Differences in breathing patterning during wakefulness in patients with mixed apnea-dominant vs obstructive-dominant sleep apnea.
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ABSTRACT:
SUBMITTER: Yamauchi M
PROVIDER: S-EPMC3130526 | biostudies-other | 2011 Jul
REPOSITORIES: biostudies-other
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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:Patients with obstructive sleep apnea (OSA) exhibit heterogeneous heart rate variability (HRV) during wakefulness and sleep. We investigated the influence of OSA severity on HRV parameters during wakefulness in a large international clinical sample. 1247 subjects (426 without OSA and 821 patients with OSA) were enrolled from the Sleep Apnea Global Interdisciplinary Consortium. HRV parameters were calculated during a 5-minute wakefulness period with spontaneous breathing prior to the sleep study, using time-domain, frequency-domain and nonlinear methods. Differences in HRV were evaluated among groups using analysis of covariance, controlling for relevant covariates. Patients with OSA showed significantly lower time-domain variations and less complexity of heartbeats compared to individuals without OSA. Those with severe OSA had remarkably reduced HRV compared to all other groups. Compared to non-OSA patients, those with severe OSA had lower HRV based on SDNN (adjusted mean: 37.4 vs. 46.2 ms; p < 0.0001), RMSSD (21.5 vs. 27.9 ms; p < 0.0001), ShanEn (1.83 vs. 2.01; p < 0.0001), and Forbword (36.7 vs. 33.0; p = 0.0001). While no differences were found in frequency-domain measures overall, among obese patients there was a shift to sympathetic dominance in severe OSA, with a higher LF/HF ratio compared to obese non-OSA patients (4.2 vs. 2.7; p = 0.009). Time-domain and nonlinear HRV measures during wakefulness are associated with OSA severity, with severe patients having remarkably reduced and less complex HRV. Frequency-domain measures show a shift to sympathetic dominance only in obese OSA patients. Thus, HRV during wakefulness could provide additional information about cardiovascular physiology in OSA patients. A Prospective Observational Cohort to Study the Genetics of Obstructive Sleep Apnea and Associated Co-Morbidities (German Clinical Trials Register - DKRS, DRKS00003966) https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00003966.
| S-EPMC8120337 | biostudies-literature
Project description:ObjectiveUnilateral hypoglossal nerve stimulation (uniHNS) is an effective treatment for obstructive sleep apnea. Bilateral hypoglossal nerve stimulation (biHNS) is a novel therapeutic option and a different approach to hypoglossal nerve stimulation. The aim of this study was to analyze the clinical outcome of the first 10 biHNS cases vs the first 10 uniHNS cases ever implanted.Study designProspective data analysis.SettingInternational multicenter comparative clinical trial.MethodsThe first 10 patients in 2020 who received a biHNS device (Genio System; Nyxoah) and the first 10 patients in 2014 who received a uniHNS system (Inspire II; Inspire Medical Systems) were included. Treatment outcome was evaluated at 3 months after surgery. Data collection included demographics, apnea hypopnea index (AHI), oxygen saturation and desaturation index, Epworth Sleepiness Scale, and adverse events.ResultsThe mean ± SD age was 52.1 ± 9.6 years (biHNS) and 58.3 ± 8.6 years (uniHNS). The mean body mass index was 26.4 ± 5.6 kg/m2 (biHNS) and 26.2 ± 2.2 kg/m2 (uniHNS). The mean preimplantation AHI (biHNS, 39.9 ± 14.8/h; uniHNS, 32.2 ± 11.0/h) decreased in both groups after 3 months (biHNS, 19.2 ± 14.0/h, P = .008; uniHNS, 13.1 ± 16.8/h, P = .037) with no significant difference between groups (P = .720). The mean preimplantation Epworth Sleepiness Scale (biHNS, 11.8 ± 6.2; uniHNS, 11.1 ± 4.9) decreased as well after 3 months (biHNS, 9.4 ± 6.3; uniHNS, 6.0 ± 5.0).ConclusionPreliminary postmarket data suggest that biHNS may be as safe and effective as uniHNS. Long-term follow-up in a larger sample size is required to assess the stability of biHNS.
