Leila Kheirandish-Gozal

National Sleep Foundation’s sleep time duration recommendations: methodology and results summary

OBJECTIVE The objective was to conduct a scientifically rigorous update to the National Sleep Foundations sleep duration recommendations. METHODS The National Sleep Foundation convened an 18-member multidisciplinary expert panel, representing 12 stakeholder organizations, to evaluate scientific literature concerning sleep duration recommendations. We determined expert recommendations for sufficient sleep durations across the lifespan using the RAND/UCLA Appropriateness Method. RESULTS The panel agreed that, for healthy individuals with normal sleep, the appropriate sleep duration for newborns is between 14 and 17 hours, infants between 12 and 15 hours, toddlers between 11 and 14 hours, preschoolers between 10 and 13 hours, and school-aged children between 9 and 11 hours. For teenagers, 8 to 10 hours was considered appropriate, 7 to 9 hours for young adults and adults, and 7 to 8 hours of sleep for older adults. CONCLUSIONS Sufficient sleep duration requirements vary across the lifespan and from person to person. The recommendations reported here represent guidelines for healthy individuals and those not suffering from a sleep disorder. Sleep durations outside the recommended range may be appropriate, but deviating far from the normal range is rare. Individuals who habitually sleep outside the normal range may be exhibiting signs or symptoms of serious health problems or, if done volitionally, may be compromising their health and well-being.

Adenotonsillectomy outcomes in treatment of obstructive sleep apnea in children: a multicenter retrospective study.

RATIONALE The overall efficacy of adenotonsillectomy (AT) in treatment of obstructive sleep apnea syndrome (OSAS) in children is unknown. Although success rates are likely lower than previously estimated, factors that promote incomplete resolution of OSAS after AT remain undefined. OBJECTIVES To quantify the effect of demographic and clinical confounders known to impact the success of AT in treating OSAS. METHODS A multicenter collaborative retrospective review of all nocturnal polysomnograms performed both preoperatively and postoperatively on otherwise healthy children undergoing AT for the diagnosis of OSAS was conducted at six pediatric sleep centers in the United States and two in Europe. Multivariate generalized linear modeling was used to assess contributions of specific demographic factors on the post-AT obstructive apnea-hypopnea index (AHI). MEASUREMENTS AND MAIN RESULTS Data from 578 children (mean age, 6.9 +/- 3.8 yr) were analyzed, of which approximately 50% of included children were obese. AT resulted in a significant AHI reduction from 18.2 +/- 21.4 to 4.1 +/- 6.4/hour total sleep time (P < 0.001). Of the 578 children, only 157 (27.2%) had complete resolution of OSAS (i.e., post-AT AHI <1/h total sleep time). Age and body mass index z-score emerged as the two principal factors contributing to post-AT AHI (P < 0.001), with modest contributions by the presence of asthma and magnitude of pre-AT AHI (P < 0.05) among nonobese children. CONCLUSIONS AT leads to significant improvements in indices of sleep-disordered breathing in children. However, residual disease is present in a large proportion of children after AT, particularly among older (>7 yr) or obese children. In addition, the presence of severe OSAS in nonobese children or of chronic asthma warrants post-AT nocturnal polysomnography, in view of the higher risk for residual OSAS.

Metabolic Alterations and Systemic Inflammation in Obstructive Sleep Apnea among Nonobese and Obese Prepubertal Children

