Nocturnal Noninvasive Ventilation and Adjuncts in Disorders of Breathing Control

  • Robert Joseph Thomas


Treatment of sleep apnea characterized by high respiratory control chemosensitivity is challenging. The key polysomnographic characteristics are non-rapid eye movement (NREM) dominance of respiratory events that exhibit a self-similar metronomic timing and spontaneous improvement during rapid eye movement (REM) sleep. As both sleep fragmentation and a narrow CO2 reserve or increased loop gain drive the disease, sedatives (to induce longer periods of stable NREM sleep and reduce the destabilizing effects of arousals in NREM sleep) and CO2-based stabilization approaches are logical. Adaptive ventilation reduces mean hyperventilation and can effectively treat central/complex apnea in a subset of patients, but can also induce ventilator-patient desynchrony. Enhanced expiratory rebreathing space (EERS, dead space during positive pressure therapy) directly stabilizes respiratory control by moving CO2 above the apnea threshold. Carbonic anhydrase inhibition can provide further adjunctive benefits. Provent, Winx, body positioning, and oral appliances can be part of effective multimodality therapy in individual patients.


Central complex apnea adaptive rebreathing 


  1. 1.
    Javaheri S, Dempsey JA. Central sleep apnea. Comprehens Physiol. 2013;3(1):141–63.Google Scholar
  2. 2.
    Berssenbrugge A, Dempsey J, Iber C, Skatrud J, Wilson P. Mechanisms of hypoxia-induced periodic breathing during sleep in humans. J physiol. 1983;343:507–26.PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Dempsey JA, Skatrud JB. A sleep-induced apneic threshold and its consequences. Am Rev Respir Dis. 1986;133(6):1163–70.PubMedGoogle Scholar
  4. 4.
    Dempsey JA, Smith CA, Przybylowski T, et al. The ventilatory responsiveness to CO(2) below eupnoea as a determinant of ventilatory stability in sleep. J Physiol. 2004;560(Pt 1):1–11.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Henke KG, Arias A, Skatrud JB, Dempsey JA. Inhibition of inspiratory muscle activity during sleep. Chemical and nonchemical influences. Am Rev Respir Dis. 1988;138(1):8–15.PubMedCrossRefGoogle Scholar
  6. 6.
    Nakayama H, Smith CA, Rodman JR, Skatrud JB, Dempsey JA. Effect of ventilatory drive on carbon dioxide sensitivity below eupnea during sleep. Am J Respir Crit Care Med. 2002;165(9):1251–60.PubMedCrossRefGoogle Scholar
  7. 7.
    Nakayama H, Smith CA, Rodman JR, Skatrud JB, Dempsey JA. Carotid body denervation eliminates apnea in response to transient hypocapnia. J Appl Physiol. 2003;94(1):155–64.PubMedCrossRefGoogle Scholar
  8. 8.
    Skatrud JB, Dempsey JA. Interaction of sleep state and chemical stimuli in sustaining rhythmic ventilation. J Appl Physiol. 1983;55(3):813–22.PubMedGoogle Scholar
  9. 9.
    Xie A, Skatrud JB, Puleo DS, Dempsey JA. Influence of arterial O2 on the susceptibility to posthyperventilation apnea during sleep. J Appl Physiol. 2006;100(1):171–7.PubMedCrossRefGoogle Scholar
  10. 10.
    Xie A, Skatrud JB, Puleo DS, Rahko PS, Dempsey JA. Apnea-hypopnea threshold for CO2 in patients with congestive heart failure. Am J Respir Crit Care Med. 2002;165(9):1245–50.PubMedCrossRefGoogle Scholar
  11. 11.
    Ainslie PN, Duffin J. Integration of cerebrovascular CO2 reactivity and chemoreflex control of breathing: mechanisms of regulation, measurement and interpretation. Am J Physiol Regul Integr Comp Physiol. 11 2009.Google Scholar
  12. 12.
    Xie A, Skatrud JB, Khayat R, Dempsey JA, Morgan B, Russell D. Cerebrovascular response to carbon dioxide in patients with congestive heart failure. Am J Respir Crit Care Med. 2005;172(3):371–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Xie A, Skatrud JB, Barczi SR, et al. Influence of cerebral blood flow on breathing stability. J Appl Physiol. 31 2008.Google Scholar
  14. 14.
    White DP. Pathogenesis of obstructive and central sleep apnea. Am J Respir Crit Care Med. 2005;172(11):1363–70.PubMedCrossRefGoogle Scholar
  15. 15.
    Bradley TD. Crossing the threshold: implications for central sleep apnea. Am J Respir Crit Care Med. 2002;165(9):1203–4.PubMedCrossRefGoogle Scholar
  16. 16.
    Ponikowski P, Banasiak W. Chemosensitivity in chronic heart failure. Heart Fail Monit. 2001;1(4):126–31.PubMedGoogle Scholar
  17. 17.
    Smith CA, Rodman JR, Chenuel BJ, Henderson KS, Dempsey JA. Response time and sensitivity of the ventilatory response to CO2 in unanesthetized intact dogs: central vs. peripheral chemoreceptors. J Appl Physiol. 2006;100(1):13–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Smith CA, Chenuel BJ, Henderson KS, Dempsey JA. The apneic threshold during non-REM sleep in dogs: sensitivity of carotid body vs. central chemoreceptors. J Appl Physiol. 2007;103(2):578–86.PubMedCrossRefGoogle Scholar
  19. 19.
    Solin P, Roebuck T, Johns DP, Walters EH, Naughton MT. Peripheral and central ventilatory responses in central sleep apnea with and without congestive heart failure. Am J Respir Crit Care Med. 2000;162(6):2194–200.PubMedCrossRefGoogle Scholar
  20. 20.
    Xie A, Rutherford R, Rankin F, Wong B, Bradley TD. Hypocapnia and increased ventilatory responsiveness in patients with idiopathic central sleep apnea. Am J Respir Crit Care Med. 1995;152(6 Pt 1):1950–5.PubMedCrossRefGoogle Scholar
  21. 21.
    Xie A, Wong B, Phillipson EA, Slutsky AS, Bradley TD. Interaction of hyperventilation and arousal in the pathogenesis of idiopathic central sleep apnea. Am J Respir Crit Care Med. 1994;150(2):489–95.PubMedCrossRefGoogle Scholar
  22. 22.
