OBJECTIVES: This revised clinical practice guideline, intended for use by primary care clinicians, provides recommendations for the diagnosis and management of the obstructive sleep apnea syndrome (OSAS) in children and adolescents. This practice guideline focuses on uncomplicated childhood OSAS, that is, OSAS associated with adenotonsillar hypertrophy and/or obesity in an otherwise healthy child who is being treated in the primary care setting. METHODS: Of 3166 articles from 1999–2010, 350 provided relevant data. Most articles were level II–IV. The resulting evidence report was used to formulate recommendations. RESULTS AND CONCLUSIONS: The following recommendations are made. (1) All children/adolescents should be screened for snoring. (2) Polysomnography should be performed in children/adolescents with snoring and symptoms/signs of OSAS; if polysomnography is not available, then alternative diagnostic tests or referral to a specialist for more extensive evaluation may be considered. (3) Adenotonsillectomy is recommended as the first-line treatment of patients with adenotonsillar hypertrophy. (4) High-risk patients should be monitored as inpatients postoperatively. (5) Patients should be reevaluated postoperatively to determine whether further treatment is required. Objective testing should be performed in patients who are high risk or have persistent symptoms/signs of OSAS after therapy. (6) Continuous positive airway pressure is recommended as treatment if adenotonsillectomy is not performed or if OSAS persists postoperatively. (7) Weight loss is recommended in addition to other therapy in patients who are overweight or obese. (8) Intranasal corticosteroids are an option for children with mild OSAS in whom adenotonsillectomy is contraindicated or for mild postoperative OSAS.

/pdf/diagnosis-and-management-of-childhood-obstructive-sleep-2wes17zrfk.pdf

Diagnosis and Management of Childhood Obstructive Sleep Apnea Syndrome

Experimental autoimmune encephalomyelitis (EAE) is the most commonly used experimental model for the human inflammatory demyelinating disease, multiple sclerosis (MS). EAE is a complex condition in which the interaction between a variety of immunopathological and neuropathological mechanisms leads to an approximation of the key pathological features of MS: inflammation, demyelination, axonal loss and gliosis. The counter-regulatory mechanisms of resolution of inflammation and remyelination also occur in EAE, which, therefore can also serve as a model for these processes. Moreover, EAE is often used as a model of cell-mediated organ-specific autoimmune conditions in general. EAE has a complex neuropharmacology, and many of the drugs that are in current or imminent use in MS have been developed, tested or validated on the basis of EAE studies. There is great heterogeneity in the susceptibility to the induction, the method of induction and the response to various immunological or neuropharmacological interventions, many of which are reviewed here. This makes EAE a very versatile system to use in translational neuro- and immunopharmacology, but the model needs to be tailored to the scientific question being asked. While creating difficulties and underscoring the inherent weaknesses of this model of MS in straightforward translation from EAE to the human disease, this variability also creates an opportunity to explore multiple facets of the immune and neural mechanisms of immune-mediated neuroinflammation and demyelination as well as intrinsic protective mechanisms. This allows the eventual development and preclinical testing of a wide range of potential therapeutic interventions.

/pdf/experimental-autoimmune-encephalomyelitis-eae-as-a-model-for-45iseycr1x.pdf

Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS)

