Indian Journal of Sleep Medicine

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VOLUME 12 , ISSUE 4 ( October-December, 2017 ) > List of Articles


Obstructive Sleep Apnea: New Concepts, Mechanism, and Therapy

Keywords : Mechanism, Newer treatment, Obstructive sleep apnea.

Citation Information : Obstructive Sleep Apnea: New Concepts, Mechanism, and Therapy. Indian Sleep Med 2017; 12 (4):64-72.

DOI: 10.5005/jp-journals-10069-0013

License: NA

Published Online: 01-12-2014

Copyright Statement:  NA


Continuous positive airway pressure (CPAP) is the gold standard for the management of obstructive sleep apnea (OSA). However, studies have shown that only around half use the device at the minimum recommended level of ≥4 hours/night. The compliance further drops to 17% after 5 years. Thus, there is need to develop and apply new modalities for the OSA. Also, if the treatment of OSA is directed toward the mechanism, the results are likely to be better. This review is aimed at mechanismdirected treatment for OSA.

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  1. Bartlett D, Wong K, Richards D, Moy E, Espie CA, Cistulli PA, Grunstein R. Increasing adherence to obstructive sleep apnea treatment with a group social cognitive therapy treatment intervention: a randomized trial. Sleep 2013 Nov;36(11): 1647-1654.
  2. Weaver TE, Sawyer A. Management of obstructive sleep apnea by continuous positive airway pressure. Oral Maxillofac Surg Clin North Am 2009;21(4):403-412.
  3. Suthrland K, Cistulli PA. Recent advances in obstructive sleep apnea pathophysiology and treatment. Sleep Biol Rhythms 2015;13:26-40.
  4. Suratt PM, Dee P, Atkinson RL, Armstrong P, Wilhoit SC. Fluoroscopic and computed tomographic features of the pharyngeal airway in obstructive sleep apnea. Am Rev Respir Dis 1983 Apr;127(4):487-492.
  5. Lam B, Ooi CG, Peh WC, Lauder I, Tsang KW, Lam WK, Ip MS. Computed tomographic evaluation of the role of craniofacial and upper airway morphology in obstructive sleep apnea in Chinese. Respir Med 2004 Apr;98(4):301-307.
  6. 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 Jan 15;165(2):260-265.
  7. Reyes EC, Bermúdez KP, Córdoba FE. New perspectives in the treatment of obstructive sleep apnea–hypopnea syndrome. Rev Colomb Anestesiol 2017;45(1):62-71.
  8. Joosten SA, O'Driscoll DM, Berger PJ, Hamilton GS. Supine position related obstructive sleep apnea in adults: pathogenesis and treatment. Sleep Med Rev 2014 Feb;18(1):7-17.
  9. Ong JS, Touyz G, Tanner S, Hillman DR, Eastwood PR, Walsh JH. Variability of human upper airway collapsibility during sleep and the influence of body posture and sleep stage. J Sleep Res 2011 Dec;20(4):533-537.
  10. Patil SP, Schneider H, Schwartz AR, Smith PL. Adult obstructive sleep apnea: pathophysiology and diagnosis. Chest 2007 Jul;132(1):325-337.
  11. Lo YL, Jordan AS, Malhotra A, Wellman A, Heinzer RA, Eikermann M, Schory K, Dover L, White DP. Influence of wakefulness on pharyngeal airway muscle activity. Thorax 2007 Sep;62(9):799-805.
  12. Jordan AS, White DP. Pharyngeal motor control and the pathogenesis of obstructive sleep apnea. Respir Physiol Neurobiol 2008 Jan 1;169(1):1-7.
  13. Pierce R, White D, Malhotra A, Edwards JK, Kleverlaan D, Palmer L, Trinder J. Upper airway collapsibility, dilator muscle activation and resistance in sleep apnoea. Eur Respir J 2007 Aug;30(2):345-353.