    Xie A, Rankin F, Rutherford R, Bradley TD. Effects of inhaled CO2 and added dead space on idiopathic central sleep apnea. J Appl Physiol. 1997;82(3):918–26.PubMedGoogle Scholar
  23. 23.
    Salloum A, Rowley JA, Mateika JH, Chowdhuri S, Omran Q, Badr MS. Increased propensity for central apnea in patients with obstructive sleep apnea: effect of nasal continuous positive airway pressure. Am J Respir Crit Care Med. 2010;181(2):189–93.PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Xie A, Bedekar A, Skatrud JB, Teodorescu M, Gong Y, Dempsey JA. The heterogeneity of obstructive sleep apnea (predominant obstructive vs pure obstructive apnea). Sleep. 2011;34(6):745–50.PubMedCentralPubMedGoogle Scholar
  25. 25.
    Loewen A, Ostrowski M, Laprairie J, et al. Determinants of ventilatory instability in obstructive sleep apnea: inherent or acquired? Sleep. 2009;32(10):1355–65.PubMedCentralPubMedGoogle Scholar
  26. 26.
    Younes M. Role of respiratory control mechanisms in the pathogenesis of obstructive sleep disorders. J Appl Physiol. 2008;105(5):1389–405.PubMedCrossRefGoogle Scholar
  27. 27.
    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(6):1929–41.PubMedCrossRefGoogle Scholar
  28. 28.
    Edwards BA, Sands SA, Eckert DJ, et al. Acetazolamide improves loop gain but not the other physiological traits causing obstructive sleep apnoea. J Physiol. 2012;590(Pt 5):1199–1211.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Wellman A, Eckert DJ, Jordan AS, et al. A method for measuring and modeling the physiological traits causing obstructive sleep apnea. J Appl Physiol. 2011;110(6):1627–37.PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    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(2):144–51.PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Suzuki M, Ogawa H, Okabe S, et al. The effect of upper airway structural changes on central chemosensitivity in obstructive sleep apnea-hypopnea. Sleep Breath Schlaf Atm. 2004;8(2):73–83.CrossRefGoogle Scholar
  32. 32.
    Hudgel DW, Weil JV. Asthma associated with decreased hypoxic ventilatory drive. A family study. Ann Intern Med. 1974;80(5):623–5.PubMedCrossRefGoogle Scholar
  33. 33.
    Kawakami Y, Yamamoto H, Yoshikawa T, Shida A. Chemical and behavioral control of breathing in adult twins. Am Rev Respir Dis. 1984;129(5):703–7.PubMedGoogle Scholar
  34. 34.
    Kawakami Y, Irie T, Kishi F, et al. Familial aggregation of abnormal ventilatory control and pulmonary function in chronic obstructive pulmonary disease. Eur J Respir Dis. 1981;62(1):56–64.PubMedGoogle Scholar
  35. 35.
    Fleetham JA, Arnup ME, Anthonisen NR. Familial aspects of ventilatory control in patients with chronic obstructive pulmonary disease. Am Rev Respir Dis. 1984;129(1):3–7.PubMedGoogle Scholar
  36. 36.
    Tankersley CG. Genetic aspects of breathing: on interactions between hypercapnia and hypoxia. Respir Physiol Neurobiol. 2003;135(2–3):167–78.PubMedCrossRefGoogle Scholar
  37. 37.
    Tankersley CG. A genomic model for differential hypoxic ventilatory responses. Adv Exp Med Biol. 2000;475:75–85.PubMedCrossRefGoogle Scholar
  38. 38.
    Collins DD, Scoggin CH, Zwillich CW, Weil JV. Hereditary aspects of decreased hypoxic response. J Clin Invest. 1978;62(1):105–10.PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Mountain R, Zwillich C, Weil J. Hypoventilation in obstructive lung disease. The role of familial factors. New Engl J Med. 1978;298(10):521–25.PubMedCrossRefGoogle Scholar
  40. 40.
    Nishimura M, Yamamoto M, Yoshioka A, Akiyama Y, Kishi F, Kawakami Y. Longitudinal analyses of respiratory chemosensitivity in normal subjects. Am Rev Respir Dis. 1991;143(6):1278–81.PubMedCrossRefGoogle Scholar
  41. 41.
    Strohl KP. Periodic breathing and genetics. Respir Physiol Neurobiol. 2003;135(2–3):179–85.PubMedCrossRefGoogle Scholar
  42. 42.
    Kawakami Y, Yoshikawa T, Shida A, Asanuma Y. Relationship between hypoxic and hypercapnic ventilatory responses in man. Jpn J Physiol. 1981;31(3):357–68.PubMedCrossRefGoogle Scholar
  43. 43.
    Zwillich C, McCullough R, Guilleminault C, Cummiskey J, Weil JV. Respiratory control in the parents of sudden infant death syndrome victims. Ventilatory control in SIDS parents. Pediatr Res. 1980;14(5):762–4.PubMedCrossRefGoogle Scholar
  44. 44.
    Weil JV. Variation in human ventilatory control-genetic influence on the hypoxic ventilatory response. Respir Physiol Neurobiol. 2003;135(2–3):239–46.PubMedCrossRefGoogle Scholar
  45. 45.
    Schiffman PL, Remolina C, Westlake RE, Santiago TV, Edelman NH. Ventilatory response to isocapnic hypoxia in parents of victims of sudden infant death syndrome. Chest. 1982;81(6):707–10.PubMedCrossRefGoogle Scholar
  46. 46.
    Huey KA, Low MJ, Kelly MA, Juarez R, Szewczak JM, Powell FL. Ventilatory responses to acute and chronic hypoxia in mice: effects of dopamine D(2) receptors. J Appl Physiol. 2000;89(3):1142–50.PubMedGoogle Scholar
  47. 47.
    Bonora M, Bernaudin JF, Guernier C, Brahimi-Horn MC. Ventilatory responses to hypercapnia and hypoxia in conscious cystic fibrosis knockout mice Cftr. Pediatr Res. 2004;55(5):738–46.PubMedCrossRefGoogle Scholar
  48. 48.
    Aizenfisz S, Dauger S, Durand E, et al. Ventilatory responses to hypercapnia and hypoxia in heterozygous c-ret newborn mice. Respir Physiol Neurobiol. 2002;131(3):213–22.PubMedCrossRefGoogle Scholar
  49. 49.
    Jokic R, Zintel T, Sridhar G, Gallagher CG, Fitzpatrick MF. Ventilatory responses to hypercapnia and hypoxia in relatives of patients with the obesity hypoventilation syndrome. Thorax. 2000;55(11):940–5.PubMedCentralPubMedCrossRefGoogle Scholar
  50. 50.
