Current Respiratory Medicine Reviews - Volume 3, Issue 4, 2007

For the last 20 years sleep medicine has been recognized as a separate clinical specialty. Pulmonary physicians first became involved in the arena of sleep medicine as obstructive sleep apnea and sleep related breathing disorders were recognized. Although sleep-disordered breathing had been recognized for centuries, it was not until recently that close attention was paid to this clinical entity. Charles Dickens, in 1836, gave a perfect description of sleep-disordered breathing with his classic writing about “Joe the fat boy”, now a synonym of obstructive sleep apnea syndrome (OSAS) [1]. The development of modern Sleep Medicine is closely linked to the discovery of the electrical activity of the brain. In 1875 in England Caton was the first to record brain electrical activity of animals [2]. Berger reported the “electroencephalogram of man” in Germany in 1929 [3]. In 1937, Loomis was the first to document the characteristic electroencephalogram (EEG) patterns of what is now called non rapid eye movement (NREM) sleep: vertex waves, sleep spindles, K complex, and Delta slowing [4]. Kleitman, in 1953, described rapid eye movement sleep (REM) and its correlation with dreaming [5]. In 1957 Dement and Kleitman [6], described the human sleep cycle of NREM sleep being followed by REM sleep. In 1968, standardized methods for characterizing normal sleep were published by Allan Rechtschaffen and Anthony Kales. In 1970, Guilleminault described obstructive sleep apnea, whereas for some the beginning was related to Colin Sullivan's findings about continuous positive airway pressure therapy (CPAP) in 1981 [7,8]. In 1993 it was Terry Young's article in New England Journal of Medicine about the prevalence of sleep-disordered breathing that led to the advent of the sleep medicine specialty [9]. The decade of the 1990s saw acceleration in the acceptance of sleep medicine throughout the world. In the United States, the National Center on Sleep Disorders Research (NCSDR) was established by statute as part of the National Heart, Lung, and Blood Institute of the National Institute of Health (NIH). Sleep related breathing disorders now appear to involve several organs and systems. There have been numerous studies published on the role of sleep related breathing disorder and the cardiovascular system, diabetes, polycystic ovarian syndrome, peri-operative assessment, and cerebrovascular accidents. In the current issue we have attempted to provide a review of some important correlations of sleep related breathing disorders and their effects on different organ systems. REFERENCES [1] Dickens C. The Pickwick Papers. Penguin Classics. Reprint of 1836-1837 Edition. London UK: Penguin Books; 1986. [2] Carlton R. The electric currents of the brain. Br Med J 1875; 2: 278. [3] Berger H. Uber das elektroenkephalogramm des menschen. Arch Psychiatr Nervenkr 1929; 97: 6-26. [4] Loomis Al, Harvey EN, Hobart GA. Cerebral states during sleep as studied by human brain potentials. Sci Mon 1937; 45(2): 191-192. [5] Aserinsky E, Kleitman N. Regularly occurring episodes of eye mobility and concomitant phenomenon during sleep. Science 1953; 118: 273-274. [6] Dement WC, Kleitman N. Cyclic variations in EEG during sleep and their relation to eye movement, body mobility and dreaming. Electroencephalogr Clin Neurophysiol 1957; 9: 673-690. [7] Guilleminault C, Dement W. 235 cases of excessive daytime sleepiness. Diagnosis and tentative classification. J Neurol Sci 1977; 31: 13-27. [8] Sullivan CE, Issa FG, Berthon-Jones M, et al. Reversal of obstructive sleep apnea by continuous airway pressure applied through the nares. Lancet 1981; 1: 862-865. [9] Young T, Palta M, Dempsey J, et al. The occurrence of sleep disordered breathing among middle-aged adults. N Engl J Med 1993; 328: 1230-1235.

Stroke is one of the leading causes of mortality, and several risk factors have been identified that may be modified to ameliorate this risk. Recently, obstructive sleep apnea (OSA) has been implicated as a possible additional risk factor for stroke. OSA is a common disorder characterized by repeated upper airway collapse during sleep leading to multiple physiologic abnormalities. Several recent studies suggest that OSA is an independent risk factor for stroke. This independent association is likely due to derangement of normal sleep physiology and the attendant consequences to autonomic, vascular endothelial, and thrombotic/fibrinolytic dysfunction leading to the development of atherosclerosis. Additionally, OSA's contribution to the development of known risk factors for stroke such as hypertension and atrial fibrillation may also predispose a patient to develop cerebrovascular disease. Patients presenting with stroke who are also diagnosed with OSA have a worse prognosis than those without OSA. Therapy with continuous positive airway pressure (CPAP), the treatment of choice for most patients with OSA, appears to be beneficial, but achieving compliance in patients post-stroke is difficult.

