Biomarkers of gut barrier dysfunction in obstructive sleep apnea: A systematic review and meta-analysis.

We conducted this systematic review and meta-analysis to evaluate the impact of obstructive sleep apnea (OSA) on gut barrier dysfunction as represented by the following biomarkers: zonulin, lipopolysaccharide, lipopolysaccharide binding protein, intestinal fatty acid binding protein, and lactic acid. A comprehensive search of the literature was conducted in Ovid MEDLINE, Embase, Scopus, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov without language restrictions from inception to October 2022. The analysis of all outcomes was performed using a random-effects model. We included eight studies (seven cross sectional and one case control) in the final quantitative synthesis with a total of 897 patients. We concluded that OSA was associated with higher levels of gut barrier dysfunction biomarkers [Hedges' g = 0.73 (95%CI 0.37-1.09, p < 0.01). Biomarker levels were positively correlated with the apnea-hypopnea index [r = 0.48 (95%CI 0.35-0.6, p < 0.01)] and oxygen desaturation index [r = 0.30 (95%CI 0.17-0.42, p < 0.01)], and negatively correlated with the nadir oxygen desaturation values [r = -0.45 (95%CI - 0.55 - - 0.32, p < 0.01). Our systematic review and meta-analysis suggests that OSA is associated with gut barrier dysfunction. Furthermore, OSA severity appears to be correlated with higher biomarkers of gut barrier dysfunction. PROSPERO REGISTRATION NUMBER: CRD42022333078.

Interactive Effect of Combined Intermittent and Sustained Hypoxia and High-Fat Diet on the Colonic Mucosal Microbiome and Host Gene Expression in Mice.

Purpose: Gut dysbiosis can cause cardiometabolic disease. Gut dysbiosis can be independently caused by high-fat diet (HFD) and intermittent hypoxia (IH; characterizing obstructive sleep apnea), but the interactive effect of combined intermittent and sustained hypoxia (IH+SH) (characterizing obesity hypoventilation syndrome) and HFD on gut dysbiosis is unclear. We aimed to investigate the interactive effect of a combination of IH and SH and HFD on proximal colonic microbiota and colonic gene expression pattern. Methods: Male mice (n=16) were randomly received four different combinations of diet (normal versus HFD) and oxygen conditions (normoxia versus IH+SH) for 4 weeks. Bacterial DNA and mucosal epithelial cell RNA from proximal colon were collected for analysis of adherent microbiome and host's gene expression analysis. Results: HFD during IH+SH (22.6 ± 5.73; SD) led to greater Firmicutes: Bacteroidetes ratio than HFD during normoxia (5.89 ± 1.19; p=0.029). HFD significantly decreased microbial diversity as compared to normal diet, but the addition of IH+SH to HFD mildly reversed such effects. When compared to HFD during normoxia, HFD with combination of IH+SH resulted in changes to host mucosal gene expression for apical junctional complexes and adhesion molecules. Specifically, when compared to HFD during normoxia, HFD during IH+SH led to upregulation of Claudin 2 and Syk (tight junction dysfunction and increased mucosal permeability), while the barrier promoting claudin 4 was downregulated. Conclusion: HFD during combined IH and SH causes greater gut dysbiosis and potentially adverse changes in colonic epithelial transcriptome than HFD during normoxia. The latter changes are suggestive of impaired gut barrier function.

Obstructive Sleep Apnea as a Risk Factor for COVID-19 Severity-The Gut Microbiome as a Common Player Mediating Systemic Inflammation via Gut Barrier Dysfunction.

