Inflammatory markers and obstructive sleep apnea in obese children: the NANOS study.
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SUBMITTER: Gileles-Hillel A
PROVIDER: S-EPMC4058796 | biostudies-literature | 2014
REPOSITORIES: biostudies-literature
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Inflammatory markers and obstructive sleep apnea in obese children: the NANOS study.
Gileles-Hillel Alex A Alonso-Álvarez María Luz ML Kheirandish-Gozal Leila L Peris Eduard E Cordero-Guevara José Aurelio JA Terán-Santos Joaquin J Martinez Mónica Gonzalez MG Jurado-Luque María José MJ Corral-Peñafiel Jaime J Duran-Cantolla Joaquin J Gozal David D
Mediators of inflammation 20140601
<h4>Introduction</h4>Obesity and obstructive sleep apnea syndrome (OSA) are common coexisting conditions associated with a chronic low-grade inflammatory state underlying some of the cognitive, metabolic, and cardiovascular morbidities.<h4>Aim</h4>To examine the levels of inflammatory markers in obese community-dwelling children with OSA, as compared to no-OSA, and their association with clinical and polysomnographic (PSG) variables. Methods. In this cross-sectional, prospective multicenter stud ...[more]
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Project description:IntroductionObesity in children is assumed to serve as a major risk factor in pediatric obstructive sleep apnea syndrome (OSAS). However, the prevalence of OSAS in otherwise healthy obese children from the community is unknown.AimTo determine the prevalence of OSAS in obese children identified and recruited from primary care centers.MethodsA cross-sectional, prospective, multicenter study. Spanish children ages 3-14 y with a body mass index (BMI) greater than or equal to the 95th percentile for age and sex were randomly selected, and underwent medical history, snoring, and Pediatric Sleep Questionnaire (PSQ) assessments, as well as physical examination, nasopharyngoscopy, and nocturnal polysomnography (NPSG) recordings.ResultsTwo hundred forty-eight children (54.4% males) with mean age of 10.8 ± 2.6 y were studied with a BMI of 28.0 ± 4.7 kg/m(2) corresponding to 96.8 ± 0.6 percentile when adjusted for age and sex. The mean respiratory disturbance index (RDI), obstructive RDI (ORDI), and obstructive apnea-hypopnea index (OAHI) were 5.58 ± 9.90, 5.06 ± 9.57, and 3.39 ± 8.78/h total sleep time (TST), respectively. Using ≥ 3/h TST as the cutoff for the presence of OSAS, the prevalence of OSAS ranged from 21.5% to 39.5% depending on whether OAHI, ORDI, or RDI were used.ConclusionsThe prevalence of obstructive sleep apnea syndrome (OSAS) in obese children from the general population is high. Obese children should be screened for the presence of OSAS. ClinicalTrials.gov identifier: NCT01322763.
| S-EPMC3985101 | biostudies-literature
Project description:Obesity 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.To 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.Obese 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.Out 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).A 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.
| S-EPMC4496251 | biostudies-literature
Project description:ObjectiveDefine the prevalence of OSA in a population of obese pregnant women. Secondary objectives were to assess its obstetric consequences and define its risk factors in this population.MethodsThis single-center prospective study took place at the Lille University Hospital from 2010 to 2016 and included pregnant women with a body mass index (BMI) > 35 kg/m2. They underwent polysomnography (type 1 sleep testing) between 24 and 32 weeks of gestation to diagnose OSA. Clinical, obstetric, and fetal data were collected monthly and at delivery. We compared the groups with and without OSA and calculated its prevalence.ResultsThis study included 67 women with a mean BMI of 42.4 ± 6.2 kg/m2. Among them, 29 had OSA, for a prevalence of 43.3% (95% confidence interval, 31.4-55.2); it was mild or moderate in 25 women and severe in 4. Comparison of the two groups showed that women in the OSA group were older (31.9 ± 4.7 years vs 29.5 ± 4.8 years, P = .045), had chronic hypertension more frequently (37.9% vs 7.9%, P = .0027), and had a higher mean BMI (43.8 ± 6.2 kg/m2 vs 41.2 ± 6 kg/m2, P = .045). During pregnancy, they developed gestational diabetes more often (48.3% vs 23.7%, P = .04). No significant differences were observed for any of the other criteria studied.ConclusionsThe prevalence of OSA was high in our study, and women with it developed gestational diabetes during pregnancy more often. No other obstetric complications were observed.
