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

Sleepiness and cardiometabolic impact of short sleep duration and OSA : what about the clock?

© 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.info:eu-repo/semantics/publishedVersio

Nocturnal Oximetry-based Evaluation of Habitually Snoring Children

Rationale: The vast majority of children around the world undergoing adenotonsillectomy for obstructive sleep apnea–hypopnea syndrome (OSA) are not objectively diagnosed by nocturnal polysomnography because of access availability and cost issues. Automated analysis of nocturnal oximetry (nSpO2), which is readily and globally available, could potentially provide a reliable and convenient diagnostic approach for pediatric OSA. Methods: DeidentifiednSpO2 recordings froma total of 4,191 children originating from13 pediatric sleep laboratories around the worldwere prospectively evaluated after developing and validating an automated neural network algorithm using an initial set of single-channel nSpO2 recordings from 589 patients referred for suspected OSA. Measurements and Main Results: The automatically estimated apnea–hypopnea index (AHI) showed high agreement with AHI from conventional polysomnography (intraclass correlation coefficient, 0.785) when tested in 3,602 additional subjects. Further assessment on the widely used AHI cutoff points of 1, 5, and 10 events/h revealed an incremental diagnostic ability (75.2, 81.7, and 90.2% accuracy; 0.788, 0.854, and 0.913 area under the receiver operating characteristic curve, respectively). Conclusions: Neural network–based automated analyses of nSpO2 recordings provide accurate identification of OSA severity among habitually snoring children with a high pretest probability of OSA. Thus, nocturnal oximetry may enable a simple and effective diagnostic alternative to nocturnal polysomnography, leading to more timely interventions and potentially improved outcomes.Supported in part by project VA037 U16 from the Consejer´ıa de Educacio´ n de la Junta de Castilla y Leo´ n and the European Regional Development Fund (FEDER), project RTC-2015-3446-1 from the Ministerio de Econom´ıa y Competitividad and FEDER, and project 153/2015 of the Sociedad Espan˜ ola de Neumolog´ıa y Cirug´ıa Tora´ cica (SEPAR). L.K.-G. is supported by NIH grant 1R01HL130984. M.F.P. was supported by a Fellowship Educational grant award from the Kingdom of Saudi Arabia. D.´A. was in receipt of a Juan de la Cierva grant from the Ministerio de Econom´ıa y Competitividad. The funders played no role in the study design, data collection, data analysis, interpretation, and writing of the manuscript

Putative contributions of circadian clock and sleep in the context of SARS-CoV-2 infection

Copyright © ERS 2020. This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the aetiological agent of the pandemic coronavirus disease 2019 (COVID-19), is a newly found member of the Coronaviridae family, and is closely related to, albeit with important differences from, SARS-CoV. It enters human cells through the binding of surface spike (S) glycoprotein with angiotensin-converting enzyme 2 (ACE2). The distal S1 subunit of the S protein is responsible for receptor binding, while the transmembrane S2 subunit mediates fusion between the viral envelope and the target cell membrane following proteolytic cleavage by specific cellular enzymes such as transmembrane serine protease 2 for S protein priming. As it is likely that expression levels of ACE2 affect the efficiency of virus attachment and entry, as well as disease severity, and the interactions between viral S protein and ACE2 may directly cause lung injury, ACE2 may be a potential target of therapeutic and preventative interventions.info:eu-repo/semantics/publishedVersio

Molecular Biomarkers of Vascular Dysfunction in Obstructive Sleep Apnea

Untreated and long-lasting obstructive sleep apnea (OSA) may lead to important vascular abnormalities, including endothelial cell (EC) dysfunction, hypertension, and atherosclerosis. We observed a correlation between microcirculatory reactivity and endothelium-dependent release of nitric oxide in OSA patients. Therefore, we hypothesized that OSA affects (micro)vasculature and we aimed to identify vascular gene targets of OSA that could possibly serve as reliable biomarkers of severity of the disease and possibly of vascular risk. Using quantitative RT-PCR, we evaluated gene expression in skin biopsies of OSA patients, mouse aortas from animals exposed to 4-week intermittent hypoxia (IH; rapid oscillations in oxygen desaturation and reoxygenation), and human dermal microvascular (HMVEC) and coronary artery endothelial cells (HCAEC) cultured under IH. We demonstrate a significant upregulation of endothelial nitric oxide synthase (eNOS), tumor necrosis factor-alpha-induced protein 3 (TNFAIP3; A20), hypoxia-inducible factor 1 alpha (HIF-1α?? and vascular endothelial growth factor (VEGF) expression in skin biopsies obtained from OSA patients with severe nocturnal hypoxemia (nadir saturated oxygen levels [SaO2]<75%) compared to mildly hypoxemic OSA patients (SaO2 75%–90%) and a significant upregulation of vascular cell adhesion molecule 1 (VCAM-1) expression compared to control subjects. Gene expression profile in aortas of mice exposed to IH demonstrated a significant upregulation of eNOS and VEGF. In an in vitro model of OSA, IH increased expression of A20 and decreased eNOS and HIF-1α expression in HMVEC, while increased A20, VCAM-1 and HIF-1αexpression in HCAEC, indicating that EC in culture originating from distinct vascular beds respond differently to IH stress. We conclude that gene expression profiles in skin of OSA patients may correlate with disease severity and, if validated by further studies, could possibly predict vascular risk in OSA patients

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

Perception of sleep duration in adult patients with suspected obstructive sleep apnea

PURPOSE: Discrepancies between subjective and objective measures of total sleep time (TST) are frequent among insomnia patients, but this issue remains scarcely investigated in obstructive sleep apnea (OSA). We aimed to evaluate if sleep perception is affected by the severity of OSA. METHODS: We performed a 3-month cross-sectional study of Brazilian adults undergoing overnight polysomnography (PSG). TST was objectively assessed from PSG and by a self-reported questionnaire (subjective measurement). Sleep perception index (SPI) was defined by the ratio of subjective and objective values. Diagnosis of OSA was based on an apnea/hypopnea index (AHI) ≥ 5.0/h, being its severity classified according to AHI thresholds: 5.0-14.9/h (mild OSA), 15.0-29.9/h (moderate OSA), and ≥ 30.0/h (severe OSA). RESULTS: Overall, 727 patients were included (58.0% males). A significant difference was found in SPI between non-OSA and OSA groups (p = 0.014). Mean SPI values significantly decreased as the OSA severity increased: without OSA (100.1 ± 40.9%), mild OSA (95.1 ± 24.6%), moderate OSA (93.5 ± 25.2%), and severe OSA (90.6 ± 28.2%), p = 0.036. Using logistic regression, increasing SPI was associated with a reduction in the likelihood of presenting any OSA (p = 0.018), moderate/severe OSA (p = 0.019), and severe OSA (p = 0.028). However, insomnia was not considered as an independent variable for the presence of any OSA, moderate/severe OSA, and severe OSA (all p-values > 0.05). CONCLUSION: In a clinical referral cohort, SPI significantly decreases with increasing OSA severity, but is not modified by the presence of insomnia symptoms.publishersversionpublishe

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 sex-matched controls participated in an auditory oddball task wearing 128-electrode nets. Parents completed the Conners Parent Rating Scales–Revised Long (CPRS–R:L). Results: Snorers scored significantly higher on four CPRS-R:L subscales. Stepwise regression indicated that two ERP variables from a region of the ERP that peaked at 844 msec post-stimulus onset predicted CPRS-R:L Attention Deficit Hyperactivity Disorder (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