Effects of adenotonsillectomy on plasma inflammatory biomarkers in obese children with obstructive sleep apnea: A community-based study.

BackgroundObesity and obstructive sleep apnea syndrome (OSA) are highly prevalent and frequently overlapping conditions in children that lead to systemic inflammation, the latter being implicated in the various end-organ morbidities associated with these conditions.AimTo examine the effects of adenotonsillectomy (T&A) on plasma levels of inflammatory markers in obese children with polysomnographically diagnosed OSA who were prospectively recruited from the community.MethodsObese children prospectively diagnosed with OSA, underwent T&A and a second overnight polysomnogram (PSG) after surgery. Plasma fasting morning samples obtained after each of the two PSGs were assayed for multiple inflammatory and metabolic markers including interleukin (IL)-6, IL-18, plasminogen activator inhibitor-1 (PAI-1), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9), adiponectin, apelin C, leptin and osteocrin.ResultsOut of 122 potential candidates, 100 obese children with OSA completed the study with only one-third exhibiting normalization of their PSG after T&A (that is, apnea-hypopnea index (AHI) ≤1/hour total sleep time). However, overall significant decreases in MCP-1, PAI-1, MMP-9, IL-18 and IL-6, and increases in adropin and osteocrin plasma concentrations occurred after T&A. Several of the T&A-responsive biomarkers exhibited excellent sensitivity and moderate specificity to predict residual OSA (that is, AHI⩾5/hTST).ConclusionsA defined subset of systemic inflammatory and metabolic biomarkers is reversibly altered in the context of OSA among community-based obese children, further reinforcing the concept on the interactive pro-inflammatory effects of sleep disorders such as OSA and obesity contributing to downstream end-organ morbidities

Murine models of sleep apnea: functional implications of altered macrophage polarity and epigenetic modifications in adipose and vascular tissues

Obstructive sleep apnea (OSA) is a highly prevalent disease across the lifespan, is characterized by chronic intermittent hypoxia and sleep fragmentation, and has been independently associated with substantial cardiometabolic morbidity. However, the reversibility of end-organ morbidity with treatment is not always apparent, suggesting that both tissue remodeling and epigenetic mechanisms may be operationally involved. Here, we review the cumulative evidence focused around murine models of OSA to illustrate the temporal dependencies of cardiometabolic dysfunction and its reversibility, and more particularly to discuss the critical contributions of tissue macrophages to adipose tissue insulin resistance and vascular atherogenesis. In addition, we describe initial findings potentially implicating epigenetic alterations in both the emergence of the cardiometabolic morbidity of OSA, and in its reversibility with treatment. We anticipate that improved understanding of macrophage biology and epigenetics in the context of intermittent hypoxia and sleep fragmentation will lead to discovery of novel therapeutic targets and improved cardiovascular and metabolic outcomes in OSA

Attention deficit hyperactivity disorder symptomatology and pediatric obesity: Psychopathology or sleep deprivation?

The relationship between attention deficit hyperactivity disorder (ADHD) and obesity in children has received considerable attention in recent years. However, the literature currently overlooks the potential causal and maintaining role that sleep problems may play in this relationship. Using a biopsychosocial framework, this article highlights how sleep problems impact the biological, psychological, and social aspects of both ADHD symptomatology and obesity. An in-depth examination of this model illustrates the imperative need for future research and clinical practice to recognize and explore the role sleep has in the link between obesity and ADHD symptomatology

Impairments in Attention in Occasionally Snoring Children: An Event-Related Potential Study

Objective—To determine whether minimal snoring is benign in children. Procedure—22 rarely snoring children (mean age=6.9 years, 11 females) and age- and sexmatched controls participated in an auditory oddball task wearing 128-electrode nets. Parents completed Conner’s Parent Rating Scales-Revised Long (CPRS-R:L). Results—Snorers scored significantly higher on 4 CPRS-R:L subscales. Stepwise regression indicated that two ERP variables from a region of the ERP that peaked at 844 ms post-stimulus onset predicted CPRS-R:L ADHD Index scores. Conclusions—Occasional snorers according to parental report do exhibit ADHD-like behaviors. Basic sensory processing is longer than in controls, suggesting that delayed frontal activation requires more effort in snorers

Hypoxia modulates cholinergic but not opioid activation of G proteins in rat hippocampus