The novel corona virus that is now known as (SARS-CoV-2) has killed more than six million people worldwide. The disease presentation varies from mild respiratory symptoms to acute respiratory distress syndrome and ultimately death. Several risk factors have been shown to worsen the severity of COVID-19 outcomes (such as age, hypertension, diabetes mellitus, and obesity). Since many of these risk factors are known to be influenced by obstructive sleep apnea, this raises the possibility that OSA might be an independent risk factor for COVID-19 severity. A shift in the gut microbiota has been proposed to contribute to outcomes in both COVID-19 and OSA. To further evaluate the potential triangular interrelationships between these three elements, we conducted a thorough literature review attempting to elucidate these interactions. From this review, it is concluded that OSA may be a risk factor for worse COVID-19 clinical outcomes, and the shifts in gut microbiota associated with both COVID-19 and OSA may mediate processes leading to bacterial translocation via a defective gut barrier which can then foster systemic inflammation. Thus, targeting biomarkers of intestinal tight junction dysfunction in conjunction with restoring gut dysbiosis may provide novel avenues for both risk detection and adjuvant therapy.

Markers of ventricular repolarization and overall mortality in sleep disordered breathing.

INTRODUCTION: Variability and prolongation of ventricular repolarization - measured by changes in QT interval and QT variability are independently associated with ventricular arrhythmias, sudden death, and mortality but such studies did not examine the role of sleep-disordered breathing. We aimed to determine whether sleep-disordered breathing moderated the association between measures of ventricular repolarization and overall mortality. METHODS: Eight hundred participants were randomly selected from each of the following four groups in the Sleep Heart Health Study: mild, moderate, severe or no sleep disordered breathing (n = 200 each). Overnight electrocardiograms were analyzed for QTc duration and QT variability (standard deviation of QT intervals, normalized QT interval variance and the short-term interval beat-to-beat QT variability). Cox proportional hazards penalized regression modeling was used to identify predictors of mortality. RESULTS: Eight hundred of 5600 participants were randomly selected. The participants (68 ± 10 years; 56.8% male) were followed for an average of 8.2 years during which time 222 (28.4%) died. QTc, SDQT, and QTVN were associated with the presence of SDB (p = 0.002, p = 0.014, and p = 0.024, respectively). After adjusting for covariates, the presence of sleep-disordered breathing did not moderate the association between QTc length, QT variability and mortality (p > 0.05). CONCLUSION: Sleep-disordered breathing was associated with some measures of ventricular repolarization. However, sleep-disordered breathing was not an effect modifier for the relationship between QTc and QT variability and mortality.

Six Months of Inspiratory Muscle Training to Lower Blood Pressure and Improve Endothelial Function in Middle-Aged and Older Adults With Above-Normal Blood Pressure and Obstructive Sleep Apnea: Protocol for the CHART Clinical Trial.

Background: Cardiovascular disease is a major global health concern and prevalence is high in adults with obstructive sleep apnea (OSA). Lowering blood pressure (BP) can greatly reduce cardiovascular disease risk and physical activity is routinely prescribed to achieve this goal. Unfortunately, many adults with OSA suffer from fatigue, daytime sleepiness, and exercise intolerance-due to poor sleep quality and nocturnal hypoxemia-and have difficulty initiating and maintaining an exercise program. High-resistance inspiratory muscle strength training (IMST) is a simple, time-efficient breathing exercise consistently reported to reduce BP in small, selective groups of both healthy and at-risk adults. Herein we present the study protocol for a randomized clinical trial to determine the long-term efficacy of IMST performed regularly for 24 weeks in middle-aged and older adults with OSA. The primary outcome is casual systolic BP. Secondary outcomes are 24-h systolic BP and circulating plasma norepinephrine concentration. Other outcomes include vascular endothelial function (endothelial-dependent and -independent dilation), aortic stiffness, casual and 24-h diastolic BP, and the influence of circulating factors on endothelial cell nitric oxide and reactive oxygen species production. Overall, this trial will establish efficacy of high-resistance IMST for lowering BP and improving cardiovascular health in middle-aged and older adults with OSA. Methods: This is a single-site, double-blind, randomized clinical trial. A minimum of 92 and maximum of 122 male and female adults aged 50-80 years with OSA and above-normal BP will be enrolled. After completion of baseline assessments, subjects will be randomized in a 1:1 ratio to participate in either high-resistance or sham (low-resistance) control IMST, performed at home, 5 min/day, 5 days/week, for 24 weeks. Repeat assessments will be taken after the 24-week intervention, and after 4 and 12 weeks of free living. Discussion: This study is designed to assess the effects of 24 weeks of IMST on BP and vascular function. The results will characterize the extent to which IMST can reduce BP when performed over longer periods (i.e., 6 months) than have been assessed previously. Additionally, this study will help to determine underlying mechanisms driving IMST-induced BP reductions that have been reported previously. Clinical Trial Registration: This trial is registered with ClinicalTrials.gov (Registration Number: NCT04932447; Date of registration June 21, 2021).

