Patient Phenotyping in OSA

  • Leon Kitipornchai
  • Andrew Jones
  • Stuart Grayson MacKayEmail author
Sleep Apnea (B Rotenberg, Section Editor)
Part of the following topical collections:
  1. Sleep Apnea
  2. Sleep Apnea


Purpose of Review

OSA treatment paradigms are evolving from a “one treatment for all” philosophy to personalised therapeutic options based on anatomical and physiological phenotypes. Understanding these different phenotypes will become vital for clinicians as OSA testing and treatment become more targeted.

Recent Findings

Phenotyping of the pharynx and upper airway is vital to inform anatomical treatment options such as surgery and mandibular advancement splints. Manipulated CPAP testing allows determination of traits such as arousal threshold, muscular responsiveness and ventilatory control. Targeted therapies of each of these physiological traits have shown promise in selected patients in the research context.


Current treatment paradigms are based on anatomical therapies (CPAP, MAS, surgery); the limitations of which may be particularly evident in patients with physiological contributors to their OSA. Physiological phenotyping is an area of ongoing research into non-anatomical traits which contribute to airway obstruction.


Obstructive sleep apnoea Phenotypes CPAP Surgery Endoscopy Upper airway Polysomnography 


Compliance with Ethical Standards

Conflict of Interest

Dr. Kitipornchai and Dr. Jones declare that they have no conflict of interest. Dr. MacKay reports non-financial support from Genio-Nyxoah Hypoglossal nerve stimulator, grants from NH&MRC, grants from Garnett Passe conjoint grant, outside the submitted work.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    •• Carberry JC, Amatoury J, Eckert DJ. Personalized management approach for OSA. Chest. 2017. Provides a summary of evidence for currently available treatment options based on physiological phenotype.
  2. 2.
    •• Eckert DJ. Phenotypic approaches to obstructive sleep apnoea - new pathways for targeted therapy. Sleep Med Rev. 2018;37:45–59 Explores the PALM scale and physiology behind each phenotype in greater detail. CrossRefGoogle Scholar
  3. 3.
    •• 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 This study describes the techniques of physiological phenotyping as well as the relative prevalence of each phenotype.CrossRefGoogle Scholar
  4. 4.
    • Pack AI. Application of personalized, predictive, preventative, and participatory (P4) medicine to obstructive sleep apnea. A roadmap for improving care? Ann Am Thorac Soc. 2016;13:1456–67 Explores the P4 approach to OSA as well as anatomical, physiological and genetic contributions to disease. CrossRefGoogle Scholar
  5. 5.
    •• Wellman A, Edwards BA, Sands SA, Owens RL, Nemati S, Butler J, et al. A simplified method for determining phenotypic traits in patients with obstructive sleep apnea. J Appl Physiol (Bethesda, Md : 1985). 2013;114:911–22 Describes the manipulated CPAP technique of physiological phenotypic testing. CrossRefGoogle Scholar
  6. 6.
    Agusti A. The path to personalised medicine in COPD. Thorax. 2014;69:857–64.CrossRefGoogle Scholar
  7. 7.
    Lötvall J, Akdis CA, Bacharier LB, Bjermer L, Casale TB, Custovic A, et al. Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome. J Allergy Clin Immunol. 2011;127:355–60.CrossRefGoogle Scholar
  8. 8.
    Hellings P, Fokkens W, Bachert C, et al. Positioning the principles of precision medicine in care pathways for allergic rhinitis and chronic rhinosinusitis – a EUFOREA-ARIA-EPOS-AIRWAYS ICP statement. Allergy. 2017;72:1297–305.CrossRefGoogle Scholar
  9. 9.