| S-EPMC7478531 | biostudies-literature
Project description:BackgroundPediatric obstructive sleep apnea (OSA) leads to multiple end-organ morbidities that are mediated by the cumulative burden of oxidative stress and inflammation. Because not all children with OSA exhibit increased systemic inflammation, genetic and environmental factors may be affecting patterns of DNA methylation in genes subserving inflammatory functions.MethodsDNA from matched children with OSA with and without high levels of high-sensitivity C-reactive protein (hsCRP) were assessed for DNA methylation levels of 24 inflammatory-related genes. Primer-based polymerase chain reaction assays in a case-control setting involving 47 OSA cases and 31 control subjects were conducted to confirm the findings; hsCRP and myeloid-related protein (MRP) 8/14 levels were also assayed.Measurements and main resultsForkhead box P3 (FOXP3) and interferon regulatory factor 1 (IRF1) showed higher methylation in six children with OSA and high hsCRP levels compared with matched children with OSA and low hsCRP levels (P < 0.05). In the case-control cohort, children with OSA and high CRP levels had higher log FOXP3 DNA methylation levels compared with children with OSA and low CRP levels and control subjects. IRF1 did not exhibit significant differences. FOXP3 DNA methylation levels correlated with hsCRP and MRP 8/14 levels and with apnea-hypopnea index (AHI), BMI z score, and apolipoprotein B levels. A stepwise multiple regression model showed that AHI was independently associated with FOXP3 DNA methylation levels (P < 0.03).ConclusionsThe FOXP3 gene, which regulates expression of T regulatory lymphocytes, is more likely to display increased methylation among children with OSA who exhibit increased systemic inflammatory responses. Thus, epigenetic modifications may constitute an important determinant of inflammatory phenotype in OSA, and FOXP3 DNA methylation levels may provide a potential biomarker for end-organ vulnerability.
| S-EPMC3297110 | biostudies-literature
Project description:Rationale: Obstructive sleep apnea (OSA) has been associated with metabolic dysregulation and systemic inflammation. This may be due to pathophysiologic effects of OSA on visceral adipose tissue. We sought to assess the transcriptional consequences of OSA on adipocytes by utilizing pathway-focused analyses. Methods: Patients scheduled to undergo ventral hernia repair surgery were recruited to wear a portable home sleep monitor for two nights prior to surgery. Visceral fat biopsies were obtained intra-operatively. RNA was extracted and whole-genome expression profiling was performed. Gene Set Enrichment Analysis (GSEA) was used to identify curated gene sets that were differentially enriched in OSA subjects. Network analysis was applied to a select set of highly enriched pathways. Results: 10 patients with OSA and 8 control subjects were recruited. There were no differences in age, gender, body mass index between the two groups, but the OSA subjects had a significantly higher respiratory disturbance index (19.2 vs. 0.6, P-value 0.05) and worse hypoxemia (minimum oxygen saturation 79.7% vs. 87.8%, P-value < 0.001). GSEA identified a number of gene sets up-regulated in adipose tissue of OSA patients including the pro-inflammatory NF-M-NM-:B pathway and the proteolytic ubiquitin/proteasome module. A critical metabolic pathway, the peroxisome proliferator-activated receptor (PPAR), was down-regulated in subjects with OSA. Network analysis linked members of these modules together and identified regulatory hubs. Conclusions: OSA is associated with alterations in visceral fat gene expression. Pathway-based network analysis highlighted perturbations in several key pathways whose coordinated interactions may contribute to the metabolic dysregulation observed in this complex disorder. Total RNA from visceral fat of 18 subjects (10 OSA, 8 Control) was hybridized to 18 Affymetrix Genechip Human Gene 1.0 ST microarrays.