The S100 protein family consists of 24 members functionally distributed into three main subgroups: those that only exert intracellular regulatory effects, those with intracellular and extracellular functions and those which mainly exert extracellular regulatory effects. S100 proteins are only expressed in vertebrates and show cell-specific expression patterns. In some instances, a particular S100 protein can be induced in pathological circumstances in a cell type that does not express it in normal physiological conditions. Within cells, S100 proteins are involved in aspects of regulation of proliferation, differentiation, apoptosis, Ca2+ homeostasis, energy metabolism, inflammation and migration/invasion through interactions with a variety of target proteins including enzymes, cytoskeletal subunits, receptors, transcription factors and nucleic acids. Some S100 proteins are secreted or released and regulate cell functions in an autocrine and paracrine manner via activation of surface receptors (e.g. the receptor for advanced glycation end-products and toll-like receptor 4), G-protein-coupled receptors, scavenger receptors, or heparan sulfate proteoglycans and N-glycans. Extracellular S100A4 and S100B also interact with epidermal growth factor and basic fibroblast growth factor, respectively, thereby enhancing the activity of the corresponding receptors. Thus, extracellular S100 proteins exert regulatory activities on monocytes/macrophages/microglia, neutrophils, lymphocytes, mast cells, articular chondrocytes, endothelial and vascular smooth muscle cells, neurons, astrocytes, Schwann cells, epithelial cells, myoblasts and cardiomyocytes, thereby participating in innate and adaptive immune responses, cell migration and chemotaxis, tissue development and repair, and leukocyte and tumor cell invasion.

Functions of S100 Proteins

Considerable evidence is available in support of an independent association between obstructive sleep apnoea syndrome (OSAS) and cardiovascular disease, which is particularly strong for systemic arterial hypertension and growing for ischaemic heart disease, stroke, heart failure, atrial fibrillation and cardiac sudden death. The pathogenesis of cardiovascular disease in OSAS is not completely understood but likely to be multifactorial, involving a diverse range of mechanisms including sympathetic nervous system overactivity, selective activation of inflammatory molecular pathways, endothelial dysfunction, abnormal coagulation and metabolic dysregulation, the latter particularly involving insulin resistance and disordered lipid metabolism. The present report, which arose out of a European Union Cooperation in the field of Scientific and Technical Research (COST) action on OSAS (COST B26), reviews the current evidence for an independent association and proposes research priorities to identify the underlying mechanisms involved, with a view to identifying novel therapeutic strategies. Large-scale collaborative studies of carefully defined patient populations with obstructive sleep apnoea syndrome, adequately controlled for potential confounders, are needed. Such studies carry the prospect of evaluating potential interactions between different basic mechanisms operating in obstructive sleep apnoea syndrome and cardiovascular disease, and interactions with other related disorders, such as obesity, diabetes and dyslipidaemia. Furthermore, translational studies involving cell culture and animal models linked to studies of obstructive sleep apnoea syndrome patients are necessary to integrate basic mechanisms with the clinical disorder.

https://erj.ersjournals.com/content/erj/29/1/156.full.pdf

Sleep apnoea as an independent risk factor for cardiovascular disease: current evidence, basic mechanisms and research priorities

Rationale: The overall efficacy of adenotonsillectomy (AT) in treatment of obstructive sleep apnea syndrome (OSAS) in children is unknown. Although success rates are likely lower than previously estimated, factors that promote incomplete resolution of OSAS after AT remain undefined.Objectives: To quantify the effect of demographic and clinical confounders known to impact the success of AT in treating OSAS.Methods: A multicenter collaborative retrospective review of all nocturnal polysomnograms performed both preoperatively and postoperatively on otherwise healthy children undergoing AT for the diagnosis of OSAS was conducted at six pediatric sleep centers in the United States and two in Europe. Multivariate generalized linear modeling was used to assess contributions of specific demographic factors on the post-AT obstructive apnea-hypopnea index (AHI).Measurements and Main Results: Data from 578 children (mean age, 6.9 ± 3.8 yr) were analyzed, of which approximately 50% of included children were obese. AT...

https://www.atsjournals.org/doi/pdf/10.1164/rccm.200912-1930OC

Adenotonsillectomy outcomes in treatment of obstructive sleep apnea in children: a multicenter retrospective study.

