Sympathetic and Catecholaminergic Alterations in Sleep Apnea with Particular Emphasis on Children

Sleep is involved in the regulation of major organ functions in the human body, and disruption of sleep potentially can elicit organ dysfunction. Obstructive sleep apnea (OSA) is the most prevalent sleep disorder of breathing in adults and children, and its manifestations reflect the interactions between intermittent hypoxia, intermittent hypercapnia, increased intra-thoracic pressure swings, and sleep fragmentation, as elicited by the episodic changes in upper airway resistance during sleep. The sympathetic nervous system is an important modulator of the cardiovascular, immune, endocrine and metabolic systems, and alterations in autonomic activity may lead to metabolic imbalance and organ dysfunction. Here we review how OSA and its constitutive components can lead to perturbation of the autonomic nervous system in general, and to altered regulation of catecholamines, both of which then playing an important role in some of the mechanisms underlying OSA-induced morbidities

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

T regulatory lymphocytes and endothelial function in pediatric obstructive sleep apnea.

BackgroundObstructive sleep apnea (OSA) is a low-grade inflammatory disease affecting the cardiovascular and metabolic systems. Increasing OSA severity reduces T-regulatory lymphocytes (Tregs) in OSA children. Since Tregs modulate endothelial activation, and attenuate insulin resistance, we hypothesized that Tregs are associated with endothelial and metabolic dysfunction in pediatric OSA.Methods50 consecutively recruited children (ages 4.8-12 years) underwent overnight polysomnography and fasting homeostatic model (HOMA) of insulin resistance was assessed. Percentage of Tregs using flow cytometry, and endothelial function, expressed as the time to peak occlusive hyperemia (Tmax), were examined. In a subgroup of children (n = 21), in vitro Treg suppression tests were performed.ResultsCirculating Tregs were not significantly associated with either BMI z score or HOMA. However, a significant inverse correlation between percentage of Tregs and Tmax emerged (p<0.0001, r = -0.56). A significant negative correlation between Tregs suppression and the sleep pressure score (SPS), a surrogate measure of sleep fragmentation emerged (p = 0.02, r = -0.51) emerged, but was not present with AHI.ConclusionsEndothelial function, but not insulin resistance, in OSA children is strongly associated with circulating Tregs and their suppressive function, and appears to correlate with sleep fragmentation. Thus, alterations in T cell lymphocytes may contribute to cardiovascular morbidity in pediatric OSA

Insulin Sensitivity, Serum Lipids, and Systemic Inflammatory Markers in School-Aged Obese and Nonobese Children

The impact of obesity as a systemic low-grade inflammatory process has only partially been explored. To this effect, 704 community-based school-aged children (354 obese children and 350 age-, gender-, and ethnicity-matched controls) were recruited and underwent assessment of plasma levels of fasting insulin and glucose, lipids, and a variety of proinflammatory mediators that are associated with cardiometabolic dysfunction. Obese children were at higher risk for abnormal HOMA and cholesterol levels. Furthermore, BMI z score, HOMA, and LDL/HDL ratio strongly correlated with levels of certain inflammatory mediators. Taken together, obesity in children is not only associated with insulin resistance and hyperlipidemia, but is accompanied by increased, yet variable, expression of markers of systemic inflammation. Future community-based intervention and phenotype correlational studies on childhood obesity will require inclusion of expanded panels of inflammatory biomarkers to provide a comprehensive assessment of risk on specific obesity-related morbidities

Fatty-acid binding protein 4 gene variants and childhood obesity: potential implications for insulin sensitivity and CRP levels

<p>Abstract</p> <p>Introduction</p> <p>Obesity increases the risk for insulin resistance and metabolic syndrome in both adults and children. FABP4 is a member of the intracellular lipid-binding protein family that is predominantly expressed in adipose tissue, and plays an important role in maintaining glucose and lipid homeostasis. The purpose of this study was to measure FABP4 plasma levels, assess FABP4 allelic variants, and explore potential associations with fasting glucose and insulin levels in young school-age children with and without obesity.</p> <p>Methods</p> <p>A total of 309 consecutive children ages 5-7 years were recruited. Children were divided based on BMI z score into Obese (OB; BMI z score >1.65) and non-obese (NOB). Fasting plasma glucose, lipids, insulin, hsCRP, and FABP4 levels were measured. HOMA was used as correlate of insulin sensitivity. Four SNPs of the human FABP4 gene (rs1051231, rs2303519, rs16909233 and rs1054135), corresponding to several critical regions of the encoding FABP4 gene sequence were genotyped.</p> <p>Results</p> <p>Compared to NOB, circulating FABP4 levels were increased in OB, as were LDL, hsCRP and HOMA. FABP4 levels correlated with BMI, and also contributed to the variance of HOMA and hsCRP, but not serum lipids. The frequency of rs1054135 allelic variant was increased in OB, and was associated with increased FABP4 levels, while the presence of rs16909233 variant allele, although similar in OB and NOB, was associated with increased HOMA values.</p> <p>Conclusions</p> <p>Childhood obesity is associated with higher FABP4 levels that may promote cardiometabolic risk. The presence of selective SNPs in the FABP4 gene may account for increased risk for insulin resistance or systemic inflammation in the context of obesity.</p

