Pharmacotherapy of Obstructive Sleep Apnea: Is Salvation Just Around a Corner?
Ontology highlight
ABSTRACT:
SUBMITTER: Fleury Curado T
PROVIDER: S-EPMC6519854 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
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: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:There remains an important and unmet need for fully effective and acceptable treatments in obstructive sleep apnea (OSA). At present, there are no approved drug treatments. Dronabinol has shown promise for OSA pharmacotherapy in a small dose-escalation pilot study. Here, we present initial findings of the Phase II PACE (Pharmacotherapy of Apnea by Cannabimimetic Enhancement) trial, a fully blinded parallel groups, placebo-controlled randomized trial of dronabinol in people with moderate or severe OSA. By random assignment, 73 adults with moderate or severe OSA received either placebo (N = 25), 2.5 mg dronabinol (N = 21), or 10 mg dronabinol (N = 27) daily, 1 hour before bedtime for up to 6 weeks. At baseline, overall apnea-hypopnea index (AHI) was 25.9 ± 11.3, Epworth Sleepiness Scale (ESS) score was 11.45 ± 3.8, maintenance of wakefulness test (MWT) mean latency was 19.2 ± 11.8 minutes, body mass index was 33.4 ± 5.4 kg/m2, and age was 53.6 ± 9.0 years. The number and severity of adverse events, and treatment adherence (0.3 ± 0.6 missed doses/week) were equivalent among all treatment groups. Participants receiving 10 mg/day of dronabinol expressed the highest overall satisfaction with treatment (p = .04). In comparison to placebo, dronabinol dose-dependently reduced AHI by 10.7 ± 4.4 (p = .02) and 12.9 ± 4.3 (p = .003) events/hour at doses of 2.5 and 10 mg/day, respectively. Dronabinol at 10 mg/day reduced ESS score by -3.8 ± 0.8 points from baseline (p < .0001) and by -2.3 ± 1.2 points in comparison to placebo (p = .05). MWT sleep latencies, gross sleep architecture, and overnight oxygenation parameters were unchanged from baseline in any treatment group. These findings support the therapeutic potential of cannabinoids in people with OSA. In comparison to placebo, dronabinol was associated with lower AHI, improved self-reported sleepiness, and greater overall treatment satisfaction. Larger scale clinical trials will be necessary to clarify the best potential approach(es) to cannabinoid therapy in OSA.
| S-EPMC5806568 | biostudies-literature
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.
2021-12-01 | GSE174245 | GEO
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.
2019-12-21 | GSE135917 | GEO
Project description:Study objectivesThe aim of the study was to investigate the effect of ambient temperature on sleep, sleep apnea, and morning alertness in patients with obstructive sleep apnea.DesignRandomized controlled trial.SettingIn-hospital investigations.ParticipantsForty patients with obstructive sleep apnea naïve to treatment, with an apnea-hypopnea index of 10-30.InterventionsThree different nights in room temperatures of 16°C, 20°C, and 24°C.MeasurementsOvernight polysomnography and Karolinska Sleepiness Scale.ResultsThe obstructive apnea-hypopnea index was 30 ± 17 at 16°C room temperature, 28 ± 17 at 20°C, and 24 ± 18 at 24°C. The obstructive apnea-hypopnea index was higher at 16°C room temperature versus 24°C (P = 0.001) and at 20°C room temperature versus 24°C (P = 0.033). Total sleep time was a mean of 30 min longer (P = 0.009), mean sleep efficiency was higher (77 ± 11% versus 71 ± 13% respectively, P = 0.012), and the patients were significantly more alert according to the Karolinska Sleepiness Scale (P < 0.028) in the morning at 16°C room temperature versus 24°C. The amount of sleep in different sleep stages was not affected by room temperature.ConclusionsUntreated patients with obstructive sleep apnea sleep longer, have better sleep efficiency, and are more alert in the morning after a night's sleep at 16°C room temperature compared with 24°C, but obstructive sleep apnea is more severe at 16°C and 20°C compared with 24°C.Clinical trial informationThis study is registered in ClinicalTrials.gov number NCT00544752.
