Jordan Gaines

Natural history of sleep disordered breathing in prepubertal children transitioning to adolescence

Because there is a lack of agreed upon diagnostic criteria, it is critical to understand the natural history of obstructive sleep apnoea (OSA) in children in order to establish treatment strategies based on objective data. The Penn State Child Cohort is a representative, general-population sample of 700 elementary school children at baseline, of whom 421 were reassessed 8 years later, during adolescence. The remission of childhood apnoea–hypopnoea index (AHI) ≥2 events per h in adolescence was 52.9%. Using the higher threshold of AHI ≥5 events per h, remission was 100.0%, with 50.0% partially remitting to AHI 2– <5 events per h and the other half remitting to AHI <2 events per h. The incidence of adolescent AHI ≥2 events per h in those with childhood AHI <2 events per h was 36.5%, while the incidence of AHI ≥5 events per h in those with childhood AHI <5 events per h was 10.6%. This longitudinal study confirms that prepubertal OSA tends to resolve naturally during the transition to adolescence, and that primary snoring and mild sleep disordered breathing (SDB) do not appear to be strongly associated with progression to more severe SDB. The key risk factors for SDB in adolescence are similar to those found in middle-aged adults (i.e. male sex, older age and obesity). Moreover, consistent with recent studies in adults, this study includes the novel cross-sectional finding that visceral fat is associated with SDB as early as adolescence. Prepubertal sleep disordered breathing tends to resolve naturally during transition to adolescence http://ow.ly/X2Uv8

Insomnia is Associated with Cortical Hyperarousal as Early as Adolescence

STUDY OBJECTIVES To examine whether insomnia is associated with spectral electroencephalographic (EEG) dynamics in the beta (15-35Hz) range during sleep in an adolescent general population sample. METHODS A case-control sample of 44 adolescents from the Penn State Child Cohort underwent a 9-h polysomnography, clinical history and physical examination. We examined low-beta (15-25 Hz) and high-beta (25-35 Hz) relative power at central EEG derivations during sleep onset latency (SOL), sleep onset (SO), non-rapid eye movement (NREM) sleep, and wake after sleep onset (WASO). RESULTS Compared to controls (n = 21), individuals with insomnia (n = 23) showed increased SOL and WASO and decreased sleep duration and efficiency, while no differences in sleep architecture were found. Insomniacs showed increased low-beta and high-beta relative power during SOL, SO, and NREM sleep as compared to controls. High-beta relative power was greater during all sleep and wake states in insomniacs with short sleep duration as compared to individuals with insomnia with normal sleep duration. CONCLUSIONS Adolescent insomnia is associated with increased beta EEG power during sleep, which suggests that cortical hyperarousal is present in individuals with insomnia as early as adolescence. Interestingly, cortical hyperarousal is greatest in individuals with insomnia with short sleep duration and may explain the sleep complaints of those with normal sleep duration. Disturbed cortical networks may be a shared mechanism putting individuals with insomnia at risk of psychiatric disorders.

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

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.

Sleep apnoea and the hypothalamic-pituitary-adrenal axis in men and women: effects of continuous positive airway pressure.

Previous findings on the association of obstructive sleep apnoea (OSA) and the hypothalamic–pituitary–adrenal (HPA) axis are inconsistent, partly due to the confounding effect of obesity and infrequent sampling. Our goal was to examine whether in a relatively nonobese population, OSA is associated with elevated cortisol levels and to assess the effects of a 2-month placebo-controlled continuous positive airway pressure (sham-CPAP) use. 72 subjects (35 middle-aged males and post-menopausal females with OSA, and 37 male and female controls) were studied in the sleep laboratory for four nights. 24-h blood sampling was performed every hour on the fourth day and night in the sleep laboratory at baseline, after sham-CPAP and after CPAP treatment. In both apnoeic men and women, OSA was associated with significantly higher 24-h cortisol levels compared with controls, whereas CPAP lowered cortisol levels significantly, close to those of controls. These results suggest that OSA in nonobese men and slightly obese women is associated with HPA axis activation, similar albeit stronger compared with obese individuals with sleep apnoea. Short-term CPAP use decreased cortisol levels significantly compared with baseline, indicating that CPAP may have a protective effect against comorbidities frequently associated with chronic activation of the HPA axis, e.g. hypertension. OSA in nonobese men/slightly obese women is associated with HPA axis activation and CPAP lowers HPA axis activity http://ow.ly/Stn94

