, Volume 190, Issue 4, pp 365–371 | Cite as

Emerging Therapies for Obstructive Sleep Apnea

  • Morohunfolu Akinnusi
  • Ranime Saliba
  • Ali A. El-Solh


Obstructive sleep apnea (OSA) is a prevalent disorder often associated with daytime sleepiness, cognitive dysfunction, and adverse cardiovascular consequences. Available therapies are limited by either lack of long-term adherence or low response rates. Two emerging therapies hold promise in providing alternatives to patients with OSA. The first stems from the importance of the upper-airway dilator muscles in maintaining pharyngeal stability. Electrical stimulation of the genioglossus muscle improves both upper-airway diameter and ameliorates pharyngeal obstruction. The results of phase I and II clinical trials hold promise, but the reported improvements in the apnea–hypopnea index vary between subjects and concerns about long-term safety await long-term studies. The second technology relies on creating an increased expiratory nasal resistance via a bidirectional valve designed to be worn just inside the nostrils. Initial findings of clinical trials suggest reduction in severity of sleep apnea and subjective daytime sleepiness. Considerable heterogeneity in response to the nasal device was noted despite the high adherence rates. It remains unclear which patients will likely benefit a priori from these devices.


Sleep apnea Hypoglossal nerve End positive expiratory pressure Stimulation 



This work was supported in part by VA Merit Review Award HSR&D 10-087-1 (AES). The opinions of the authors herein are the private views of the authors and are not to be construed as reflecting the views of the Department of Veterans Affairs.

Conflict of interest

The authors have no conflicts of interest to disclose.