Intermittent hypoxia, such as that associated with obstructive sleep apnea, can cause neuronal death and neurobehavioral dysfunction. The cellular and molecular mechanisms through which hypoxia alter hippocampal function are incompletely understood. This study used in vitro [ 35 S]guanylyl-5′- O -(Γ-thio)-triphosphate ([ 35 S]GTPΓS) autoradiography to test the hypothesis that carbachol and DAMGO activate hippocampal G proteins. In addition, this study tested the hypothesis that in vivo exposure to different oxygen (O 2 ) concentrations causes a differential activation of G proteins in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus. G protein activation was quantified as nCi/g tissue in CA1, CA3, and DG from rats housed for 14 days under one of three different oxygen conditions: normoxic (21% O 2 ) room air, or hypoxia (10% O 2 ) that was intermittent or sustained. Across all regions of the hippocampus, activation of G proteins by the cholinergic agonist carbachol and the mu opioid agonist [D-Ala 2 , N-Met-Phe 4 , Gly 5 ] enkephalin (DAMGO) was ordered by the degree of hypoxia such that sustained hypoxia > intermittent hypoxia > room air. Carbachol increased G protein activation during sustained hypoxia (38%), intermittent hypoxia (29%), and room air (27%). DAMGO also activated G proteins during sustained hypoxia (52%), intermittent hypoxia (48%), and room air (43%). Region-specific comparisons of G protein activation revealed that the DG showed significantly less activation by carbachol following intermittent hypoxia and sustained hypoxia than the CA1. Considered together, the results suggest the potential for hypoxia to alter hippocampal function by blunting the cholinergic activation of G proteins within the DG. © 2007 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/57386/1/20312_ftp.pd

Snoring in Portuguese primary school children

OBJECTIVE: To determine the prevalence of snoring and its potential associations with sleep problems, such as daytime symptoms, medical conditions, school performance, and behavioral disturbances in Portuguese children attending primary school. METHODS: A previously validated questionnaire was sent to the parents of 1381 children attending primary schools in a parish of Coimbra, Portugal. To assess behavioral disturbances, the Portuguese version of Rutter's Children's Behavior Questionnaire for completion by teachers was used. RESULTS: Of the 988 questionnaires returned (71.5%), complete information concerning snoring was obtained for 976 children (496 girls and 480 boys; mean age: 8.1 +/- 1.5 years). Loud snoring during sleep was reported as frequent or constantly present (LSn) in 84 children (8.6%), as occasionally present in 299 children (30.6%), and as never present (NSn) by 593 children (60.8%). The LSn and NSn groups did not differ with respect to age, gender, sleep duration, time to fall asleep, frequency of night wakings, bedwetting, daytime tiredness, and school achievement. However, LSn was significantly associated with increased bedtime problems (fears and struggles), increased need for comforting activities to fall asleep, behaviors suggestive of parasomnias (sleep talking, teeth grinding, and night terrors), increased daytime sleepiness and irritability, and behavioral disturbances. Children in the LSn group were also more likely to report recurrent medical problems particularly those involving infections of the respiratory tract. CONCLUSIONS: Snoring is a common symptom in Portuguese children that is associated with behavioral daytime and sleep time disturbances. Children with loud snoring may benefit from early evaluation and intervention

Cluster Analysis of Home Polygraphic Recordings in Symptomatic Habitually-Snoring Children: A Precision Medicine Perspective

