Obstructive sleep apnea is a common disorder characterized by multiple pathogenetic roots. Continuous positive airway pressure (CPAP) is almost always prescribed as the first-line treatment to all patients regardless of the heterogeneous pathophysiology, because it mechanically splints the airways open and reduces the collapsibility of the upper airway. Despite its high efficacy, CPAP is burdened by poor adherence and compliance rates. In this pilot study, we treated OSA patients with composite approaches different than CPAP, tailoring the therapeutic choice on OSA phenotypic traits.
We used the CPAP dial down technique to assess phenotypic traits in eight OSA patients with BMI<35. According to these traits, patients received personalized therapies for 2-week period, after which we ran a second polygraphy to compare apnea-hypopnea index (AHI) before and after therapy.
Two weeks of combined behavioral and pharmacological therapy induced a significant reduction in mean AHI, which dropped from 26 ± 15 at baseline to 9 ± 7 post-treatment (p = 0.01). Furthermore, there was a significant reduction in mean ODI (p = 0.03) and subjective sleepiness (p = 0.01) documented by Epworth Sleepiness Scale (ESS) from baseline to post-treatment recordings.
Treating OSA patients with a personalized combination of pharmacological and behavioral therapies according to phenotypic traits leads to a significant improvement in AHI, ODI, and subjective sleepiness.
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Franklin K, Lindberg E (2015) Obstructive sleep apnea is a common disorder in the population-a review on the epidemiology of sleep apnea. J Thorac Dis 7(8):1311–1322
Wellman A, Eckert D, Jordan A, Edwards B, Passaglia C, Jackson A, Gautam S, Owens R, Malhotra A, White D (2011) A method for measuring and modeling the physiological raits causing obstructive sleep apnea. J Appl Physiol 110(6):1627–1637
Gleadhill I, Schwartz A, Wise R, Permutt S, Smith P (1991) Upper airway collabsibility in snorers and in patients with obstructive hypopnea and apnea. Am Rev Respir Dis 43:1300–1303
Isono S, Remmers J, Tanaka A, Sho Y (1997) Anatomy of pharynx in patients with obstructive sleep apnea and in normal subjects. J Appl Physiol 82:1319–1326
Campana L, Eckert D, Patel S, Malhotra A (2010) Pathophysiology & genetics of obstructive sleep apnoea. Indian J Med Res 131:176–187
Pharm L, Schwartz A (2015) The pathogenesis of obstructive sleep apnea. J Thorac Dis 7(8):1358–1372
Taranto Montemurro L, Bettinzoli M, Corda L, Redolfi S, Novali M, Braghini A, Tantucci C (2012) Influence of upper airway size on volume exhaled under negative pressure during evaluation of upper airway collapsibility. Sleep Breath 16(2):399–404. doi:10.1007/s11325-011-0511-3
Patil S, Schneider H, Marx J, Gladmon E, Schwartz A, Smith P (2007) Neuromechanical control of upper airway patency during sleep. J Appl Physiol 102:547–556
Eckert D, Lo Y, Saboisky J, Jordan A, White D, Malhotra A (2011) Sensorimotor function of the upper-airway muscles and respiratory sensory processing in untreated obstructive sleep apnea. J Appl Physiol 11:1644–1653
Younes M (2004) Role of arousals in the pathogenesis of obstructive sleep apnea. Am J Respir Crit Care Med 169:623–633
Younes M, Ostrowski M, Thompson W, Leslie C, Shewchuk W (2001) Chemical control stability in patients with obstructive sleep apnea. Am J Respir Crit Care Med 163:1181–1190
Wellman A, Jordan A, Malhotra A, Fogel R, Katz E, Schory K, Edwards J, White D (2001) Ventilatory control and airway anatomy in obstructive sleep apnea. Am J Respir Crit Care Med 170:1225–1232
Weaver T, Grunstein T (2008) Adherence to continuous positive airway pressure: the challenge to effective treatment. Proc Am Thorac Soc 15(5):173–178
Wolkove N, Baltzan M, Kamel H, Dabrusin R, Palayew M (2008) Long-term compliance with continuous positive airway pressure in patients with obstructive sleep apnea. Can Respir J 15(7):365–369
Eckert D, White D, Jordan A, Malhotra A, Wellman A (2013) Defining phenotypic causes of obstructive sleep apnea. Identification of novel therapeutic targets. Am J Respir Crit Care Med 188(8):996–1004
Berry R, Budhiraja R, Gottlieb D, Gozal D, Iber C, Kapur V et al (2012) Rules for scoring respiratory events in sleep: update of the 2007 AASM manual for the scoring of sleep and associated events. Deliberations of the sleep apnea definitions task force of the American Academy of sleep medicine. J Clin Sleep Med 8(5):597–619
Wellman A, Edwards E, Sands S, Owens R, Butler S, Passaglia C, Jackson A, Malhotra A, White D (2013) A simplified method for determining phenotypic traits in patients with obstructive sleep apnea. J App Physiol 114:911–922
Owens R, Edwards B, Eckert D, Jordan A, Sands S, Malhotra A, White D, Loring S, Butler J, Wellman A (2015) An integrative model of physiological traits can be used to predict obstructive sleep apnea and response to non positive airway pressure therapy. Sleep 38(6):961–970
Edwards B, Sands S, Owens R, Eckert D, Landry S, White D, Malhotra A, Wellman A (2016) The combination of supplemental oxygen and a hypnotic markedly improves obstructive sleep apnea in patients with a mild to moderate upper airway collapsibility. Sleep 39(11):1973–1983