  14. Mezzanotte WS, Tangel DJ, White DP. Waking genioglossal electromyogram in sleep apnea patients versus normal controls (a neuromuscular compensatory mechanism). J Clin Invest 1992 May;89(5):1571-1579.
  15. Berry RB, White DP, Roper J, Pillar G, Fogel RB, Stanchina M, Malhotra A. Awake negative pressure reflex response of the genioglossus in OSA patients and normal subjects. J Appl Physiol 2003 May;94(5):1875-1882.
  16. Ballard RD, Irvin CG, Martin RJ, Pak J, Pandey R, White DP. Influence of sleep on lung volume in asthmatic patients and normal subjects. J Appl Physiol 1990 May;68(5):2034-2041.
  17. Owens RL, Malhotra A, Eckert DJ, White DP, Jordan AS. The influence of end-expiratory lung volume on measurements of pharyngeal collapsibility. J Appl Physiol 2010 Feb;108(2):445-451.
  18. Heinzer RC, Stanchina ML, Malhotra A, Fogel RB, Patel SR, Jordan AS, Schory K, White DP. Lung volume and continuous positive airway pressure requirements in obstructive sleep apnea. Am J Respir Crit Care Med 2005 Jul;172(1):114-117.
  19. Series F, Cormier Y, Desmeules M. Influence of passive changes of lung volume on upper airways. J Appl Physiol 1990 May;68(5):2159-2164.
  20. Van de Graaff WB. Thoracic influence on upper airway patency. J Appl Physiol 1988 Nov;65(5):2124-2131.
  21. Van de Graaff WB. Thoracic traction on the trachea: mechanisms and magnitude. J Appl Physiol 1991 Mar;70(3): 1328-1336.
  22. Kairaitis K, Byth K, Parikh R, Stavrinou R, Wheatley JR, Amis TC. Tracheal traction effects on upper airway patency in rabbits: the role of tissue pressure. Sleep 2007 Feb;30(2): 179-186.
  23. Dempsey JA, Veasey SC, Morgan BJ, O'Donnell CP. Pathophysiology of sleep apnea. Physiol Rev 2010 Jan;90(1):47-112.
  24. Younes M, Ostrowski M, Thompson W, Leslie C, Shewchuk W. Chemical control stability in patients with obstructive sleep apnea. Am J Respir Crit Care Med 2001 Apr;163(5):1181-1190.
  25. Wellman A, Jordan AS, Malhotra A, Fogel RB, Katz ES, Schory K, Edwards JK, White DP. Ventilatory control and airway anatomy in obstructive sleep apnea. Am J Respir Crit Care Med 2004 Dec;170(11):1225-1232.
  26. Younes M. Role of respiratory control mechanisms in the pathogenesis of obstructive sleep disorders. J Appl Physiol 2008 Nov;105(5):1389-1405.
  27. 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 Jul 31;162(2):144-151.
  28. Campana L, Eckert DJ, Patel SR, Malhotra A. Pathophysiology & genetics of obstructive sleep apnoea. Indian J Med Res 2010 Feb;131:176-187.
  29. Younes M. Role of arousals in the pathogenesis of obstructive sleep apnea. Am J Respir Crit Care Med 2004 Mar;169(5): 623-633.
  30. Jordan AS, Wellman A, Heinzer RC, Lo YL, Schory K, Dover L, Gautam S, Malhotra A, White DP. Mechanisms used to restore ventilation after partial upper airway collapse during sleep in humans. Thorax 2007 Oct;62(10):861-867.
  31. Jordan AS, Eckert DJ, Catcheside PG, McEvoy RD. Ventilatory response to brief arousal from non-rapid eye movement sleep is greater in men than in women. Am J Respir Crit Care Med 2003 Dec;168(12):1512-1519.
  32. Dempsey JA. Crossing the apnoeic threshold: causes and consequences. Exp Physiol 2005 Jan;90(1):13-24.
  33. Rowley JA, Zhou XS, Diamond MP, Badr MS. The determinants of the apnea threshold during NREM sleep in normal subjects. Sleep 2006 Jan;29(1):95-103.
