Project description:Plasmatic microRNA sequencing was conducted in specific matched subgroups of subjects (n = 53) with and without OSA using HTG EdgeSeq miRNA WTA Assay technology.
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.
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.
Project description:Obstructive sleep apnea (OSA) has been linked to dysregulated metabolic states and treatment of sleep apnea may improve these conditions. Subcutaneous adipose tissue is a readily samplable fat depot that plays an important role in regulating metabolism. However, neither the pathophysiologic consequences of OSA nor the effects of continuous positive airway pressure (CPAP) in altering this compartment’s molecular pathways are understood. This study aimed to systematically identify subcutaneous adipose tissue transcriptional programs modulated in OSA and in response to its effective treatment with CPAP. Two subject groups were investigated: Study Group 1 was comprised of 10 OSA and 8 controls; Study Group 2 included 24 individuals with OSA studied at baseline and following CPAP. For each subject, genome-wide gene expression measurement of subcutaneous fat was performed. Differentially activated pathways elicited by OSA (Group 1) and in response to its treatment (Group 2) were determined using network and Gene Set Enrichment Analysis (GSEA). In Group 2, treatment of OSA with CPAP improved apnea hypopnea index, daytime sleepiness, and blood pressure, but not anthropometric measures. In Group 1, GSEA revealed many up-regulated gene sets in OSA subjects, most of which were involved in immuno-inflammatory (e.g., interferon-γ signaling), transcription, and metabolic processes such as adipogenesis. Unexpectedly, CPAP therapy in Group 2 subjects was also associated with up-regulation of several immune pathways as well as cholesterol biosynthesis. Collectively, our findings demonstrate that OSA alters distinct inflammatory and metabolic programs in subcutaneous fat, but these transcriptional signatures are not reversed with short-term effective therapy.
Project description:Obstructive sleep apnea (OSA) is characterized by recurrent complete or partial obstruction of the upper airway. The prevalence is 1-4% in children aged between 2 and 8 years and rising due to the increase in obesity rates in children. Although persistent OSA following adenotonsillectomy is usually associated with obesity and underlying complex disorders, it can also affect otherwise healthy children. Medical treatment strategies are frequently required when adenotonsillectomy is not indicated in children with OSA or if OSA is persistent following adenotonsillectomy. Positive airway pressure treatment is a very effective modality for persistent OSA in childhood; however, adherence rates are low. The aim of this review article is to summarize medical treatment options for OSA in children.
Project description:PurposeThe existence of a bidirectional relationship between poor sleep and pain intensity has been studied, and good sleep quality has been found to be a key factor underlying pain control. The purpose of this prospective cohort study was to observe if OSA treatment provides a reduction in temporo-mandibular disorder (TMD) pain and headache attributed to TMD in patients with obstructive sleep apnea (OSA) after 18 months of OSA treatment.MethodsA prospective cohort study was conducted on consecutive patients suffering from OSA. Patients underwent polysomnography and TMD examination according to the DC/TMD protocol at baseline and after 18 months. Intensity of TMD pain and headache attributed to TMD were analyzed.ResultsOf 40 patients (31 men, mean age 51.3 ± 10.3 years), 33 underwent OSA treatment. At the follow-up examination after 18 months, significant improvements in the intensity of pain-related TMD and headache attributed to TMD were observed (p < 0.05). Seven patients did not start treatment for OSA or discontinued treatment. These patients did not show any significant difference in intensity of TMD-pain or headache attributed to TMD after 18 months (p > 0.05).ConclusionsSignificant reductions in intensity of pain-related TMD and headache attributed to TMD were observed in patients with OSA after 18 months of OSA treatment onset, while no difference was observed in subjects not undergoing or discontinuing OSA treatment.Trial registrationThe protocol was registered on ClinicalTrials.gov database with number NCT04948541.
