Significance of endothelial dysfunction in sleep‐related breathing disorder

The endothelium functions not only as a semi‐selective barrier between body tissue and circulation; it also plays an active role in the maintenance of a healthy vasculature. Endothelial dysfunction is increasingly found to play a pivotal role in the pathogenesis of atherosclerosis. Impaired endothelium‐dependent vasodilation, as a marker of endothelial dysfunction, predates and predicts cardiovascular disease. Endothelial dysfunction is thought to result from oxidative stress, inflammatory gene activation and cytokine cascade, as well as impairment of endothelial repair mechanisms. In the context of sleep‐related breathing disorders, obstructive sleep apnoea (OSA) is postulated to contribute independently to cardiovascular morbidity and mortality. Thus, endothelial dysfunction is an important target of research in vascular pathogenesis and also serves as an intermediary outcome indicator in clinical trials evaluating cardiovascular sequelae in OSA. Basic or translational studies have identified cellular and molecular mechanisms of potential relevance to endothelial dysfunction in OSA, while epidemiological or clinical studies have shown endothelial dysfunction attributable to sleep‐disordered breathing, which could improve with effective treatment of OSA. Endothelial dysfunction is poised to serve as a call for timely intervention with possibility of halting or even reverting vascular injury in sleep‐related breathing disorders. Much remains to be explored about the complex pathways of endothelial dysfunction and its clinical manifestations in subjects with OSA, which are likely to involve multiple contributing factors. Evidence‐based information will allow us to construct the framework for guiding individualized clinical management and public health strategies for OSA, as well as cardiometabolic diseases.     

OSA and cardiometabolic risk: What's the bottom line?

Obstructive sleep apnoea (OSA) is a common condition characterized by repetitive upper airway obstruction during sleep. OSA promotes wide intrathoracic pressure swings, intermittent hypoxia and sleep fragmentation. Growing evidence derived from animal models mimicking the oxygen profile observed in patients with OSA as well as clinical studies support that this important sleep‐disordered breathing is associated with increased cardiovascular risk. Although the precise mechanisms are not fully established, it is conceivable that the metabolic deregulation promoted by the components of OSA may have an important causal role in the poor cardiovascular prognosis. In this review, we summarize the potential role of OSA and its components on cardiometabolic disease. We also summarize evidence evaluating the impact of OSA treatment (notably continuous positive airway pressure) on reversing the metabolic deregulation promoted by OSA. Finally, we discuss the research agenda and perspectives for this important research area.     

Wait times for sleep apnea care in Ontario: A multidisciplinary assessment

BACKGROUND:

Obstructive sleep apnea (OSA) is a highly prevalent disorder that is associated with significant patient morbidity and societal burden. In general, wait times for health care in Ontario are believed to be lengthy; however, many diseases lack specific corroborative wait time data.

OBJECTIVE:

To characterize wait times for OSA care in Ontario.

METHODS:

Cross-sectional survey. A survey tool was designed and validated to question physicians involved in OSA care about the length of the wait times their patients experience while traversing a simplified model of OSA care. The survey was sent to all otolaryngologists and respirologists in the province, as well as to a random sample of provincial family physicians.

RESULTS:

Patients waited a mean of 11.6 months to initiate medical therapy (continuous positive airway pressure), and 16.2 months to initiate surgical therapy. Sleep laboratory availability appeared to be the major restriction in the patient management continuum, with each additional sleep laboratory in a community associated with a 20% decrease in overall wait times. Smaller community sizes were paradoxically associated with shorter wait times for sleep studies (P<0.01) but longer wait times for OSA surgery (P<0.05). Regression analysis yielded an r² of 0.046; less than 5% of the wait time variance could be explained by the simplified model.

CONCLUSION:

Patients experienced considerable wait times when undergoing management for OSA. This has implications for both individual patient care and public health in general.     

Obstruktive Schlafapnoe bei Patienten mit Typ-2-Diabetes

In patients with type 2 diabetes obstructive sleep apnea (OSA) is in addition to obesity, hyperlipidemia and arterial hypertension a common comorbidity which is characterized by repetitive apnea, arousals from sleep and surges of heart rate and arterial blood pressure. Symptoms related to OSA include morning tiredness, daytime hypersomnolence, nocturnal dyspnea and nocturia and justify treatment of OSA. Patients with type 2 diabetes can profit from treatment of OSA in terms of symptom relief, blood pressure lowering effects and potential beneficial effects on lipid and glucose metabolism. Diagnostics of OSA with an ambulatory polygraphy is indicated in patients with type 2 diabetes and OSA-related symptoms or other typical clinical signs for OSA, such as arterial hypertension refractory to drug treatment or non-dipping in 24?h blood pressure monitoring.     