    Redline S, Leitner J, Arnold J, Tishler PV, Altose MD. Ventilatory-control abnormalities in familial sleep apnea. Am J Respir Crit Care Med. 1997;156(1):155–60.PubMedCrossRefGoogle Scholar
  51. 51.
    Tankersley CG, Fitzgerald RS, Kleeberger SR. Differential control of ventilation among inbred strains of mice. Am J Physiol. 1994;267(5 Pt 2):R1371–R7.PubMedGoogle Scholar
  52. 52.
    Kuwaki T, Cao WH, Kurihara Y, et al. Impaired ventilatory responses to hypoxia and hypercapnia in mutant mice deficient in endothelin-1. Am J Physiol. 1996;270(6 Pt 2):R1279–R86.PubMedGoogle Scholar
  53. 53.
    Kline DD, Prabhakar NR. Peripheral chemosensitivity in mutant mice deficient in nitric oxide synthase. Adv Exp Med Biol. 2000;475:571–9.PubMedCrossRefGoogle Scholar
  54. 54.
    Renolleau S, Dauger S, Vardon G, et al. Impaired ventilatory responses to hypoxia in mice deficient in endothelin-converting-enzyme-1. Pediatr Res. 2001;49(5):705–12.PubMedCrossRefGoogle Scholar
  55. 55.
    Chen J, He L, Dinger B, Stensaas L, Fidone S. Role of endothelin and endothelin A-type receptor in adaptation of the carotid body to chronic hypoxia. Am J Physiol Lung Cell Mol Physiol. 2002;282(6):L1314–L23.PubMedCrossRefGoogle Scholar
  56. 56.
    Gosselin LE, Barkley JE, Spencer MJ, McCormick KM, Farkas GA. Ventilatory dysfunction in mdx mice: impact of tumor necrosis factor-alpha deletion. Muscle Nerve. 2003;28(3):336–43.PubMedCrossRefGoogle Scholar
  57. 57.
    Rong W, Gourine AV, Cockayne DA, et al. Pivotal role of nucleotide P2 × 2 receptor subunit of the ATP-gated ion channel mediating ventilatory responses to hypoxia. J Neurosci. 2003;23(36):11315–21.PubMedGoogle Scholar
  58. 58.
    Adachi T, Ishikawa K, Hida W, et al. Hypoxemia and blunted hypoxic ventilatory responses in mice lacking heme oxygenase-2. Biochem Biophys Res Commun. 2004;320(2):514–22.PubMedCrossRefGoogle Scholar
  59. 59.
    Boudinot E, Yamada M, Wess J, Champagnat J, Foutz AS. Ventilatory pattern and chemosensitivity in M1 and M3 muscarinic receptor knockout mice. Respir Physiol Neurobiol. 2004;139(3):237–45.PubMedCrossRefGoogle Scholar
  60. 60.
    Malik MT, Peng YJ, Kline DD, Adhikary G, Prabhakar NR. Impaired ventilatory acclimatization to hypoxia in mice lacking the immediate early gene fos B. Respir Physiol Neurobiol. 2005;145(1):23–31.PubMedCrossRefGoogle Scholar
  61. 61.
    Zhang Y, Furuyama K, Adachi T, et al. Hypoxemia and attenuated hypoxic ventilatory responses in mice lacking heme oxygenase-2: evidence for a novel role of heme oxygenase-2 as an oxygen sensor. Adv Exp Med Biol. 2006;580:161–6. discussion 351–169.PubMedCrossRefGoogle Scholar
  62. 62.
    Oyamada Y, Yamaguchi K, Murai M, Hakuno H, Ishizaka A. Role of Kir2.2 in hypercapnic ventilatory response during postnatal development of mouse. Respir Physiol Neurobiol. 2005;145(2–3):143–51.PubMedCrossRefGoogle Scholar
  63. 63.
    Lahiri S, Maret K, Sherpa MG. Dependence of high altitude sleep apnea on ventilatory sensitivity to hypoxia. Respir Physiol. 1983;52(3):281–301.PubMedCrossRefGoogle Scholar
  64. 64.
    Kobayashi S, Nishimura M, Yamamoto M, Akiyama Y, Kishi F, Kawakami Y. Dyspnea sensation and chemical control of breathing in adult twins. Am Rev Respiratory Dis. 1993;147(5):1192–8.PubMedCrossRefGoogle Scholar
  65. 65.
    Moore GC, Zwillich CW, Battaglia JD, Cotton EK, Weil JV. Respiratory failure associated with familial depression of ventilatory response to hypoxia and hypercapnia. New Engl J Med. 1976;295(16):861–5.PubMedCrossRefGoogle Scholar
  66. 66.
    Funada Y, Nishimura Y, Kamemura K, et al. Familial adult onset primary alveolar hypoventilation syndrome. Intern Med. 2001;40(6):526–31.PubMedCrossRefGoogle Scholar
  67. 67.
    Scoggin CH, Doekel RD, Kryger MH, Zwillich CW, Weil JV. Familial aspects of decreased hypoxic drive in endurance athletes. J Appl Physiol. 1978;44(3):464–8.PubMedGoogle Scholar
  68. 68.
    Dunai J, Kleiman J, Trinder J. Ventilatory instability during sleep onset in individuals with high peripheral chemosensitivity. J Appl Physiol. 1999;87(2):661–72.PubMedGoogle Scholar
  69. 69.
    Bhaumik G, Sharma RP, Dass D, et al. Hypoxic ventilatory response changes of men and women 6 to 7 days after climbing from 2100 m to 4350 m altitude and after descent. High Alt Med Biol. 2003;4(3):341–8.PubMedCrossRefGoogle Scholar
  70. 70.
    Garcia N, Hopkins SR, Powell FL. Effects of intermittent hypoxia on the isocapnic hypoxic ventilatory response and erythropoiesis in humans. Respir Physiol. 2000;123(1–2):39–49.PubMedCrossRefGoogle Scholar
  71. 71.
    Hupperets MD, Hopkins SR, Pronk MG, et al. Increased hypoxic ventilatory response during 8 weeks at 3800 m altitude. Respir Physiol Neurobiol. 2004;142(2–3):145–52.PubMedCrossRefGoogle Scholar
  72. 72.