Association of Sleep-Related Hypoxia With Risk of COVID-19 Hospitalizations and Mortality in a Large Integrated Health System.

Importance: The influence of sleep-disordered breathing (SDB) and sleep-related hypoxemia in SARS-CoV-2 viral infection and COVID-19 outcomes remains unknown. Controversy exists regarding whether to continue treatment for SDB with positive airway pressure given concern for aerosolization with limited data to inform professional society recommendations. Objective: To investigate the association of SDB (identified via polysomnogram) and sleep-related hypoxia with (1) SARS-CoV-2 positivity and (2) World Health Organization (WHO)-designated COVID-19 clinical outcomes while accounting for confounding including obesity, underlying cardiopulmonary disease, cancer, and smoking history. Design, Setting, and Participants: This case-control study was conducted within the Cleveland Clinic Health System (Ohio and Florida) and included all patients who were tested for COVID-19 between March 8 and November 30, 2020, and who had an available sleep study record. Sleep indices and SARS-CoV-2 positivity were assessed with overlap propensity score weighting, and COVID-19 clinical outcomes were assessed using the institutional registry. Exposures: Sleep study-identified SDB (defined by frequency of apneas and hypopneas using the Apnea-Hypopnea Index [AHI]) and sleep-related hypoxemia (percentage of total sleep time at <90% oxygen saturation [TST <90]). Main Outcomes and Measures: Outcomes were SARS-CoV-2 infection and WHO-designated COVID-19 clinical outcomes (hospitalization, use of supplemental oxygen, noninvasive ventilation, mechanical ventilation or extracorporeal membrane oxygenation, and death). Results: Of 350 710 individuals tested for SARS-CoV-2, 5402 (mean [SD] age, 56.4 [14.5] years; 3005 women [55.6%]) had a prior sleep study, of whom 1935 (35.8%) tested positive for SARS-CoV-2. Of the 5402 participants, 1696 were Black (31.4%), 3259 were White (60.3%), and 822 were of other race or ethnicity (15.2%). Patients who were positive vs negative for SARS-CoV-2 had a higher AHI score (median, 16.2 events/h [IQR, 6.1-39.5 events/h] vs 13.6 events/h [IQR, 5.5-33.6 events/h]; P < .001) and increased TST <90 (median, 1.8% sleep time [IQR, 0.10%-12.8% sleep time] vs 1.4% sleep time [IQR, 0.10%-10.8% sleep time]; P = .02). After overlap propensity score-weighted logistic regression, no SDB measures were associated with SARS-CoV-2 positivity. Median TST <90 was associated with the WHO-designated COVID-19 ordinal clinical outcome scale (adjusted odds ratio, 1.39; 95% CI, 1.10-1.74; P = .005). Time-to-event analyses showed sleep-related hypoxia associated with a 31% higher rate of hospitalization and mortality (adjusted hazard ratio, 1.31; 95% CI, 1.08-1.57; P = .005). Conclusions and Relevance: In this case-control study, SDB and sleep-related hypoxia were not associated with increased SARS-CoV-2 positivity; however, once patients were infected with SARS-CoV-2, sleep-related hypoxia was an associated risk factor for detrimental COVID-19 outcomes.