(1) Background: Sleep-disordered breathing (SDB) is a frequent problem in children. Cluster analyses offer the possibility of identifying homogeneous groups within a large clinical database. The application of cluster analysis to anthropometric and polysomnographic measures in snoring children would enable the detection of distinctive clinically-relevant phenotypes; (2) Methods: We retrospectively collected the results of nocturnal home-based cardiorespiratory polygraphic recordings and anthropometric measurements in 326 habitually-snoring otherwise healthy children. K-medoids clustering was applied to standardized respiratory and anthropometric measures, followed by Silhouette-based statistics. Respiratory Disturbance Index (RDI) and oxygen desaturation index (<= 3%) were included in determining the optimal number of clusters; (3) Results: Mean age of subjects was 8.1 +/- 4.1 years, and 57% were males. Cluster analyses uncovered an optimal number of three clusters. Cluster 1 comprised 59.5% of the cohort (mean age 8.69 +/- 4.14 years) with a mean RDI of 3.71 +/- 3.23 events/hour of estimated sleep (e/ehSleep). Cluster 2 included 28.5% of the children (mean age 6.92 +/- 3.43 years) with an RDI of 6.38 +/- 3.92 e/ehSleep. Cluster 3 included 12% of the cohort (mean age 7.58 +/- 4.73 years) with a mean RDI of 25.5 +/- 19.4 e/ehSleep. Weight z-score was significantly lower in cluster 3 [-0.14 +/- 1.65] than in cluster 2 [0.86 +/- 1.78; p = 0.015] and cluster 1 [1.04 +/- 1.78; p = 0.002]. Similar findings emerged for BMI z scores. However, the height z-score was not significantly different among the 3 clusters; (4) Conclusions: Cluster analysis of children who are symptomatic habitual snorers and are referred for clinical polygraphic evaluation identified three major clusters that differed in age, RDI, and anthropometric measures. An increased number of children in the cluster with the highest RDI had reduced body weight. We propose that the implementation of these approaches to a multicenter-derived database of home-based polygraphic recordings may enable the delineation of objective unbiased severity categories of pediatric SDB. Our findings could be useful for clinical implementation, formulation of therapeutic decision guidelines, clinical management, prevision of complications, and long-term follow-up

Endothelial dysfunction in obese non-hypertensive children without evidence of sleep disordered breathing

<p>Abstract</p> <p>Background</p> <p>Endothelial dysfunction is a complication of both obesity and obstructive sleep apnea syndrome (OSAS), the latter being highly prevalent among obese children. It is unknown whether obesity causes endothelial dysfunction in children in the absence of OSAS. This study examines endothelial function in obese and non-obese children without OSAS.</p> <p>Methods</p> <p>Pre-pubertal non-hypertensive children were recruited. Endothelial function was assessed in a morning fasted state, using a modified hyperemic test involving cuff-induced occlusion of the radial and ulnar arteries. The absence of OSAS was confirmed by overnight polysomnography. Anthropometry was also performed.</p> <p>Results</p> <p>55 obese children (mean age 8.6 ± 1.4 years, mean BMI z-score: 2.3 ± 0.3) were compared to 50 non-obese children (mean age 8.0 ± 1.6 years, mean BMI z-score 0.3 ± 0.9). Significant delays to peak capillary reperfusion after occlusion release occurred in obese compared to non-obese children (45.3 ± 21.9 sec <it>vs</it>. 31.5 ± 14.1 sec, p < 0.01), but no differences in the magnitude of hyperemia emerged. Time to peak reperfusion and percentage of body fat were positively correlated (r = 0.365, p < 0.01).</p> <p>Conclusions</p> <p>Our findings confirm that endothelial dysfunction occurs early in life in obese children, even in the absence of OSAS. Thus, mechanisms underlying endothelial dysfunction in pediatric obesity are operational in the absence of sleep-disordered breathing.</p

Intermittent Hypoxia-Induced Cognitive Deficits Are Mediated by NADPH Oxidase Activity in a Murine Model of Sleep Apnea

Background: In rodents, exposure to intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), is associated with neurobehavioral impairments, increased apoptosis in the hippocampus and cortex, as well as increased oxidant stress and inflammation. Excessive NADPH oxidase activity may play a role in IH-induced CNS dysfunction. Methods and Findings: The effect of IH during light period on two forms of spatial learning in the water maze and well as markers of oxidative stress was assessed in mice lacking NADPH oxidase activity (gp91phox _/Y) and wild-type littermates. On a standard place training task, gp91phox _/Y displayed normal learning, and were protected from the spatial learning deficits observed in wild-type littermates exposed to IH. Moreover, anxiety levels were increased in wild-type mice exposed to IH as compared to room air (RA) controls, while no changes emerged in gp91phox _/Y mice. Additionally, wild-type mice, but not gp91phox _/Y mice had significantly elevated levels of NADPH oxidase expression and activity, as well as MDA and 8-OHDG in cortical and hippocampal lysates following IH exposures. Conclusions: The oxidative stress responses and neurobehavioral impairments induced by IH during sleep are mediated, at least in part, by excessive NADPH oxidase activity, and thus pharmacological agents targeting NADPH oxidase may provid