    Katayama K, Sato Y, Morotome Y, et al. Intermittent hypoxia increases ventilation and Sa(O2) during hypoxic exercise and hypoxic chemosensitivity. J Appl Physiol. 2001;90(4):1431–40.PubMedGoogle Scholar
  73. 73.
    Powell FL, Milsom WK, Mitchell GS. Time domains of the hypoxic ventilatory response. Respir Physiol. 1998;112(2):123–34.PubMedCrossRefGoogle Scholar
  74. 74.
    Townsend NE, Gore CJ, Hahn AG, et al. Hypoxic ventilatory response is correlated with increased submaximal exercise ventilation after live high, train low. Eur J Appl Physiol. 2005;94(1–2):207–15.PubMedCrossRefGoogle Scholar
  75. 75.
    Townsend NE, Gore CJ, Hahn AG, et al. Living high-training low increases hypoxic ventilatory response of well-trained endurance athletes. J Appl Physiol. 2002;93(4):1498–505.PubMedCrossRefGoogle Scholar
  76. 76.
    Nopmaneejumruslers C, Kaneko Y, Hajek V, Zivanovic V, Bradley TD. Cheyne-Stokes respiration in stroke: relationship to hypocapnia and occult cardiac dysfunction. Am J Respir Crit Care Med. 2005;171(9):1048–52.PubMedCrossRefGoogle Scholar
  77. 77.
    Mansfield DR, Solin P, Roebuck T, Bergin P, Kaye DM, Naughton MT. The effect of successful heart transplant treatment of heart failure on central sleep apnea. Chest. 2003;124(5):1675–81.PubMedCrossRefGoogle Scholar
  78. 78.
    McGinty D, Littner M, Beahm E, Ruiz-Primo E, Young E, Sowers J. Sleep related breathing disorders in older men: a search for underlying mechanisms. Neurobiol Aging. 1982;3(4):337–50.PubMedCrossRefGoogle Scholar
  79. 79.
    Hader C, Schroeder A, Hinz M, Micklefield GH, Rasche K. Sleep disordered breathing in the elderly: comparison of women and men. J Physiol Pharmacol. 2005;56(Suppl 4):85–91.PubMedGoogle Scholar
  80. 80.
    Peterson DD, Pack AI, Silage DA, Fishman AP. Effects of aging on ventilatory and occlusion pressure responses to hypoxia and hypercapnia. Am Rev Respir Dis. 1981;124(4):387–91.PubMedGoogle Scholar
  81. 81.
    Littner M, Young E, McGinty D, Beahm E, Riege W, Sowers J. Awake abnormalities of control of breathing and of the upper airway. Occurrence in healthy older men with nocturnal disordered breathing. Chest. 1984;86(4):573–9.PubMedCrossRefGoogle Scholar
  82. 82.
    Chapman KR, Cherniack NS. Aging effects on the interaction of hypercapnia and hypoxia as ventilatory stimuli. J Gerontol. 1987;42(2):202–9.PubMedCrossRefGoogle Scholar
  83. 83.
    Guilleminault C, Cummiskey J. Progressive improvement of apnea index and ventilatory response to CO2 after tracheostomy in obstructive sleep apnea syndrome. Am Rev Respir Dis. 1982;126(1):14–20.PubMedGoogle Scholar
  84. 84.
    Fletcher EC. Recurrence of sleep apnea syndrome following tracheostomy. A shift from obstructive to central apnea. Chest. 1989;96(1):205–9.PubMedCrossRefGoogle Scholar
  85. 85.
    Chenuel BJ, Smith CA, Skatrud JB, Henderson KS, Dempsey JA. Increased propensity for apnea in response to acute elevations in left atrial pressure during sleep in the dog. J Appl Physiol. 2006;101(1):76–83.PubMedCrossRefGoogle Scholar
  86. 86.
    Dursunoglu N, Dursunoglu D, Ozkurt S, Gur S, Ozalp G, Evyapan F. Effects of CPAP on right ventricular myocardial performance index in obstructive sleep apnea patients without hypertension. Respir Res. 2006;7(1):22.PubMedCentralPubMedCrossRefGoogle Scholar
  87. 87.
    Shivalkar B, Van de Heyning C, Kerremans M, et al. Obstructive sleep apnea syndrome: more insights on structural and functional cardiac alterations, and the effects of treatment with continuous positive airway pressure. J Am Coll Cardiol. 2006;47(7):1433–9.PubMedCrossRefGoogle Scholar
  88. 88.
    Niroumand M, Kuperstein R, Sasson Z, Hanly PJ. Impact of obstructive sleep apnea on left ventricular mass and diastolic function. Am J Respir Crit Care Med. 2001;163(7):1632–6.PubMedCrossRefGoogle Scholar
  89. 89.
    Mahamed S, Hanly PJ, Gabor J, Beecroft J, Duffin J. Overnight changes of chemoreflex control in obstructive sleep apnoea patients. Respir Physiol Neurobiol. 2005;146(2–3):279–90.PubMedCrossRefGoogle Scholar
  90. 90.
    Verbraecken J, De Backer W, Willemen M, De Cock W, Wittesaele W, Van de H. Chronic CO2 drive in patients with obstructive sleep apnea and effect of CPAP. Respir Physiol. 1995;101(3):279–87.PubMedCrossRefGoogle Scholar
  91. 91.
    Verbraecken J, Willemen M, De Cock W, et al. Influence of longterm CPAP therapy on CO(2) drive in patients with obstructive sleep apnea. Respir Physiol. 2000;123(1–2):121–30.PubMedCrossRefGoogle Scholar
  92. 92.
    Verbraecken J, Willemen M, Wittesaele W, Van de Heyning P, De Backer W. Short-term CPAP does not influence the increased CO2 drive in idiopathic central sleep apnea. Monaldi Arch Chest Dis (Archivio Monaldi per le malattie del torace/Fondazione clinica del lavoro, IRCCS [and] Istituto di clinica tisiologica e malattie apparato respiratorio, Universita di Napoli, Secondo ateneo). 2002;57(1):10–8.PubMedGoogle Scholar
  93. 93.
    Spicuzza L, Bernardi L, Balsamo R, Ciancio N, Polosa R, Di Maria G. Effect of treatment with nasal continuous positive airway pressure on ventilatory response to hypoxia and hypercapnia in patients with sleep apnea syndrome. Chest. 2006;130(3):774–9.PubMedCrossRefGoogle Scholar
  94. 94.