RATIONALE Obstructive sleep apnea (OSA) has been associated with a higher prevalence and severity of the metabolic syndrome in adult patients, even after controlling for obesity. In contrast, OSA in prepubertal children does not appear to correlate with the magnitude of such metabolic derangements. OBJECTIVES To further establish the potential mechanistic role of OSA in metabolic regulation in prepubertal children. METHODS Fasting glucose, insulin, C-reactive protein, apolipoprotein B, and serum lipid concentrations were determined during the initial polysomnographic diagnosis of OSA and 6-12 months after adenotonsillectomy in both obese and nonobese children. MEASUREMENTS AND MAIN RESULTS Sixty-two children with OSA (37 obese and 25 nonobese), age 7.40 +/- 2.6 years (mean +/- SD) completed the study. After adenotonsillectomy, significant improvements in apnea-hypopnea index and sleep fragmentation occurred, particularly among nonobese children. In nonobese children, adenotonsillectomy was associated with mild increases in body mass index z scores, no changes in either fasting glucose or insulin, significant increases in high-density lipoprotein and reciprocal decreases in low-density lipoprotein, and reductions in plasma C-reactive protein and apolipoprotein B levels. In obese children, adenotonsillectomy did not result in body mass index or glucose changes, but was associated with marked improvements in all other measures. CONCLUSIONS OSA does not appear to induce insulin resistance in nonobese pediatric patients but seems to play a significant role in obese patients. The significant improvements in lipid profiles, C-reactive protein, and apolipoprotein B after adenotonsillectomy in the two groups suggest a pathogenic role for OSA in lipid homeostasis and systemic inflammation independent of the degree of adiposity.

National Sleep Foundation's updated sleep duration recommendations: final report ☆

OBJECTIVE To make scientifically sound and practical recommendations for daily sleep duration across the life span. METHODS The National Sleep Foundation convened a multidisciplinary expert panel (Panel) with broad representation from leading stakeholder organizations. The Panel evaluated the latest scientific evidence and participated in a formal consensus and voting process. Then, the RAND/UCLA Appropriateness Method was used to formulate sleep duration recommendations. RESULTS The Panel made sleep duration recommendations for 9 age groups. Sleep duration ranges, expressed as hours of sleep per day, were designated as recommended, may be appropriate, or not recommended. Recommended sleep durations are as follows: 14-17 hours for newborns, 12-15 hours for infants, 11-14 hours for toddlers, 10-13 hours for preschoolers, 9-11 hours for school-aged children, and 8-10 hours for teenagers. Seven to 9 hours is recommended for young adults and adults, and 7-8 hours of sleep is recommended for older adults. The self-designated basis for duration selection and critical discussions are also provided. CONCLUSIONS Consensus for sleep duration recommendations was reached for specific age groupings. Consensus using a multidisciplinary expert Panel lends robust credibility to the results. Finally, limitations and caveats of these recommendations are discussed.

Intranasal Budesonide Treatment for Children With Mild Obstructive Sleep Apnea Syndrome

OBJECTIVES. Intranasal corticosteroids have been advanced as a nonsurgical therapeutic alternative for pediatric obstructive sleep apnea syndrome, particularly for patients with mild disease, and aims at reducing the size of hypertrophic adenotonsillar tissue. METHODS. Of 71 possible candidates, 62 children with polysomnographically diagnosed mild obstructive sleep apnea syndrome were recruited onto a double-blind, randomized, crossover trial of intranasal budesonide (32 μg per nostril at bedtime) or placebo for 6 weeks followed by an additional 6-week treatment in the alternative treatment arm after allowing for a 2-week washout period. Polysomnographic assessment and radiographs for assessment of adenoid size were performed after completion of each phase. RESULTS. There were significant improvements in both polysomnographic measures (sleep latency, slow-wave sleep, and rapid-eye-movement sleep), in the magnitude of respiratory disturbance (apnea/hypopnea index, nadir pulse oxygen saturation), and in adenoid size among the 48 children who completed the treatment phase compared with 32 children who received placebo in their initial arm, with normalization of sleep measures in 54.1% of the treated children. Furthermore, discontinuation of treatment for 8 weeks for 25 children revealed a sustained duration of the initial treatment effect. CONCLUSIONS. A 6-week treatment with intranasal budesonide effectively reduced the severity of mild obstructive sleep apnea syndrome and the magnitude of the underlying adenoidal hypertrophy, and this effect persisted for at least 8 weeks after cessation of therapy. These findings justify the use of topical steroids as the initial therapeutic option in otherwise healthy children with mild obstructive sleep apnea.

