Sera of elderly obstructive sleep apnea patients alter blood-brain barrier integrity in vitro: a pilot study.
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ABSTRACT:
SUBMITTER: Voirin AC
PROVIDER: S-EPMC7347951 | biostudies-literature | 2020 Jul
REPOSITORIES: biostudies-literature
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Sera of elderly obstructive sleep apnea patients alter blood-brain barrier integrity in vitro: a pilot study.
Voirin Anne-Cloé AC Celle Sébastien S Perek Nathalie N Roche Frédéric F
Scientific reports 20200709 1
Obstructive sleep apnea syndrome (OSAS) is characterized by repeated episodes of hypoxia during the night. The severity of the disorder can be evaluated using an apnea-hypopnea index (AHI). The physiological consequences are mainly cardiovascular and neuronal dysfunctions. One hypothesis to explain such associated neurological disorders is disruption of the blood-brain barrier (BBB), which protects the brain from endovascular cytotoxic compounds. We selected two subgroups of volunteers from the ...[more]
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Project description:Study objectivesWe aimed to characterize the cerebral hemodynamic response to obstructive sleep apnea/hypopnea events, and evaluate their association to polysomnographic parameters. The characterization of the cerebral hemodynamics in obstructive sleep apnea (OSA) may add complementary information to further the understanding of the severity of the syndrome beyond the conventional polysomnography.MethodsSevere OSA patients were studied during night sleep while monitored by polysomnography. Transcranial, bed-side diffuse correlation spectroscopy (DCS) and frequency-domain near-infrared diffuse correlation spectroscopy (NIRS-DOS) were used to follow microvascular cerebral hemodynamics in the frontal lobes of the cerebral cortex. Changes in cerebral blood flow (CBF), total hemoglobin concentration (THC), and cerebral blood oxygen saturation (StO2) were analyzed.ResultsWe considered 3283 obstructive apnea/hypopnea events from sixteen OSA patients (Age (median, interquartile range) 57 (52-64.5); females 25%; AHI (apnea-hypopnea index) 84.4 (76.1-93.7)). A biphasic response (maximum/minimum followed by a minimum/maximum) was observed for each cerebral hemodynamic variable (CBF, THC, StO2), heart rate and peripheral arterial oxygen saturation (SpO2). Changes of the StO2 followed the dynamics of the SpO2, and were out of phase from the THC and CBF. Longer events were associated with larger CBF changes, faster responses and slower recoveries. Moreover, the extrema of the response to obstructive hypopneas were lower compared to apneas (p < .001).ConclusionsObstructive apneas/hypopneas cause profound, periodic changes in cerebral hemodynamics, including periods of hyper- and hypo-perfusion and intermittent cerebral hypoxia. The duration of the events is a strong determinant of the cerebral hemodynamic response, which is more pronounced in apnea than hypopnea events.
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Project description:Background The purpose of this study was to evaluate the prevalence of position-dependent obstructive sleep apnea (POSA) in elderly patients (?65 years old). Adult (range 19-65 years old) and elderly patients were also compared in order to show differences in the incidence of POSA between these two groups of patients. Methods A prospective bi-center study was performed between January 2018 and May 2019. A total of 434 participants underwent polysomnography (PSG) study at home (Embletta MPR). Body position during the PSG recordings was determined. Patients were subdivided in two groups: those aged between 19 and 65 years old (adult patients) and ?65 years old (elderly patients). POSA patients were defined using Cartwright's system, Bignold classification, and the new Amsterdam Positional OSA Classification (APOC). Results The prevalence of POSA in elderly patients differed according to the classification system used: 49.3% using Cartwright's classification system, 20.5% with the Bignold classification, and 22.6%, 38.9%, and 5.4% of APOC 1, APOC 2, and APOC3 sub-classes were respectively identified for the APOC classification system. No difference between adult and elderly patients regarding the prevalence of POSA was observed. No statistical differences emerged between the two groups of patients in terms of supine (p = 0.9) and non-supine AHI (p = 0.4). Conclusions A significant number of elderly patients could be considered treatable with positional therapy according to the APOC classification. However, the efficacy and applicability of positional therapy in elderly patients must be confirmed by further research.
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2012-09-01 | E-GEOD-38792 | biostudies-arrayexpress
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:Objectives: Obstructive Sleep Apnea (OSA) is related to repeated upper airway collapse, intermittent hypoxia, and intestinal barrier dysfunction. The resulting damage to the intestinal barrier may affect or be affected by the intestinal microbiota. Methods: A prospective case-control was used, including 48 subjects from Sleep Medicine Center of Nanfang Hospital. Sleep apnea was diagnosed by overnight polysomnography. Fecal samples and blood samples were collected from subjects to detect intestinal microbiome composition (by 16S rDNA gene amplification and sequencing) and intestinal barrier biomarkers – intestinal fatty acid-binding protein (I-FABP) and D-lactic acid (D-LA) (by ELISA and colorimetry, respectively). Results: The severity of OSA was related to differences in the structure and composition of the intestinal microbiome. Enriched Fusobacterium, Megamonasa, Lachnospiraceae_UCG_006, and reduced Anaerostipes was found in patients with severe OSA. Enriched Ruminococcus_2, Lachnoclostridium, Lachnospiraceae_UCG_006, and Alloprevotella was found in patients with high intestinal barrier biomarkers. Lachnoclostridium and Lachnospiraceae_UCG_006 were the common dominant bacteria of OSA and intestinal barrier damage. Fusobacterium and Peptoclostridium was independently associated with apnea-hypopnea index (AHI). The dominant genera of severe OSA were also related to glucose, lipid, neutrophils, monocytes and BMI. Network analysis identified links between the intestinal microbiome, intestinal barrier biomarkers, and AHI. Conclusions: The study confirms that changes in the intestinal microbiota are related to intestinal barrier biomarkers among patients in OSA. These changes may play a pathophysiological role in the systemic inflammation and metabolic comorbidities associated with OSA, leading to multi-organ morbidity of OSA.
