Recent advances in obesity hypoventilation syndrome

Obesity hypoventilation syndrome (OHS) consists of a combination of obesity and chronic hypercapnia accompanied by sleep-disordered breathing. During the last 3 decades, the prevalence of extreme obesity has markedly increased in the United States and other countries. With a global epidemic of obesity, the prevalence of OHS is bound to increase. Patients with OHS have a lower quality of life with increased health-care expenses and are at a higher risk for the development of pulmonary hypertension and early mortality compared to eucapnic patients with sleep-disordered breathing. Despite the significant morbidity and mortality associated with this syndrome, it is often unrecognized and treatment is frequently delayed. Clinicians must maintain a high index of suspicion since early recognition and treatment reduces the high burden of morbidity and mortality associated with this syndrome. In this review, we will discuss the definition and clinical presentation of OHS, provide a summary of its prevalence, review the current understanding of the pathophysiology, and discuss the recent advances in the therapeutic options.     

Obesity hypoventilation syndrome: from sleep-disordered breathing to systemic comorbidities and the need to offer combined treatment strategies

Obesity hypoventilation syndrome (OHS) is defined as a combination of obesity (body mass index ≥ 30 kg/m(2)), daytime hypercapnia (partial arterial carbon dioxide concentration ≥45 mm Hg) and sleep-disordered breathing after ruling out other disorders that may cause alveolar hypoventilation. Through the prism of the International Classification of Functioning, OHS is a chronic condition associated with respiratory, metabolic, hormonal and cardiovascular impairments, leading to a decrease in daily life activities, a lack of social participation and high risk of hospitalization and death. Despite its severity, OHS is largely underdiagnosed and the health-related costs are higher than those of apnoeic or obese eucapnic patients. The present review discusses the definition, epidemiology, physiopathology and treatment modalities of OHS. Although nocturnal positive airway pressure therapies represent first-line treatment and are effective in improving patient outcomes, there is a need to offer combined treatment strategies and to assess the effect of multimodal therapeutic strategies on morbidity and mortality.     

Obesity hypoventilation syndrome: mechanisms and management

Obesity hypoventilation syndrome describes the association between obesity and the development of chronic daytime alveolar hypoventilation. This syndrome arises from a complex interaction between sleep-disordered breathing, diminished respiratory drive, and obesity-related respiratory impairment, and is associated with significant morbidity and mortality. Therapy directed toward reversing these abnormalities leads to improved daytime breathing, with available treatment options including positive pressure therapy, weight loss, and pharmacological management. However, a lack of large-scale, well-designed studies evaluating these various therapies has limited the development of evidence-based treatment recommendations. Although treatment directed toward improving sleep-disordered breathing is usually effective, not all patients tolerate mask ventilation and awake hypercapnia may persist despite effective use. In the longer term, weight loss is desirable, but data on the success and sustainability of this approach in obesity hypoventilation are lacking. The review outlines the major mechanisms believed to underlie the development of hypoventilation in this subgroup of obese patients, their clinical presentation, and current therapy options.     

An organ systems-based review of outcomes associated with sleep apnea in hospitalized patients

The current global health crisis due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has prompted the medical community to investigate the effects of underlying medical conditions, including sleep-disordered breathing, on inpatient care. Obstructive sleep apnea (OSA) is a common form of sleep-disordered breathing that may complicate numerous acquired conditions, particularly in inpatient and critical care settings. Viral pneumonia is a major contributor to intensive care unit (ICU) admissions and often presents more severely in patients with underlying pulmonary disease, especially those with obesity and OSA. This review summarizes the most recent data regarding complications of both OSA and obesity and highlights their impact on clinical outcomes in hospitalized patients. Additionally, it will highlight pertinent evidence for the complications of OSA in an organ-systems approach. Finally, this review will also discuss impatient treatment approaches for OSA, particularly in relation to the SARS-CoV-2 pandemic.     

Sleep-disordered breathing and cardiovascular health

PURPOSE OF REVIEW: Sleep-disordered breathing is a widely prevalent condition and may have serious medical, social, and economic consequences. This review evaluates the role of sleep-disordered breathing in cardiovascular morbidity and mortality on the basis of recent literature. RECENT FINDINGS: Epidemiologic studies, retrospective reviews, and prospective clinical trials suggest a strong association between sleep-disordered breathing and adverse cardiovascular events. Individuals with sleep-disordered breathing have a higher prevalence of hypertension, which attenuates with treatment. Furthermore, the presence of sleep-disordered breathing augurs an increased risk of coronary artery disease, cardiac arrhythmias, and heart failure. SUMMARY: Recent research provides an emerging evidence of the role of sleep-disordered breathing as a risk factor for diverse cardiovascular disorders.     

