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Personalized Medicine for OSA – Are we there yet?

Obstructive sleep apnea (OSA) is a common disorder, (1) characterized by repetitive pharyngeal collapse during sleep, with  a number of adverse cardiovascular (2-6), neurocognitive (7), and quality of life (8) consequences. Therefore, understanding the pathophysiology and developing treatments is important. While the leading treatment for OSA, continuous positive airway pressure (CPAP), is highly effective at abolishing OSA and its consequences, it is poorly tolerated by many individuals (9, 10). Thus, new therapeutic approaches are needed.

Importantly, recent evidence demonstrates that OSA is not simply an anatomical disorder. Other factors (or traits) play an important role in its pathophysiology as well. Available data suggest that at least three non-anatomical physiological traits also contribute to the pathogenesis of OSA. Importantly, the relative contribution of these traits varies substantially between individuals (11-15). That is, OSA occurs for different reasons in different people. Despite the multifactorial nature of OSA, available treatments (CPAP, upper airway surgery, dental appliances) are directed at only one component – the upper airway anatomy. However, if the traits could be measured, then therapies directed at the other (abnormal) components could be offered in a targeted manner. Furthermore, targeted therapies, especially if used in combination, could have a meaningful clinical effect as they could maximise treatment effectiveness while avoid administering treatments that are poorly tolerated or suboptimal in given patients.

In this podcast, Dr. Bradley Edwards chats with Dr. David White, a clinical Professor of Sleep Medicine at Harvard Medical School who is an expert investigator in the pathophysiology of OSA. Professor White was among the first to develop the hypothesis that a number of phenotypic traits are important in determining the presence and severity of OSA in a given individual. His group, along with others around the world, are now developing simple ways to measure the multiple pathogenic causes of OSA so that novel and targeted therapies can be given to the right individual.  Dr White discusses the current state of affairs in the field's ability to provide individualised treatment for OSA patients.

Presenter Disclosures

Bradley Edwards: No relevant commercial interests.
David White: Employee (Chief Medical Officer), Apnicure. Advisory Committee, Night Balance. Consultant, Phillips Respironics.

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References

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  8. Findley LJ, Unverzagt ME, Suratt PM. Automobile accidents involving patients with obstructive sleep apnea. Am Rev Respir Dis 1988; 138: 337-340.

  9. Kribbs NB, Pack AI, Kline LR, Smith PL, Schwartz AR, Schubert NM, Redline S, Henry JN, Getsy JE, Dinges DF. Objective measurement of patterns of nasal CPAP use by patients with obstructive sleep apnea [see comments]. Am Rev Respir Dis 1993; 147: 887-895.

  10. Engelman H, Wild MR. Improving CPAP use by patients with the sleep apnea/hypopnea syndrome (SAHS). Sleep Med Rev 2003; 71: 81-99.

  11. Wellman A, Eckert DJ, Jordan AS, Edwards BA, Passaglia CL, Jackson AC, Gautam S, Owens RL, Malhotra A, White DP. A method for measuring and modeling the physiological traits causing obstructive sleep apnea. J Appl Physiol 2011; 110: 1627-1637.

  12. Younes M. Role of respiratory control mechanisms in the pathogenesis of obstructive sleep disorders. J Appl Physiol 2008; 105: 1389-1405.

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  14. Wellman A, Edwards BA, Sands SA, Owens RL, Nemati S, Butler JP, Passaglia CL, Jackson AC, Malhotra A, White DP. A simplified method for determining phenotypic traits in patients with obstructive sleep apnea. J Appl Physiol 2013.

  15. Eckert DJ, White DP, Jordan AS, Malhotra A, Wellman A. Defining phenotypic causes of obstructive sleep apnea. Identification of novel therapeutic targets. Am J Respir Crit Care Med 2013; 188: 996-1004.

Last Reviewed: June 2016