Obstructive sleep apnea and COVID-19 clinical outcomes during hospitalization: a cohort study.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is an extremely common sleep disorder. A potential association between OSA and coronavirus disease 2019 (COVID-19) severity has been proposed on the basis of similar comorbid medical conditions associated with both OSA and COVID-19. METHODS: We performed a retrospective review of 1,738 patients who were hospitalized with COVID-19 between March and October of 2020. Patients were classified based on the presence or absence of OSA diagnosis based upon the International Classification of Diseases (ICD; codes G47.33 and U07.1 for OSA and COVID-19, respectively). Other data were collected, including demographics, body mass index, and comorbid conditions. COVID-19 severity was compared between groups using the quick COVID-19 severity index. RESULTS: Quick COVID-19 severity index scores were higher in patients with OSA compared with those without OSA. However, the prevalence rates of type 2 diabetes (P < .0001), coronary artery disease (P < .0001), congestive heart failure (P < .0001), and chronic obstructive pulmonary diseases (P < .0001) were also significantly greater in the OSA group. Unadjusted models revealed higher risk of intensive care unit admission in patients with COVID-19 and OSA. However, such an association was attenuated and became nonsignificant after adjusting for age, sex, body mass index, and comorbid disease. CONCLUSIONS: In our study, OSA does not appear to be an independent risk factor for worse COVID-19 outcomes in hospitalized patients. Further studies with larger sample sizes are needed to delineate the potential role of OSA in determining outcomes in hospitalized patients with COVID-19. CITATION: Mashaqi S, Lee-Iannotti J, Rangan P, et al. Obstructive sleep apnea and COVID-19 clinical outcomes during hospitalization: a cohort study. J Clin Sleep Med. 2021;17(11):2197-2204.

The Hypoglossal Nerve Stimulation as a Novel Therapy for Treating Obstructive Sleep Apnea-A Literature Review.

Obstructive sleep apnea (OSA) is a common sleep disorder that affects all age groups and is associated with many co-morbid diseases (especially cardiovascular diseases). Continuous positive airway pressure (CPAP) is the gold standard for treating OSA. However, adherence to PAP therapy has been a major challenge with an estimated adherence between 20% and 80%. Mandibular advancement devices (MAD) are a good alternative option if used in the appropriate patient. MAD are most effective in mild and moderate OSA but not severe OSA. Surgical options are invasive, not appropriate for severe OSA, and associated with pain and long healing time. Hypoglossal nerve stimulation (HGNS), or upper airway stimulation (UAS), is a novel therapy in treating moderate and severe degrees of OSA in patients who cannot tolerate CPAP therapy. We reviewed the MEDLINE (PubMed) database. The search process yielded 303 articles; 31 met the inclusion and exclusion criteria and were included. We concluded that hypoglossal nerve stimulation is a very effective and novel alternative therapy for moderate and severe OSA in patients who cannot tolerate CPAP therapy. Adherence to HGNS is superior to CPAP. However, more developments are needed to ensure the highest safety profile.

Matrix metalloproteinase-9 as a messenger in the cross talk between obstructive sleep apnea and comorbid systemic hypertension, cardiac remodeling, and ischemic stroke: a literature review.

STUDY OBJECTIVES: OSA is a common sleep disorder. There is a strong link between sleep-related breathing disorders and cardiovascular and cerebrovascular diseases. Matrix metalloproteinase-9 (MMP-9) is a biological marker for extracellular matrix degradation, which plays a significant role in systemic hypertension, myocardial infarction and postmyocardial infarction heart failure, and ischemic stroke. This article reviews MMP-9 as an inflammatory mediator and a potential messenger between OSA and OSA-induced comorbidities. METHODS: We reviewed the MEDLINE database (PubMed) for publications on MMP-9, OSA, and cardiovascular disease, identifying 1,592 studies and including and reviewing 50 articles for this work. RESULTS: There is strong evidence that MMP-9 and tissue inhibitor of metalloproteinase-1 levels are elevated in patients with OSA (mainly MMP-9), systemic hypertension, myocardial infarction, and postmyocardial infarction heart failure. Our study showed variable results that could be related to the sample size or to laboratory methodology. CONCLUSIONS: MMP-9 and its endogenous inhibitor, tissue inhibitor of metalloproteinase-1, are a common denominator in OSA, systemic hypertension, myocardial infarction, and heart failure. This characterization makes MMP-9 a target for developing novel selective inhibitors that can serve as adjuvant therapy in patients with OSA, which may ameliorate the cardiovascular and cerebrovascular mortality associated with OSA.