| S-EPMC9272182 | biostudies-literature
Project description:We performed respiratory-gated magnetic resonance imaging to evaluate airway dynamics during tidal breathing in 10 children with obstructive sleep apnea syndrome (OSAS; age, 4.3 +/- 2.3 years) and 10 matched control subjects (age, 5.0 +/- 2.0 years). We hypothesized that respiratory cycle fluctuations in upper airway cross-sectional area would be larger in children with OSAS.Studies were performed under sedation. Respiratory gating was performed automatically at 10, 30, 50, 70, and 90% of inspiratory and expiratory volume. Airway cross-sectional area was measured at four ascending oropharyngeal levels at each increment of the respiratory cycle.We noted the following in subjects with OSAS compared with control subjects: (1) a smaller upper airway cross-sectional area, particularly during inspiration; (2) airway narrowing occurred during inspiration without evidence of complete airway collapse; (3) airway dilatation occurred during expiration, particularly early in the phase; and (4) magnitude of cross-sectional areas fluctuations during tidal breathing noted in OSAS at levels 1 through 4 were 317, 422, 785, and 922%, compared with 19, 15 17, and 24% in control subjects (p < 0.001, p < 0.005, p < 0.001, and p < 0.001, respectively).Fluctuations in airway area during tidal breathing are significantly greater in subjects with OSAS compared with control subjects. Resistive pressure loading is a probable explanation, although increased airway compliance may be a contributing factor.
| S-EPMC2718463 | biostudies-other
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:STUDY OBJECTIVES:The carbonic anhydrase inhibitor acetazolamide (AZT) modulates blood pressure at high altitude and reduces sleep-disordered breathing in patients with obstructive sleep apnea (OSA). We aimed to investigate the treatment effect of AZT and in combination with continuous positive airway pressure (CPAP) on blood pressure in patients with hypertension and OSA. METHODS:In a prospective, randomized, three-way crossover study, 13 male patients with hypertension and moderate to severe OSA (age 64 ± 7 years, body mass index 29 ± 4 kg/m2, and mean apnea-hypopnea index 37 ± 23 events/h) received AZT, CPAP, or AZT plus CPAP for 2-week periods. Antihypertensive medication was washed out. Office and 24-hour blood pressure, arterial stiffness, polygraphic sleep study data, and blood chemistry were compared. RESULTS:AZT alone and AZT plus CPAP, but not CPAP alone, reduced office mean arterial pressure compared to baseline (-7 [95% CI -11 to -4], -7 [95% CI -11 to -4] and -1 [95% CI -5 to 4] mmHg, respectively; repeated- measures analysis of variance (RM-ANOVA; P = .015). Aortic systolic pressure and augmentation index, assessed by radial artery oscillatory tonometry, were unaffected by CPAP but decreased after AZT and AZT plus CPAP (RM-ANOVA P = .030 and .031, respectively). The apnea-hypopnea index was significantly reduced in all three treatment arms, most prominently by AZT plus CPAP (RM-ANOVA P = .003). The reduction of venous bicarbonate concentration following AZT was correlated with the change of apnea-hypopnea index (r = 0.66, P = .013). CONCLUSIONS:AZT reduced blood pressure, vascular stiffness, and sleep-disordered breathing in patients with OSA and comorbid hypertension. Carbonic anhydrase inhibition may constitute a potential target for drug therapy in patients with sleep apnea and comorbid hypertension. CLINICAL TRIAL REGISTRATION:Registry: ClinicalTrials.gov; Identifier: NCT02220803; Title: A Short Term Open, Randomized Cross-over Trial Exploring the Effect of Carbonic Anhydrase Inhibition by Acetazolamide on Sleep Apnea Associated Hypertension and Vascular Dysfunction; URL: https://clinicaltrials.gov/ct2/show/NCT02220803 and Registry: EU Clinical Trials Register; EudraCT Number: 2013-004866-33; Title: A short term open, randomized cross over trial exploring the effect of carbonic anhydrase inhibition by acetazolamide on sleep apnea associated hypertension; URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2013-004866-33.