  34. Kirkness JP, Madronio M, Stavrinou R, Wheatley JR, Amis TC. Relationship between surface tension of upper airway lining liquid and upper airway collapsibility during sleep in obstructive sleep apnea hypopnea syndrome. J Appl Physiol 2003 Nov;95(5):1761-1766.
  35. Kirkness JP, Madronio M, Stavrinou R, Wheatley JR, Amis TC. Surface tension of upper airway mucosal lining liquid in obstructive sleep apnea/hypopnea syndrome. Sleep 2005 Apr;28(4):457-463.
  36. Schwartz AR, Schneider H, Smith PL. Upper airway surface tension: is it a significant cause of airflow obstruction during sleep? J Appl Physiol 2003 Nov;95(5):1759-1760.
  37. Ahmad S, Gupta M, Gupta R, Dhyani M. Prevalence and correlates of insomnia and obstructive sleep apnea in chronic kidney disease. North Am J Med Sci 2013 Nov;5(11):641-646.
  38. Ferrier K, Campbell A, Yee B, Richards M, O'Meeghan T, Weatherall M, Neill A. Sleep-disordered breathing occurs frequently in stable outpatients with congestive heart failure. Chest 2005 Oct;128(4):2116-2122.
  39. Shiota S, Ryan CM, Chiu KL, Ruttanaumpawan P, Haight J, Arzt M, Floras JS, Chan C, Bradley TD. Alterations in upper airway cross-sectional area in response to lower body positive pressure in healthy subjects. Thorax 2007 Oct;62(10):868-872.
  40. Su MC, Chiu KL, Ruttanaumpawan P, Shiota S, Yumino D, Redolfi S, Haight JS, Bradley TD. Lower body positive pressure increases upper airway collapsibility in healthy subjects. Respir Physiol Neurobiol 2008 May;161(3):306-312.
  41. White LH, Motwani S, Kasai T, Yumino D, Amirthalingam V, Bradley TD. Effect of rostral fluid shift on pharyngeal resistance in men with and without obstructive sleep apnea. Respir Physiol Neurobiol 2014 Feb;192:17-22.
  42. Redolfi S, Yumino D, Ruttanaumpawan P, Yau B, Su MC, Lam J, Bradley TD. Relationship between overnight rostral fluid shift and Obstructive Sleep Apnea in nonobese men. Am J Respir Crit Care Med 2009 Feb;179(3):241-246.
  43. Kasai T, Motwani SS, Yumino D, Mak S, Newton GE, Bradley TD. Differing relationship of nocturnal fluid shifts to sleep apnea in men and women with heart failure. Circ Heart Fail 2012 Jul;5(4):467-474.
  44. Su MC, Chiu KL, Ruttanaumpawan P, Shiota S, Yumino D, Redolfi S, Haight JS, Yau B, Lam J, Bradley TD. Difference in upper airway collapsibility during wakefulness between men and women in response to lower-body positive pressure. Clin Sci 2009 May;116(9):713-720.
  45. Sutherland K, Vanderveken OM, Tsuda H, Marklund M, Gagnadoux F, Kushida CA, Cistulli PA. Oral appliance treatment for obstructive sleep apnea: an update. J Clin Sleep Med 2014 Feb;10(2):215-227.
  46. Chan AS, Sutherland K, Schwab RJ, Zeng B, Petocz P, Lee RW, Darendeliler MA, Cistulli PA. The effect of mandibular advancement on upper airway structure in obstructive sleep apnoea. Thorax 2010 Aug;65(8):726-732.
  47. Browm EC, Cheng S, Mckenzie DK, Butler JE, Gandevia SC, Bilston LE. Tongue and lateral upper airway movement with mandibular advancement. Sleep 2013 Mar;36(3):397-404.