Obesity and cardiovascular risk in children and adolescents

The global prevalence of overweight and obesity in children and adolescents has increased substantially over the past several decades. These trends are also visible in developing economies like India. Childhood obesity impacts all the major organ systems of the body and is well known to result in significant morbidity and mortality. Obesity in childhood and adolescence is associated with established risk factors for cardiovascular diseases and accelerated atherosclerotic processes, including elevated blood pressure (BP), atherogenic dyslipidemia, atherosclerosis, metabolic syndrome, type II diabetes mellitus, cardiac structural and functional changes and obstructive sleep apnea. Probable mechanisms of obesity-related hypertension include insulin resistance, sodium retention, increased sympathetic nervous system activity, activation of the renin-angiotensin-aldosterone system and altered vascular function. Adiposity promotes cardiovascular risk clustering during childhood and adolescence. Insulin resistance has a strong association with childhood obesity. A variety of proinflammatory mediators that are associated with cardiometabolic dysfunction are also known to be influenced by obesity levels. Obesity in early life promotes atherosclerotic disease in vascular structures such as the aorta and the coronary arteries. Childhood and adolescent adiposity has strong influences on the structure and function of the heart, predominantly of the left ventricle. Obesity compromises pulmonary function and increases the risk of sleep-disordered breathing and obstructive sleep apnea. Neglecting childhood and adolescent obesity will compromise the cardiovascular health of the pediatric population and is likely to result in a serious public health crisis in future.     

Obesity hypoventilation syndrome: prevalence and predictors in patients with obstructive sleep apnea

Patients with obesity hypoventilation syndrome (OHS) have a lower quality of life, more healthcare expenses, a greater risk of pulmonary hypertension, and a higher mortality compared to eucapnic patients with obstructive sleep apnea (OSA). Despite significant morbidity and mortality associated with OHS, it is often unrecognized and treatment is frequently delayed. The objective of this observational study was to determine the prevalence of OHS in patients with OSA seen at the sleep disorders clinic of a large public urban hospital serving predominantly minority population and to identify clinical—not mechanistic—predictors that should prompt clinicians to measure arterial blood gases. In the first stage, we randomly selected 180 patients referred to our sleep disorders clinic between 2000 and 2004 for suspicion of OSA. From this retrospective random sample we calculated the prevalence of OHS in patients with OSA and identified independent clinical predictors using logistic regression. In the second stage, we prospectively validated these predictors in a sample of 410 consecutive patients referred to the sleep disorders clinic for suspicion of OSA between 2005 and 2006. The prevalence of OHS in patients with OSA was 30% in the retrospective random sample and 20% in the prospective sample. Three variables independently predicted OHS in both samples: serum bicarbonate level (p < 0.001), apnea–hypopnea index (p = 0.006), and lowest oxygen saturation during sleep (p < 0.001). Due to the serious morbidity associated with OHS, we selected a highly sensitive threshold of serum bicarbonate level. A threshold of 27 mEq/l had a sensitivity of 92% and a specificity of 50%. Only 3% of patients with a serum bicarbonate level <27 mEq/l had hypercapnia compared to 50% with a serum bicarbonate ≥27 mEq/l. In conclusion, OHS is common in severe OSA. A normal serum bicarbonate level excludes hypercapnia and an elevated serum bicarbonate level should prompt clinicians to measure arterial blood gases.     

Sleep-disordered breathing in patients with sickle cell disease

Sickle cell disease is one of the most common hereditary hemoglobinopathies worldwide, and its vaso-occlusive and hemolytic crises cause considerable patient morbidity. A growing body of evidence has shown that sleep-disordered breathing, and in particular, obstructive sleep apnea, occurs at high frequency in the sickle cell population, and that there is significant overlap in the underlying pathophysiology of these two conditions. Through a variety of mechanisms including nocturnal hypoxemia and increased oxidative stress, production of pro-inflammatory cytokines, and endothelial dysfunction, sickle cell anemia and sleep-disordered breathing potentiate each other’s clinical effects and end-organ complications. Here, we will review the shared pathophysiologic mechanisms of these conditions and discuss their clinical sequelae. We will also examine the results of studies that have been carried out with clinical intervention of nocturnal hypoxemia in patients with sickle cell disease in the attempts to overcome the complications of the disease. Finally, we will propose the areas of investigation that merit further investigations in future in patients with sickle cell disease and sleep-disordered breathing.     