Patients with obstructive sleep apnea (OSA) are at increased risk to sustain adverse events during the perioperative period including difficulty with airway control, hypoxemia, airway obstruction requiring reintubation, arrhythmias, myocardial ischemia, and death. Numerous factors appear to be responsible for these consequences, including the effects of anesthetic agents, narcotics, postoperative supine positioning and, in some cases, the surgical intervention itself. The situation is complicated by the fact that most patients with OSA are undiagnosed and there is often insufficient time for adequate evaluation prior to surgery. Perioperative care providers need to maintain a high index of suspicion for OSA and should consider guidelines to help with the recognition and management of these patients. This review will discuss the available literature regarding the preoperative, intraoperative and postoperative evaluation and management of patients with known or suspected OSA undergoing surgery.

Obstructive sleep apnea (OSA) is characterized by repetative obstruction of the upper airway. Positive airway pressure has evolved as the preferred therapeutic modality for OSA. PAP can be used successfully to treat both OSA and central sleep apnea (CSA). PAP usage affects a variety of medical diseases. Proper titration and attention to compliance is paramount in proper usage of PAP. Finally, auto-titrating devices and adaptive servo ventilation may be used to treat and possibly diagnose sleep disorder breathing and the later may have role in treating complex sleep apnea.

Sleep-Disordered Breathing (SDB) is characterized by repetitive partial or complete upper airway occlusion during sleep with a high prevalence in the general community, and associated with considerable morbidity and mortality. In the US, approximately 12 million people 30 to 60 years of age have SDB, and 38,000 die each year from cardiovascular disease attributed to SDB. Substantial morbidity and economic costs are associated with untreated SDB, including those related to daytime sleepiness and hypertension, and cardiovascular co-morbidity. There is a crucial need to address the public health impact of this common condition, including the extent to which treatment of SDB may modify the course of other chronic health conditions such as cardiovascular disease. The public health impact of SDB in large part relates to the association of SDB with cardiovascular disease, a leading cause of mortality in the U.S. Several large epidemiological studies have clearly demonstrated that individuals with SDB have a higher prevalence of cardiovascular disease after controlling for potential confounders. These data, along with the high prevalence of SDB, support a high population attributable risk, suggesting that a high percentage of cardiovascular morbidity in the population may be due to SDB.

Continuous positive airway pressure (CPAP) is the first line treatment for obstructive sleep apnea (OSA), and resolves the majority of complications associated with untreated OSA. However, many patients are unable to tolerate CPAP and may be offered alternate treatments. Positional therapy is most helpful in some OSA patients with a low body mass index (BMI). Both dietary and surgical weight loss are effective in improving OSA; a 10% weight reduction can decrease AHI by 26%, Oral appliances (OA) are effective in 57-81% of patients with mild-moderate OSA. Though oral appliances have a lower success rate (14-61%) in patients with severe OSA, they may be helpful in patients who have failed CPAP or upper airway surgery. A follow up polysomnography and close follow up for dental occlusion changes is recommended in all patients. Uvulopalatopharyngoplasty (UPPP) is effective in half (52.3%) of patients with retro-palatal narrowing, and is effective in a very small proportion of patients (5.3%) with retro-lingual or both retro-palatal and retro-lingual narrowing. Maxillomandibular osteotomy and advancement (MMO) enlarges both the retro-lingual and retro-palatal airway. Patients with normal BMI's and skeletal abnormalities are most likely to benefit from it. A follow up polysomnography is recommended after upper airway surgery. Palatal implants need to be studied further before they can be considered a mainstream treatment. Improvement in nasal patency with intranasal corticosteroids and treatment of residual daytime sleepiness with modafinil may be beneficial in some patients.

Polycystic ovarian syndrome (PCOS) is a clinical syndrome characterized by irregular menstrual cycles, signs of androgen access including hirsutism and acne, and infertility, with ovaries showing cystic changes. Many women with this condition are obese, and it is now well established that insulin resistance makes up a very important component of this syndrome. Recently, there has been increased focus on sleep-disordered breathing (SDB) in patients with PCOS. Several articles recently published have shown clearly, increased incidence of SDB in patients with PCOS. In this review, we shall explore the inter-relationship between the pathophysiology of PCOS and SDB.