Background— Obstructive sleep apnea (OSA) in children is associated with cardiovascular morbidity such as systemic and pulmonary hypertension. However, it remains unclear whether endothelial dysfunction occurs in pediatric OSA and whether it is reversible on effective treatment of OSA. Methods and Results— Consecutive nonobese children (aged 6 to 11 years) who were diagnosed with OSA after overnight polysomnography and control children matched on the basis of age, gender, ethnicity, and body mass index underwent blood draw the next morning for soluble CD40 ligand, asymmetric dimethylarginine (ADMA), and nitrotyrosine levels, as well as 2 iterations of 60-second cuff-occlusion tests for assessment of endothelial function. These tests were repeated 4 to 6 months after adenotonsillectomy. OSA children showed blunted reperfusion kinetics after release of occlusion, which completely normalized in 20 of 26 patients after adenotonsillectomy. All 6 children in whom no improvements occurred had a strong family his...

Obstructive Sleep Apnea and Endothelial Function in School-Aged Nonobese Children Effect of Adenotonsillectomy

J. Neurochem. (2012) 120, 644–659.



Abstract

S100B is a calcium-binding protein concentrated in glial cells, although it has also been detected in definite extra-neural cell types. Its biological role is still debated. When secreted, S100B is believed to have paracrine/autocrine trophic effects at physiological concentrations, but toxic effects at higher concentrations. Elevated S100B levels in biological fluids (CSF, blood, urine, saliva, amniotic fluid) are thus regarded as a biomarker of pathological conditions, including perinatal brain distress, acute brain injury, brain tumors, neuroinflammatory/neurodegenerative disorders, psychiatric disorders. In the majority of these conditions, high S100B levels offer an indicator of cell damage when standard diagnostic procedures are still silent. The key question remains as to whether S100B is merely leaked from injured cells or is released in concomitance with both physiological and pathological conditions, participating at high concentrations in the events leading to cell injury. In this respect, S100B levels in biological fluids have been shown to increase in physiological conditions characterized by stressful physical and mental activity, suggesting that it may be physiologically regulated and raised during conditions of stress, with a putatively active role. This possibility makes this protein a candidate not only for a biomarker but also for a potential therapeutic target.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1471-4159.2011.07612.x

The S100B protein in biological fluids: more than a lifelong biomarker of brain distress

Systemic Inflammation in Non-Obese Children with Obstructive Sleep Apnea

Experimental autoimmune encephalomyelitis (EAE), an animal model for human multiple sclerosis, is characterized by demyelination, inflammation and neurodegeneration of CNS in which free radicals play a role. Recently, the efficacy of murine mesenchimal stem cells (MSCs) as treatment of EAE induced in mice by the encephalitogenic peptide MOG(35-55) was demonstrated. The present study analyzed some markers of oxidative stress, inflammation/degeneration and apoptosis such as metallothioneins (MTs), antioxidant enzymes (superoxide dismutase, catalase and glutathione-S-transferase), poly(ADP-ribose) polymerase-1 and p53 during EAE progression and following MSC treatment. Expression of the three brain MT isoforms increased significantly in EAE mice compared with healthy controls, but while expression of MT-1 and MT-3 increased along EAE course, MT-2 was up-regulated at the onset, but returned to levels similar to those of controls in chronic phase. The changes in the transcription and activity of the antioxidant enzymes and in expression of poly(ADP-ribose) polymerase-1 and p53 showed the same kinetics observed for MT-1 and MT-3 during EAE. Interestingly, i.v. administration of MSCs reduced the EAE-induced increases in levels/activities of all these proteins. These results support an antioxidant and neuroprotective activity for MSCs that was also confirmed in vitro on neuroblastoma cells exposed to an oxidative insult.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1471-4159.2009.06268.x

Laura D. Serpero

Papers

Obstructive Sleep Apnea and Endothelial Function in School-Aged Nonobese Children Effect of Adenotonsillectomy

The S100B protein in biological fluids: more than a lifelong biomarker of brain distress

Systemic Inflammation in Non-Obese Children with Obstructive Sleep Apnea

Neuroprotective mesenchymal stem cells are endowed with a potent antioxidant effect in vivo.

Inflammatory Mediators in Exhaled Breath Condensate of Children With Obstructive Sleep Apnea Syndrome