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Published in: Sleep and Breathing 4/2017

01-12-2017 | Sleep Breathing Physiology and Disorders • Original Article

Phenotyping-based treatment improves obstructive sleep apnea symptoms and severity: a pilot study

Authors: Ludovico Messineo, Roberto Magri, Luciano Corda, Laura Pini, Luigi Taranto-Montemurro, Claudio Tantucci

Published in: Sleep and Breathing | Issue 4/2017

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.
Literature
1.
go back to reference 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):1311–1322PubMedPubMedCentral 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):1311–1322PubMedPubMedCentral
2.
go back to reference 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):1627–1637CrossRefPubMedPubMedCentral 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):1627–1637CrossRefPubMedPubMedCentral
3.
go back to reference 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 43:1300–1303CrossRef 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 43:1300–1303CrossRef
4.
go back to reference 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 82:1319–1326PubMed 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 82:1319–1326PubMed
5.
go back to reference Campana L, Eckert D, Patel S, Malhotra A (2010) Pathophysiology & genetics of obstructive sleep apnoea. Indian J Med Res 131:176–187PubMedPubMedCentral Campana L, Eckert D, Patel S, Malhotra A (2010) Pathophysiology & genetics of obstructive sleep apnoea. Indian J Med Res 131:176–187PubMedPubMedCentral
6.
go back to reference Pharm L, Schwartz A (2015) The pathogenesis of obstructive sleep apnea. J Thorac Dis 7(8):1358–1372 Pharm L, Schwartz A (2015) The pathogenesis of obstructive sleep apnea. J Thorac Dis 7(8):1358–1372
7.
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
8.
go back to reference Patil S, Schneider H, Marx J, Gladmon E, Schwartz A, Smith P (2007) Neuromechanical control of upper airway patency during sleep. J Appl Physiol 102:547–556CrossRefPubMed Patil S, Schneider H, Marx J, Gladmon E, Schwartz A, Smith P (2007) Neuromechanical control of upper airway patency during sleep. J Appl Physiol 102:547–556CrossRefPubMed
9.
go back to reference 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 11:1644–1653CrossRef 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 11:1644–1653CrossRef
10.
go back to reference Younes M (2004) Role of arousals in the pathogenesis of obstructive sleep apnea. Am J Respir Crit Care Med 169:623–633CrossRefPubMed Younes M (2004) Role of arousals in the pathogenesis of obstructive sleep apnea. Am J Respir Crit Care Med 169:623–633CrossRefPubMed
11.
go back to reference 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 163:1181–1190CrossRefPubMed 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 163:1181–1190CrossRefPubMed
12.
go back to reference 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 170:1225–1232CrossRef 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 170:1225–1232CrossRef
13.
go back to reference Weaver T, Grunstein T (2008) Adherence to continuous positive airway pressure: the challenge to effective treatment. Proc Am Thorac Soc 15(5):173–178CrossRef Weaver T, Grunstein T (2008) Adherence to continuous positive airway pressure: the challenge to effective treatment. Proc Am Thorac Soc 15(5):173–178CrossRef
14.
go back to reference 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):365–369CrossRefPubMedPubMedCentral 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):365–369CrossRefPubMedPubMedCentral
15.
go back to reference 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):996–1004CrossRefPubMedPubMedCentral 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):996–1004CrossRefPubMedPubMedCentral
16.
go back to reference 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):597–619PubMedPubMedCentral 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):597–619PubMedPubMedCentral
17.
go back to reference 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 114:911–922CrossRef 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 114:911–922CrossRef
18.
go back to reference 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):961–970PubMedPubMedCentral 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):961–970PubMedPubMedCentral
19.
go back to reference 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):1973–1983CrossRefPubMedPubMedCentral 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):1973–1983CrossRefPubMedPubMedCentral
20.
go back to reference 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):494–498CrossRefPubMed 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):494–498CrossRefPubMed
21.
go back to reference 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):241–246CrossRef 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):241–246CrossRef
22.
go back to reference 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):390–393CrossRefPubMed 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):390–393CrossRefPubMed
23.
go back to reference 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 32:361–368CrossRefPubMedPubMedCentral 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 32:361–368CrossRefPubMedPubMedCentral
24.
go back to reference 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):811–819CrossRefPubMedPubMedCentral 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):811–819CrossRefPubMedPubMedCentral
25.
go back to reference 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):758–764CrossRefPubMedPubMedCentral 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):758–764CrossRefPubMedPubMedCentral
26.
go back to reference 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):1199–1211CrossRefPubMedPubMedCentral 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):1199–1211CrossRefPubMedPubMedCentral
27.
go back to reference 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):281–285CrossRefPubMedPubMedCentral 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):281–285CrossRefPubMedPubMedCentral
28.
go back to reference 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):77–83CrossRefPubMed 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):77–83CrossRefPubMed
29.
go back to reference 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 PubMedPubMedCentral 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 PubMedPubMedCentral
30.
go back to reference 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):1355–1365CrossRefPubMedPubMedCentral 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):1355–1365CrossRefPubMedPubMedCentral
31.
go back to reference 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):259–264CrossRefPubMed 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):259–264CrossRefPubMed
32.
go back to reference 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):163–167CrossRefPubMed 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):163–167CrossRefPubMed
33.
go back to reference 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 200:795–801CrossRefPubMed 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 200:795–801CrossRefPubMed
35.
go back to reference 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):561–569CrossRef 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):561–569CrossRef
Metadata
Title
Phenotyping-based treatment improves obstructive sleep apnea symptoms and severity: a pilot study
Authors
Ludovico Messineo
Roberto Magri
Luciano Corda
Laura Pini
Luigi Taranto-Montemurro
Claudio Tantucci
Publication date
01-12-2017
Publisher
Springer International Publishing
Published in
Sleep and Breathing / Issue 4/2017
Print ISSN: 1520-9512
Electronic ISSN: 1522-1709
DOI
https://doi.org/10.1007/s11325-017-1485-6

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