Schwartz A, Gold A, Schubert N, Stryzak A, Wise R, Permutt S, Smith P (1991) Effect of weight loss on upper airway collapsibility in obstructive sleep apnea. Am Rev Respir Dis 144(3):494–498
Redolfi S, Yumino D, Ruttanaumpawan P, Yau B, Su M, Lam J, Bradley T (2009) Relationship between overnight rostral fluid shift and obstructive sleep apnea in nonobese men. Am J Respir Crit Care Med 173(3):241–246
Redolfi S, Arnulf I, Pottier M, Bradley T, Similowski T (2011) Effects of compression of the legs on overnight rostral fluid shift and obstructive sleep apnea. Respir Physiol Neurobiol 175(3):390–393
Jordan A, White D, Lo Y, Wellman A, Eckert D, Yim-Yeh S, Eikermann M, Smith S, Stevenson K, Malhotra A (2009) Airway dilator muscle activity and lung volume during stable breathing in obstructive sleep apnea. Sleep 32:361–368
Eckert D, Malhotra A, Wellman A, White D (2014) Trazodone increases the respiratory arousal threshold in patients with obstructive sleep apnea and a low arousal threshold. Sleep 37(4):811–819
Smales E, Edwards B, Deyoung P, McSharry D, Wellman A, Velasquez A, Owens R, Orr J, Malhotra A (2015) Trazodone effects on obstructive sleep apnea and NON-REM arousal threshold. Ann Am Thorac Soc 12(5):758–764
Edwards B, Sands S, Eckert D, White D, Butler J, Owens R, Malhotra A, Wellman A (2012) Acetazolamide improves loop gain but not the other physiological traits causing obstructive sleep apnea. J Physiol 590(5):1199–1211
Edwards B, Connolly J, Campana L, Sands S, Trinder J, White D, Wellman A, Malhotra A (2013) Acetazolamide attenuates the ventilatory response to arousal in patients with obstructive sleep apnea. Sleep 36(2):281–285
Kezirian E, Goding GJ, Malhotra A, O'Donoghue F, Zammit G, Wheatley J, Catcheside P, Smith P, Schwartz A, Walsh J, Maddison K, Claman C, Huntley T, Park S, Campbell M, Palme C, Iber C, Eastwood P, Hillman D, Barnes M (2014) Hypoglossal nerve stimulation improves obstructive sleep apnea; 12-month outcomes. J Sleep Res 23(1):77–83
Taranto-Montemurro L, Edwards B, Sands S, Marques M, Eckert D, White D, Wellman A (2016) Desipramine increases genioglossus activity and reduces upper airway collapsibility during non-REM sleep in healthy subjects. Am J Respir Crit Care Med. doi:10.1164/rccm.201511-2172OC
Loewen A, Ostrowski M, Laprairie J, Atkar R, Gnitecki J, Hanly P, Younes M (2009) Determinants of ventilatory instability in obstructive sleep apnea: inherent or acquired? Sleep 32(10):1355–1365
Koo B, Dostal J, Ioachimescu O, Budur K (2008) The effect of gender and age on REM-related sleep-disordered breathing. Sleep Breath 12(3):259–264
Levendowski D, Zack N, Rao S, Wong K, Gendreau M, Kranzler J, Zavora T, Westbrook P (2009) Assessment of the test-retest reliability of laboratory polysomnography. Sleep Breath 13(2):163–167
Newell J, Mairesse O, Verbanck P, Neu D (2012) Is a one-night stay in the lab really enough to conclude? First-night effect and night-to-night variability in polysomnographic recordings among different clinical population samples. Psychiatry Res 200:795–801
Sands S, Owens R (2015) Congestive heart failure and central sleep apnea. Crit Care Clin 31(3):473–495
McSharry D, Saboisky J, Deyoung P, Jordan A, Trinder J, Smales E, Hess L, Chamberlin N, Malhotra A (2014) Physiological mechanisms of upper airway hypotonia during REM sleep. Sleep Breath 37(3):561–569
Dr. Messineo contributed to study design, data collection, data analysis and interpretation, and drafting and review of the manuscript for important intellectual content. Dr. Magri contributed to the study design, data collection and interpretation, and drafting and review of the manuscript for important intellectual content. Dr. Corda contributed to data collection and review of the manuscript. Dr. Pini contributed to data collection and review of the manuscript. Dr. Taranto-Montemurro contributed to data analysis and interpretation, and drafting and review of the manuscript for important intellectual content. Dr. Tantucci contributed to the final approval of the version submitted for publication, study design, data analysis and interpretation, and review of the manuscript for important intellectual content
No funding was received for this research.
Conflict of interests
Luigi Taranto-Montemurro reports personal fees from Novion Pharmaceuticals, outside the submitted work.
The other authors certify that they have no affiliation with or involvement in any organization or entity with any financial interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
This is the first time that the Wellman/Brigham and Women’s/Harvard phenotyping method has been put into clinical practice by another lab. It shows the promise and potential limitations of this approach.
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Messineo, L., Magri, R., Corda, L. et al. Phenotyping-based treatment improves obstructive sleep apnea symptoms and severity: a pilot study. Sleep Breath 21, 861–868 (2017). https://doi.org/10.1007/s11325-017-1485-6
- OSA phenotyping
- OSA pharmacological therapy
- OSA behavioral therapy
- Alternative treatment for sleep apnea