Differences in sleep timing and related effects between African Americans and non-Hispanic Whites.

STUDY OBJECTIVES: Prior studies have shown a morning chronotype for African Americans compared with non-Hispanic Whites, yet self-reported sleep timing is delayed in African Americans compared with Whites. METHODS: We analyzed data from the Multi-Ethnicity Study of Atherosclerosis, a multisite community-based cohort. Self-reported and actigraphic sleep timing, chronotype measured by the modified Horne-Östberg Morningness-Eveningness Questionnaire, and risk of depression measured by the Center for Epidemiologic Studies Depression scale were examined using nonparametric approaches and linear or logistic regression while comparing between African Americans and Whites and evaluating the effects of delayed sleep phase. RESULTS: In 1,401 participants, there was no difference in chronotype between African Americans and Whites. African Americans were 80% more likely to report a delayed sleep phase (defined as bedtime after midnight) on weekdays and 50% more likely on weekends than were Whites. Actigraphic data showed similar results. Actigraphic midsleep time was delayed 38 minutes on weekdays and 24 minutes on weekends in African Americans compared with Whites. Stratified analysis by chronotype showed that African Americans with a morning or intermediate chronotype had a significantly delayed sleep phase compared with Whites, but there was no difference between African Americans and Whites with an evening chronotype. Delayed sleep phase was associated with depression, but this relationship was only significant in White participants. CONCLUSIONS: African Americans had a delayed sleep phase compared with Whites that was more pronounced in individuals with a morning or intermediate chronotype. Consequences of delayed sleep phase may vary by race and ethnicity.

The gut microbiome as a target for adjuvant therapy in obstructive sleep apnea.

Introduction: Gut dysbiosis is assumed to play a role in obstructive sleep apnea (OSA)-associated morbidities. Pre- and probiotics, short chain fatty acids (SCFA) and fecal matter transplantation (FMT) may offer potential as novel therapeutic strategies that target this gut dysbiosis. As more mechanisms of OSA-induced dysbiosis are being elucidated, these novel approaches are being tested in preclinical and clinical development. Areas covered: We examined the evidence linking OSA to gut dysbiosis and discuss the effects of pre- and probiotics on associated cardiometabolic, neurobehavioral and gastrointestinal disorders. The therapeutic potential of SCFA and FMT are also discussed. We reviewed the National Center for Biotechnology Information database, including PubMed and PubMed Central between 2000 - 2020. Expert opinion: To date, there are no clinical trials and only limited evidence from animal studies describing the beneficial effects of pre- and probiotic supplementation on OSA-mediated dysbiosis. Thus, more work is necessary to assess whether prebiotics, probiotics and SCFA are promising future novel strategies for targeting OSA-mediated dysbiosis.

Combined nocturnal pulse oximetry and questionnaire-based obstructive sleep apnea screening - A cohort study.