Project description:Objective. Obstructive sleep apnea (OSA) decreases sleep spindle density and frequency. We evaluated the effects of continuous positive airway pressure (CPAP) treatment on different features of sleep spindles. Methods. Twenty OSA patients underwent two night polysomnographies in a diagnostic phase and one night polysomnography after 6 months of CPAP treatment. The control group comprised 20 healthy controls. Sleep spindles were analyzed by a previously developed automated method. Unilateral and bilateral spindles were identified in central and frontopolar brain locations. Spindle density and frequency were determined for the first and last half of the NREM time. Results. The density of bilateral central spindles, which did not change in the untreated OSA patients, increased towards the morning hours during CPAP treatment and in the controls. Central spindles did not become faster with sleep in OSA patients and the central spindles remained slow in the left hemisphere even with CPAP. Conclusion. CPAP treatment normalized spindle features only partially. The changes may be associated with deficits in thalamocortical spindle generating loops. Significance. This study shows that some sleep spindle changes persist after CPAP treatment in OSA patients. The association of these changes to daytime symptoms in OSA patients needs to be further evaluated.
Project description:Obstructive sleep apnea (OSA) is a common disease in adults, which influences human relations, quality of life and associates with major complications. Continuous positive airway pressure (CPAP) is the gold standard treatment modality in OSA patients. For patients incompliant or unwilling to CPAP therapy, surgery is an alternative treatment. Sleep surgery for OSA include intrapharyngeal surgery, extrapharyngeal surgery and bariatric surgery addressing upper airway soft tissue, maxillofacial bone, and obesity, respectively. Among sleep surgeries, intrapharyngeal surgery (soft tissue surgery) is widespread used and serves overwhelming majority in OSA surgical patients. Despite the popularity of intrapharyngeal surgery, its outcomes can be influenced by multiple factors and consequently need conjunctive remedy to enhance at the short-term and sustain in the long-term. In this article, we introduce updated indications for treating OSA, practical principle in decision-making between CPAP and surgery, hybrid procedures in treating obstruction at the nose, palate, tongue and epiglottis, and postoperative integrated treatment including oropharyngeal myofunctional therapy (local), positional therapy (regional), and body weight reduction (systemic), and circadian rhythm (central). In summary, intrapharyngeal surgery is a target-oriented procedure that needs to be performed precisely and combines with integrated treatment as a holistic care for OSA patients.
Project description:PurposeThis review will trace the elements of neurostimulation for obstructive sleep apnea and details on its implementation, efficacy and safety, immediate clinical outcomes, and future prospects.MethodsThe literature on upper airway neurostimulation was surveyed from July, 2013, to July 2019, with a focus on the components of devices, evidence for clinical utility, and adverse events.ResultsCurrent technology is focused on the hypoglossal nerve stimulation (HNS). The most long-term experience is with the Inspire Medical System (Maple Grove, MN USA) which has both FDA and European regulatory approval. Given the inclusion criteria (BMI <35, ideally <32), AHI 15-65/h, and a favorable anterior-posterior velopharyngeal collapse pattern on DISE), across many centers ~65% of patients who are intolerant to primary therapy achieve clinical success (AHI <20/h with a reduction of <50% in AHI), and more have symptomatic relief. Adverse events are generally mild, often self-limited, with occasional need for uncomplicated surgical adjustments or replacement of the implantable generator. Three other devices are in various phases of development, each with a differences in nerve electrodes, implantable components, power sources, proprietary programming, and activation patterns.ConclusionsHNS is not considered a first-line treatment option. HNS therapy, however, should be considered as one alternative therapeutic option for patients meeting the inclusion criteria when more traditional therapeutic options have been considered.
Project description:ObjectiveDetermine risk factors for failure to receive surgical treatment among patients with obstructive sleep apnea.Study designPopulation-based observational longitudinal cohort study.SettingPopulation-based database.MethodsMultivariate analysis of 500,792 individuals with obstructive sleep apnea from Optum's deidentified Clinformatics Data Mart database (2004-2018).ResultsBlack race, increased age, diabetes, atrial fibrillation, obesity, and congestive heart failure were independently associated with a decreased rate of surgery for obstructive sleep apnea. Asian race, hypertension, arrhythmias other than atrial fibrillation, pulmonary disease, and liver disease were independently associated with an increased rate of surgery for obstructive sleep apnea.ConclusionRacial disparities in health outcomes related to health care access and in economic resources have an enormous impact on public health and social equity. We found differences in rates of surgery for obstructive sleep apnea based on race. These data are consistent with others demonstrating disparities in medical treatment of sleep apnea with positive pressure and underline a need for a change in awareness and treatment in these populations.