| S-EPMC3296793 | biostudies-literature
Project description:IntroductionEnhanced characterization of sleep architecture, compared with routine polysomnographic metrics such as stage percentages and sleep efficiency, may improve the predictive phenotyping of fragmented sleep. One approach involves using stage transition analysis to characterize sleep continuity.Methods and principal findingsWe analyzed hypnograms from Sleep Heart Health Study (SHHS) participants using the following stage designations: wake after sleep onset (WASO), non-rapid eye movement (NREM) sleep, and REM sleep. We show that individual patient hypnograms contain insufficient number of bouts to adequately describe the transition kinetics, necessitating pooling of data. We compared a control group of individuals free of medications, obstructive sleep apnea (OSA), medical co-morbidities, or sleepiness (n = 374) with mild (n = 496) or severe OSA (n = 338). WASO, REM sleep, and NREM sleep bout durations exhibited multi-exponential temporal dynamics. The presence of OSA accelerated the "decay" rate of NREM and REM sleep bouts, resulting in instability manifesting as shorter bouts and increased number of stage transitions. For WASO bouts, previously attributed to a power law process, a multi-exponential decay described the data well. Simulations demonstrated that a multi-exponential process can mimic a power law distribution.Conclusion and significanceOSA alters sleep architecture dynamics by decreasing the temporal stability of NREM and REM sleep bouts. Multi-exponential fitting is superior to routine mono-exponential fitting, and may thus provide improved predictive metrics of sleep continuity. However, because a single night of sleep contains insufficient transitions to characterize these dynamics, extended monitoring of sleep, probably at home, would be necessary for individualized clinical application.
| S-EPMC2893208 | biostudies-literature
Project description: Not available
| S-EPMC8534615 | biostudies-literature
Project description:Obstructive sleep apnea (OSA) is probably the most common respiratory disorder, with recent data from the United States and Europe suggesting that between 14% and 49% of middle-aged men have clinically significant OSA. The intimate relationship between OSA and obesity means that its prevalence will only increase as the global obesity epidemic evolves. At an individual level, OSA leads to a significant decrease in quality of life (QOL) and functional capacity, alongside a markedly increased risk of cardiovascular disease and death. Emerging data also suggest that the presence and severity of OSA and associated nocturnal hypoxemia are associated with an increased risk of diabetes and cancer. At a societal level, OSA not only leads to reduced economic productivity, but also constitutes a major treatable risk factor for hypertension, coronary artery disease (CAD) and stroke. This article addresses OSA from an epidemiological perspective, from prevalence studies to economic aspects to co-morbidity.
| S-EPMC4454867 | biostudies-literature
Project description:Obstructive sleep apnea (OSA) is common among patients with cardiac rhythm disorders. OSA may contribute to arrhythmias due to acute mechanisms, such as generation of negative intrathoracic pressure during futile efforts to breath, intermittent hypoxia, and surges in sympathetic activity. In addition, OSA may lead to heart remodeling and increases arrhythmia susceptibility. Atrial distension and remodeling, that has been shown to be associated with OSA, is a well-known anatomical substrate for atrial fibrillation (AF). AF is the arrhythmia most commonly described in patients with OSA. Several observational studies have shown that the treatment of OSA with continuous positive airway pressure (CPAP) reduces recurrence of AF after electrical cardioversion and catheter ablation. There is also evidence that nocturnal hypoxemia, a hallmark of OSA, predicts sudden cardiac death (SCD) independently of well-established cardiovascular risk factors. Among patients with an implantable cardiac defibrillator, those with OSA have a higher risk of receiving treatment for life-threatening arrhythmias. Nocturnal hypoxemia may also increase vagal tone, which increases susceptibility to bradycardic and conduction rhythm disorders that have also been described in patients with OSA. In conclusion, there are several biological pathways linking OSA and increased cardiac arrhythmogenesis propensity. However, the independent association is derived from observational studies and the direction of the association still needs clarification due to the lack of large clinical trials. This review focuses on the current scientific evidence linking OSA to cardiac rhythm disorders and point out future directions.
| S-EPMC6321897 | biostudies-other