    White DP, Douglas NJ, Pickett CK, Weil JV, Zwillich CW. Sexual influence on the control of breathing. J Appl Physiol. 1983;54(4):874–9.PubMedGoogle Scholar
  95. 95.
    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;168(12):1512–9.PubMedCrossRefGoogle Scholar
  96. 96.
    Hume KI, Van F, Watson A. A field study of age and gender differences in habitual adult sleep. J Sleep Res. 1998;7(2):85–94.Google Scholar
  97. 97.
    Marrone O, Stallone A, Salvaggio A, Milone F, Bellia V, Bonsignore G. Occurrence of breathing disorders during CPAP administration in obstructive sleep apnoea syndrome. Eur Respir J. 1991;4(6):660–6.PubMedGoogle Scholar
  98. 98.
    Thomas RJ, Terzano MG, Parrino L, Weiss JW. Obstructive sleep-disordered breathing with a dominant cyclic alternating pattern–a recognizable polysomnographic variant with practical clinical implications. Sleep. 2004;27(2):229–34.PubMedGoogle Scholar
  99. 99.
    Gilmartin GS, Daly RW, Thomas RJ. Recognition and management of complex sleep-disordered breathing. Curr Opin Pulm Med. 2005;11(6):485–93.PubMedCrossRefGoogle Scholar
  100. 100.
    Morgenthaler TI, Kagramanov V, Hanak V, Decker PA. Complex sleep apnea syndrome: is it a unique clinical syndrome? Sleep. 2006;29(9):1203–9.PubMedGoogle Scholar
  101. 101.
    Goldstein C, Kuzniar TJ. The emergence of central sleep apnea after surgical relief of nasal obstruction in obstructive sleep apnea. J Clin Sleep Med JCSM Off Publ Am Acad Sleep Med. 2012;8(3):321–2.Google Scholar
  102. 102.
    Gilmartin G, McGeehan B, Vigneault K, et al. Treatment of positive airway pressure treatment-associated respiratory instability with enhanced expiratory rebreathing space (EERS). J Clin Sleep Med JCSM Off Publ Am Acad Sleep Med. 2010;6(6):529–38.Google Scholar
  103. 103.
    Kuzniar TJ, Kovacevic-Ristanovic R, Freedom T. Complex sleep apnea unmasked by the use of a mandibular advancement device. Sleep Breath Schlaf Atm. 2011;15(2):249–252.CrossRefGoogle Scholar
  104. 104.
    Weil JV. Sleep at high altitude. High Alt Med Biol. 2004;5(2):180–9.PubMedCrossRefGoogle Scholar
  105. 105.
    Badr S. Central sleep apnea in patients with congestive heart failure. Heart Fail Rev. 2009;14(3):135–41.PubMedCentralPubMedCrossRefGoogle Scholar
  106. 106.
    Berry RB, Budhiraja R, Gottlieb DJ, et al. Rules for scoring respiratory events in sleep: update of the 2007 AASM manual for the scoring of sleep and associated events. J Clin Sleep Med JCSM Off Publ Am Acad Sleep Med. 2012;8(5):597–619.Google Scholar
  107. 107.
    Jobin V, Rigau J, Beauregard J, et al. Evaluation of upper airway patency during cheyne-stokes breathing in heart failure patients. Eur Respir J Off J Eur Soc Clin Respir Physiol. 2012;40(6):1523–30.Google Scholar
  108. 108.
    Thomas RJ, Tamisier R, Boucher J, et al. Nocturnal hypoxia exposure with simulated altitude for 14 days does not significantly alter working memory or vigilance in humans. Sleep. 2007;30(9):1195–203.PubMedCentralPubMedGoogle Scholar
  109. 109.
    Badr MS, Toiber F, Skatrud JB, Dempsey J. Pharyngeal narrowing/occlusion during central sleep apnea. J Appl Physiol. 1995;78(5):1806–15.PubMedGoogle Scholar
  110. 110.
    Sankri-Tarbichi AG, Rowley JA, Badr MS. Expiratory pharyngeal narrowing during central hypocapnic hypopnea. Am J Respir Crit Care Med. 2009;179(4):313–9.PubMedCentralPubMedCrossRefGoogle Scholar
  111. 111.
    Westhoff M, Arzt M, Litterst P. Prevalence and treatment of central sleep apnoea emerging after initiation of continuous positive airway pressure in patients with obstructive sleep apnoea without evidence of heart failure. Sleep Breath Schlaf Atm. 2012;16(1):71–8.CrossRefGoogle Scholar
  112. 112.
    Javaheri S, Smith J, Chung E. The prevalence and natural history of complex sleep apnea. J Clin Sleep Med JCSM Off Publ Am Acad Sleep Med. 2009;5(3):205–11.Google Scholar
  113. 113.
    Thomas RJ, Mietus JE, Peng CK, et al. Differentiating obstructive from central and complex sleep apnea using an automated electrocardiogram-based method. Sleep. 2007;30(12):1756–69.PubMedCentralPubMedGoogle Scholar
  114. 114.
    American Academy of Sleep Medicine. International classification of sleep disorders reD. IL: American Academy of Sleep Medicine; 2014.Google Scholar
  115. 115.
    Rao H, Thomas RJ. Complex sleep apnea. Current treatment options in neurology. 2013;15(6):677–91.PubMedCrossRefGoogle Scholar
  116. 116.
    Del Rio R, Moya EA, Parga MJ, Madrid C, Iturriaga R. Carotid body inflammation and cardiorespiratory alterations in intermittent hypoxia. Eur Respir J Off J Eur Soc Clin Respir Physiol. 2012;39(6):1492–500.Google Scholar
  117. 117.
    Meza S, Younes M. Ventilatory stability during sleep studied with proportional assist ventilation (PAV). Sleep. 1996;19(10 Suppl):S164–S6.PubMedGoogle Scholar
  118. 118.
    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;163(5):1181–90.PubMedCrossRefGoogle Scholar
  119. 119.
    Fabbrini M, Bonanni E, Maestri M, et al. Automatic analysis of EEG pattern during sleep in Cheyne-Stokes respiration in heart failure. Sleep Med. 2011;12(5):529–30.PubMedCrossRefGoogle Scholar
  120. 120.
    Suhas SR, Vijendra S, Burk JR, Lucas EA, Behbehani K. Classification of Cheyne-Stokes breathing and obstructive sleep apnea using ECG. Conf Proc … Annu Internatl Conf IEEE Eng Med Biol Soc IEEE Eng Med Biol Soc Conf. 2006;1:3561–4.CrossRefGoogle Scholar
  121. 121.