    Han MK, Agusti A, Calverley PM, et al. Chronic obstructive pulmonary disease phenotypes: the future of COPD. Am J Respir Crit Care Med. 2010;182:598–604.CrossRefGoogle Scholar
  10. 10.
    Kapur VK, Auckley DH, Chowdhuri S, Kuhlmann DC, Mehra R, Ramar K, et al. Clinical practice guideline for diagnostic testing for adult obstructive sleep apnea: an American Academy of sleep medicine clinical practice guideline. J Clin Sleep Med. 2017;13:479–504.CrossRefGoogle Scholar
  11. 11.
    Ruehland WR, Rochford PD, O’donoghue FJ, Pierce RJ, Singh P, Thornton AT. The new AASM criteria for scoring hypopneas: impact on the apnea hypopnea index. Sleep. 2009;32:150–7.CrossRefGoogle Scholar
  12. 12.
    Levendowski DJ, Zack N, Rao n, Wong K, Gendreau M, Kranzler J, et al. Assessment of the test–retest reliability of laboratory polysomnography. Sleep Breath. 2009;13:163–7.CrossRefGoogle Scholar
  13. 13.
    Wu H, Zhan X, Zhao M, Wei Y. Mean apnea-hypopnea duration (but not apnea-hypopnea index) is associated with worse hypertension in patients with obstructive sleep apnea. Medicine. 2016;95:e5493.CrossRefGoogle Scholar
  14. 14.
    Koch H, Schneider L, Finn LA, Leary EB, Peppard PE, Hagen E, et al. Breathing disturbances without hypoxia are associated with objective sleepiness in sleep apnea. Sleep. 2017;40.
  15. 15.
    Osman AM, Carter SG, Carberry JC, Eckert DJ. Obstructive sleep apnea: current perspectives. Nat Sci Sleep. 2018;10:21–34.CrossRefGoogle Scholar
  16. 16.
    Camacho M, Riley RW, Capasso R, O’Connor P, Chang ET, Reckley LK, et al. Sleep surgery tool: a medical checklist to review prior to operating. J Cranio-Maxillofac Surg. 2017;45:381–6.CrossRefGoogle Scholar
  17. 17.
    Rotenberg BW, Vicini C, Pang EB, Pang KP. Reconsidering first-line treatment for obstructive sleep apnea: a systematic review of the literature. J Otolaryngol Head Neck Surg. 2016;45:23.CrossRefGoogle Scholar
  18. 18.
    Rosvall BR, Chin CJ. Is uvulopalatopharyngoplasty effective in obstructive sleep apnea? Laryngoscope. 2017;127:2201–2.CrossRefGoogle Scholar
  19. 19.
    Friedman M, Ibrahim H, Bass L. Clinical staging for sleep-disordered breathing. J Otolaryngol Head Neck Surg. 2002;127:13–21.CrossRefGoogle Scholar
  20. 20.
    Fujita S, Conway W, Zorick F, Roth T. Surgical correction of anatomic abnormalities in obstructive sleep apnea syndrome: Uvulopalatopharyngoplasty. Otolaryngol Head Neck Surg. 1981;89:923–34.CrossRefGoogle Scholar
  21. 21.
    Sher AE, Schechtman KB, Piccirillo JF. The efficacy of surgical modifications of the upper airway in adults with obstructive sleep apnea syndrome. Sleep. 1996;19:156–77.CrossRefGoogle Scholar
  22. 22.
    • Friedman M, Lapatas A, Bonzelaar LB. Updated Friedman staging system for obstructive sleep apnea. Adv Otorhinolaryngol. 2017;80:41–8 Describes the updated Friedman staging for transoral assessment. Google Scholar
  23. 23.
    Young T, Shahar E, Nieto FJ, Redline S, Newman AB, Gottlieb DJ, Walsleben JA, Finn L, Enright P, Samet JM. Predictors of sleep-disordered breathing in community-dwelling adults: the Sleep Heart Health Study. Arch Intern Med. 2002;162:893–900Google Scholar
  24. 24.
    Peker Y, Hedner J, Norum J, Kraiczi H, Carlson J. Increased incidence of cardiovascular disease in middle-aged men with obstructive sleep apnea: a 7-year follow-up. Am J Respir Crit Care Med. 2002;166:159–65.CrossRefGoogle Scholar
  25. 25.
    Newman AB, Foster G, Givelber R, Nieto F, Redline S, Young T. Progression and regression of sleep-disordered breathing with changes in weight: the Sleep Heart Health Study. Arch Intern Med. 2005;165:2408–13.CrossRefGoogle Scholar
