Project description:There is not a clinically available technique for measuring the physiological traits causing obstructive sleep apnea (OSA). Therefore, it is often difficult to determine why an individual has OSA or to what extent the various traits contribute to the development of OSA. In this study, we present a noninvasive method for measuring four important physiological traits causing OSA: 1) pharyngeal anatomy/collapsibility, 2) ventilatory control system gain (loop gain), 3) the ability of the upper airway to dilate/stiffen in response to an increase in ventilatory drive, and 4) arousal threshold. These variables are measured using a single maneuver in which continuous positive airway pressure (CPAP) is dropped from an optimum to various suboptimum pressures for 3- to 5-min intervals during sleep. Each individual's set of traits is entered into a physiological model of OSA that graphically illustrates the relative importance of each trait in that individual. Results from 14 subjects (10 with OSA) are described. Repeatability measurements from separate nights are also presented for four subjects. The measurements and model illustrate the multifactorial nature of OSA pathogenesis and how, in some individuals, small adjustments of one or another trait (which might be achievable with non-CPAP agents) could potentially treat OSA. This technique could conceivably be used clinically to define a patient's physiology and guide therapy based on the traits.
Project description:BackgroundObstructive sleep apnea (OSA) has been associated with cardiac abnormalities. Whether any cardiac dysfunction is present in ischemic stroke patients with OSA is not known. The purpose of this study was to compare echocardiographic findings in ischemic stroke patients with and without OSA.MethodsNocturnal polysomnography was performed on 28 ischemic stroke subjects within 7 days of symptom onset. OSA was defined as an apnea-hypopnea index of ≥10. Echocardiographic variables were compared between the OSA and non OSA groups using Wilcoxon signed-rank, chi-square, or Fisher's exact tests.ResultsThe 14 (50%) subjects with OSA had comparable cardiac function and structure to those without OSA (n=14). Left ventricular (LV) mass index, LV ejection fraction, LV diastolic function, left atrial area, and right ventricular systolic function were not different between groups. Ischemic stroke subjects, regardless of their OSA status, had LV diastolic dysfunction with preserved systolic function.ConclusionsSubjects with and without OSA, based on polysomnography in the first 7 days after stroke, have comparable right and left ventricular function.
Project description:The objective of this study was to evaluate the determinants of long-term adherence to positive airway pressure treatment among patients with obstructive sleep apnea, with special emphasis on patients who stop positive airway pressure treatment within 1 year. This is a prospective long-term follow-up of subjects in the Icelandic Sleep Apnea Cohort who were diagnosed with obstructive sleep apnea between 2005 and 2009, and started on positive airway pressure treatment. In October 2014, positive airway pressure adherence was obtained by systematically evaluating available clinical files (n = 796; 644 males, 152 females) with moderate to severe obstructive sleep apnea (apnea-hypopnea index ≥15 events per h). The mean follow-up time was 6.7 ± 1.2 years. In total, 123 subjects (15.5%) returned their positive airway pressure device within the first year, 170 (21.4%) returned it later and 503 (63.2%) were still using positive airway pressure. The quitters within the first year had lower body mass index, milder obstructive sleep apnea, less sleepiness, and more often had symptoms of initial and late insomnia compared with long-term positive airway pressure users at baseline. Both initial and late insomnia were after adjustment still significantly associated with being an early quitter among subjects with body mass index <30 kg m-2 , but not among those with body mass index ≥30 kg m-2 . The prevalence of early quitters decreased significantly during the study period (2005-2009). Almost two-thirds of patients with moderate to severe obstructive sleep apnea are positive airway pressure users after 7 years. Obesity level, obstructive sleep apnea severity and daytime sleepiness are important determinants of long-term adherence. Symptoms of initial and late insomnia are associated with early quitting on positive airway pressure among non-obese subjects.
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:PurposeThis study aimed to evaluate the 10-year adherence to and identify the predictors of dropout from continuous positive airway pressure (CPAP) treatment for patients with moderate-to-severe obstructive sleep apnea (OSA).MethodsWe retrospectively analyzed the continuity, dropout, or other behaviors of 181 patients who initiated CPAP treatment at the Tokyo Dental College Ichikawa General Hospital from January 2003 to June 2005.ResultsAmong a total of 181 patients, 56 (30.9%) dropped out of the treatment. Among the 125 patients who did not dropout, 54 continued CPAP treatment for > 10 years, 16 completed the treatment with OSA improvement, and 7 could not complete the treatment owing to unavoidable reasons such as death, dementia, hospitalization for serious illness, or migration to other countries. Further, 47 patients moved to another facility, whereas 1 patient purchased a CPAP device and stopped visiting our facility. Among the 56 patients who dropped out, approximately 50% of the patients dropped out within a year, and all dropped out within 76 months. Comparing demographics, OSA parameters, and CPAP parameters between the patients who did and did not drop out of the treatment, Cox regression analysis indicated that body mass index (BMI) and the first-month utilization rate were clinical variables that were independently associated with discontinuation of CPAP treatment.ConclusionThe results of this study show that BMI and the first-month utilization rate of CPAP treatment are the predictors of the long-term adherence to this treatment.