Atrial fibrillation and sleep-disordered breathing

Atrial fibrillation (AF) is a common supraventricular arrhythmia that increases in prevalence with increasing age and in the presence of comorbidities such as heart failure (HF). AF increases the risk of a number of serious complications, including stroke and HF. As a result, the rate of hospitalization is high, making AF a costly disease. Treatment strategies for AF are broadly based around rate and rhythm control, either pharmacological or mechanical. There appear to be a number of links between sleep-disordered breathing (SDB) and AF, although further studies are needed to fully understand the physiological mechanisms that link these conditions. Patients with AF and SDB share a number of risk factors and comorbidities, including age, male sex, hypertension, congestive HF and coronary artery disease (CAD), and the prevalence of SDB in AF is higher than in the general population. Prevalence rates of obstructive sleep apnea (OSA) in patients with AF have been reported to range from 21% to just over 80%. The prevalence of central sleep apnea (CSA) in patients with AF is less well defined, but appears to be particularly high in patients who also have HF and a reduced left ventricular ejection fraction (LVEF). The frequency of apneas can be reduced by effective treatment of AF, while co-existing OSA reduces the effectiveness of treatments for AF and there is an increased risk of arrhythmia recurrence in the presence of SDB. Treating OSA with continuous positive airway pressure (CPAP) therapy has shown the potential to decrease the incidence of AF, improve the effectiveness of AF interventions, and decrease the risk of arrhythmia recurrence, although data from large randomized, controlled clinical trials are lacking. Based on available data, inclusion of SDB recognition and management strategies as part of AF management appears to have the potential to reduce the impact of this arrhythmia at both the individual and societal levels, and has been recognized as important in recent guidelines.     

The pathogenesis of obstructive sleep apnea

Obstructive sleep apnea (OSA) is a major source of cardiovascular morbidity and mortality, and represents an increasing burden on health care resources. Understanding underlying pathogenic mechanisms of OSA will ultimately allow for the development of rational therapeutic strategies. In this article, we review current concepts about the pathogenesis of OSA. Specifically, we consider the evidence that the upper airway plays a primary role in OSA pathogenesis and provide a framework for modelling its biomechanical properties and propensity to collapse during sleep. Anatomical and neuromuscular factors that modulate upper airway obstruction are also discussed. Finally, we consider models of periodic breathing, and elaborate generalizable mechanisms by which upper airway obstruction destabilizes respiratory patterns during sleep. In our model, upper airway obstruction triggers a mismatch between ventilatory supply and demand. In this model, trade-offs between maintaining sleep stability or ventilation can account for a full range of OSA disease severity and expression. Recurrent arousals and transient increases in airway patency may restore ventilation between periods of sleep, while alterations in neuromuscular and arousal responses to upper airway obstruction may improve sleep stability at still suboptimal levels of ventilation.     

Behavioural weight management for the primary careprovider

Primary care providers (PCPs) provide the majority of weight management care in clinical settings; however, they often lack the time or resources to apply strategies recommended in treatment guidelines. This review surveyed randomized clinical trials and prospective weight management studies from 1990 to present to identify evidence‐based behavioural strategies for weight management applicable to the PCP treatment environment. Data supported, time‐limited weight management strategies included self‐monitoring, portion control, sleep hygiene, restaurant eating and television viewing. The current review suggests that a number of behavioural strategies are available to enhance the effectiveness of PCPs weight management interventions. Increasing PCP awareness of these evidence‐based strategies may increase their attention to overweight and obesity concerns in clinical encounters and encourage more collaborative efforts with patients towards weight management goals.     

Obstructive sleep apnoea – an update

Obstructive sleep apnoea (OSA) is a common disorder characterized by the repetitive complete or partial collapse of the upper airway during sleep. It results in intermittent hypoxaemia and hypercapnia, cortical arousals and surges of sympathetic activity. The occurrence of OSA has also been linked to serious long‐term adverse health consequences; such as hypertension, metabolic dysfunction, cardiovascular disease, neurocognitive deficits and motor vehicle accidents. There have been several advances in the field of particular clinical importance: (i) the development of portable monitoring as part of a simplified clinical algorithm for the diagnosis of OSA in selected patients; (ii) growing awareness of the cardio‐metabolic health consequences of OSA and (iii) emerging evidence to support a range of non‐continuous positive airway pressure (CPAP) treatment modalities, such as oral appliances.     

Non‐invasive ventilation for obese patients with chronic respiratory failure: Are two pressures always better than one?