  26. 26.
    •• Choi J, Cho S, Kim S-N, Suh JD, Cho J. Predicting outcomes after uvulopalatopharyngoplasty for adult obstructive sleep apnea. Otolaryngol Head Neck Surg. 2016;155:904–13 This meta-analysis summarises the current anatomical predictors for positive outcomes following upper airway surgery. CrossRefGoogle Scholar
  27. 27.
    Marklund M, Stenlund H, Franklin KA. Mandibular advancement devices in 630 men and women with obstructive sleep apnea and snoring: tolerability and predictors of treatment success. Chest. 2004;125:1270–8.CrossRefGoogle Scholar
  28. 28.
    Lai C, Friedman M, Lin H, Wang P, Hwang MS, Hsu C, et al. Clinical predictors of effective continuous positive airway pressure in patients with obstructive sleep apnea/hypopnea syndrome. Laryngoscope. 2015;125:1983–7.CrossRefGoogle Scholar
  29. 29.
    Chai-Coetzer C, Luo Y-M, Antic NA, et al. Predictors of long-term adherence to continuous positive airway pressure therapy in patients with obstructive sleep apnea and cardiovascular disease in the SAVE study. Sleep. 2013;36:1929–37.CrossRefGoogle Scholar
  30. 30.
    Woodson B, Feroah T, Connolly L, Toohill R. A method to evaluate upper airway mechanics following intervention in snorers. Am J Otolaryngol. 1997;18:306–14.CrossRefGoogle Scholar
  31. 31.
    Hsu PP, Tan BY, Chan YH, Tay HN, Lu PK, Blair RL. Clinical predictors in obstructive sleep apnea patients with computer-assisted quantitative videoendoscopic upper airway analysis. Laryngoscope. 2004;114:791–9.CrossRefGoogle Scholar
  32. 32.
    Certal VF, Pratas R, Guimarães L, Lugo R, Tsou Y, Camacho M, et al. Awake examination versus DISE for surgical decision making in patients with OSA: a systematic review. Laryngoscope. 2016;126:768–74.CrossRefGoogle Scholar
  33. 33.
    Blumen MB, Latournerie V, Bequignon E, Guillere L, Chabolle F. Are the obstruction sites visualized on drug-induced sleep endoscopy reliable? Sleep Breath. 2015;19:1021–6.CrossRefGoogle Scholar
  34. 34.
    Vanderveken OM, Maurer JT, Hohenhorst W, Hamans E, Lin H-SS, Vroegop AV, et al. Evaluation of drug-induced sleep endoscopy as a patient selection tool for implanted upper airway stimulation for obstructive sleep apnea. J Clin Sleep Med. 2013;9:433–8.Google Scholar
  35. 35.
    Heyning PH, Badr SM, Baskin JZ, Bornemann MA, Backer WA, Dotan Y, et al. Implanted upper airway stimulation device for obstructive sleep apnea. Laryngoscope. 2012;122:1626–33.CrossRefGoogle Scholar
  36. 36.
    •• Woodson B. A method to describe the pharyngeal airway. Laryngoscope. 2015;125:1233–8 Describes an endoscopic method of phenotyping the pharynx. Provides a novel and significant method of describing hard and soft palate anatomy. CrossRefGoogle Scholar
  37. 37.
    Moore KE, Phillips C. A practical method for describing patterns of tongue-base narrowing (modification of Fujita) in awake adult patients with obstructive sleep apnea. J Oral Maxillofac Surg. 2002;60:252–60.CrossRefGoogle Scholar
  38. 38.
    Friedman M, Yalamanchali e, Gorelick G, Joseph NJ, Hwang MS. A standardized lingual tonsil grading system. Otolaryngol Head Neck Surg. 2015;152:667–72.CrossRefGoogle Scholar
  39. 39.
    Watanabe T, Isono S, Tanaka A, Tanzawa H, Nishino T. Contribution of body habitus and craniofacial characteristics to segmental closing pressures of the passive pharynx in patients with sleep-disordered breathing. Am J Respir Crit Care Med. 2002;165:260–5.CrossRefGoogle Scholar
  40. 40.
    Rotenberg BW, Murariu D, Pang KP. Trends in CPAP adherence over twenty years of data collection: a flattened curve. J Otolaryngol Head Neck Surg. 2016;45:43.CrossRefGoogle Scholar