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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-? 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.
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Project description:Small uncontrolled series suggest that treatment of obstructive sleep apnea (OSA) in patients with epilepsy may improve seizure control. Prior to conducting a definitive randomized controlled trial, we addressed critical design issues in a pilot study.We identified a cohort of adult patients with medically refractory epilepsy and coexisting OSA, documented by polysomnography (PSG). After an 8-week baseline period, subjects with OSA were randomized to therapeutic or sham continuous positive airway pressure (CPAP) for 10 weeks. Subjects maintained seizure calendars and antiepileptic drug dosages were held constant.Sixty-eight subjects with suspected OSA were enrolled and 35 subjects randomized to therapeutic CPAP (22 subjects) or sham (13 subjects) CPAP. Male gender and an elevated sleep apnea questionnaire score were predictive of OSA on PSG. Nineteen subjects in the therapeutic group and all 13 subjects in the sham group completed the trial. Baseline apnea-hypopnea index (AHI) and CPAP adherence were comparable between groups. A significant reduction in AHI was observed in the therapeutic CPAP group as compared to the sham group. Subjects, study coordinators, and principal investigators were unable to predict treatment allocation.This pilot study provided critical information related to study design and feasibility for planning a comprehensive trial to test the hypothesis that treating obstructive sleep apnea in patients with epilepsy improves seizure control.
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Project description:Illumina MiSeq next generation sequencing chip was used to identify differentially expressed miRs by comparing peripheral blood mononuclear cell samples between OSA patients and healthy non-snorers.
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Project description:BackgroundThis study assessed the prevalence of obstructive sleep apnea syndrome (OSAS) and CPAP adherence in the elderly Chinese in Hong Kong.MethodsWe conducted a sleep questionnaire survey among the elders aged ≥60 years in the community centres followed by level 3 home sleep study (Embletta). Subjects with an apnea hypopnea index (AHI) ≥ 15/hr alone and those with AHI ≥ 5/hr plus either cardiovascular risk factors or Epworth Sleepiness Score (ESS) ≥ 10 were offered CPAP treatment.ResultsAltogether 819 subjects were interviewed with mean (SD) age of 73.9 (7.5) years, BMI 24.2 (3.6) kg/m2, neck circumference 34.9 (3.4) cm and ESS 6.6 (5.2). Daytime sleepiness was reported by 72.4%, snoring loudly 5.1% and witnessed apnea 4%. Among 234 subjects who underwent home sleep study, 156 (66.7%), 102 (43.6%), 70 (29.9%) and 45 (19.2%) had AHI ≥ 5, ≥ 10, ≥ 15 and ≥ 20/hr respectively, with the prevalence increasing with age and BMI. In the sample, 149 subjects (63.7%) were classified as having OSAS, as defined by an AHI ≥ 5/hr with associated symptoms, involving 81 men (74.3%) and 68 women (54.4%). Neck circumference and snoring frequency were the only positive independent factors associated with the AHI and the diagnosis of OSAS. Among 141 subjects who were offered CPAP treatment, 30 accepted CPAP prescription with improvement of ESS and cognitive function over 12 months with CPAP usage of 4.2 (2.2) h/night.ConclusionThis study showed a high prevalence of OSAS among the community elders in Hong Kong. Home CPAP acceptance was low but there was significant improvement of subjective sleepiness and cognitive function among those on CPAP treatment.
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Project description:Study objectivesHypoglossal nerve stimulation (HNS) is an effective surgical alternative for patients with obstructive sleep apnea (OSA). HNS therapy relies on the stimulation of the hypoglossal nerve to open the upper airways. This stimulation could lead to alterations in tongue strength and fatigability, which could alter treatment outcome over time. The aim of the study was to investigate whether HNS alters tongue strength and fatigability.MethodsTongue protrusion strength (peak pressure in kPa) and fatigability (time to task failure during 50% of peak pressure contraction) were measured with a pressure transducer at least 2 months after HNS implantation (n = 30). These results were compared to a group of patients with OSA (n = 38) and a non-OSA control group (n = 35).ResultsMedian tongue protrusion strength was lower (54.7 [43.8, 63.0] versus 60.7 [53.7, 66.0] kPa, P = .013) and fatigue occurred more quickly (21.3 [17.4, 26.3] versus 26.0 [19.3, 31.3] seconds, P = .017) in the patients with OSA compared to the non-OSA control group. In multiple regression analysis, age was a significant factor for tongue strength and diagnosis of OSA for tongue fatigability. Tongue strength and fatigability did not differ between patients with OSA with conservative therapy or observation versus after HNS implantation (51.8 [41.3, 63.4] versus 56.3 [45.0, 62.3] kPa, P = .502; 20.8 [16.3, 26.2] versus 21.8 [18.3, 26.8] seconds, P = .418).ConclusionsTongue strength decreases with age. Tongue fatigability is more pronounced in people with OSA. However, approximately 1.5 years of HNS therapy on average does not alter tongue strength or fatigability compared to an OSA control group.Clinical trial registrationRegistry: ClinicalTrials.gov; Title: Change in Tongue Strength and Fatigue After Upper Airway Stimulation Therapy; Identifier: NCT03980158.
| S-EPMC7053026 | biostudies-literature