    Lehman S, Antic NA, Thompson C, Catcheside PG, Mercer J, McEvoy RD. Central sleep apnea on commencement of continuous positive airway pressure in patients with a primary diagnosis of obstructive sleep apnea-hypopnea. J Clin Sleep Med JCSM Off Publ Am Acad Sleep Med. 2007;3(5):462–6.Google Scholar
  122. 122.
    Kuzniar TJ, Pusalavidyasagar S, Gay PC, Morgenthaler TI. Natural course of complex sleep apnea–a retrospective study. Sleep Breath Schlaf Atm. 2008;12(2):135–9.CrossRefGoogle Scholar
  123. 123.
    Kuzniar TJ, Morgenthaler TI. Treatment of complex sleep apnea syndrome. Current treatment options in neurology. 2008;10(5):336–41.PubMedCrossRefGoogle Scholar
  124. 124.
    Gay PC. Complex sleep apnea: it really is a disease. J Clin Sleep Med JCSM Off Publ Am Acad Sleep Med. 2008;4(5):403–5.Google Scholar
  125. 125.
    Endo Y, Suzuki M, Inoue Y, et al. Prevalence of complex sleep apnea among Japanese patients with sleep apnea syndrome. Tohoku J Exp Med. 2008;215(4):349–54.PubMedCrossRefGoogle Scholar
  126. 126.
    Kuzniar TJ, Morgenthaler TI. Treatment of complex sleep apnea syndrome. Chest. 2012;142(4):1049–57.PubMedCrossRefGoogle Scholar
  127. 127.
    Kuzniar TJ, Kasibowska-Kuzniar K, Ray DW, Freedom T. Clinical heterogeneity of patients with complex sleep apnea syndrome. Sleep Breath Schlaf Atm. 2013;17(4):1209–14.CrossRefGoogle Scholar
  128. 128.
    Dernaika T, Tawk M, Nazir S, Younis W, Kinasewitz GT. The significance and outcome of continuous positive airway pressure-related central sleep apnea during split-night sleep studies. Chest. 2007;132(1):81–7.PubMedCrossRefGoogle Scholar
  129. 129.
    Cassel W, Canisius S, Becker HF, et al. A prospective polysomnographic study on the evolution of complex sleep apnoea. Eur Respir J. 2011;38(2):329–37.PubMedCrossRefGoogle Scholar
  130. 130.
    Kuzniar TJ, Patel S, Nierodzik CL, Smith LC. Comparison of two servo ventilator devices in the treatment of complex sleep apnea. Sleep Med. 2011;12(6):538–41.PubMedCrossRefGoogle Scholar
  131. 131.
    Bitter T, Westerheide N, Hossain MS, et al. Complex sleep apnoea in congestive heart failure. Thorax. 2011;66(5):402–7.PubMedCrossRefGoogle Scholar
  132. 132.
    Morgenthaler TI, Kuzniar TJ, Wolfe LF, Willes L, McLain WC 3rd, Goldberg R. The complex sleep apnea resolution study: a prospective randomized controlled trial of continuous positive airway pressure versus adaptive servoventilation therapy. Sleep. 2014;37(5):927–34.PubMedCentralPubMedGoogle Scholar
  133. 133.
    Javaheri S, Brown LK, Randerath WJ. Positive airway pressure therapy with adaptive servoventilation: part 1: operational algorithms. Chest. 2014;146(2):514–23.PubMedCrossRefGoogle Scholar
  134. 134.
    Javaheri S, Brown LK, Randerath WJ. Clinical applications of adaptive servoventilation devices: part 2. Chest. 2014;146(3):858–68.PubMedCrossRefGoogle Scholar
  135. 135.
    Teschler H, Dohring J, Wang YM, Berthon-Jones M. Adaptive pressure support servo-ventilation: a novel treatment for Cheyne-Stokes respiration in heart failure. Am J Respir Crit Care Med. 2001;164(4):614–9.PubMedCrossRefGoogle Scholar
  136. 136.
    Koyama T, Watanabe H, Tamura Y, Oguma Y, Kosaka T, Ito H. Adaptive servo-ventilation therapy improves cardiac sympathetic nerve activity in patients with heart failure. Eur J Heart Fail. 15 2013.Google Scholar
  137. 137.
    Koyama T, Watanabe H, Igarashi G, Terada S, Makabe S, Ito H. Short-term prognosis of adaptive servo-ventilation therapy in patients with heart failure. Circ J. 2011;75(3):710–2.PubMedCrossRefGoogle Scholar
  138. 138.
    Iwaya S, Yoshihisa A, Nodera M, et al. Suppressive effects of adaptive servo-ventilation on ventricular premature complexes with attenuation of sympathetic nervous activity in heart failure patients with sleep-disordered breathing. Heart Vessels. 2013;29(4):470–7.PubMedCrossRefGoogle Scholar
  139. 139.
    D'Elia E, Vanoli E, La Rovere MT, et al. Adaptive servo ventilation reduces central sleep apnea in chronic heart failure patients: beneficial effects on autonomic modulation of heart rate. J Cardiovasc Med (Hagerstown). 2013;14(4):296–300.CrossRefGoogle Scholar
  140. 140.
    Randerath WJ, Nothofer G, Priegnitz C, et al. Long-term auto-servoventilation or constant positive pressure in heart failure and coexisting central with obstructive sleep apnea. Chest. 2012;142(2):440–7.PubMedCrossRefGoogle Scholar
  141. 141.
    Javaheri S, Goetting MG, Khayat R, Wylie PE, Goodwin JL, Parthasarathy S. The performance of two automatic servo-ventilation devices in the treatment of central sleep apnea. Sleep. 2011;34(12):1693–8.PubMedCentralPubMedGoogle Scholar
  142. 142.
    Arzt M, Schroll S, Series F, et al. Auto-servo ventilation in heart failure with sleep apnea—a randomized controlled trial. Eur Respir J 2013; 42:1244–54.Google Scholar
  143. 143.
    Oldenburg O, Bitter T, Wellmann B, et al. Trilevel adaptive servoventilation for the treatment of central and mixed sleep apnea in chronic heart failure patients. Sleep Med. 2013;14(5):422–7.PubMedCrossRefGoogle Scholar
  144. 144.
    Szollosi I, Jones M, Morrell MJ, Helfet K, Coats AJ, Simonds AK. Effect of CO2 inhalation on central sleep apnea and arousals from sleep. Respir Internatl Rev Thorac Dis. 2004;71(5):493–8.Google Scholar
  145. 145.
