© 2008 American Thoracic Society doi: 10.1164/rccm.200711-1717ED
Respiratory Sleep MedicineA Coming of Age
Sleep Research Laboratories of the Toronto Rehabilitation Institute Respiratory sleep medicine began in 1965 with the original polysomnographic description of obstructive sleep apnea (OSA) by Gastaut and colleagues (1). Since then, we have witnessed a series of medical and scientific advances that have transformed this initially obscure field into one of the most rapidly expanding and dynamic areas of pulmonary medicine. Following closely on the heals of Gastaut's discovery, Kuhlo and associates (2) pioneered the use of tracheostomy to treat OSA. In a landmark paper published in 1981, Sullivan and associates revolutionized the treatment of OSA through application of continuous positive airway pressure (CPAP) via a nasal mask (3). This ushered in the era of modern respiratory sleep medicine by providing a highly effective and acceptable therapy for OSA. Subsequently, there has been a dramatic upsurge in the number of publications on sleep-related breathing disorders—from three publications in 1965, to 1,569 in 2006 (PubMed search). The American Thoracic Society has acknowledged the importance of sleep medicine by designating it, along with pulmonary and critical care, as one of its priorities. The Journal has also recognized the great strides made in this field by commissioning a series of six articles on sleep-related breathing disorders, the last of which appears in this issue (4). The objective of this series was to highlight for readers new developments and clinical controversies. In the first of this series, White (5) reviewed the pathogenesis of OSA and central sleep apnea (CSA). In addition to the well-established concept that upper airway obstruction in OSA arises from the normal sleep-related reduction in pharyngeal dilator muscle tone superimposed upon a collapsible pharynx, he considered the newer concept that respiratory control system instability may predispose to pharyngeal occlusion in some patients. According to this concept, in some patients, pharyngeal occlusion during sleep may have a primarily central, rather than anatomic, origin, related to augmented controller (i.e., loop) gain. Should this concept prove valid, it has the potential to open new avenues of therapy for a subset of patients with OSA through the use of agents such O2, CO2, and respiratory stimulants that stabilize respiratory control (6). There is, however, better evidence that respiratory control system instability contributes to the pathogenesis of CSA, in which apnea results from cessation of central respiratory drive, but without pharyngeal occlusion. The demonstration that inhalation of CO2 or O2 generally alleviates CSA provides proof of this concept (7, 8). In the second article, Arzt and Bradley (9) reviewed treatment of OSA and CSA in patients with heart failure. The concept has arisen that OSA and CSA contribute to the development and progression of heart failure through mechanical, autonomic, and oxidative stresses that are potentially reversible. Several randomized trials have demonstrated that treatment of OSA with CPAP in patients with heart failure improves cardiovascular function, but such trials have been too small to determine whether this leads to reductions in morbidity and mortality. With respect to CSA, there has been one multicenter, long-term trial involving 258 patients in which it was shown that CPAP improved cardiovascular function, but not morbidity or mortality (10). It was concluded that, whereas treatment of OSA and CSA does improve cardiovascular function in patients with heart failure, larger multicenter trials are required to determine whether such treatment translates into reductions in morbidity and mortality. In the third article, Ievers-Landis and Redline (11) discussed the implications of increasing rates of childhood obesity for OSA. The data are truly alarming: the prevalence of overweight adolescents in the United States tripled from 5% in the 1970s to 15% in 2000. Since increasing weight increases the risk of OSA, one can predict higher rates of OSA, with consequences among children ranging from behavioral problems, to increased risk of cardiovascular complications as they age. The authors call for increased awareness of OSA in children as a treatable condition, but more importantly, for measures to prevent obesity in childhood. A controversial issue addressed by Montserrat and colleagues (12) in the fourth article was treatment of the nonsleepy patient with OSA. Less than 50% of patients meeting polysomnographic criteria for OSA complain of sleepiness, which is the usual indication for therapy (13). Practitioners are faced with a dilemma when they consider therapy for such nonsleepy patients. The few randomized trials that have addressed this issue showed, in uncomplicated patients with OSA, that CPAP had no beneficial influence on alertness, quality of life, neurocognitive function, or blood pressure, even among those with an apnea–hypopnea index of more than 30 events per hour of sleep. However, in heart failure patients with OSA, but without sleepiness, treatment by CPAP improved cardiovascular function, but it was not determined whether it provided clinical benefits. These authors concluded that the evidence provides no compelling reason to treat patients with OSA who do not complain of sleepiness. On the other hand, they argue that randomized trials are needed to determine whether treating nonsleepy patients with coexisting cardiovascular disease improves clinical outcomes. The controversial issue of how to approach car crash risk associated with OSA was addressed by George (14) in the fifth article. Although there is epidemiologic evidence of a higher car crash risk in individuals with OSA than in subjects without it, the overall risk remains quite low. Nevertheless, nonrandomized trial data suggest that treating OSA can lower car crash risk. On the basis of evidence that previous car crashes predict increased risk of future crashes, and that sleepiness impairs simulated driving performance, he advocated reporting patients with OSA to motor vehicle departments regarding this risk if they had a previous history of car crashes, or complained of sleepiness, but not to report those without these problems. He further argues that the threshold for reporting patients with OSA should be lower for professional drivers. Important recommendations were to advise patients with OSA not to drive if they are sleepy, and to initiate therapy for OSA as soon after the diagnosis as possible to reduce car crash risk. Clearly, more research about actual driving risk associated with OSA, particularly among professional drivers, is required to formulate rational recommendations about who should or should not drive. In this issue of the Journal (pp. 369–375), Gozal and Kheirandish-Gozal (4) argue that recurrent hypoxia–reoxygenation arising from OSA can unleash a cascade of oxygen free radicals and inflammatory mediators that contribute to vascular endothelial dysfunction through nitric oxide–mediated pathways. In concert with dysregulation of lipid metabolism, these factors may promote atherosclerosis. Such a pathophysiologic scheme could help to explain epidemiologic associations between OSA and a variety of cardiovascular diseases. Indeed, recent articles have demonstrated that, compared with subjects without OSA, those with OSA have greater evidence of subclinical atherosclerosis that is partially reversible by treatment with CPAP (15–17). The authors of these articles have done an admirable job in providing readers with fresh insights into pathophysiologic, clinical, and therapeutic implications of sleep-related breathing disorders. They have also raised awareness of deficiencies in our knowledge and of controversies in need of resolution. As the broad scope and high quality of these articles make abundantly clear, respiratory sleep medicine has truly come of age: nevertheless, exciting challenges remain. FOOTNOTES Supported by operating grant MOP-82731 from the Canadian Institutes of Health Research. Conflict of Interest Statement: T.D.B. has no financial relationship with a commercial entity that has an interest in the subject of this manuscript. REFERENCES
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