  1. 1.
    Remmers JE, deGroot WJ, Sauerland EK, Anch AM (1978) Pathogenesis of upper airway occlusion during sleep. J Appl Physiol 44:931–938PubMedGoogle Scholar
  2. 2.
    Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S (1993) The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 328:1230–1235PubMedCrossRefGoogle Scholar
  3. 3.
    Kim J, In K, You S, Kang K, Shim J, Lee S, Lee J, Park C, Shin C (2004) Prevalence of sleep-disordered breathing in middle-aged Korean men and women. Am J Respir Crit Care Med 170:1108–1113PubMedCrossRefGoogle Scholar
  4. 4.
    Reddy EV, Kadhiravan T, Mishra HK, Sreenivas V, Handa KK, Sinha S, Sharma SK (2009) Prevalence and risk factors of obstructive sleep apnea among middle-aged urban Indians: a community-based study. Sleep Med 10:913–918PubMedCrossRefGoogle Scholar
  5. 5.
    McNicholas WT, Bonsigore MR (2007) Sleep apnoea as an independent risk factor for cardiovascular disease: current evidence, basic mechanisms and research priorities. Eur Respir J 29:156–178PubMedCrossRefGoogle Scholar
  6. 6.
    Somers VK, White DP, Amin R, Abraham WT, Costa F, Culebras A, Daniels S, Floras JS, Hunt CE, Olson LJ, Pickering TG, Russell R, Woo M, Young T (2008) Sleep Apnea and Cardiovascular Disease: an American Heart Association/American College of Cardiology Foundation Scientific Statement From the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Council on Cardiovascular Nursing In Collaboration With the National Heart, Lung, and Blood Institute National Center on Sleep Disorders Research (National Institutes of Health). Circulation 118:1080–1111PubMedCrossRefGoogle Scholar
  7. 7.
    Bradley TD, Floras JS (2009) Obstructive sleep apnoea and its cardiovascular consequences. Lancet 373:82–93PubMedCrossRefGoogle Scholar
  8. 8.
    Johnson KG, Johnson DC (2010) Frequency of sleep apnea in stroke and TIA patients: a meta-analysis. J Clin Sleep Med 6:131–137PubMedGoogle Scholar
  9. 9.
    Sharma B, Owens R, Malhotra A (2010) Sleep in congestive heart failure. Med Clin N Am 94:447–464PubMedCrossRefGoogle Scholar
  10. 10.
    Yumino D, Wang H, Floras JS, Newton GE, Mak S, Ruttanaumpawan P, Parker JD, Bradley TD (2009) Prevalence and physiological predictors of sleep apnea in patients with heart failure and systolic dysfunction. J Card Fail 15:279–285PubMedCrossRefGoogle Scholar
  11. 11.
    Maurer JT (2009) Update on surgical treatments for sleep apnea. Swiss Med Wkly 139:624–629PubMedGoogle Scholar
  12. 12.
    Rosenberg R, Doghramji P (2009) Optimal treatment of obstructive sleep apnea and excessive sleepiness. Adv Ther 26:295–312PubMedCrossRefGoogle Scholar
  13. 13.
    Gordon P, Sanders MH (2005) Sleep. 7: positive airway pressure therapy for obstructive sleep apnoea/hypopnoea syndrome. Thorax 60:68–75PubMedCrossRefGoogle Scholar
  14. 14.
    Sanders MH, Montserrat JM, Farre R, Givelber RJ (2008) Positive pressure therapy: a perspective on evidence-based outcomes and methods of application. Proc Am Thorac Soc 5:161–172PubMedCrossRefGoogle Scholar
  15. 15.
    Ferguson KA, Cartwright R, Rogers R, Schmidt-Nowara W (2006) Oral appliances for snoring and obstructive sleep apnea: a review. Sleep 29:244–262PubMedGoogle Scholar
  16. 16.
    Won CH, Li KK, Guilleminault C (2008) Surgical treatment of obstructive sleep apnea: upper airway and maxillomandibular surgery. Proc Am Thorac Soc 5:193–199PubMedCrossRefGoogle Scholar
  17. 17.
    Holty JE, Guilleminault C (2010) Surgical options for the treatment of obstructive sleep apnea. Med Clin N Am 94:479–515PubMedCrossRefGoogle Scholar
  18. 18.
    Tuomilehto HP, Seppa JM, Partinen MM, Peltonen M, Gylling H, Tuomilehto JO, Vanninen EJ, Kokkarinen J, Sahlman JK, Martikainen T, Soini EJ, Randell J, Tukiainen H, Uusitupa M (2009) Lifestyle intervention with weight reduction: first-line treatment in mild obstructive sleep apnea. Am J Respir Crit Care Med 179:320–327PubMedCrossRefGoogle Scholar
  19. 19.
    Johansson K, Neovius M, Lagerros YT, Harlid R, Rossner S, Granath F, Hemmingsson E (2009) Effect of a very low energy diet on moderate and severe obstructive sleep apnoea in obese men: a randomised controlled trial. BMJ 339:b4609PubMedCrossRefGoogle Scholar
  20. 20.
    Saboisky JP, Butler JE, Fogel RB, Taylor JL, Trinder JA, White DP, Gandevia SC (2006) Tonic and phasic respiratory drives to human genioglossus motoneurons during breathing. J Neurophysiol 95:2213–2221PubMedCrossRefGoogle Scholar
  21. 21.
    Eckert DJ, Malhotra A (2008) Pathophysiology of adult obstructive sleep apnea. Proc Am Thorac Soc 5:144–153PubMedCrossRefGoogle Scholar
  22. 22.
    Mann EA, Burnett T, Cornell S, Ludlow CL (2002) The effect of neuromuscular stimulation of the genioglossus on the hypopharyngeal airway. Laryngoscope 112:351–356PubMedCrossRefGoogle Scholar