BACKGROUND: Screening for obstructive sleep apnea (OSA) in both inpatient and outpatient settings to pursue diagnostic testing is becoming increasingly relevant, particularly given the estimates of 85-90% of patients with OSA remaining undiagnosed. Although many questionnaires are available for OSA screening, the STOP-BANG questionnaire is becoming increasingly used due to ease of use and positive performance characteristics. The utility of nocturnal oximetry, in conjunction with standard questionnaire-based strategies to enhance OSA screening in adults, has yet to be systematically examined. RESEARCH OBJECTIVES: To evaluate the utility of nocturnal oximetry measures combined with the standard STOP-BANG questionnaire as a screening strategy for OSA in the hospital setting and outpatient clinics. STUDY DESIGN AND METHODS: We conducted a retrospective cohort study. We reviewed the electronic medical records of 130 patients who were referred to Sanford sleep center from both inpatient and outpatient settings over one year (August 1st, 2016 to August 1st, 2017). Nocturnal oximetry was conducted at home (in the outpatient group) and in the medical wards (in the inpatient group), and the following measures were obtained: Oxygen Desaturation Index (ODIPOx), mean SaO2POx and time spent below 88% SaO2 (T88Pox). Apnea-hypopnea index (AHI), mean SaO2PSG, and T88PSG from overnight polysomnography (PSG) and STOP-BANG score. RESULTS: Based upon likelihood ratio testing comparing discriminative ability, a model of (ODIPox + STOPBANG) was superior and more accurate than STOP-BANG alone in detecting mild OSA in the overall sample (AUC = 0.644 [0.549-0.739], p = 0.003) and inpatient sample (AUC = 0.710 [0.582-0.839], p = 0.001). This approach was also more accurate in detecting severe OSA in full sample (AUC = 0.839 [0.763-0.914], p < 0.0001), inpatient sample (AUC = 0.825 [0.711-0.939], p < 0.0001) and outpatient sample (AUC = 0.827 [0.699-0.955], p < 0.0001). The ODIPox alone was more accurate than STOP-BANG alone in detecting mild OSA in the overall sample (AUC = 0.620 [0.524-0.717], p = 0.014) and inpatient sample (AUC = 0.704 [0.574-0.835], p = 0.002) and severe OSA in full sample (AUC = 0.839 [0.764-0.915], p < 0.0001), inpatient sample (AUC = 0.827 [0.714-0.940], p < 0.0001) and outpatient sample (AUC = 0.861 [0.771-0.950], p < 0.0001). CONCLUSION: The use of nocturnal oximetry measures (ODIPOx) improved the accuracy of standard OSA screening with the STOP-BANG questionnaire as a screening tool in severe OSA in both inpatient and outpatient settings. CLINICAL IMPLICATION: Obstructive sleep apnea is a common sleep disorder that impacts many co-morbidities in different age groups. Enhancing affordable screening methods for OSA can facilitate early diagnosis and treatment and subsequently ameliorate morbidity and mortality related to sleep-disordered breathing.

"Circadian misalignment and the gut microbiome. A bidirectional relationship triggering inflammation and metabolic disorders"- a literature review.

Over the last decade, emerging studies have related the gut microbiome and gut dysbiosis to sleep and sleep disorders. For example, intermittent hypoxia associated with obstructive sleep apnea was shown to reproducibly alter the gut microbiome. Circadian rhythm disorders (CRD) (eg, shift work disorders, delayed sleep phase syndrome, and advanced sleep phase syndrome) constitute another group of conditions that might be influenced by gut dysbiosis. Indeed, both central and peripheral clocks can affect and be affected by gut microbiota and their metabolites. In addition, the tight rhythmic regulation of almost all metabolic pathways involved in the anabolism and catabolism of carbohydrates, protein, and lipids in addition to detoxification processes that take place in specific cells could be ultimately linked to changes in the microbiota. Since there are no studies to date examining the impact of gut dysbiosis on delayed sleep phase and advanced sleep phase syndrome, and considering the ever-increasing number of people engaging in shift work, more accurate and informed delineation of the association between gut dysbiosis and shift work can provide guidance and opportunities for new avenues of treating circadian rhythm disorders and preventing the metabolic complications of shiftwork via restoration of gut dysbiosis. In this review, the potential bidirectional relationships between gut dysbiosis and circadian rhythm misalignment, their impact on different metabolic pathways, and the potential development of metabolic and systemic disorders, especially in shift work models are critically assessed.

Effect of wearables on sleep in healthy individuals: a randomized crossover trial and validation study.