Project description:PurposeObstructive sleep apnea (OSA) is associated with increased risk for stroke, which is known to further impair respiratory functions. However, it is unknown whether the type and severity of respiratory events are linked to stroke or transient ischemic attack (TIA). Thus, we investigate whether the characteristics of individual respiratory events differ between patients experiencing TIA or acute ischemic stroke and matched patients with clinically suspected sleep-disordered breathing.MethodsPolygraphic data of 77 in-patients with acute ischemic stroke (n?=?49) or TIA (n?=?28) were compared to age, gender, and BMI-matched patients with suspected sleep-disordered breathing and no cerebrovascular disease. Along with conventional diagnostic parameters (e.g., apnea-hypopnea index), durations and severities of individual apneas, hypopneas and desaturations were compared between the groups separately for ischemic stroke and TIA patients.ResultsStroke and TIA patients had significantly shorter apneas and hypopneas (p?<?0.001) compared to matched reference patients. Furthermore, stroke patients had more central apnea events (p?=?0.007) and a trend for higher apnea/hypopnea number ratios (p?=?0.091). The prevalence of OSA (apnea-hypopnea index ??5) was 90% in acute stroke patients and 79% in transient ischemic attack patients.ConclusionStroke patients had different characteristics of respiratory events, i.e., their polygraphic phenotype of OSA differs compared to matched reference patients. The observed differences in polygraphic features might indicate that stroke and TIA patients suffer from OSA phenotype recently associated with increased cardiovascular mortality. Therefore, optimal diagnostics and treatment require routine OSA screening in patients with acute cerebrovascular disease, even without previous suspicion of OSA.
Project description:RationaleAlthough obstructive sleep apnea is associated with physiological perturbations that increase risk of hypertension and are proatherogenic, it is uncertain whether sleep apnea is associated with increased stroke risk in the general population.ObjectivesTo quantify the incidence of ischemic stroke with sleep apnea in a community-based sample of men and women across a wide range of sleep apnea.MethodsBaseline polysomnography was performed between 1995 and 1998 in a longitudinal cohort study. The primary exposure was the obstructive apnea-hypopnea index (OAHI) and outcome was incident ischemic stroke.Measurements and main resultsA total of 5,422 participants without a history of stroke at the baseline examination and untreated for sleep apnea were followed for a median of 8.7 years. One hundred ninety-three ischemic strokes were observed. In covariate-adjusted Cox proportional hazard models, a significant positive association between ischemic stroke and OAHI was observed in men (P value for linear trend: P = 0.016). Men in the highest OAHI quartile (>19) had an adjusted hazard ratio of 2.86 (95% confidence interval, 1.1-7.4). In the mild to moderate range (OAHI, 5-25), each one-unit increase in OAHI in men was estimated to increase stroke risk by 6% (95% confidence interval, 2-10%). In women, stroke was not significantly associated with OAHI quartiles, but increased risk was observed at an OAHI greater than 25.ConclusionsThe strong adjusted association between ischemic stroke and OAHI in community-dwelling men with mild to moderate sleep apnea suggests that this is an appropriate target for future stroke prevention trials.
Project description:Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy of the upper extremity. It is usually associated with the compression of the median nerve in the median groove. Because the main symptoms of CTS pain and numbness worsen at night, sleep disorders in CTS patients and the impact of preferred sleeping position on CTS development have been formerly studied. However, to the best of our knowledge, this is the first study assessing the frequency of CTS in obstructive sleep apnea (OSA) patients. This study aimed to determine the frequency of CTS in OSA patients and evaluate the causative relation between the two diseases.Records of individuals who were admitted to our sleep laboratory were retrospectively scanned. Eighty patients who were diagnosed with OSA and did not have comorbidities that might cause OSA (e.g., diabetes mellitus, hypothyroiditis, rheumatic diseases, and cervical radiculopathy) were included in the study along with 80 healthy controls who matched for age, sex, and BMI of OSA patients. To maintain observer blindness, patients were not questioned regarding their symptoms or the clinical data that would be used in the study. All participants underwent nerve conduction studies. Those who were diagnosed with CTS were questioned regarding CTS symptoms and the preferred sleeping position. Subsequently, patients were given the Boston CTS questionnaire.CTS frequency in OSA patients was found to be 27.5%. There was no significant relation between preferred sleeping position or being a manual worker and having CTS.CTS frequency in OSA patients is significantly higher than that in healthy individuals. In contrast to previous studies that have been performed in the absence of polysomnographic and electrophysiological data, in our study biomechanical factors were not associated with CTS presence. Therefore, we conclude that intermittent hypoxemia is the main etiological factor for CTS in OSA patients. Inflammation may be a common factor for etiopathogenesis for both diseases, but this hypothesis needs further investigation.