Obesity and Excessive Daytime Sleepiness in Prepubertal Children With Obstructive Sleep Apnea

INTRODUCTION. The epidemic of childhood obesity has prompted remarkable changes in the relative proportions of symptomatic overweight or obese children being referred for evaluation of habitual snoring. However, it remains unclear whether obesity modifies the relative frequency of daytime symptoms such as excessive daytime sleepiness. METHODS. Fifty consecutive, nonobese, habitually snoring, otherwise-healthy children (age range: 6–9 years) and 50 age-, gender-, and ethnicity-matched obese children (BMI z score: >1.67) underwent an overnight polysomnographic evaluation, followed by a multiple sleep latency test the following day. RESULTS. The mean obstructive apnea/hypopnea index values for the 2 groups were similar (nonobese: 12.0 ± 1.7 episodes per hour of total sleep time; obese: 10.9 ± 1.5 episodes per hour of total sleep time). However, the mean sleep latency for obese children was significantly shorter (12.9 ± 0.9 minutes) than that for nonobese children (17.9 ± 0.7 minutes). Furthermore, 21 obese children had mean sleep latencies of ≤12.0 minutes, compared with only 5 nonobese children. Although significant associations emerged between mean sleep latency, obstructive apnea/hypopnea index, proportion of total sleep time with oxygen saturation of <95%, and respiratory arousal index for the whole cohort, the slopes and intersects of the linear correlation of mean sleep latency with any of these polygraphic measures were consistently greater in the obese cohort. CONCLUSIONS. The likelihood of excessive daytime sleepiness for obese children is greater than that for nonobese children at any given level of obstructive sleep apnea severity and is strikingly reminiscent of excessive daytime sleepiness patterns in adults with obstructive sleep apnea.

Neurocognitive and behavioral morbidity in children with sleep disorders.

Purpose of review This review examines in detail progress made regarding our understanding of the presence and pathophysiology of cognitive and behavioral morbidities among children with sleep disorders in general. Particular focus is given to pediatric obstructive sleep apnea. Recent findings In recent years, increased awareness of the morbid consequences of respiratory sleep disturbances in children has emerged. Evidence suggesting a causal association of intermittent hypoxia and sleep fragmentation with alterations in memory, attention, and intelligence has accumulated. Research has also identified a link between sleep disorders, and problematic and hyperactive behaviors and mood disturbances. Furthermore, there is considerable inter-individual variability in the presence and magnitude of neurobehavioral morbidity at any given level of disease severity. This further suggests that, in addition to the disease per se, both genetic (individual susceptibility) and environmental modifiers play a role in determining morbidity. Summary A more individually tailored approach to detecting morbidity associated with sleep disorders in children, employing biomarkers and gene-related single nucleotide polymorphisms, may ultimately be required to allow more rational prioritization of treatment.

APOE ε4 allele, cognitive dysfunction, and obstructive sleep apnea in children

Background: Obstructive sleep apnea (OSA) in children is associated with severity-dependent changes in neurocognitive functioning. However, the severity of OSA accounts for only approximately 40% of the variance in cognitive performance. Thus, genetic determinants of individual susceptibility may also contribute to the morbidity of OSA. Considering the unique susceptibility of apolipoprotein E (ApoE) knock-out mice to an experimental model of OSA, we examined whether the APOE ε4 allele contributes to increased neurocognitive morbidity in pediatric OSA. Methods: Consecutive habitually snoring and nonsnoring 5- to 7-year-old children underwent overnight polysomnography, neurocognitive testing, and a blood draw the next morning. Children were divided into OSA or no OSA, and OSA children were further subdivided into those with ≥2 abnormal cognitive subtest scores and those with normal cognitive scores. The presence of the APOE ε4 allele was determined from blood genomic DNA. Results: Among all children without OSA, APOE ε4 was present in 3 of 199 children, whereas in those with OSA, APOE ε4 was found in 16 of 146 children (p < 0.0002). Furthermore, 16 of 74 children with OSA and cognitive scores <85% had the APOE ε4 allele compared with 3 of 72 children with OSA with abnormal cognitive scores (p < 0.002). Conclusions: APOE ε4 allele is more frequent in children with obstructive sleep apnea and particularly in those who develop neurocognitive deficits, suggesting that the APOE ε4 allele is associated with not only increased odds of having sleep-disordered breathing, but also with an increased risk for neurocognitive dysfunction.