    Khayat RN, Xie A, Patel AK, Kaminski A, Skatrud JB. Cardiorespiratory effects of added dead space in patients with heart failure and central sleep apnea. Chest. 2003;123(5):1551–60.PubMedCrossRefGoogle Scholar
  146. 146.
    Xie A, Teodorescu M, Pegelow DF, et al. Effects of stabilizing or increasing respiratory motor outputs on obstructive sleep apnea. J Appl Physiol. 2013;115(1):22–33.PubMedCentralPubMedCrossRefGoogle Scholar
  147. 147.
    Thomas RJ, Daly RW, Weiss JW. Low-concentration carbon dioxide is an effective adjunct to positive airway pressure in the treatment of refractory mixed central and obstructive sleep-disordered breathing. Sleep. 2005;28(1):69–77.PubMedGoogle Scholar
  148. 148.
    Sakakibara M, Sakata Y, Usui K, et al. Effectiveness of short-term treatment with nocturnal oxygen therapy for central sleep apnea in patients with congestive heart failure. J Cardiol. 2005;46(2):53–61.PubMedGoogle Scholar
  149. 149.
    Gold AR, Bleecker ER, Smith PL. A shift from central and mixed sleep apnea to obstructive sleep apnea resulting from low-flow oxygen. Am Rev Respir Dis. 1985;132(2):220–3.PubMedGoogle Scholar
  150. 150.
    Allam JS, Olson EJ, Gay PC, Morgenthaler TI. Efficacy of adaptive servoventilation in treatment of complex and central sleep apnea syndromes. Chest. 2007;132(6):1839–46.PubMedCrossRefGoogle Scholar
  151. 151.
    Chowdhuri S, Ghabsha A, Sinha P, Kadri M, Narula S, Badr MS. Treatment of central sleep apnea in U.S. veterans. J Clin Sleep Med JCSM Off Publ Am Acad Sleep Med. 2012;8(5):555–63.Google Scholar
  152. 152.
    Parrino L, Ferri R, Bruni O, Terzano MG. Cyclic alternating pattern (CAP): the marker of sleep instability. Sleep Med Rev. 2012;16(1):27–45.Google Scholar
  153. 153.
    Thomas RJ, Mietus JE, Peng CK, Goldberger AL. An electrocardiogram-based technique to assess cardiopulmonary coupling during sleep. Sleep. 2005;28(9):1151–61.PubMedGoogle Scholar
  154. 154.
    Eckert DJ, Owens RL, Kehlmann GB, 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 (Lond). 2011;120(12):505–14.CrossRefGoogle Scholar
  155. 155.
    Quadri S, Drake C, Hudgel DW. Improvement of idiopathic central sleep apnea with zolpidem. J Clin Sleep Med JCSM Off Publ Am Acad Sleep Med. 2009;5(2):122–9.Google Scholar
  156. 156.
    Bonnet MH, Dexter JR, Arand DL. The effect of triazolam on arousal and respiration in central sleep apnea patients. Sleep. 1990;13(1):31–41.PubMedGoogle Scholar
  157. 157.
    Guilleminault C, Crowe C, Quera-Salva MA, Miles L, Partinen M. Periodic leg movement, sleep fragmentation and central sleep apnoea in two cases: reduction with Clonazepam. Eur Respir J. 1988;1(8):762–5.PubMedGoogle Scholar
  158. 158.
    Nickol AH, Leverment J, Richards P, et al. Temazepam at high altitude reduces periodic breathing without impairing next-day performance: a randomized cross-over double-blind study. J Sleep Res. 2006;15(4):445–54.PubMedCrossRefGoogle Scholar
  159. 159.
    Eckert DJ, Younes MK. Arousal from sleep: implications for obstructive sleep apnea pathogenesis and treatment. J Appl Physiol. 2014;116(3):302–13.PubMedCrossRefGoogle Scholar
  160. 160.
    Michelson D, Snyder E, Paradis E, et al. Safety and efficacy of suvorexant during 1-year treatment of insomnia with subsequent abrupt treatment discontinuation: a phase 3 randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2014;13(5):461–71.PubMedCrossRefGoogle Scholar
  161. 161.
    Sun H, Kennedy WP, Wilbraham D, et al. Effects of suvorexant, an orexin receptor antagonist, on sleep parameters as measured by polysomnography in healthy men. Sleep. 2013;36(2):259–67.PubMedCentralPubMedGoogle Scholar
  162. 162.
    Kuwaki T, Li A, Nattie E. State-dependent central chemoreception: a role of orexin. Respir Physiol Neurobiol. 2010;173(3):223–29.PubMedCentralPubMedCrossRefGoogle Scholar
  163. 163.
    Nakamura A, Zhang W, Yanagisawa M, Fukuda Y, Kuwaki T. Vigilance state-dependent attenuation of hypercapnic chemoreflex and exaggerated sleep apnea in orexin knockout mice. J Appl Physiol. 2007;102(1):241–8.PubMedCrossRefGoogle Scholar
  164. 164.
    Wang D, Teichtahl H, Drummer O, et al. Central sleep apnea in stable methadone maintenance treatment patients. Chest. 2005;128(3):1348–56.PubMedCrossRefGoogle Scholar
  165. 165.
    Sharkey KM, Kurth ME, Anderson BJ, Corso RP, Millman RP, Stein MD. Obstructive sleep apnea is more common than central sleep apnea in methadone maintenance patients with subjective sleep complaints. Drug Alcohol Depend. 2010;108(1–2):77–83.PubMedCentralPubMedCrossRefGoogle Scholar
  166. 166.
    Charpentier A, Bisac S, Poirot I, Vignau J, Cottencin O. Sleep quality and apnea in stable methadone maintenance treatment. Subst Use Misuse. 2010;45(9):1431–4.PubMedCrossRefGoogle Scholar
  167. 167.
    Walker JM, Farney RJ, Rhondeau SM, et al. Chronic opioid use is a risk factor for the development of central sleep apnea and ataxic breathing. J Clin Sleep Med JCSM Off Publ Am Acad Sleep Med. 2007;3(5):455–61.Google Scholar
  168. 168.
    Davis MJ, Livingston M, Scharf SM. Reversal of central sleep apnea following discontinuation of opioids. J Clin Sleep Med JCSM Off Publ Am Acad Sleep Med. 2012;8(5):579–80.Google Scholar
  169. 169.
