepiness (EDS) is a common problem in children, with estimates of 15%; few studies have investigated the sequelae of EDS in young children. We investigated the association of EDS with objective neurocognitive measures and parent reported learning, attention/hyperactivity, and conduct problems in a large general population sample of children. DESIGN: Cross-sectional. SETTING: Population based. PARTICIPANTS: 508 children from The Penn State Child Cohort. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Children underwent a 9-h polysomnogram, comprehensive neurocognitive testing, and parent rating scales. Children were divided into 2 groups: those with and without parent-reported EDS. Structural equation modeling was used to examine whether processing speed and working memory performance would mediate the relationship between EDS and learning, attention/hyperactivity, and conduct problems. Logistic regression models suggest that parent-reported learning, attention/hyperactivity, and conduct problems, as well as objective measurement of processing speed and working memory are significant sequelae of EDS, even when controlling for AHI and objective markers of sleep. Path analysis demonstrates that processing speed and working memory performance are strong mediators of the association of EDS with learning and attention/hyperactivity problems, while to a slightly lesser degree are mediators from EDS to conduct problems. CONCLUSIONS: This study suggests that in a large general population sample of young children, parent-reported EDS is associated with neurobehavioral (learning, attention/hyperactivity, conduct) problems and poorer performance in processing speed and working memory. Impairment due to EDS in daytime cognitive and behavioral functioning can have a significant impact on children's development.

Mediterranean diet and metabolic syndrome in an urban population: the Athens Study.

BACKGROUND: Previous studies demonstrated the beneficial impact of the Mediterranean diet (MedDiet) on metabolic syndrome (MetS). The aim of this study was to retrospectively investigate the association between MedDiet and MetS in a representative sample of the Athenian population in the early 1980s, when MetS had not been established as an entity yet. METHODS: In a cross-sectional epidemiologic survey of cardiovascular disease (CVD), 2,074 randomly selected adults were examined: 900 men and 1,174 women (age, 46.9 ± 14.9 years). MetS was defined according to criteria of the National Cholesterol Education Program-Adult Treatment Panel III. A validated questionnaire concerning nutrition habits was administered, and MedDiet was assessed according to guidelines of the Division of Nutrition/Epidemiology, Athens University Medical School. RESULTS: Overall, 1,023 participants (49.3%) followed MedDiet (47.3% men, 52.0% women, P = .033) with similar rates across age groups (P = .337). MetS was diagnosed in 24.0% of those following MedDiet, compared with 27.9% of those not following it (P = .041). Participants with CVD or diabetes mellitus were less likely to follow MedDiet (43% vs 50%, P = .009). Multivariate analysis revealed that MedDiet is associated with a 20% reduction in MetS (odds ratio = 0.80, 95% confidence interval = 0.65-0.98), after adjustment for age, gender, smoking, light physical activity, serum levels of low-density lipoprotein cholesterol and γ-glutamyl transferase, diabetes mellitus, CVD, family history of hypertension, and/or hyperlipidemia. CONCLUSIONS: Results indicate that adherence to MedDiet may attenuate the prevalence of MetS and, consequently, the increasing burden of diabetes mellitus and CVD, especially in urban populations.

Prevalence and risk factors of excessive daytime sleepiness in a community sample of young children: the role of obesity, asthma, anxiety/depression, and sleep.

STUDY OBJECTIVES: We investigated the prevalence and association of excessive daytime sleepiness (EDS) with a wide range of factors (e.g., medical complaints, obesity, objective sleep [including sleep disordered breathing], and parent-reported anxiety/depression and sleep difficulties) in a large general population sample of children. Few studies have researched the prevalence and predictors of EDS in young children, none in a general population sample of children, and the results are inconsistent. DESIGN: Cross-sectional SETTING: Population -based. PARTICIPANTS: 508 school-aged children from the general population. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Children underwent a 9-hour polysomnogram (PSG), physical exam, and parent completed health, sleep and psychological questionnaires. Children were divided into 2 groups: those with and without parent reported EDS. The prevalence of subjective EDS was approximately 15%. Significant univariate relationships were found between children with EDS and BMI percentile, waist circumference, heartburn, asthma, and parent reported anxiety/depression, and sleep difficulties. The strongest predictors of EDS were waist circumference, asthma, and parent-reported symptoms of anxiety/depression and trouble falling asleep. All PSG sleep variables including apnea/hypopnea index, caffeine consumption, and allergies were not significantly related to EDS. CONCLUSIONS: It appears that the presence of EDS is more strongly associated with obesity, asthma, parent reported anxiety/depression, and trouble falling asleep than with sleep disordered breathing (SDB) or objective sleep disruption per se. Our findings suggest that children with EDS should be thoroughly assessed for anxiety/depression, nocturnal sleep difficulties, asthma, obesity, and other metabolic factors, whereas objective sleep findings may not be as clinically useful.