  23. 23.
    Schwartz AR, Eisele DW, Hari A, Testerman R, Erickson D, Smith PL (1996) Electrical stimulation of the lingual musculature in obstructive sleep apnea. J Appl Physiol 81:643–652PubMedGoogle Scholar
  24. 24.
    Oliven A, O’Hearn DJ, Boudewyns A, Odeh M, De Backer W, van de Heyning P, Smith PL, Eisele DW, Allan L, Schneider H, Testerman R, Schwartz AR (2003) Upper airway response to electrical stimulation of the genioglossus in obstructive sleep apnea. J Appl Physiol 95:2023–2029PubMedGoogle Scholar
  25. 25.
    Oliven A, Tov N, Geitini L, Steinfeld U, Oliven R, Schwartz AR, Odeh M (2007) Effect of genioglossus contraction on pharyngeal lumen and airflow in sleep apnoea patients. Eur Respir J 30:748–758PubMedCrossRefGoogle Scholar
  26. 26.
    Miki H, Hida W, Chonan T, Kikuchi Y, Takishima T (1989) Effects of submental electrical stimulation during sleep on upper airway patency in patients with obstructive sleep apnea. Am Rev Respir Dis 140:1285–1289PubMedCrossRefGoogle Scholar
  27. 27.
    Hida W, Okabe S, Miki H, Kikuchi Y, Taguchi O, Takishima T, Shirato K (1994) Effects of submental stimulation for several consecutive nights in patients with obstructive sleep apnoea. Thorax 49:446–452PubMedCrossRefGoogle Scholar
  28. 28.
    Decker MJ, Haaga J, Arnold JL, Atzberger D, Strohl KP (1993) Functional electrical stimulation and respiration during sleep. J Appl Physiol 75:1053–1061PubMedGoogle Scholar
  29. 29.
    Smith PL, Eisele DW, Podszus T, Penzel T, Grote L, Peter JH, Schwartz AR (1996) Electrical stimulation of upper airway musculature. Sleep 19:S284–S287PubMedGoogle Scholar
  30. 30.
    Oliven A, Odeh M, Schnall RP (1996) Improved upper airway patency elicited by electrical stimulation of the hypoglossus nerves. Respiration 63:213–216PubMedCrossRefGoogle Scholar
  31. 31.
    Eisele DW, Schwartz AR, Hari A, Thut DC, Smith PL (1995) The effects of selective nerve stimulation on upper airway airflow mechanics. Arch Otolaryngol Head Neck Surg 121:1361–1364PubMedCrossRefGoogle Scholar
  32. 32.
    Bishara H, Odeh M, Schnall RP, Gavriely N, Oliven A (1995) Electrically-activated dilator muscles reduce pharyngeal resistance in anaesthetized dogs with upper airway obstruction. Eur Respir J 8:1537–1542PubMedGoogle Scholar
  33. 33.
    Bailey EF, Fregosi RF (2003) Pressure-volume behaviour of the rat upper airway: effects of tongue muscle activation. J Physiol 548:563–568PubMedCrossRefGoogle Scholar
  34. 34.
    Fregosi RF (2008) Influence of tongue muscle contraction and dynamic airway pressure on velopharyngeal volume in the rat. J Appl Physiol 104:682–693PubMedCrossRefGoogle Scholar
  35. 35.
    Goding GS Jr (1998) Correlation of laryngeal chemoreflex severity with laryngeal muscle response. Laryngoscope 108:863–872PubMedCrossRefGoogle Scholar
  36. 36.
    Goding GS Jr, Eisele DW, Testerman R, Smith PL, Roertgen K, Schwartz AR (1998) Relief of upper airway obstruction with hypoglossal nerve stimulation in the canine. Laryngoscope 108:162–169PubMedCrossRefGoogle Scholar
  37. 37.
    Schwartz AR, Barnes M, Hillman D, Malhotra A, Kezirian E, Smith PL, Hoegh T, Parrish D, Eastwood PR (2012) Acute upper airway responses to hypoglossal nerve stimulation during sleep in obstructive sleep apnea. Am J Respir Crit Care Med. doi:10.1164/rccm.201109-1614OC
  38. 38.
    Schwartz AR, Bennett ML, Smith PL, De Backer W, Hedner J, Boudewyns A, Van de Heyning P, Ejnell H, Hochban W, Knaack L, Podszus T, Penzel T, Peter JH, Goding GS, Erickson DJ, Testerman R, Ottenhoff F, Eisele DW (2001) Therapeutic electrical stimulation of the hypoglossal nerve in obstructive sleep apnea. Arch Otolaryngol Head Neck Surg 127:1216–1223PubMedGoogle Scholar
  39. 39.
    Dotan Y, Golibroda T, Oliven R, Netzer A, Gaitini L, Toubi A, Oliven A (2011) Parameters affecting pharyngeal response to genioglossus stimulation in sleep apnoea. Eur Respir J 38:338–347PubMedCrossRefGoogle Scholar
  40. 40.
    Longobardo GS, Evangelisti CJ, Cherniack NS (2008) Analysis of the interplay between neurochemical control of respiration and upper airway mechanics producing upper airway obstruction during sleep in humans. Exp Physiol 93:271–287PubMedCrossRefGoogle Scholar
  41. 41.
    Eastwood PR, Barnes M, Walsh JH, Maddison KJ, Hee G, Schwartz AR, Smith PL, Malhotra A, McEvoy RD, Wheatley JR, O’Donoghue FJ, Rochford PD, Churchward T, Campbell MC, Palme CE, Robinson S, Goding GS, Eckert DJ, Jordan AS, Catcheside PG, Tyler L, Antic NA, Worsnop CJ, Kezirian EJ, Hillman DR (2011) Treating obstructive sleep apnea with hypoglossal nerve stimulation. Sleep 34:1479–1486PubMedGoogle Scholar
  42. 42.