Prevalence of suspected obesity hypoventilation syndrome in Hungarian Intensive Care Units during the COVID-19 pandemic

Introduction

The symptoms of obesity hypoventilation syndrome (OHS) may be present for years with concomitant progressive comorbidities, and the condition is frequently diagnosed late as a result of acute-on-chronic hypercapnic respiratory failure. Although some data exist on intensive care unit (ICU) prevalence, mortality and morbidity of OHS, little is known about the ICU mortality of these chronic respiratory failure patients during the COVID-19 pandemic.

Methods

We performed a cross-sectional observational study in five Hungarian Intensive Care Units for 4 months during the COVID-19 pandemic. All ICU patients were screened for OHS risk factors by treating physicians. Risk factors were defined as obesity (body mass index [BMI] ≥ 30 kg/m²) and at least one of the following: Epworth Sleepiness Score ≥ 6; symptoms of right heart failure; daytime or night-time hypoxemia; presence of loud snoring; witnessed apnoea. We calculated prevalence, mortality and factors associated with unfavourable outcome.

Results

A total of 904 ICU patients were screened for OHS risk factors. Overall 79 (8.74 ± 5.53%) patients were reported to have met the criteria for suspected OHS with a mortality rate of 40.5%; 69% (54 patients) of the cohort displayed at least 3 symptoms related to OHS before their acute illness. COVID-19 infection was associated with higher mortality in OHS-suspected patients, independently of actual BMI.

Conclusion

Despite the increased risk of obese patients, suspected OHS did not show higher prevalence than expected during the COVID-19 pandemic in critically ill patients. COVID-19 infection however was a risk for mortality in these patients, independent of actual BMI.     

Non-invasive Positive Airway Pressure in Obesity Hypoventilation Syndrome and Chronic Obstructive Pulmonary Disease: Present and Future Perspectives

Obesity hypoventilation syndrome (OHS) is a sleep disorder that has acquired great importance worldwide because of its prevalence and association with obesity leading to increased morbidity and mortality with reduced quality of life. The primary feature is insufficient sleep-related ventilation, resulting in abnormally elevated arterial carbon dioxide pressure (PaCO₂) during sleep and demonstration of daytime hypoventilation. There are three main mechanisms that can generate diurnal hypoventilation in obese patients: alteration of the respiratory mechanics secondary to obesity; central hypoventilation secondary to leptin resistance and sleep disorder with sleep hypoventilation and obstructive apnoeas, which can be potentially solved with the use of positive airway pressure: non-invasive ventilation (NIV) and continuous positive airway pressure (CPAP). There are no established guidelines for the treatment of OHS, and only a few randomised controlled trials have been published. In this review, we have gone over the role of positive airway pressure, in particular the mechanisms that produce improvement, ventilatory modes available, clinical applications, technical considerations and future research. In addition, we added a review on NIV efficacy in chronic obstructive pulmonary disease (COPD), both in acute respiratory failure due to exacerbation and mainly in stable setting where more controversy and scientific contributions are coming.     

Sleep-Disordered breathing in patients referred for angina evaluation--association with left ventricular dysfunction

BACKGROUND: Clinical observations have linked sleep-disordered breathing to cardiovascular morbidity and mortality, and especially to coronary artery disease. HYPOTHESIS: The study was undertaken to determine the prevalence of sleep-disordered breathing in consecutive patients referred for angina evaluation, and analyzed the parameters influencing the severity of sleep-disordered breathing. METHODS: In all, 68 consecutive patients (53 men, 15 women, aged 63.4 +/- 10.0 years) referred for angina evaluation were studied. Coronary angiography, selective left ventriculography, and a polygraphic study with a validated six-channel monitoring device were performed. Full-night polysomnography was used to reevaluate patients with an apnea/hypopnea index > or = 10/h. RESULTS: Sleep-disordered breathing as defined by an apnea/hypopnea index > or = 10/h was found in 30.9% of patients; its prevalence was not increased in patients with and without coronary artery disease (26.5 vs. 42.1%). Multiple stepwise linear regression analysis revealed that the severity of sleep-disordered breathing was significantly and independently associated with left ventricular ejection fraction (r = -0.38; p = 0.002), but not with age, body mass index, gender, diabetes mellitus, hypertension, hyperuricemia, hypercholesterolemia, smoking habits, or coronary artery disease. In this group of patients, multiple logistic regression analysis could not demonstrate sleep-disordered breathing to be an independent predictor of coronary artery disease. CONCLUSIONS: Sleep-disordered breathing is common in patients referred for angina evaluation. The degree of sleep-disordered breathing is mainly determined by the extent of left ventricular dysfunction.     