  48. Zhu Y, Long H, Jian F, Lin J, Zhu J, Gao M, Lai W. The effectiveness of oral appliances for obstructive sleep apnea syndrome: a meta-analysis. J Dent 2015 Dec;43(12):1394-1402.
  49. Correa LP. Overview of oral appliance therapy for management of obstructive sleep apnea. Sleep Med Clin 2013;8: 505-516.
  50. Ramar K, Dort LC, Katz SG, Lettieri CJ, Harrod CG, Thomas SM, Chervin RD. Clinical practice guideline for the treatment of obstructive sleep apnea and snoring with oral appliance therapy: an update for 2015. J Clin Sleep Med 2015 Jul;11(7):773-827.
  51. Doff MH, Finnema KJ, Hoekema A, Wijkstra PJ, Stengenga B. Long-term oral appliance therapy in obstructive sleep apnea syndrome: a controlled study on dental side effects. Clin Oral Investig 2013 Mar;17(2):475-482.
  52. Phillips CL, Grunstein RR, Darendeliler MA, Mihailidou AS, Srinivasan VK, Yee BJ, Marks GB, Cistulli PA. Health outcomes of continuous positive airway pressure versus oral appliance treatment for obstructive sleep apnea: a randomized controlled trial. Am J Respir Crit Care Med 2013 Apr;187(8): 879-887.
  53. Almeida FR, Henrich N, Marra C, Lynd LD, Lowe AA, Tsuda H, Fleetham JA, Pliska B, Ayas N. Patient preferences and experiences of CPAP and oral appliances for the treatment of obstructive sleep apnea: a qualitative analysis. Sleep Breath 2013 May;17(2):659-666.
  54. Calik MW. Treatments for obstructive sleep apnea. J Clin Outcomes Manag 2016 Apr;23(4):181-192.
  55. Gillespie MB, Smith JE, Clarke J, Nguyen SA. Effectiveness of Pillar palatal implants for snoring management. Otolaryngol Head Neck Surg 2009 Mar;140(3):363-368.
  56. Lin HC, Friedman M, Chang HW, Lai CC, Chin CH, Lin MC, Pott T, Samuelson C. Effects of Pillar implants for sleepbreathing disorders on middle ear function. Eur Arch Otorhinolaryngol 2013 Aug;270(8):2339-2343.
  57. Choi JH, Kim SN. Efficacy of the pillar implant in the treatment of snoring and mild-to-moderate obstructive sleep apnea: a meta-analysis. Laryngoscope 2013 Jan;123(1):269-276.
  58. Haytoglu S, Kayabasoglu G, Sezen OS. Comparison of two techniques in simple snoring and obstructive sleep apnea syndrome patients: palatal implant or uvulopalatal flap. Eur J Gen Med 2014;11:179-186.
  59. Friedman M, Schalch P, Lin HC, Kakodkar KA, Mazllom N. Palatal implants for the treatment of snoring and obstructive sleep apnea/hypopnea syndrome. Otolaryngol Head Neck Surg 2008 Feb;138(2):209-216.
  60. Steward DL, Huntley TC, Woodson BT, Surdulescu V. Palate implants for obstructive sleep apnea: multi-institution, randomized, placebo-controlled study. Otolaryngol Head Neck Surg 2008 Oct;139(4):506-510.
  61. Neruntarat C. Long-term results of palatal implants for obstructive sleep apnea. Eur Arch Otorhinolaryngol 2011 Jul;268(7):1077-1080.
  62. Blackman A, Foster GD, Zammit G, Rosenberg R, Aronne L, Wadden T, Claudius B, Jensen CB, Mignot E. Effect of liraglutide 3.0 mg in individuals with obesity and moderate or severe obstructive sleep apnea: the SCALE Sleep Apnea randomized clinical trial. Int J Obes 2016 Aug;40(8):1310-1319.
  63. Young T, Peppard PE, Taheri S. Excess weight and sleepdisordered breathing. J Appl Physiol (1985) 2005 Oct;99(4): 1592-1599.