  41. 41.
    Ravesloot MJ, de Vries N, Stuck BA. Treatment adherence should be taken into account when reporting treatment outcomes in obstructive sleep apnea. Laryngoscope. 2014;124:344–5.CrossRefGoogle Scholar
  42. 42.
    Camacho M, Teixeira J, Abdullatif J, Acevedo JL, Certal V, Capasso R, et al. Maxillomandibular advancement and tracheostomy for morbidly obese obstructive sleep apnea: a systematic review and meta-analysis. J Otolaryngol Head Neck Surg. 2015;152:619–30.CrossRefGoogle Scholar
  43. 43.
    Browaldh N, Bring J, Friberg D. SKUP3 : 6 and 24 months follow-up of changes in respiration and sleepiness after modified UPPP. Laryngoscope. 2018;128:1238–44.CrossRefGoogle Scholar
  44. 44.
    Stewart S, Huang J, Mohorikar A, Jones A, Holmes S, MacKay SG. AHI outcomes are superior after upper airway reconstructive surgery in adult CPAP failure patients. J Otolaryngol Head Neck Surg. 2016;154:553–7.CrossRefGoogle Scholar
  45. 45.
    Gleadhill I, Schwartz A, Schubert N, Wise R, Permutt S, Smith P. Upper airway collapsibility in snorers and in patients with obstructive hypopnea and apnea. Am Rev Respir Dis. 1991;143:1300–3.CrossRefGoogle Scholar
  46. 46.
    Smith P, Wise R, Gold A, Schwartz A, Permutt S. Upper airway pressure-flow relationships in obstructive sleep apnea. J Appl Physiol (Bethesda, Md : 1985). 1988;64:789–95.CrossRefGoogle Scholar
  47. 47.
    Landry SA, Joosten SA, Eckert DJ, Jordan AS, Sands SA, White DP, et al. Therapeutic CPAP level predicts upper airway collapsibility in patients with obstructive sleep apnea. Sleep. 2017;40(6).
  48. 48.
    Sands SA, Edwards BA, Terrill PI, Taranto-Montemurro L, Azarbarzin A, Marques M, et al. Phenotyping pharyngeal pathophysiology using polysomnography in patients with obstructive sleep apnea. Am J Respir Crit Care Med. 2018;197:1187–97.CrossRefGoogle Scholar
  49. 49.
    • Pham LV, Schwartz AR. The pathogenesis of obstructive sleep apnea. J Thorac Dis. 2015;7:1358–72 Provides a thorough summary of current understanding of OSA pathophysiology. Google Scholar
  50. 50.
    Schneider H, Boudewyns A, Smith PL, O’Donnell CP, Canisius S, Stammnitz A, et al. Modulation of upper airway collapsibility during sleep: influence of respiratory phase and flow regimen. J Appl Physiol. 2002;93:1365–76.CrossRefGoogle Scholar
  51. 51.
    Horner R, Innes J, Morrell M, Shea S, Guz A. The effect of sleep on reflex genioglossus muscle activation by stimuli of negative airway pressure in humans. J Physiol. 1994;476:141–51.Google Scholar
  52. 52.
    Schwartz A, Thut D, Brower R, Gauda E, Roach D, Permutt S, et al. Modulation of maximal inspiratory airflow by neuromuscular activity: effect of CO2. J Appl Physiol. 1993;74:1597–605.CrossRefGoogle Scholar
  53. 53.
    Carberry JC, Jordan AS, White DP, Wellman A, Eckert DJ. Upper airway collapsibility (Pcrit) and pharyngeal dilator muscle activity are sleep stage dependent. Sleep. 2016;39:511–21.CrossRefGoogle Scholar
  54. 54.
    Jordan AS, Wellman A, Heinzer RC, Lo Y-L, Schory K, Dover L, et al. Mechanisms used to restore ventilation after partial upper airway collapse during sleep in humans. Thorax. 2007;62:861–7.CrossRefGoogle Scholar
  55. 55.
    Woodson B, Strohl KP, Soose RJ, et al. Upper airway stimulation for obstructive sleep apnea: 5-year outcomes. Otolaryngol Head Neck Surg. 2018;194599818762383.Google Scholar
  56. 56.
    Schwab RJ, Wang SH, Verbraecken J, Vanderveken OM, de Heyning P, Vos WG, et al. Anatomic predictors of response and mechanism of action of upper airway stimulation therapy in patients with obstructive sleep apnea. Sleep. 2018;41.