Gender differences in the association of sleep apnea and inflammation

Over the last 15years, many studies have established an association of sleep apnea with inflammation and metabolic aberrations. However, no controlled studies have examined potential gender effects in this association. We recruited 120 middle-aged, predominantly non-obese mild-to-moderate sleep apneics and controls (62 males, 58 females). All participants underwent a clinical history, physical examination, and 1-night 8-h polysomnography recording and provided a single fasting blood sample for assessment of interleukin-6 (IL-6), tumor necrosis factor receptor 1 (TNFR1), C-reactive protein (CRP), leptin, and adiponectin levels. Among non-sleep apneics, females had higher levels of TNFR1 (p=0.01), CRP (p=0.005), leptin (p<0.001), and adiponectin (p<0.001) compared to males, independent of age and body mass index. When analyzed separately by gender, sleep apneic men had elevated TNFR1 (p=0.04), CRP (p=0.06) and IL-6 (p=0.11) relative to control men; in sleep apneic females, only CRP was elevated (p=0.04). Furthermore, CRP was associated with apnea severity in a dose-response manner (p-linear=0.04 in both genders) and was independently associated with comorbid hypertension in apnea (p-linear=0.005 for women; p-linear=0.09 for men). In conclusion, although women have naturally higher levels of inflammatory and metabolic markers than men, sleep apneic men appear to have a more severe inflammatory profile compared to women. Our findings suggest that these markers should be analyzed and interpreted separately in men and women, and that a single measure of plasma CRP appears to be a clinically-useful marker of apnea severity and comorbid cardiovascular morbidity.

Inflammation mediates the association between visceral adiposity and obstructive sleep apnea in adolescents

Only a handful of studies, primarily in clinical samples, have reported an association between obesity, inflammation, and obstructive sleep apnea (OSA) in children and adolescents. No studies, however, have examined the pathogenetic link between visceral adiposity, systemic inflammation, and incident OSA in a large general population sample using objective measures of sleep and body fat. Adolescents (n = 392; mean age 17.0 ± 2.2 yr, 54.0% male) from the Penn State Child Cohort (PSCC) underwent 9-h overnight polysomnography; a DXA scan to assess body fat distribution; and a single fasting blood draw for the assessment of plasma interleukin-6 (IL-6), IL-6 soluble receptor (IL-6 sR), tumor necrosis factor alpha (TNFα), tumor necrosis factor receptor 1A (TNFR1), C-reactive protein (CRP), leptin, and adiponectin levels via ELISA. Visceral fat area was significantly elevated in moderate OSA (AHI ≥ 5), especially in boys. IL-6, CRP, and leptin were highest in adolescents with moderate OSA, even after adjusting for BMI percentile. Mediation analysis revealed that 42% of the association between visceral fat and OSA in adolescents was mediated by IL-6 (p = 0.03), while 82% of the association was mediated by CRP (p = 0.01). These data are consistent with the model of a feed-forward, vicious cycle, in which the release of proinflammatory cytokines by visceral adipocytes largely explains the association between central obesity and OSA; in turn, inflammation is also elevated in OSA independent of BMI. These findings, in a large, representative, non-clinical sample of young people, add to our understanding of the developmental pathogenesis of sleep apnea.

Objective, but Not Subjective, Sleepiness is Associated With Inflammation in Sleep Apnea