  64. Lindberg E, Gislason T. Epidemiology of sleep-related obstructive breathing. Sleep Med Rev 2000 Oct;4(5):411-433.
  65. Johansson K, Neovius M, Lagerros YT, Harlid R, Rossner S, Granath F, Hemmingsson E. Effect of a very low energy diet on moderate and severe obstructive sleep apnoea in obese men: a randomised controlled trial. BMJ 2009 Dec 3;339:b4609.
  66. Kuna ST, Reboussin DM, Borradaile KE, Sanders MH, Millman RP, Zammit G, Newman AB, Wadden TA, Jakicic JM, Wing RR, et al. Long-term effect of weight loss on obstructive sleep apnea severity in obese patients with type 2 diabetes. Sleep 2013 May;36(5):641-649.
  67. Tuomilehto H, Seppa J, Uusitupa M, Tuomilehto J, Gylling H. Weight reduction and increased physical activity to prevent the progression of obstructive sleep apnea: a 4-year observational postintervention follow-up of a randomized clinical trial. [corrected]. JAMA Intern Med 2013 May;173(10): 929-930.
  68. Tuomilehto H, Seppa J, Uusitupa M, Peltonen M, Martikainen T, Sahlman J, Kokkarinen J, Randell J, Pukkila M, Vanninen E, et al. The impact of weight reduction in the prevention of the progression of obstructive sleep apnea: an explanatory analysis of a 5-year observational follow-up trial. Sleep Med 2014 Mar;15(3):329-335.
  69. Epstein LJ, Kristo D, Strollo PJ Jr, Friedman N, Malhotra A, Patil SP, Ramar K, Rogers R, Schwab RJ, Weaver EM, et al. Clinical guideline for the evaluation, management and longterm care of obstructive sleep apnea in adults. J Clin Sleep Med 2009 Jun;5(3):263-276.
  70. Qaseem A, Holty JE, Owens DK, Dallas P, Starkey M, Shekelle P. Management of obstructive sleep apnea in adults: a clinical practice guideline from the America College of Physicians. Ann Intern Med 2013 Oct;159(7):471-483.
  71. Blonde L, Russell-Jones D. The safety and efficacy of liraglutide with or without oral antidiabetic drug therapy in type 2 diabetes: an overview of the LEAD 1-5 studies. Diabetes Obes Metab 2009 Dec;11(Suppl 3):26-34.
  72. Mehta A, Marso SP, Neeland IJ. Liraglutide for weight management: a critical review of the evidence. Obes Sci Pract 2017 Mar;3(1):3-14.
  73. Van Can J, Sloth B, Jensen CB, Flint A, Blaak EE, Saris WH. Effects of the once-daily GLP-1 analog liraglutide on gastric emptying, glycemic parameters, appetite and energy metabolism in obese, non-diabetic adults. Int J Obes (Lond) 2014 Jun;38(6):784-793.
  74. Guilleminault C, Powell N, Bowman B, Stoohs R. The effect of electrical stimulation on obstructive sleep apnea syndrome. Chest 1995 Jan;107(1):67-73.
  75. Steier J, Seymour J, Rafferty GF, Jolley CJ, Solomon E, Luo Y, Man WD, Polkey MI, Moxham J. Continuous transcutaneous submental electrical stimulation in obstructive sleep apnea: a feasibility study. Chest 2011 Oct;140(4):998-1007.
  76. Eastwood PR, Barnes M, Walsh JH, Maddison KJ, Hee G, Schwartz AR, Smith PL, Malhotra A, McEvoy RD, Wheatley JR, et al. Treating obstructive sleep apnea with hypoglossal nerve stimulation. Sleep 2011 Nov;34(11):1479-1486.
  77. Kezirian EJ, Goding GS Jr, Malhotra A, O'Donoghue FJ, Zammit G, Wheatley JR, Catcheside PG, Smith PL, Schwartz AR, Walsh JH, et al. Hypoglossal nerve stimulation improves obstructive sleep apnea: 12-month outcomes. J Sleep Res 2014 Feb;23(1):77-83.
