Sleep and Respiration

 

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This issue of Seminars in Respiratory and Critical Care Medicine includes articles on the wide variety of sleep-disordered breathing syndromes, focusing predominantly on the most common one, obstructive sleep apnea (OSA). There is much work to be done to further elucidate the pathophysiology, develop ideal methods for diagnosis, and discover improved treatment for this syndrome. Some of the more pressing issues include developing a more streamlined and efficient method of diagnosis, which might include identifying biomarkers for disease; improving on current treatment modalities, with the “Holy Grail” being to develop a medication that is effective; and determining whether our current treatment methods actually do lower the associated morbidity and mortality of the syndrome.

With regard to where we are currently, the latest developments in OSA include the discovery of various biomarkers linked to OSA and cardiovascular diseases; the association between OSA and metabolic syndrome; the genetics of OSA; the role of portable monitoring for diagnosis; and bariatric surgery in OSA patients.

OSA has been suggested to be an important risk factor for cardiovascular disease akin to hyperlipidemia, smoking, and family history. Numerous investigators have shown that several biomarkers related to cardiovascular disease are also elevated in OSA, including homocysteine, C-reactive protein, plasminogen activator inhibitor-1, and fibrinogen.[1] Although uncertain, it is thought that the common link may be intermittent hypoxia, triggering a generalized inflammatory response and causing systemic release of these inflammatory mediators. It is hoped that further study will isolate unique biomarkers that may distinguish either individuals with OSA or those at elevated risk for the cardiovascular consequences associated with OSA.

Along similar lines, the link between metabolic syndrome and OSA has generated significant interest in recent years. The metabolic syndrome includes central obesity, hypertension, insulin resistance and impaired glucose tolerance, and dyslipidemia. Several studies have now shown that patients with OSA have significantly impaired glucose tolerance and it has been suggested that the metabolic syndrome (“Syndrome X”) encompass OSA and should be termed “Syndrome Z.”[2] Similarly to the aforementioned biomarkers, adipokines, including leptin, adiponectin, tumor necrosis factor-α, and interleukin 6[3] [4] [5] have also been shown to be elevated in OSA, and it is thought that differential expression of these adipokines between subcutaneous and visceral fat may account for the development of the metabolic syndrome in these patients. Because obesity is so closely linked to both OSA and the metabolic syndrome, the role of sleep-disordered breathing in its pathogenesis is unclear; however, again, intermittent hypoxemia is thought to play a major role.

The study of the genetic predisposition to diseases is an extremely important area of research in this day and age. This holds true for the study of OSA. Most of the studies that have been done are small in number and suggest the link is strongest to obesity genes.[6] There are also a few studies looking at gene polymorphisms in angiotensisn-converting enzymes, which may predispose OSA patient to develop hypertension.[7] [8] This is an area of intense interest that we will be hearing more about in the days to come.

The quest for a quicker, more efficient, and less expensive way to diagnose OSA has prompted much interest in the role of portable monitoring. An extensive evidence review and a practice parameter based on the review was published on this subject in 2003.[9] [10] The evidence was not felt to be strong enough to accept unattended portable monitoring, at any level, to be utilized to make the diagnosis of OSA. This was reviewed in 2004 by CMS (Centers for Medicare and Medicaid Services) and, again, there was not strong enough evidence to allow the use of portable monitoring on a widespread basis. Although most believe that portable monitoring should play some role in the diagnosis of OSA on some level, it is felt that better diagnosis and treatment algorithms should be in place prior to its dissemination. This debate will undoubtedly continue.

Finally, in the United States, there is a rising demand for bariatric surgery. Recent figures among adults at least 20 years of age suggest that 65.1% are overweight, 30.4% are obese, and 4.9% are extremely obese.[11] Because the rate of OSA rises with increasing body mass index, it has been estimated that 10% or more of the U.S. adult population has OSA. A recent meta-analysis shows that bariatric surgery improves or eliminates OSA in almost 85% of patients.[12] The study of obesity, its effect on OSA, and the promise of bariatric surgery as a long-term solution will be another fertile area for research in the future.

In conclusion, OSA is an extremely common syndrome that afflicts a large proportion of the adult population in the United States. Although we are making progress, we still have much work to do to understand this syndrome and improve our diagnostic and treatment algorithms. In this issue, you will read about these challenges and more by our superb authors. we would like to thank them for their exemplary contributions.

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Teofilo L Lee-Chiong Jr.M.D. 

National Jewish Medical and Research Center

1400 Jackson St., Rm. J232, Denver, CO 80206

Email: Lee-chiongt@njc.org