Prenatal and perinatal complications: is it the link between race and SES and childhood sleep disordered breathing?

STUDY OBJECTIVES: Recent evidence has suggested that low socioeconomic status (SES), race, prematurity, and maternal smoking during pregnancy are associated with childhood sleep disordered breathing (SDB). We investigated (1) the association of SDB with a wide range of risk factors, including prenatal and perinatal complications; (2) the association of these complications with SES and race; and (3) the association of SDB with developmental milestones. METHODS: Six hundred thirteen school-aged children (105 clinically referred and 508 community control subjects) underwent overnight polysomnography and had a complete history and physical examination. A comprehensive child development questionnaire was completed by a parent. We compared clinically referred children with SDB to population-based control children without SDB from The Penn State Children's Cohort. RESULTS: Maternal smoking during pregnancy; maternal age and weight gain during pregnancy; prenatal complications, such as maternal high blood pressure and gestational diabetes; perinatal complications related to prematurity; delayed motor milestones; race and SES were significantly associated with the presence of childhood SDB. Most of the risk factors became nonsignificant when analyses controlled for race and SES. Delayed motor milestones remained significantly associated with SDB after controlling for race and SES. CONCLUSION: These data suggest that there is a significant association between children who experience prenatal or perinatal distress and the development of moderate to severe childhood SDB. SES and race may be mediating the impact on SDB through increased prenatal and perinatal risks. The significant delay in motor milestones suggests that prenatal and perinatal distress may result in neurologic insult, which could influence the development of SDB in later childhood.

Leptin and hunger levels in young healthy adults after one night of sleep loss.

Short-term sleep curtailment associated with activation of the stress system in healthy, young adults has been shown to be associated with decreased leptin levels, impaired insulin sensitivity, and increased hunger and appetite. To assess the effects of one night of sleep loss in a less stressful environment on hunger, leptin, adiponectin, cortisol and blood pressure/heart rate, and whether a 2-h mid-afternoon nap reverses the changes associated with sleep loss, 21 young healthy individuals (10 men, 11 women) participated in a 7-day sleep deprivation experiment (four consecutive nights followed by one night of sleep loss and two recovery nights). Half of the subjects were randomly assigned to take a mid-afternoon nap (14:00-16:00 hours) the day following the night of total sleep loss. Serial 24-h blood sampling and hunger scales were completed on the fourth (predeprivation) and sixth day (postdeprivation). Leptin levels were significantly increased after one night of total sleep loss, whereas adiponectin, cortisol levels, blood pressure/heart rate, and hunger were not affected. Daytime napping did not influence the effects of sleep loss on leptin, adiponectin, or hunger. Acute sleep loss, in a less stressful environment, influences leptin levels in an opposite manner from that of short-term sleep curtailment associated with activation of the stress system. It appears that sleep loss associated with activation of the stress system but not sleep loss per se may lead to increased hunger and appetite and hormonal changes, which ultimately may lead to increased consumption of 'comfort' food and obesity.

Sleep-disordered breathing in obese children is associated with prevalent excessive daytime sleepiness, inflammation, and metabolic abnormalities.