2012-09-01 | E-GEOD-38792 | biostudies-arrayexpress
Project description:Study objectivesIncreased neck circumference, a surrogate for the neck fat that can narrow the upper airway in obese individuals, is a risk factor for obstructive sleep apnea syndrome (OSAS) in adults, but the association between neck fat and OSAS in adolescent males and females is unknown. We hypothesized that obese adolescents with OSAS have more neck fat than controls, females more neck fat than males, and that neck fat correlates with obesity and OSAS severity.MethodsObese adolescents with OSAS and obese and normal-weight controls underwent upper airway magnetic resonance imaging, polysomnography, and anthropometrics, including neck circumference measurement. Intra-neck and subcutaneous neck fat measurements were manually segmented and compared among the three groups using ANOVA and between males and females using t-tests. The relationship between polysomnographic parameters and neck fat measurements was assessed in adolescents with OSAS using Pearson correlations.ResultsOne-hundred nineteen adolescents (38 females) were studied: 39 obese with OSAS, 34 obese controls, and 46 normal-weight controls. Neck fat was not greater in adolescents with OSAS compared to obese controls (p=0.35), and neck fat volume was not related to OSAS severity (p = 0.36). However, obese adolescents had more neck fat than normal-weight controls (p < 0.001), and neck fat volume correlated with neck circumference (r = 0.53, p < 0.001). Females had significantly greater cross-sectional neck fat than males (p < 0.001).ConclusionsWhile neck fat is associated with obesity and neck circumference in adolescents and is greater in females versus males, it does not appear to correlate with presence and severity of OSAS.
| S-EPMC8598172 | biostudies-literature
Project description:BackgroundObesity is prevalent among pregnant women in the United States; obstructive sleep apnea is highly comorbid with obesity and is associated with adverse pregnancy outcomes. Screening for obstructive sleep apnea in pregnant women has remained a challenge because of a lack of validated screening tools.ObjectiveThe purpose of this study was to evaluate established obstructive sleep apnea screening tools, a sleepiness scale, and individual component items in a cohort of pregnant women with extreme obesity in mid pregnancy with the use of objective testing to determine obstructive sleep apnea status and to describe the prevalence of obstructive sleep apnea among women with extreme obesity.Study designAdult pregnant subjects, between 24 and 35 weeks gestation, with a body mass index ≥40 kg/m2 at the time of enrollment completed obstructive sleep apnea screening tools (Berlin Questionnaire, American Society of Anesthesiologists checklist, and STOP-BANG questionnaire) and the Epworth Sleepiness Scale; they also underwent physical examination of the neck, mouth, and airway. The published obstructive sleep apnea in pregnancy prediction score was calculated for each subject. Obstructive sleep apnea status for each subject was determined by the results of an overnight, unattended type III home sleep apnea test.ResultsTwenty-four percent of pregnant women with extreme obesity had obstructive sleep apnea on home sleep apnea testing in mid pregnancy (Apnea-Hypopnea Index, ≥5 events per hour]. Established obstructive sleep apnea screening tools performed very poorly to screen for obstructive sleep apnea in this cohort. Age, body mass index, neck circumference, frequently witnessed apneas, and highly likely to fall asleep while driving were associated most strongly with obstructive sleep apnea status in this cohort.ConclusionWe found that 24% of pregnant women with body mass index ≥40 kg/m2 between 24 and 35 weeks gestation have obstructive sleep apnea, defined as Apnea-Hypopnea Index ≥5 events per hour on an overnight type III home sleep apnea test. We found the Berlin Questionnaire, American Society of Anesthesiologists checklist, STOP-BANG, obstructive sleep apnea in pregnancy score by Facco et al, and the Epworth Sleepiness Scale were not useful screening tools for obstructive sleep apnea in a cohort of obese pregnant women. However, age, body mass index, neck circumference, frequently witnessed apneas, and likely to fall asleep while driving were associated with obstructive sleep apnea in this cohort. Further studies are needed to adjust the criteria and thresholds within the available screening tools to better predict obstructive sleep apnea in pregnant women with obesity.
| S-EPMC6733412 | biostudies-literature
Project description:Rationale: Obstructive sleep apnea (OSA) has been associated with metabolic dysregulation and systemic inflammation. This may be due to pathophysiologic effects of OSA on visceral adipose tissue. We sought to assess the transcriptional consequences of OSA on adipocytes by utilizing pathway-focused analyses. Methods: Patients scheduled to undergo ventral hernia repair surgery were recruited to wear a portable home sleep monitor for two nights prior to surgery. Visceral fat biopsies were obtained intra-operatively. RNA was extracted and whole-genome expression profiling was performed. Gene Set Enrichment Analysis (GSEA) was used to identify curated gene sets that were differentially enriched in OSA subjects. Network analysis was applied to a select set of highly enriched pathways. Results: 10 patients with OSA and 8 control subjects were recruited. There were no differences in age, gender, body mass index between the two groups, but the OSA subjects had a significantly higher respiratory disturbance index (19.2 vs. 0.6, P-value 0.05) and worse hypoxemia (minimum oxygen saturation 79.7% vs. 87.8%, P-value < 0.001). GSEA identified a number of gene sets up-regulated in adipose tissue of OSA patients including the pro-inflammatory NF-κB pathway and the proteolytic ubiquitin/proteasome module. A critical metabolic pathway, the peroxisome proliferator-activated receptor (PPAR), was down-regulated in subjects with OSA. Network analysis linked members of these modules together and identified regulatory hubs. Conclusions: OSA is associated with alterations in visceral fat gene expression. Pathway-based network analysis highlighted perturbations in several key pathways whose coordinated interactions may contribute to the metabolic dysregulation observed in this complex disorder.