STUDY OBJECTIVES: The purpose of this study was to determine whether a wearable sleep-tracker improves perceived sleep quality in healthy participants and to test whether wearables reliably measure sleep quantity and quality compared with polysomnography. METHODS: This study included a single-center randomized crossover trial of community-based participants without medical conditions or sleep disorders. A wearable device (WHOOP, Inc.) was used that provided feedback regarding sleep information to the participant for 1 week and maintained sleep logs versus 1 week of maintained sleep logs alone. Self-reported daily sleep behaviors were documented in sleep logs. Polysomnography was performed on 1 night when wearing the wearable. The Patient-Reported Outcomes Measurement Information System sleep disturbance sleep scale was measured at baseline, day 7 and day 14 of study participation. RESULTS: In 32 participants (21 women; 23.8 ± 5 years), wearables improved nighttime sleep quality (Patient-Reported Outcomes Measurement Information System sleep disturbance: B = -1.69; 95% confidence interval, -3.11 to -0.27; P = .021) after adjusting for age, sex, baseline, and order effect. There was a small increase in self-reported daytime naps when wearing the device (B = 3.2; SE, 1.4; P = .023), but total daily sleep remained unchanged (P = .43). The wearable had low bias (13.8 minutes) and precision (17.8 minutes) errors for measuring sleep duration and measured dream sleep and slow wave sleep accurately (intraclass coefficient, 0.74 ± 0.28 and 0.85 ± 0.15, respectively). Bias and precision error for heart rate (bias, -0.17%; precision, 1.5%) and respiratory rate (bias, 1.8%; precision, 6.7%) were very low compared with that measured by electrocardiogram and inductance plethysmography during polysomnography. CONCLUSIONS: In healthy people, wearables can improve sleep quality and accurately measure sleep and cardiorespiratory variables. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Assessment of Sleep by WHOOP in Ambulatory Subjects; Identifier: NCT03692195.

The impact of obstructive sleep apnea and PAP therapy on all-cause and cardiovascular mortality based on age and gender - a literature review.

BACKGROUND: Obstructive sleep apnea (OSA) is a common sleep disorder which negatively impacts different body systems, especially the cardiovascular system. The correlation between sleep related breathing disorders and cardiovascular diseases has been well studied. However, the impact of OSA on cardiovascular related mortality and the role of positive airway pressure therapy in decreasing mortality is unclear. We reviewed studies investigating the impact of OSA on all-cause and cardiovascular related mortality in both genders, and in different age groups. METHODS: A literature search (PubMed) using two phrases "obstructive sleep apnea and co-morbidities in males and females" and "obstructive sleep apnea and co-morbidities by age" yielded a total of 214 articles. Nineteen articles met the inclusion criteria. RESULTS: The studies reviewed showed conflicting results. Some showed that OSA increases all cause and cardiovascular related mortality predominantly in the middle-aged group (40-65) followed by a plateau or a reduction in mortality. Other studies showed a positive linear correlation between OSA and mortality up to the age of 80. The same controversy was noted for gender; some studies did not observe an increase in mortality in females with OSA, while others observed a trend for an increase in mortality in females. CONCLUSION: There is a debate in the literature regarding the impact of OSA on all-cause and cardiovascular mortality in both genders and in different age groups. However, the variation in results might be related to different study designs and significant epidemiological prevalence of OSA in males and females.

Obstructive Sleep Apnea and Systemic Hypertension: Gut Dysbiosis as the Mediator?

INTRODUCTION: Obstructive sleep apnea (OSA) and systemic hypertension (SH) are common and interrelated diseases. It is estimated that approximately 75% of treatment-resistant hypertension cases have an underlying OSA. Exploration of the gut microbiome is a new advance in medicine that has been linked to many comorbid illnesses, including SH and OSA. Here, we will review the literature in SH and gut dysbiosis, OSA and gut dysbiosis, and whether gut dysbiosis is common in both conditions. METHODS: We reviewed the National Center for Biotechnology Information database, including PubMed and PubMed Central. We identified a total of 230 articles. The literature search was conducted using the phrase "obstructive sleep apnea and gut dysbiosis." Only original research articles were included. This yielded a total of 12 articles. RESULTS: Most of the research conducted in this field was on animal models, and almost all trials confirmed that intermittent hypoxia models resulted in gut dysbiosis. Gut dysbiosis, however, can cause a state of low-grade inflammation through damage to the gut wall barrier resulting in "leaky gut." Neuroinflammation is a hallmark of the pathophysiology of OSA-induced SH. CONCLUSIONS: Gut dysbiosis seems to be an important factor in the pathophysiology of OSA-induced hypertension. Reversing gut dysbiosis at an early stage through prebiotics and probiotics and fecal microbiota transplantation combined with positive airway pressure therapy may open new horizons of treatment to prevent SH. More studies are needed in humans to elicit the effect of positive airway pressure therapy on gut dysbiosis.