Study objectives: Objective and subjective measures of excessive daytime sleepiness (EDS) are only weakly associated. No study, however, has examined whether these two measures of EDS differ in terms of underlying mechanisms and prognostic value. Pro‐inflammatory cytokines, that is, interleukin‐6 (IL‐6) appear to promote sleepiness/fatigue, while the stress hormone cortisol promotes vigilance. We hypothesized that objective sleepiness is associated with increased levels of IL‐6 and decreased levels of cortisol. Methods: We studied 58 obstructive sleep apnea (OSA) patients with clinical EDS and/or cardiovascular comorbidities who underwent 8‐hour in‐lab polysomnography for four consecutive nights. Objective and subjective daytime sleepiness were measured by Multiple Sleep Latency Test (MSLT), Epworth Sleepiness Scale (ESS), and Stanford Sleepiness Scale (SSS), respectively. Twenty‐four‐hour profiles of IL‐6 and cortisol levels were assessed on the fourth day. Results: The agreement between objective and subjective EDS in OSA patients was fair (kappa = 0.22). Objective EDS (lower MSLT) in OSA patients was associated with significantly elevated 24‐hour (&bgr; = −0.34, p = .01), daytime (&bgr; = −0.30, p = .02) and nighttime (&bgr; = −0.38, p < .01) IL‐6 levels, and significantly decreased daytime (&bgr; = 0.35, p = .01) cortisol levels. In contrast, subjective EDS (higher ESS/SSS) was not associated with either elevated IL‐6 levels or decreased cortisol levels. Conclusions: Our findings suggest that OSA with objective EDS is the more severe phenotype of the disorder associated with low‐grade inflammation, a link to cardiometabolic morbidity and mortality. Compared to subjective EDS, objective EDS is a stronger predictor of OSA severity and may be useful in the clinical management of the disorder.

Insomnia symptoms with objective short sleep duration are associated with systemic inflammation in adolescents.

Inflammation has been suggested as a potential pathway by which insomnia and short sleep can affect risk of morbidity in adults. However, few studies have examined the association of insomnia with inflammation in adolescents, despite accumulating evidence that pathophysiologic changes may already occur during this critical developmental period. The present study sought to examine the association of insomnia symptoms with systemic inflammation and the role of objective sleep duration in this association. Participants were 378 adolescents (16.9±2.3y, 45.8% female) from the Penn State Child Cohort, a population-based sample who underwent 9-h polysomnography (PSG) followed by a single fasting blood draw to assess plasma levels of C-reactive protein (CRP) and other inflammatory markers. Insomnia symptoms were defined by a self-report of difficulties falling and/or staying asleep, while objective sleep duration groups were defined as a PSG total sleep time ⩾8, 8-7, and ⩽7h. We assessed the association of insomnia symptoms, objective sleep duration, and their interaction with inflammatory markers, while adjusting for multiple potential confounders. Adolescents reporting insomnia symptoms had significantly higher levels of CRP compared to controls and a significant interaction (p<0.01) showed that objective sleep duration modified this association. Elevated CRP was present in adolescents with insomnia symptoms and ⩽7h of sleep (1.79mg/L) as compared to controls or adolescents with insomnia symptoms and ⩾8h of sleep (0.90mg/L and 0.98mg/L, respectively) or controls with ⩽7h of sleep (0.74mg/L; all p-values <0.01). In sum, insomnia symptoms with objective short sleep duration are associated with systemic inflammation as early as adolescence. This study suggests that chronic low-grade inflammation may be a common final pathway towards morbidity in adulthood in this insomnia phenotype.

Moderate sleep apnoea: a "silent" disorder, or not a disorder at all?

Most sleep clinicians and scientists will agree that if a patient with sleep apnoea is symptomatic and has an apnoea/hypopnea index (AHI) of more than 15 events per hour, he or she deserves treatment. However, there is a large group of patients with mild and moderate sleep apnoea who are asymptomatic. For these individuals, the decision of when to treat is a grey area, and current guidelines leave clinicians wondering what to do. New ERJ study adds to the evidence casting doubt on the utility of recommended cut-offs for sleep apnoea treatment http://ow.ly/VgjBL

CrossTalk proposal: Metabolic syndrome causes sleep apnoea

Obstructive sleep apnoea (OSA) is a prevalent sleep disorder characterized by upper airway obstruction during sleep, resulting in intermittent breathing pauses despite effort, reduced blood oxygen saturation, hypoxia and arousals. With prevalence in the general population estimated at 17–24% of men and 5–9% of women (Young et al. 1993; Bixler et al. 1998, 2001), OSA has been linked to the key components of the metabolic syndrome: central obesity, insulin resistance (Vgontzas et al. 2000; Coughlin et al. 2004), elevated triglycerides, reduced HDL cholesterol (Coughlin et al. 2004), and elevated blood pressure (Bixler et al. 2000; Coughlin et al. 2004). While many have proposed that inflammation resulting from intermittent hypoxia is the culprit behind the development of metabolic aberrations in those with OSA, obesity and the metabolic syndrome in fact appear to precede the development of the disorder. Rather, considerable evidence suggests that OSA is