| S-EPMC5837832 | biostudies-literature
Project description:Importance:Adenotonsillectomy (ATE) is the primary surgical method for treating obstructive sleep apnea (OSA) in children. However, children with severe OSA have an increased risk for residual OSA after ATE. Previous studies indicate that adenopharyngoplasty (APP), a modified ATE with closure of the tonsillar pillars, might improve the surgical outcome, but the overall evidence is weak. Objective:To determine whether APP is more effective than ATE for treating severe OSA in otherwise healthy children. Design, Setting, and Participants:A blinded randomized clinical trial was conducted at the otorhinolaryngology department at Karolinska University Hospital, Stockholm, Sweden. Eighty-three children, aged 2 to 4 years, with an obstructive apnea-hypopnea index (OAHI) score of 10 or higher, were randomized to APP (n?=?36) or ATE (n?=?47). Participants were recruited from December 1, 2014, through November 31, 2016. Interventions:Adenotonsillectomy was performed in all 83 patients in both groups by the cold steel technique. The APP group also underwent closure of the tonsillar pillars with 2 inverted sutures on each side. Main Outcomes and Measures:The primary outcome was the difference between the groups in OAHI score change before and after surgery. A higher score indicates worse problems and a score of 10 or higher is defined as severe OSA. The outcome was evaluated per protocol and with intention-to-treat analysis. Secondary outcomes were other polysomnography variables and the Obstructive Sleep Apnea-18 (OSA-18) questionnaire (possible total symptom score range, 18-126; higher scores indicate worse quality of life). Polysomnography was performed and the OSA-18 questionnaire was completed preoperatively and 6 months postoperatively. Results:A total of 83 children (49 [59%] boys; mean [SD] age, 36.6 [9.2] months) were included in the study. Of these, 74 (89%) (APP, n?=?30; ATE, n?=?44) completed the study. The mean (SD) preoperative OAHI score was 23.8 (11.8) for APP and 23.8 (11.5) for ATE. Both the APP and ATE groups had a significant decrease in mean OAHI score after surgery (-21.7; 95% CI, -26.3 to -17.2; and -21.1; 95% CI, -24.5 to -17.7, respectively), but there was no significant difference between the groups (0.7; 95% CI, -4.8 to 6.1). Furthermore, no significant differences between the groups were seen regarding other polysomnography variables (eg, respiratory distress index: mean, 0.6; 95% CI, -5.0 to 6.3) or the OSA-18 questionnaire (eg, total symptom score: -0.5; 95% CI, -13 to 12). One patient from each group was readmitted owing to postoperative bleeding, but no other complications were seen. Conclusions and Relevance:This trial did not show that APP was more effective than ATE alone to treat otherwise healthy children with severe OSA. This finding suggests that ATE should continue to be the primary treatment for OSA in children. Trial Registration:ClinicalTrials.gov Identifier: NCT02315911.
| S-EPMC6145782 | biostudies-literature
Project description:The bases for sex disparities in obstructive sleep apnea (OSA), is poorly understood. We quantified the influences of event definitions, sleep-state, and body position on apnea-hypopnea indices (AHIs) in men and women, and evaluated sex differences in pathophysiological endotypes. Polysomnography (PSG) data were analyzed from 2057 participants from the multi-ethnic study of atherosclerosis. Alternative AHIs were compared using various desaturation and arousal criteria. Endotypes (loop gain, airway collapsibility, arousal threshold) were derived using breath-by-breath analysis of PSG signals. Regression models estimated the extent to which endotypes explained sex differences in AHI. The sample (mean 68.5 ± 9.2 years) included 54% women. OSA (AHI4P ≥15/h, defined by events with ≥4% desaturations) was found in 41.1% men and 21.8% women. Compared to AHI4P, male/female AHI ratios decreased by 5%-10% when using 3%-desaturation and/or arousal criteria; p < 0.05. REM-OSA (REM-AHI ≥15/h) was similar in men and women regardless of event desaturation criteria. REM-AHI4P ≥15/h was observed in 57% of men and women each. In NREM, AHI4P in men was 2.49 (CI95: 2.25, 2.76) of that in women. Women demonstrated lower loop gain, less airway collapsibility, and lower arousal threshold in NREM (ps < 0.0005). Endotypes explained 30% of the relative sex differences in NREM-AHI4P. There are significant sex differences in NREM-AHI levels and in physiological endotypes. Physiological endotypes explained a significant portion of the relative sex differences in NREM-AHI. Definitions that use 4%-desaturation criteria under-estimate AHI in women. Combining NREM and REM events obscures OSA prevalence in REM in women.
| S-EPMC7215264 | biostudies-literature
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