  78. Strollo PJ Jr, Soose RJ, Maurer JT, de Vries N, Cornelius J, Froymovich O, Hanson RD, Padhya TA, Steward DL, Gillespie MB, et al. Upper-airway stimulation for obstructive sleep apnea. N Engl J Med 2014 Jan;370(2):139-149.
  79. Van de Heyning PH, Badr MS, Baskin JZ, Cramer Bornemann MA, De Backer WA, Dotan Y, Hohenhorst W, Knaack L, Lin HS, Maurer JT, et al. Implanted upper airway stimulation device for obstructive sleep apnea. Laryngoscope 2012 Jul;122(7):1626-1633.
  80. Kezirian EJ, Boudewyns A, Eisele DW, Schwartz AR, Smith PL, Van de Heyning PH, De Backer WA. Electrical stimulation of the hypoglossal nerve in the treatment of obstructive sleep apnea. Sleep Med Rev 2010 Oct;14(5):299-305.
  81. Strollo PJ, Gillespie MB, Soose RJ, Maurer JT, de Vries N, Cornelius J, Hanson RD, Padhya TA, Steward DL, Woodson BT, et al. Upper airway stimulation for obstructive sleep apnea: durability of the treatment effect at 18 months. Sleep 2015 Oct;38(10):1593-1598.
  82. Soose RJ, Woodson BT, Gillespie MB, Maurer JT, de Vries N, Steward DL, Strohl KP, Baskin JZ, Padhya TA, Badr MS, et al. Upper airway stimulation for obstructive sleep apnea: selfreported outcomes at 24 months. J Clin Sleep Med 2016 Jan;12(1):43-48.
  83. Woodson BT, Gillespie MB, Soose RJ, Maurer JT, de Vries N, Steward DL, Baskin JZ, Padhya TA, Lin HS, Mickelson S, et al. Randomized controlled withdrawal study of upper airway stimulation on OSA: short- and long-term effect. Otolaryngol Head Neck Surg 2014 Nov;151(5):880-887.
  84. Woodson BT, Soose RJ, Gillespie MB, Strohl KP, Maurer JT, de Vries N, Steward DL, Baskin JZ, Badr MS, Lin HS, et al. Three-year outcomes of cranial nerve stimulation for obstructive sleep apnea: the STAR trial. Otolaryngol Head Neck Surg 2016 Jan;154(1):181-188.
  85. Heinzer RC, Stanchina ML, Malhotra A, Jordan AS, Patel SR, Lo YL, Wellman A, Schory K, Dover L, White DP. Effect of increased lung volume on sleep disordered breathing in patients with sleep apnoea. Thorax 2006 May;61(5):435-439.
  86. Morrell MJ, Arabi Y, Zahn B, Badr MS. Progressive retropalatal narrowing preceding obstructive apnea. Am J Respir Crit Care Med 1998 Dec;158(6):1974-1981.
  87. Berry RB, Kryger MH, Massie CA. A novel nasal expiratory positive airway pressure (EPAP) device for the treatment of obstructive sleep apnea: a randomized controlled trial. Sleep 2011 Apr;34(4):479-485.
  88. Riaz M, Certal V, Nigam G, Abdullatif J, Zaghi S, Kushida CA, Camacho M. Nasal expiratory positive airway pressure devices (Provent) for OSA: a systematic review and metaanalysis. Sleep Disorders 2015;2015:734-798.
  89. Walsh JK, Griffin KS, Forts EH. A convenient expiratory positive airway pressure nasal device for the treatment of sleep apnea in patients non-adherent with continuous positive airway pressure. J Clin Sleep Med 2011 Feb;12(2):147-152.
  90. Cartwright RD. Effect of sleep position on sleep apnea severity. Sleep 1984;7(2):110-114.
  91. Joosten SA, Hamza K, Sands S, Turton A, Berger P, Hamilton G. Phenotypes of patients with mild to moderate obstructive sleep apnoea as confirmed by cluster analysis. Respirology 2012 Jan;17(1):99-107.