Obesity‐related respiratory failure is increasingly common but remains under‐diagnosed and under‐treated. There are several clinical phenotypes reported, including severe obstructive sleep apnoea (OSA), isolated nocturnal hypoventilation with or without severe OSA and OSA complicating chronic obstructive pulmonary disease (COPD). The presence of hypercapnic respiratory failure is associated with poor clinical outcomes in each of these groups. While weight loss is a core aim of management, this is often unachievable, and treatment of sleep‐disordered breathing with positive airway pressure (PAP) therapy is the mainstay of clinical practice. Although there are few long‐term clinical efficacy trials, the lack of equipoise would prevent the utilization of an untreated control group. The current data support the use of PAP therapy to improve respiratory failure and is associated with improvements in health‐related quality of life, reduced healthcare utilization and reduced mortality. Both continuous PAP (CPAP) and non‐invasive ventilation (NIV) appear safe and effective in patients with obesity‐related respiratory failure and OSA, with or without COPD, and the current evidence would not support a single therapy choice in all patients. There are no studies of CPAP in patients with isolated nocturnal hypoventilation, and NIV would be the current recommendation in this patient group. Whichever starting therapy is used, titration should be performed to correct sleep‐disordered breathing and reverse chronic respiratory failure, with consideration of step‐down of the treatment based on a clinical re‐evaluation. In contrast, failure to reach physiological and clinical treatment targets should lead to the consideration of treatment escalation.     

Blood pressure, cardiac structure and severity of obstructive sleep apnea in a sleep clinic population.

OBJECTIVES : We investigated whether the severity of obstructive sleep apnea (OSA) predicts blood pressure or cardiac left ventricular thickness in a clinical population of OSA patients, if adjustments are made for age, gender, use of antihypertensive agents, smoking, body mass index, history of coronary artery disease, hypercholesterolemia and circulating C-peptide concentrations. DESIGN : Relationships in this cross-sectional study were investigated with correlation analysis and multiple regression procedures. PATIENTS AND METHODS : Apnea-hypopnea index (AHI, polysomnography) and office systolic and diastolic blood pressures (SBP and DBP) were measured in 81 subjects referred to a university hospital sleep laboratory. Ambulatory blood pressures were recorded during one 24 h cycle. Left ventricular (LV) muscle size was quantified as two-dimensionally directed M-mode-derived end-diastolic thickness of interventricular septum and posterior chamber wall. RESULTS : After adjustment for separate or the entire set of covariates, AHI predicted office SBP and DBP as well as daytime ambulatory DBP and night-time ambulatory SBP and DBP, but not daytime ambulatory SBP. In contrast, associations between AHI and LV muscle thickness reflected complex inter-relationships with confounding variables. Smoking and age suppressed, whereas body mass index (BMI) and hypertension inflated the relationship between OSA severity and LV muscle thickness in this study. CONCLUSIONS : AHI is an independent predictor of several measures of blood pressure. OSA severity and LV muscle thickness appear to be primarily linked via increased blood pressure.     

Advances in sleep-disordered breathing

Since the original clarification of the obstructive nature of obstructive sleep apnea (OSA) in 1965, much has been learned about the disorder. It is a condition with a high prevalence with obesity as a major risk factor. It aggregates in families, a relationship that is not simply explained by obesity. Premenopausal women are relatively protected from the disorder because OSA is uncommon in this group. Its prevalence in women rises after menopause. Although OSA is a risk factor for excessive sleepiness, there is developing evidence that it is also a risk factor for hypertension, acute cardiovascular events, and insulin resistance. The first line of therapy is nasal continuous positive airway pressure. Data as to the efficacy of continuous positive airway pressure in severe OSA have come from randomized, placebo-controlled clinical trials with the endpoints being sleepiness, quality of life, and 24-h ambulatory blood pressure. Data are currently less convincing for treatment outcomes in mild to moderate OSA, and new clinical trials to assess outcomes in this group are underway. Thus, even though this field only began toward the end of the first century of the American Thoracic Society, substantial progress has been made, and OSA has increasingly emerged as a major public health concern.     