Bariatric surgery and its impact on sleep architecture, sleep-disordered breathing, and metabolism

Over the last several decades, the prevalence of obesity has increased significantly worldwide. This has translated into an increased prevalence of obesity-associated morbidities including sleep-disordered breathing and metabolic disorders. While the medical management of obesity is relatively ineffective, bariatric surgery is the most successful method for sustained weight loss and markedly reduces obesity-related morbidity and mortality. The anatomical changes created with different types of procedures lead to variable weight loss and improvement of co-morbidities; however the latter does not appear to be exclusively dependent on the amount of weight loss. Bariatric surgery does not always lead to complete resolution of obstructive sleep apnea and age, gender and severity of the obstructive sleep apnea predict the residual disease after peak weight loss. Metabolic disorders and specifically diabetes often improve dramatically early after the procedure, before any significant weight loss has occurred. The modified gastrointestinal anatomy and physiology may explain this phenomenon.     

Sleep apnea-hypopnea syndromes and heart failure

Heart failure (HF) and sleep-disordered breathing are conditions highly prevalent in the general population that often co-exist in the same patient. Epidemiological and pathophysiological studies indicate that there may be a causal link between sleep-disordered breathing and HF with either left ventricular systolic dysfunction or preserved ejection fraction. The presence of sleep-disordered breathing in HF patients expose the cardiovascular system to intermittent hypoxia, sympathetic activation, and increased preload and afterload and they trigger several inflammatory, oxidative and neurohumoral mechanisms that may precipitate the progression of the disease. Although there are no available data to indicate that treating sleep-disordered breathing in HF patients reduce cardiac mortality, several studies demonstrate a significant improvement in structural and functional cardiovascular parameters. This review focuses on the clinical and epidemiological bases, the pathophysiological mechanisms and the therapeutic implications between HF and sleep apnea-hypopnea syndromes.     

慢性肺曲霉病研究进展

慢性肺曲霉病是一组由曲霉菌引起的临床综合症,好发于存在肺部基础疾病患者,其发病率及病死率较高,对全球健康造成严重负担,亟需我们对其临床表现及治疗提高认识.现对慢性肺曲霉病近年来有关临床分类、临床表现、治疗及耐药进展进行综述.     

Recognition and Management of Sleep-Disordered Breathing in Chronic Heart Failure

It is increasingly recognized that sleep-disordered breathing (SDB) is a common modifiable risk factor for cardiovascular disease with significant impact on morbidity and potentially mortality. SDB is highly prevalent in patients with systolic or diastolic heart failure. A high index of suspicion is necessary to diagnose SDB in patients with heart failure because the vast majority of affected patients do not report daytime symptoms. Recent clinical trials have demonstrated improvement in heart function, exercise tolerance, and quality of life after treatment of SDB in patients with heart failure. Accumulating evidence suggests that treatment of SDB should complement the established pharmacologic therapy for chronic heart failure. However, mortality benefit has yet to be demonstrated.     

Obesity as a multisystem disease: Trends in obesity rates and obesity-related complications

Obesity is a chronic multisystem disease associated with increased morbidity and mortality. The increasing prevalence of obesity makes it a major healthcare challenge across both developed and developing countries. Traditional measures such as body mass index do not always identify individuals at increased risk of comorbidities, yet continue to be used in deciding who qualifies for weight loss treatment. A better understanding of how obesity is associated with comorbidities, in particular non-metabolic conditions, is needed to identify individuals at risk in order to prioritize treatment. For metabolic disorders such as type 2 diabetes (T2D), weight loss can prevent T2D in individuals with prediabetes. It can improve and reverse T2D if weight loss is achieved early in the course of the disease. However, access to effective weight loss treatments is a significant barrier to improved health for people with obesity. In the present paper, we review the rising prevalence of obesity and why it should be classed as a multisystem disease. We will discuss potential mechanisms underlying its association with various comorbidities and how these respond to treatment, with a particular focus on cardiometabolic disease, malignancy and mental health.     

Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism

Obesity is becoming a global epidemic in both children and adults. It is associated with numerous comorbidities such as cardiovascular diseases (CVD), type 2 diabetes, hypertension, certain cancers, and sleep apnea/sleep-disordered breathing. In fact, obesity is an independent risk factor for CVD, and CVD risks have also been documented in obese children. Obesity is associated with an increased risk of morbidity and mortality as well as reduced life expectancy. Health service use and medical costs associated with obesity and related diseases have risen dramatically and are expected to continue to rise. Besides an altered metabolic profile, a variety of adaptations/alterations in cardiac structure and function occur in the individual as adipose tissue accumulates in excess amounts, even in the absence of comorbidities. Hence, obesity may affect the heart through its influence on known risk factors such as dyslipidemia, hypertension, glucose intolerance, inflammatory markers, obstructive sleep apnea/hypoventilation, and the prothrombotic state, in addition to as-yet-unrecognized mechanisms. On the whole, overweight and obesity predispose to or are associated with numerous cardiac complications such as coronary heart disease, heart failure, and sudden death because of their impact on the cardiovascular system. The pathophysiology of these entities that are linked to obesity will be discussed. However, the cardiovascular clinical evaluation of obese patients may be limited because of the morphology of the individual. In this statement, we review the available evidence of the impact of obesity on CVD with emphasis on the evaluation of cardiac structure and function in obese patients and the effect of weight loss on the cardiovascular system.     

Mind-Body Connection: Cardiovascular Sequelae of Psychiatric Illness

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the world. Mental health disorders are associated with the onset and progression of cardiac disease. The adverse sequelae of this association include worsened quality of life, adverse cardiovascular outcomes, and heightened mortality. The increased prevalence of CVD is partly explained by increased rates of traditional cardiovascular risk factors including hypertension, hyperlipidemia, diabetes mellitus, obesity, and smoking, but mental illness is an independent risk factor for CVD and mortality. Given the association between mental health disorders and poor cardiovascular health, it is vital to have an early and accurate identification and treatment of these disorders. Our review article shares the current literature on the adverse cardiovascular events associated with psychiatric disorders. We present a review on depression, anxiety, bipolar disorder, schizophrenia, type A and D personality disorders, obsessive-compulsive disorder, and stress.     

Diabetes and HIV: Current Understanding and Future Perspectives

Diabetes mellitus is a chronic disease with a higher risk of associated infections. HIV infection severely affects diabetic patients and acts as a significant health concern. Highly active antiretroviral therapy (HAART) has changed HIV from an acute infection to a chronic infection with associated significant metabolic abnormalities such as insulin resistance, impaired glucose tolerance, metabolic syndrome, diabetes, dyslipidemia, obesity, and lipodystrophy. These metabolic disturbances add complexity to the standards of care in HIV infection and further increase the risk for cardiovascular disease and renal complications. The co-association of diabetes and HIV needs to be managed appropriately to prevent mortality and morbidity and improve patient outcome. The current understanding of diabetes and other metabolic abnormalities along with management strategies in HIV infected patients are summarized in this article. The review also focuses on recent challenges in the diagnosis and management of co-existent diabetes and HIV infection.     

Obstructive Sleep Apnea Syndrome: Blood Viscosity, Blood Coagulation Abnormalities, and Early Atherosclerosis

Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for atherosclerosis and arterial thrombosis, which are associated with high cardiovascular (CV) morbidity and mortality. In studies performed in clinical populations with elevated CV event risk profiles, the occurrence of moderate to severe OSAS was very often accompanied by a worsened vascular function and increased prevalence of structural abnormalities. Recent investigations of atherosclerosis in OSAS have focused on thrombotic tendency and blood viscosity, providing new insight into mechanisms of the disease. Despite that knowledge about the mechanisms of development of CV disease in patients with OSAS is still incomplete, observations confirm a relationship between sleep-disordered breathing and the rheological properties (flow properties) of blood. While platelet dysfunction and hypercoagulability (PDMPs, PaI-1, and SF) play important roles in the pathogenesis of vascular disease, there are limited studies on the potential role of blood viscosity in the development of vascular disease in OSAS.