Obesity and Obstructive Sleep Apnea Syndrome in Children: A Tale of Inflammatory Cascades

Obesity has emerged as one of the most prevalent diseases in the western hemisphere, and its prevalence continues to increase. Obese children are at increased risk for several disorders, particularly affecting the cardiovascular and metabolic systems. The mechanisms leading to obesity‐related morbidities are likely multifactorial, and include activation of inflammatory pathways ultimately leading to end‐organ injury. Furthermore, the concurrent presence of obesity and other diseases facilitated by increased fat deposition poses a theoretical risk of accentuating obesity‐related complications. One of the conditions whose prevalence is increased by obesity in childhood is the obstructive sleep apnea syndrome (OSAS). OSAS in non‐obese children may lead to co‐morbidities that are not only remarkably similar to those associated with obesity but recruit similar inflammatory mechanisms as those activated by obesity, suggesting that the two disorders may amplify each other and synergistically augment the magnitude of their respective adverse consequences. The objective of this review is to critically review the effects of both obesity and OSAS in inducing systemic inflammation in children and will examine the latest evidence pertaining to the up‐regulation of specific inflammatory mediators. Pediatr Pulmonol. 2011; 46:313–323.

Endothelial Progenitor Cells and Vascular Dysfunction in Children with Obstructive Sleep Apnea

RATIONALE Endothelial dysfunction is a potential complication of obstructive sleep apnea syndrome (OSAS) in children ascribed to systemic inflammatory changes. However, not all children with OSAS will manifest endothelial dysfunction. OBJECTIVES The variability in endothelial function in pediatric OSAS may be related to the ability to recruit repair mechanisms such as endothelial progenitor cells (EPCs). METHODS Prepubertal nonhypertensive children with or without polysomonographically confirmed OSAS had endothelial function assessed in a morning fasted state using a modified hyperemic test involving cuff-induced occlusion of the radial and ulnar arteries. Blood was drawn and EPCs were assessed by flow cytometry and triple staining using antibodies against CD133, CD34, and vascular endothelial growth factor receptor-2 after isolation of peripheral blood mononuclear cells. SDF-1 levels were measured by ELISA. MEASUREMENTS AND MAIN RESULTS Eighty children with OSAS (mean age 8.2 +/- 1.4 yr, mean body mass index [BMI] z-score, 1.43 +/- 0.3) and 20 controls (CO) matched for BMI, age, sex, and ethnicity were studied. Significant delays to peak capillary reperfusion after occlusion release (Tmax) occurred in OSAS children, but substantial variability was present. Despite similar OSAS severity, EPC counts, and stromal cell-derived factor-1 (SDF-1) levels were significantly lower among the 20 OSAS children with the longest Tmax, when compared with either the 20 children with normal Tmax values or to CO ( P < 0.01). Furthermore, Tmax was significantly and inversely correlated with EPCs (r(2), 0.51; P < 0.01), but neither EPCs nor Tmax were associated with apnea-hyponea index (AHI). CONCLUSIONS Endothelial dysfunction is frequently present in OSAS. Variance in endothelial functional phenotype may not only reside in the individual susceptibility but also in the ability to recruit endothelial repair mechanisms.