Sleep deprivation and sleep disruption have long been associated with mood disorders, both as a cause as well as an effect. Sleep-disordered breathing results in significant and persistent sleep disruption, which in turn leads to significant neurocognitive deficits [1,2] and major depression [3-6]. Various pathophysiologic mechanisms may play a role in modulating mood changes in these patients. Treatment for sleep-disordered breathing often improves mood [4, 7], though the data may suggest a placebo response [8]. Patients with sleep-disordered breathing should be carefully screened for mood disorders, and patients with major depression should be screened for possible underlying sleep-disordered breathing.

Adequate sleep is important for health and quality of life at all ages. Refreshing sleep requires both quality and quantity, so much so that an inadequacy of either leads to overall higher mortality rates. Numerous studies have sited significant changes in sleep that typically occur with aging and primary sleep disorders are more common in the elderly than in younger patients. As many as half of persons over 65 have some complaint relating to sleep. There is a high prevalence of insomnia in the elderly population and elderly patients also frequently suffer from sleep-disordered breathing, restless legs syndrome, periodic leg movement disorder, circadian rhythm disturbances, narcolepsy, and rapid eye movement behavior disorder. Unfortunately, sleep problems in the elderly are often mistakenly considered a normal part of aging. The aim of this article is to review normal sleep, sleep and the major causes of sleep disturbances in the elderly. Attention has been given to diagnosis and appropriate interventions, since sleep disturbances left untreated can have significant negative impact in terms of life expectancy, general health outcome and quality of life.

Several studies have shown a correlation between obstructive sleep apnea (OSA) and obesity, as well as obesity and diabetes mellitus. This is probably related to the fact that patients with OSA are likely to have a high prevalence of the risk factors that comprise metabolic syndrome. It has been shown that sleep deprivation when induced experimentally can cause glucose intolerance and many studies have established the association between sleep apnea and type two diabetes mellitus. There is also a proven association between snoring and sleep apnea as well as snoring and metabolic syndrome. In the current article we review the patho-physiology of hyperglycemia, insulin resistance due to sleep apnea, and treatment of OSA with continuous positive airway pressure therapy. Continuous positive airway pressure (CPAP) does, in fact, lead to improvement in insulin resistance and lowered hemoglobin A1C levels. The question that remains to be answered is whether the association between sleep apnea and the components of metabolic syndrome is one of co-existence or causality, but it can no longer be denied that there is a strong relationship which should lead to investigation of one if the other is found.

Airway remodeling (the structural changes which occur in the airways) is one of the characteristic features of severe persistent asthma. These changes include thickening of the laminar reticularis, an increase in the bulk of the airway smooth muscle, thickening of the basement membrane and alterations in the profile of extracellular matrix proteins in the airway wall. The mechanisms leading to airway remodeling are not well understood. Current asthma therapies are effective at reducing airway inflammation and hyperresponsiveness but their effect on airway remodeling is not as evident. Inhaled glucocorticoids have been reported to reduce the thickness of the basement membrane but also to be ineffective at combating remodeling. Similarly, leukotriene receptor antagonists have been shown to prevent or reverse matrix protein deposition in some models of asthma but to be without effect or increase extracellular matrix protein deposition from airway smooth muscle cells. Less is known about the effects of β2-agonists on airway remodeling. Another class of drugs that is currently being trialed as asthma therapeutics are the phosphodiesterase 4 inhibitors. Recent studies have indicated that this class of drugs may have a role to play in the prevention or reversal of airway remodeling. This review aims to discuss what is currently known about the effectiveness of current therapies for the management of airway remodeling in asthma and to summarize the recent advances that may represent valuable additions for the reversal or prevention of airway remodeling in asthma.

Critical illness is associated with multiple system organ dysfunction, and neurologic dysfunction is increasingly assessed and recognized. Neurologic dysfunction includes encephalopathy, cognitive, neuromuscular and psychiatric impairments, all of which can be severe and are associated with significant morbidity. Medical technological advances have improved central nervous system monitoring in critically ill patients, allowing quick and reliable diagnosis neurologic dysfunction such as delirium, sensory processing deficits, seizures, and encephalopathy to name a few. A number of neurologic evaluation tools are available to assess the neurologic status of critically ill patients both acutely, as well as longterm. Each tool provides unique information regarding neurologic status and has associated strengths and weakness. Identification of neurologic dysfunction allows for the development of working plans for prognostication, therapeutics, and rehabilitation that address the needs of each ICU survivor. This review focuses on the evaluation of neurologic sequelae during critical illness and long-term neurologic outcomes in survivors of critical illness.