Non-positive airway pressure modalities: mandibular advancement devices/positional therapy

Although positive airway pressure is the most efficacious treatment for obstructive sleep apnea (OSA), its clinical effectiveness is limited by its obtrusive interface. Two alternative treatment modalities used in clinical practice are mandibular advancement devices (MADs) and positional therapy. The goals in treatment of OSA are to prevent obstructive apneas and hypopneas, to improve symptoms, and to modify the increased cardiovascular risk. MADs achieve this by mechanically protruding the mandible, thereby increasing the dimensions of the upper airway and reducing its collapsibility. By avoiding supine sleep, positional therapy improves the patency of the upper airway in those with positional OSA. There is now a relatively strong evidence base to support the use of MADs in clinical practice, with research studies assessing the impact of treatment on a range of health outcomes. The revised clinical practice parameters of the American Academy of Sleep Medicine recommend their use for mild to moderate OSA; or for patients with severe OSA who are unable to tolerate or refuse treatment with positive airway pressure. The evidence base for positional therapy is emerging, but is less well developed. A better understanding of the range of OSA phenotypes and predictors of response to different treatment modalities is required to allow physicians to tailor the choice of treatment to the individual patient.     

Upcoming Scenarios for the Comprehensive Management of Obstructive Sleep Apnea: An Overview of the Spanish Sleep Network

Sleep is considered an essential part of life and plays a vital role in good health and well-being. Equally important as a balanced diet and adequate exercise, quality and quantity of sleep are essential for maintaining good health and quality of life. Sleep-disordered breathing is one of the most prevalent conditions that compromises the quality and duration of sleep, with obstructive sleep apnea (OSA) being the most prevalent disorder among these conditions. OSA is a chronic and highly prevalent disease that is considered to be a true public health problem. OSA has been associated with increased cardiovascular, neurocognitive, metabolic and overall mortality risks, and its management is a challenge facing the health care system. To establish the main future lines of research in sleep respiratory medicine, the Spanish Sleep Network (SSN) promoted the 1st World Café experts’ meeting. The overall vision was established by consensus as “Sleep as promoter of health and the social impact of sleep disturbances”. Under this leitmotiv and given that OSA is the most prevalent sleep disorder, five research lines were established to develop a new comprehensive approach for OSA management: (1) an integrated network for the comprehensive management of OSA; (2) the biological impact of OSA on comorbidities with high mortality, namely, cardiovascular and metabolic diseases, neurocognitive diseases and cancer; (3) Big Data Analysis for the identification of OSA phenotypes; (4) personalized medicine in OSA; and (5) OSA in children: current needs and future perspectives.     

Obstructive sleep apnea: role in the risk and severity of diabetes

Obstructive sleep apnea (OSA) is a treatable sleep disorder that is pervasive among overweight and obese individuals. Current evidence supports a robust association between OSA and insulin resistance, glucose intolerance and the risk of type 2 diabetes, independent of obesity. Up to 83% of patients with type 2 diabetes suffer from unrecognized OSA and increasing severity of OSA is independently associated with poorer glucose control. Evidence from animal and human models that mimic OSA supports a potential causal role for OSA in altered glucose metabolism. Robust prospective and randomized clinical trials are still needed to test the hypothesis that effective treatment of OSA may prevent the development of type 2 diabetes and its complications, or reduce its severity. Type 2 diabetes is occurring at alarming rates worldwide and despite available treatment options, the economic and public health burden of this epidemic remains enormous. OSA might represent a novel, modifiable risk factor for the development of prediabetes and type 2 diabetes.     

Perioperative management of obstructive sleep apnea

Obstructive sleep apnea (OSA) is the most common breathing disorder, with a high prevalence in both the general and surgical populations. OSA is frequently undiagnosed, and the initial recognition often occurs during medical evaluation undertaken to prepare for surgery. Adverse respiratory and cardiovascular outcomes are associated with OSA in the perioperative period; therefore, it is imperative to identify and treat patients at high risk for the disease. In this review, we discuss the epidemiology of OSA in the surgical population and examine the available data on perioperative outcomes. We also review the identification of high-risk patients using clinical screening tools and suggest intraoperative and postoperative treatment regimens. Additionally, the role of continuous positive airway pressure in perioperative management of OSA and a brief discussion of ambulatory surgery in patients with OSA is provided. Finally, an algorithm to guide perioperative management is suggested.     

Sleep disordered breathing: management update

The term sleep disordered breathing encompasses a spectrum of abnormalities, including snoring, obstructive sleep apnoea (OSA), central sleep apnoea (CSA), respiratory‐related arousals and hypoventilation. This review focuses on both OSA and CSA. It provides a clinical update of recent advances in the diagnosis, management and prognosis of these two conditions. An increasing array of treatment modalities, particularly for OSA, broadens the opportunity for personalised therapy tailored to the individual patient.     