Automated Analysis of Nocturnal Oximetry as Screening Tool for Childhood Obstructive Sleep Apnea-Hypopnea Syndrome

Producción CientíficaChildhood obstructive sleep apnea-hypopnea syndrome (OSAHS) is a highly prevalent condition that negatively affects health, performance and quality of life of infants and young children. Early detection and treatment improves neuropsychological and cognitive deficits linked with the disease. The aim of this study was to assess the performance of automated analysis of blood oxygen saturation (SpO2) recordings as a screening tool for OSAHS. As an initial step, statistical, spectral and nonlinear features were estimated to compose an initial feature set. Then, fast correlation-based filter (FCBF) was applied to search for the optimum subset. Finally, the discrimination power (OSAHS negative vs. OSAHS positive) of three pattern recognition algorithms was assessed: linear discriminant analysis (LDA), quadratic discriminant analysis (QDA) and logistic regression (LR). Three clinical cutoff points commonly used in the literature for positive diagnosis of the disease were applied: apnea-hypopnea index (AHI) of 1, 3 and 5 events per hour (e/h). Our methodology reached 88.6% accuracy (71.4% sensitivity and 100.0% specificity, 100.0% positive predictive value, and 84.0% negative predictive value) in an independent test set using QDA for a clinical cut-off point of 5 e/h. These results suggest that SpO2 nocturnal recordings may be used to develop a reliable and efficient screening tool for childhood OSAHSJunta de Castilla y León (project VA059U13

Wavelet analysis of overnight airflow to detect obstructive sleep apnea in children

Producción CientíficaThis study focused on the automatic analysis of the airflow signal (AF) to aid in the diagnosis of pediatric obstructive sleep apnea (OSA). Thus, our aims were: (i) to characterize the overnight AF characteristics using discrete wavelet transform (DWT) approach, (ii) to evaluate its diagnostic utility, and (iii) to assess its complementarity with the 3% oxygen desaturation index (ODI3). In order to reach these goals, we analyzed 946 overnight pediatric AF recordings in three stages: (i) DWT-derived feature extraction, (ii) feature selection, and (iii) pattern recognition. AF recordings from OSA patients showed both lower detail coefficients and decreased activity associated with the normal breathing band. Wavelet analysis also revealed that OSA disturbed the frequency and energy distribution of the AF signal, increasing its irregularity. Moreover, the information obtained from the wavelet analysis was complementary to ODI3. In this regard, the combination of both wavelet information and ODI3 achieved high diagnostic accuracy using the common OSA-positive cutoffs: 77.97%, 81.91%, and 90.99% (AdaBoost.M2), and 81.96%, 82.14%, and 90.69% (Bayesian multi-layer perceptron) for 1, 5, and 10 apneic events/hour, respectively. Hence, these findings suggest that DWT properly characterizes OSA-related severity as embedded in nocturnal AF, and could simplify the diagnosis of pediatric OSA.Ministerio de Ciencia, Innovación y Universidades, Agencia Estatal de Investigación y Fondo Europeo de Desarrollo Regional (FEDER) - (Projects DPI2017-84280-R and RTC-2017-6516-1)Comisión Europea y Fondo Europeo de Desarrollo Regional (FEDER) - (POCTEP 0702_MIGRAINEE_2_E)Instituto de Salud Carlos III y Fondo Europeo de Desarrollo Regional (FEDER) - (CIBER-BBN)Ministerio de Ciencia e Innovación, Agencia Estatal de Investigación y Fondo Social Europeo - (grant RYC2019- 028566-I)Ministerio de Educación, Cultura y Deporte - (grant FPU16/02938)Institutes of Health - (grants HL130984, HL140548, and AG061824