    Badr MS, Oliven A, Maurer J, Woodson BT, Knaack L, Cramer Bornemann M, Verbraecken J, De Backer W (2011) Predictors of response for upper airway stimulation in obstructive sleep apnea. Am J Respir Crit Care Med 183:A2727Google Scholar
  43. 43.
    Rodenstein DO, Rombaux P, Dury M, Lengele B, Mwenge GB (2011) Unilateral targeted hypoglossal neurostimulation (THN) for the treatment of obstructive sleep apnea. Am J Respir Crit Care Med 183:A6383Google Scholar
  44. 44.
    Sanders MH, Moore SE (1983) Inspiratory and expiratory partitioning of airway resistance during sleep in patients with sleep apnea. Am Rev Respir Dis 127:554–558PubMedGoogle Scholar
  45. 45.
    Morrell MJ, Arabi Y, Zahn B, Badr MS (1998) Progressive retropalatal narrowing preceding obstructive apnea. Am J Respir Crit Care Med 158:1974–1981PubMedGoogle Scholar
  46. 46.
    Yucel A, Unlu M, Haktanir A, Acar M, Fidan F (2005) Evaluation of the upper airway cross-sectional area changes in different degrees of severity of obstructive sleep apnea syndrome: cephalometric and dynamic CT study. Am J Neuroradiol 26:2624–2629PubMedGoogle Scholar
  47. 47.
    Heinzer RC, Stanchina ML, Malhotra A, Fogel RB, Patel SR, Jordan AS, Schory K, White DP (2005) Lung volume and continuous positive airway pressure requirements in obstructive sleep apnea. Am J Respir Crit Care Med 172:114–117PubMedCrossRefGoogle Scholar
  48. 48.
    Owens RL, Malhotra A, Eckert DJ, White DP, Jordan AS (2010) The influence of end-expiratory lung volume on measurements of pharyngeal collapsibility. J Appl Physiol 108:445–451PubMedCrossRefGoogle Scholar
  49. 49.
    Mahadevia AK, Onal E, Lopata M (1983) Effects of expiratory positive airway pressure on sleep-induced respiratory abnormalities in patients with hypersomnia-sleep apnea syndrome. Am Rev Respir Dis 128:708–711PubMedGoogle Scholar
  50. 50.
    Heinzer RC, Stanchina ML, Malhotra A, Jordan AS, Patel SR, Lo YL, Wellman A, Schory K, Dover L, White DP (2006) Effect of increased lung volume on sleep disordered breathing in patients with sleep apnoea. Thorax 61:435–439PubMedCrossRefGoogle Scholar
  51. 51.
    Colrain IM, Brooks S, Black J (2008) A pilot evaluation of a nasal expiratory resistance device for the treatment of obstructive sleep apnea. J Clin Sleep Med 4:426–433PubMedGoogle Scholar
  52. 52.
    Rosenthal L, Massie CA, Dolan DC, Loomas B, Kram J, Hart RW (2009) A multicenter, prospective study of a novel nasal EPAP device in the treatment of obstructive sleep apnea: efficacy and 30-day adherence. J Clin Sleep Med 5:532–537PubMedGoogle Scholar
  53. 53.
    Walsh JK, Griffin KS, Forst EH, Ahmed HH, Eisenstein RD, Curry DT, Hall-Porter JM, Schweitzer PK (2011) A convenient expiratory positive airway pressure nasal device for the treatment of sleep apnea in patients non-adherent with continuous positive airway pressure. Sleep Med 12:147–152PubMedCrossRefGoogle Scholar
  54. 54.
    Berry RB, Kryger MH, Massie CA (2011) A novel nasal expiratory positive airway pressure (EPAP) device for the treatment of obstructive sleep apnea: a randomized controlled trial. Sleep 34:479–485PubMedGoogle Scholar
  55. 55.
    Kryger MH, Berry RB, Massie CA (2011) Long-term use of a nasal expiratory positive airway pressure (EPAP) device as a treatment for obstructive sleep apnea (OSA). J Clin Sleep Med 7:449–453BPubMedGoogle Scholar
  56. 56.
    Patel AV, Hwang D, Masdeu MJ, Chen GM, Rapoport DM, Ayappa I (2011) Predictors of response to a nasal expiratory resistor device and its potential mechanisms of action for treatment of obstructive sleep apnea. J Clin Sleep Med 7:13–22PubMedGoogle Scholar
  57. 57.
    Suratt PM, Wilhoit SC, Cooper K (1984) Induction of airway collapse with subatmospheric pressure in awake patients with sleep apnea. J Appl Physiol 57:140–146PubMedGoogle Scholar
  58. 58.
    Owens RL, Wellman A, Malhotra A (2011) Which OSA patients might respond to nasal valves? J Clin Sleep Med 7:23–24PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Morohunfolu Akinnusi
    • 1
    • 2
    • 3
  • Ranime Saliba
    • 1
    • 2
    • 3
  • Ali A. El-Solh
    • 1
    • 2
    • 3
    • 4
  1. 1.The Veterans Affairs Western New York Healthcare SystemBuffaloUSA
  2. 2.Western New York Respiratory Research Center, Division of Pulmonary, Critical Care, and Sleep Medicine, Department of MedicineState University of New York at Buffalo School of Medicine and Biomedical Sciences and School of Public Health and Health ProfessionsBuffaloUSA
  3. 3.Department of Social and Preventive MedicineState University of New York at Buffalo School of Medicine and Biomedical Sciences and School of Public Health and Health ProfessionsBuffaloUSA
  4. 4.Medical Research, Bldg. 20 (151) VISN02VA Western New York Healthcare SystemBuffaloUSA

Personalised recommendations