The Impact of Obstructive Sleep Apnea and Positive Airway Pressure Therapy on Metabolic Peptides Regulating Appetite, Food Intake, Energy Homeostasis, and Systemic Inflammation: A Literature Review.

INTRODUCTION: Sleep-related breathing disorders are very common and highly associated with many comorbid diseases. They have many metabolic consequences that impact appetite, energy expenditure, and systemic inflammation. These consequences are mediated through peptides (eg, ghrelin, leptin, adiponectin, resistin, apelin, obestatin, and neuropeptide Y). METHODS: We searched the literature (PubMed) for sleep-disordered breathing (SDB) and metabolic peptides and included 15, 22, 14, 4 and 2 articles for ghrelin, leptin, adiponectin, resistin, and apelin respectively. RESULTS: Our review of the published literature suggests that leptin levels seem to correlate with body mass index and adiposity rather than obstructive sleep apnea. Conversely, levels of adiponectin and ghrelin are influenced by obstructive sleep apnea alone. Finally, resistin and apelin seem to be not correlated with obstructive sleep apnea. Regarding positive airway pressure (PAP) impact, it seems that PAP therapy affected the levels of these peptides (mainly ghrelin). CONCLUSIONS: There is significant controversy in the literature regarding the impact of SDB and PAP therapy on these metabolic peptides. This could be due to the lack of randomized clinical trials and the variability of the methodology used in these studies. Further research is needed to assess the impact of SDB and PAP therapy on the levels of these peptides and whether this impact is also related to body mass index and body fat composition.

The Impact of Bariatric Surgery on Sleep Disordered Breathing Parameters From Overnight Polysomnography and Home Sleep Apnea Test.

Background Obstructive sleep apnea (OSA) is a common sleep disorder, especially in patients with obesity. Bariatric surgery is an effective tool to reduce weight and treat co-morbid diseases in patients with morbid obesity. One of these disorders is OSA. The most common bariatric procedures currently performed are Roux-en-Y gastric bypass (RYGB) and laparoscopic sleeve gastrectomy (LSG). Objectives Our study demonstrates that bariatric surgery is a very effective tool to reduce the severity of OSA, if not resolve it. Methods The medical charts of nine patients who had OSA and underwent bariatric surgery (LSG or RYGB) were reviewed and the apnea-hypopnea index (AHI) was compared before and after surgery. The study was conducted at the Sanford sleep center which is affiliated with the University of North Dakota School of Medicine. Results One patient was excluded from the statistical analysis since he was the only male patient, the remaining nine female patients had a significant reduction in AHI after surgery. The mean AHI before surgery was 40 events per hour and seven events per hour after surgery (P 0.004). The mean follow-up with sleep study after surgery was 16 months. The mean reduction in AHI was 80%. There was also an improvement in oxygen saturation (SpO2) before and after surgery (90% and 94% respectively, P 0.008). Conclusion The study confirms the significant reduction in AHI after bariatric surgery in female patients with OSA especially short term (one to two years postoperatively).

Obstructive Sleep Apnea in a Patient with Cornelia de Lange Syndrome.

Cornelia de Lange syndrome (CdLS) is a rare genetic disorder that is characterized by specific facial, skeletal, and behavioral features associated with variable degrees of intellectual disabilities. Sleep disturbances have been reported in patients with CdLS including insomnia, sleep-disordered breathing, intrinsic sleep disorders, and circadian rhythm disorders. The prevalence of sleep-related breathing disorders, in particular, obstructive sleep apnea (OSA), was conducted using validated questionnaires. We report the first case of CdLS that confirmed a moderate to severe degree of OSA using overnight polysomnography, which is the gold standard diagnostic test for OSA.