Obstructive sleep apnea syndrome

Obstructive sleep apnea (OSA) syndrome is a common but often unrecognized disorder caused by pharyngeal collapse during sleep and characterized by frequent awakenings, disrupted sleep and consequent excessive daytime sleepiness. With the increasing epidemic of obesity, the most important risk factor for OSA, prevalence of the disease will increase over the coming years thus representing an important public-health problem. In fact, it is now recognized that there is an association between OSA and hypertension, metabolic syndrome, diabetes, heart failure, coronary artery disease, arrhythmias, stroke, pulmonary hypertension, neurocognitive and mood disorders. Diagnosis is based on the combined evaluation of clinical manifestations and objective sleep study findings. Cardinal symptoms include snoring, sleepiness and significant reports of sleep apnea episodes. Polysomnography represents the gold standard to confirm the clinical suspicion of OSA syndrome, to assess its severity and to guide therapeutic choices. Behavioral, medical and surgical options are available for the treatment. Continuous positive airway pressure (CPAP) represents the treatment of choice in most patients. CPAP has been demonstrated to be effective in reducing symptoms, cardiovascular morbidity and mortality and neurocognitive sequelae, but it is often poorly tolerated. The results of clinical studies do not support surgery and pharmacological therapy as first-line treatment, but these approaches might be useful in selected patients. A better understanding of mechanisms underlying the disease could improve therapeutic strategies and reduce the social impact of OSA syndrome.     

Does remote monitoring change OSA management and CPAP adherence?

It is increasingly recognized that the high prevalence of obstructive sleep apnoea (OSA), and its associated cardio‐metabolic morbidities make OSA a burden for society. Continuous positive airway pressure (CPAP), the gold standard treatment, needs to be used for more than 4 h/night to be effective, but suffers from relatively poor adherence. Furthermore, CPAP is likely to be more effective if combined with lifestyle changes. Thus, the remote telemonitoring (TM) of OSA patients in terms of CPAP use, signalling of device problems, following disease progression, detection of acute events and monitoring of daily physical activity is an attractive option. In the present review, we aim to summarize the recent scientific data on remote TM of OSA patients, and whether it meets expectations. We also look at how patient education and follow‐up via telemedicine is used to improve adherence and we discuss the influence of the profile of the healthcare provider. Then, we consider how TM might be extended to encompass the patient's cardio‐metabolic health in general. Lastly, we explore how TM and the deluge of data it potentially generates could be combined with electronic health records in providing personalized care and multi‐disease management to OSA patients.     

Obstructive sleep apnea in infants and its management with nasal continuous positive airway pressure.

STUDY OBJECTIVES: Nasal continuous positive airway pressure (nCPAP) is the most common treatment for obstructive sleep apnea (OSA) in adults, and it has been effective in the treatment of OSA in children. We wanted to determine the effectiveness of long-term nCPAP therapy for OSA in infants. PATIENTS: Twenty-four infants who had OSA were treated with nCPAP via nose mask. These infants had clinical histories that included a family history of sudden infant death syndrome, an apparent life-threatening event, or facial and upper airway anatomic abnormalities. INTERVENTIONS: Overnight polysomnographic studies were performed to assess the severity of OSA in each infant and to determine the appropriate level of continuous positive airway pressure (CPAP). Studies were repeated to determine the progress of OSA and the continuing need for CPAP in each infant. RESULTS: nCPAP pressures between 4 and 6 cm H2O prevented obstruction and reversed sleep disturbances that were associated with OSA. Eighteen of the infants continued treatment at home from 1 month to > 4 years. CPAP therapy was discontinued in 13 infants after their OSA resolved. Five infants who have upper airway anatomic abnormalities remain on CPAP, and the pressure level required to prevent obstructive events during sleep has needed to be increased to as high as 10 cm H2O. CONCLUSIONS: nCPAP is an effective therapy for the management of OSA in infants, and it can be used effectively in the home environment. Regular follow-up is necessary, because the requirements for CPAP and pressure levels change with the infant's growth and development.     

Indications for positive airway pressure treatment of adult obstructive sleep apnea patients: a consensus statement

We developed a short-length document that clearly delineates a prudent approach to and criteria for reimbursement of positive airway pressure (PAP) costs for the treatment of obstructive sleep apnea (OSA). Treatment modalities for OSA with PAP include continuous positive airway pressure, bilevel or variable PAP, and autotitrating PAP. This guidance on the appropriate criteria for PAP use in OSA is based on widely acknowledged peer-reviewed studies and widely accepted clinical practice. These criteria reflect current opinion on the appropriate clinical management of OSA in lieu of data pending from the Sleep Heart Health Study and upcoming outcome studies. This document is not intended to provide a complete review and analysis of the OSA clinical literature. The key to the success of this document is to foster consensus within and outside the clinical sleep community by providing a common sense and easily understood approach to the treatment of OSA with PAP.