  57. 57.
    Eckert DJ, Younes MK. Arousal from sleep: implications for obstructive sleep apnea pathogenesis and treatment. J Appl Physiol (Bethesda, Md : 1985). 2014;116:302–13.CrossRefGoogle Scholar
  58. 58.
    Berry R, Kouchi K, Der D, Dickel M, Light R. Sleep apnea impairs the arousal response to airway occlusion. Chest. 1996;109:1490–6.CrossRefGoogle Scholar
  59. 59.
    Younes M, Ostrowski M, Atkar R, Laprairie J, Siemens A, Hanly P. Mechanisms of breathing instability in patients with obstructive sleep apnea. J Appl Physiol. 2007;103:1929–41.CrossRefGoogle Scholar
  60. 60.
    Younes M. Role of arousals in the pathogenesis of obstructive sleep apnea. Am J Respir Crit Care Med. 2004;169:623–33.CrossRefGoogle Scholar
  61. 61.
    Gray EL, McKenzie DK, Eckert DJ. Obstructive sleep apnea without obesity is common and difficult to treat: evidence for a distinct pathophysiological phenotype. J Clin Sleep Med. 2017;13:81–8.CrossRefGoogle Scholar
  62. 62.
    Eckert DJ, Owens RL, Kehlmann GB, Wellman A, Rahangdale S, Yim-Yeh S, et al. Eszopiclone increases the respiratory arousal threshold and lowers the apnoea/hypopnoea index in obstructive sleep apnoea patients with a low arousal threshold. Clin Sci (London, England : 1979). 2011;120:505–14.CrossRefGoogle Scholar
  63. 63.
    Carter SG, Berger MS, Carberry JC, et al. Zopiclone increases the arousal threshold without impairing genioglossus activity in obstructive sleep apnea. Sleep. 2016;39:757–6664.CrossRefGoogle Scholar
  64. 64.
    Eckert D, Malhotra A, Wellman A, Sleep WD (2014) Trazodone increases the respiratory arousal threshold in patients with obstructive sleep apnea and a low arousal threshold.
  65. 65.
    Wellman A, Jordan AS, Malhotra A, Fogel RB, Katz ES, Schory K, et al. Ventilatory control and airway anatomy in obstructive sleep apnea. Am J Respir Crit Care Med. 2004;170:1225–32.CrossRefGoogle Scholar
  66. 66.
    Wellman A, Malhotra A, Jordan AS, Stevenson KE, Gautam S, White DP. Effect of oxygen in obstructive sleep apnea: role of loop gain. Respir Physiol Neurobiol. 2008;162:144–51.CrossRefGoogle Scholar
  67. 67.
    Edwards BA, Sands SA, Eckert DJ, White DP, Butler JP, Owens RL, et al. Acetazolamide improves loop gain but not the other physiological traits causing obstructive sleep apnoea. J Physiol. 2012;590:1199–211.CrossRefGoogle Scholar
  68. 68.
    Joosten SA, Leong P, Landry SA, Sands SA, Terrill PI, Mann D, et al. Loop gain predicts the response to upper airway surgery in patients with obstructive sleep apnoea. Sleep. 2017;40.
  69. 69.
    Bonsignore MR, Giron MC, Marrone O, Castrogiovanni A, Montserrat JM. Personalised medicine in sleep respiratory disorders: focus on obstructive sleep apnoea diagnosis and treatment. Eur Respir Rev. 2017;26:170069.CrossRefGoogle Scholar
  70. 70.
    Edwards BA, Sands SA, Owens RL, Eckert DJ, Landry S, White DP, et al. The combination of supplemental oxygen and a hypnotic markedly improves obstructive sleep apnea in patients with a mild to moderate upper airway collapsibility. Sleep. 2016;39:1973–83.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Leon Kitipornchai
    • 1
    • 2
  • Andrew Jones
    • 3
    • 4
  • Stuart Grayson MacKay
    • 1
    • 3
    Email author
  1. 1.Department of Otolaryngology, Head and Neck SurgeryIllawarra Shoalhaven Local Health DistrictWollongongAustralia
  2. 2.University of QueenslandBrisbaneAustralia
  3. 3.University of WollongongWollongongAustralia
  4. 4.Department of Respiratory MedicineIllawarra Shoalhaven Local Health DistrictWollongongAustralia

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