BACKGROUND: In obese adults, sleep apnea is associated with excessive daytime sleepiness (EDS) and cardiometabolic risk factors. In children, on the other hand, sleep-disordered breathing (SDB) is primarily associated with anatomic abnormalities and neurocognitive impairment, whereas studies on potential concurrent metabolic aberrations and EDS have been limited and inconsistent. In this study, we examined the joint effect of SDB and obesity in EDS as well as proinflammatory and metabolic markers. METHODS: One hundred fifty children, aged 5-17 yr, were consecutively recruited from our sleep disorders clinic and a subset of the Penn State Children's Cohort. Every child had a thorough history and physical examination, 9-h polysomnographic study, and a single blood draw for the assessment of IL-6, TNFalpha, soluble IL-6 receptor, TNF receptor-1, hypersensitive C-reactive protein, leptin, and adiponectin. In addition, parents completed a subjective questionnaire to assess EDS. Analysis of covariance was performed on four groups that were separated by SDB severity and body mass index. RESULTS: EDS frequency increased progressively and significantly in the four groups. There was a significant linear trend in plasma IL-6, TNF receptor-1, hypersensitive C-reactive protein, and leptin concentrations, with lowest levels observed in lean controls and highest in overweight/obese with moderate SDB. Adiponectin followed the opposite pattern. CONCLUSIONS: This study suggests that in a clinical sample of obese children, SDB is associated with EDS, elevation of proinflammatory cytokines, increased leptin, and decreased adiponectin. All these changes point to an inflammatory/insulin resistance state, suggesting that SDB in obese children share many similarities with SDB in obese adults.

No relationship between neurocognitive functioning and mild sleep disordered breathing in a community sample of children.

STUDY OBJECTIVES: Our objective was to examine the relationship between sleep disordered breathing (SDB) and neurocognitive functioning in a large general-population sample of children who underwent a full-night polysomnogram and comprehensive neuropsychological testing. METHODS: A population-based study of 571 school-aged children (6-12 years) underwent a 9-hour polysomnogram and a comprehensive neuropsychological battery. RESULTS: No significant relationship was found between children with a mild apnea-hypopnea index (1 < or = apnea-hypopnea index < 5) and any measure of neuropsychological functioning (intelligence, verbal and nonverbal reasoning ability, attention, executive functioning, memory, processing speed, and visual-motor skill). Partial correlations between apnea-hypopnea index and neuropsychological test scores and polynominal trend analysis were all nonsignificant. CONCLUSIONS: Children with mild SDB showed no significant neuropsychological impairment compared to children without SDB. This study suggests that children with mild SDB are not at risk for neuropsychological impairment and that the coexistence of mild SDB with any neuropsychological impairment should be considered comorbid and not causal. However, the association between neurobehavioral issues and children with mild SDB remains uncertain.

Medical complaints are more common in young school-aged children with parent reported insomnia symptoms.

OBJECTIVE: Studies in adults have found significant association between sleep disturbances and various medical symptoms/disorders. However, in children, few studies have explored this complex association in clinical samples. In this study, we examined prevalence of medical complaints in children with insomnia symptoms in a large general population of school aged children. METHODS: We conducted a cross sectional study of 700 children, ages 5-12 years, from the Penn State Children's Cohort. All children underwent a medical and psychiatric history, physical examination, 9-h overnight polysomnography, and neuropsychological testing. Comprehensive sleep and development questionnaires were completed by a parent. We compared 135 (19.3%) children with parent-reported sleep disturbances to 565 (80.7%) children with no parent-reported sleep disturbances. RESULTS: Insomnia symptoms were significantly associated with gastrointestinal regurgitation and headaches after controlling for demographic variables, apnea hypopnea index, ADHD, learning disorder or other psychiatric/behavioral disorder, socioeconomic status, and minority status. Children with gastrointestinal regurgitation and headaches compared to children without these symptoms were 3.3 times and 2.3 times as likely to suffer from sleep disturbances, respectively. Objectively, sleep latency increased in the sleep disturbance group, and there were significant differences between groups in REM latency, slow wave, and stage 2 sleep. DISCUSSION: These results underscore the importance of inquiring about insomnia symptoms when children present with medical complaints particularly gastrointestinal regurgitation or headaches and taking a comprehensive medical history when children present with sleep complaints. Future studies are needed to replicate these findings and explore the possible underlying pathophysiological abnormalities of such comorbidity between insomnia symptoms and medical symptoms in children.