  92. Lee CH, Kim DK, Kim SY, Rhee CS, Won TB. Changes in site of obstruction in obstructive sleep apnea patients according to sleep position: a DISE study. Laryngoscope 2015 Jan;125(1):248-254.
  93. Maanen JP, Richard W, Van-Kesteren ER, Ravesloot MJ, Lama DM, Hilgevoord AA, de Vries N. Evaluation of a new simple treatment for positional sleep apnoea patients J Sleep Res 2012 Jun;21(3):322-329.
  94. Levendowsli DJ, Seagraves S, Popovic D, Westbrook PR. Assessment of a neck-based treatment and monitoring device for positional obstructive sleep apnea. J Clin Sleep Med 2014 Aug;10(8):863-871.
  95. Jackson M, Collins A, Berlowitz D, Howard M, O'Donoghue F, Barnes M. Efficacy of sleep position modification to treat positional obstructive sleep apnea. Sleep Med 2015 Apr;16(4): 545-552.
  96. Mason M, Welsh EJ, Smith I. Drug therapy for obstructive sleep apnoea in adults. Cochrane Database Syst Rev 2013 May;(5):CD003002.
  97. Eckert DJ, Owens RL, Kehlmann GB, Wellman A, Rahangdale S, Yim-Yeh S, White DP, Malhotra A. Eszopiclone increases the respiratory arousal threshold and lowers the apnoea/hypopnoea index in obstructive sleep apnoea patients with a low arousal threshold. Clin Sci 2011 Jun;120(12):505-514.
  98. Edwards BA, Connolly JG, Campana LM, Sands SA, Trinder JA, White DP, Wellman A, Malhotra A. Acetazolamide attenuates the ventilatory response to arousal in patients with obstructive sleep apnea. Sleep 2013 Feb;36(2):281-285.
  99. Edwards BA, Sands SA, Eckert DJ, White DP, Butler JP, Owens RL, Malhotra A, Wellman A. Acetazolamide improves loop gain but not the other physiological traits causing obstructive sleep apnoea. J Physiol 2012 Mar;590(Pt 5):1199-1211.
  100. Farabi SS, Prasad B, Quinn L, Carley DW. Impact of dronabinol on quantitative electroencephalogram (qEEG) measures of sleep in obstructive sleep apnea syndrome. J Clin Sleep Med 2014 Jan;10(1):49-56.
  101. Prasad B, Radulovacki MG, Carley DW. Proof of concept trial of dronabinol in obstructive sleep apnea. Front Psychiatry 2013;4:1.
  102. Calik MW, Carley DW. Cannabinoid type 1 and type 2 receptor antagonists prevent attenuation of serotonin-induced reflex apneas by dronabinol in Sprague-Dawley rats. PLoS One 2014 Oct;9(10):e111412.
  103. Deacon NL, Jen R, Li Y, Malhotra A. Treatment of obstructive sleep apnea. prospects for personalized combined modality therapy. Ann Am Thorac Soc 2016 Jan;13(1):101-108.
  104. Shin W, Jen R, Li Y, Malhotra A. Tailored treatment strategies for obstructive sleep apnea. Respir Investig 2016 Jan;54(1): 2-7.
  105. Dieltjens M, Vroegop AV, Verbruggen AE, Wouters K, Willemen M, De Backer WA, Verbraecken JA, Van de Heyning PH, Braem MJ, de Vries N, et al. A promising concept of combination therapy for positional obstructive sleep apnea. Sleep Breath 2015 May;19(2):637-644.
  106. Wellman A, Edwards BA, Sands SA, Owens RL, Nemati S, Butler J, Passaglia CL, Jackson AC, Malhotra A, White DP. A simplified method for determining phenotypic traits in patients with obstructive sleep apnea. J Appl Physiol (1985) 2013 Apr;114(7):911-922.
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