2012-09-01 | GSE38792 | GEO
Project description:ObjectiveThe reasons why adenotonsillectomy (AT) is less effective treating obese children with obstructive sleep apnea syndrome (OSAS) are not understood. Thus, the aim of the study was to evaluate how anatomical factors contributing to airway obstruction are affected by AT in these children.MethodsTwenty-seven obese children with OSAS (age 13.0 ± 2.3 y, body mass index Z-score 2.5 ± 0.3) underwent polysomnography and magnetic resonance imaging of the head during wakefulness before and after AT. Volumetric analysis of the upper airway and surrounding tissues was performed using commercial software (AMIRA®).ResultsPatients were followed for 6.1 ± 3.6 mo after AT. AT improved mean obstructive apnea-hypopnea index (AHI) from 23.7 ± 21.4 to 5.6 ± 8.7 (P < 0.001). Resolution of OSAS was noted in 44% (12 of 27), but only in 22% (4 of 18) of those with severe OSAS (AHI > 10). AT increased the volume of the nasopharynx and oropharynx (2.9 ± 1.3 versus 4.4 ± 0.9 cm(3), P < 0.001, and 3.2 ± 1.2 versus 4.3 ± 2.0 cm(3), P < 0.01, respectively), reduced tonsils (11.3 ± 4.3 versus 1.3 ± 1.4 cm(3), P < 0.001), but had no effect on the adenoid, lingual tonsil, or retropharyngeal nodes. A small significant increase in the volume of the soft palate and tongue was also noted (7.3 ± 2.5 versus 8.0 ± 1.9 cm(3), P = 0.02, and 88.2 ± 18.3 versus 89.3 ± 24.4 cm(3), P = 0.005, respectively).ConclusionsThis is the first report to quantify volumetric changes in the upper airway in obese children with OSAS after adenotonsillectomy showing significant residual adenoid tissue and an increase in the volume of the tongue and soft palate. These findings could explain the low success rate of AT reported in obese children with OSAS and are important considerations for clinicians treating these children.
| S-EPMC3648674 | biostudies-literature
Project description:RationaleMechanisms leading to obstructive sleep apnea syndrome (OSAS) in obese children are not well understood.ObjectivesThe aim of the study was to determine anatomical risk factors associated with OSAS in obese children as compared with obese control subjects without OSAS.MethodsMagnetic resonance imaging was used to determine the size of upper airway structure, and body fat composition. Paired analysis was used to compare between groups. Mixed effects regression models and conditional multiple logistic regression models were used to determine whether body mass index (BMI) Z-score was an effect modifier of each anatomic characteristic as it relates to OSAS.Measurements and main resultsWe studied 22 obese subjects with OSAS (12.5 ± 2.8 yr; BMI Z-score, 2.4 ± 0.4) and 22 obese control subjects (12.3 ± 2.9 yr; BMI Z-score, 2.3 ± 0.3). As compared with control subjects, subjects with OSAS had a smaller oropharynx (P < 0.05) and larger adenoid (P < 0.01), tonsils (P < 0.05), and retropharyngeal nodes (P < 0.05). The size of lymphoid tissues correlated with severity of OSAS whereas BMI Z-score did not have a modifier effect on these tissues. Subjects with OSAS demonstrated increased size of parapharyngeal fat pads (P < 0.05) and abdominal visceral fat (P < 0.05). The size of these tissues did not correlate with severity of OSAS and BMI Z-score did not have a modifier effect on these tissues.ConclusionsUpper airway lymphoid hypertrophy is significant in obese children with OSAS. The lack of correlation of lymphoid tissue size with obesity suggests that this hypertrophy is caused by other mechanisms. Although the parapharyngeal fat pads and abdominal visceral fat are larger in obese children with OSAS we could not find a direct association with severity of OSAS or with obesity.
| S-EPMC3081285 | biostudies-literature