    Teichtahl H, Wang D, Cunnington D, et al. Ventilatory responses to hypoxia and hypercapnia in stable methadone maintenance treatment patients. Chest. 2005;128(3):1339–47.PubMedCrossRefGoogle Scholar
  170. 170.
    Javaheri S, Harris N, Howard J, Chung E. Adaptive servoventilation for treatment of opioid-associated central sleep apnea. J Clin Sleep Med JCSM Off Publ Am Acad Sleep Med. 2014;10(6):637–43.Google Scholar
  171. 171.
    Farney RJ, Walker JM, Boyle KM, Cloward TV, Shilling KC. Adaptive servoventilation (ASV) in patients with sleep disordered breathing associated with chronic opioid medications for non-malignant pain. J Clin Sleep Med JCSM Off Publ Am Acad Sleep Med. 2008;4(4):311–9.Google Scholar
  172. 172.
    Ren J, Ding X, Funk GD, Greer JJ. Ampakine CX717 protects against fentanyl-induced respiratory depression and lethal apnea in rats. Anesthesiology. 2009;110(6):1364–70.PubMedCrossRefGoogle Scholar
  173. 173.
    Oertel BG, Felden L, Tran PV, et al. Selective antagonism of opioid-induced ventilatory depression by an ampakine molecule in humans without loss of opioid analgesia. Clin Pharmacol Ther. 2010;87(2):204–11.PubMedCrossRefGoogle Scholar
  174. 174.
    Shore ET, Millman RP. Central sleep apnea and acetazolamide therapy. Arch Intern Med. 1983;143(6):1278, 1280.PubMedCrossRefGoogle Scholar
  175. 175.
    Inoue Y, Takata K, Sakamoto I, Hazama H, Kawahara R. Clinical efficacy and indication of acetazolamide treatment on sleep apnea syndrome. Psychiatr Clin Neurosci.1999;53(2):321–2.CrossRefGoogle Scholar
  176. 176.
    Edwards BA, Connolly JG, Campana LM, et al. Acetazolamide attenuates the ventilatory response to arousal in patients with obstructive sleep apnea. Sleep. 2013;36(2):281–5.PubMedCentralPubMedGoogle Scholar
  177. 177.
    Javaheri S. Acetazolamide improves central sleep apnea in heart failure: a double-blind, prospective study. Am J Respir Crit Care Med. 2006;173(2):234–7.PubMedCrossRefGoogle Scholar
  178. 178.
    Latshang TD, Nussbaumer-Ochsner Y, Henn RM, et al. Effect of acetazolamide and autoCPAP therapy on breathing disturbances among patients with obstructive sleep apnea syndrome who travel to altitude: a randomized controlled trial. JAMA. 2012;308(22):2390–8.PubMedCrossRefGoogle Scholar
  179. 179.
    Glidewell RN, Orr WC, Imes N. Acetazolamide as an adjunct to CPAP treatment: a case of complex sleep apnea in a patient on long-acting opioid therapy. J Clin Sleep Med JCSM Off Publ Am Acad Sleep Med. 2009;5(1):63–4.Google Scholar
  180. 180.
    De Simone G, Fiore A D, Menchise V, et al. Carbonic anhydrase inhibitors. Zonisamide is an effective inhibitor of the cytosolic isozyme II and mitochondrial isozyme V: solution and X-ray crystallographic studies. Bioorg Med Chem Lett. 2005;15(9):2315–20.PubMedCrossRefGoogle Scholar
  181. 181.
    Westwood AJ, Vendrame M, Montouris G, Auerbach SH. Pearls & Oy-sters: treatment of central sleep apnea with topiramate. Neurology. 2012;78(16):e97–e9.PubMedCrossRefGoogle Scholar
  182. 182.
    Sankri-Tarbichi AG, Grullon K, Badr MS. Effects of clonidine on breathing during sleep and susceptibility to central apnoea. Respir Physiol Neurobiol. 2013;185(2):356–61.PubMedCrossRefGoogle Scholar
  183. 183.
    Chowdhuri S, Bascom A, Mohan D, Diamond MP, Badr MS. Testosterone conversion blockade increases breathing stability in healthy men during NREM sleep. Sleep. 2013;36(12):1793–8.PubMedCentralPubMedGoogle Scholar
  184. 184.
    Wang S, Moffitt JR, Dempsey GT, Xie XS, Zhuang X. Characterization and development of photoactivatable fluorescent proteins for single-molecule-based superresolution imaging. Proc Natl Acad Sci U S A. 2014;111(23):8452–7.PubMedCentralPubMedCrossRefGoogle Scholar
  185. 185.
    Fewell JE, Kondo CS, Dascalu V, Filyk SC. Influence of carotid-denervation on the arousal and cardiopulmonary responses to alveolar hypercapnia in lambs. J Develop Physiol. 1989;12(4):193–9.Google Scholar
  186. 186.
    Fewell JE, Taylor BJ, Kondo CS, Dascalu V, Filyk SC. Influence of carotid denervation on the arousal and cardiopulmonary responses to upper airway obstruction in lambs. Pediatr Res. Oct 1990;28(4):374–8.PubMedCrossRefGoogle Scholar
  187. 187.
    Fewell JE, Kondo CS, Dascalu V, Filyk SC. Influence of carotid denervation on the arousal and cardiopulmonary response to rapidly developing hypoxemia in lambs. Pediatr Res. 1989;25(5):473–7.PubMedCrossRefGoogle Scholar
  188. 188.
    Marcus NJ, Del Rio R, Schultz EP, Xia XH, Schultz HD. Carotid body denervation improves autonomic and cardiac function and attenuates disordered breathing in congestive heart failure. J Physiol. 2014;592(Pt 2):391–408.PubMedCentralPubMedCrossRefGoogle Scholar
  189. 189.
    Del Rio R, Marcus NJ, Schultz HD. Inhibition of hydrogen sulfide restores normal breathing stability and improves autonomic control during experimental heart failure. J Appl Physiol (Bethesda, Md.: 1985). 2013;114(9):1141–50.PubMedCentralPubMedCrossRefGoogle Scholar
  190. 190.
    Niewinski P, Janczak D, Rucinski A, et al. Carotid body removal for treatment of chronic systolic heart failure. Internatl J Cardiol. 2013;168(3):2506–9.CrossRefGoogle Scholar
  191. 191.
    Whipp BJ, Ward SA. Physiologic changes following bilateral carotid-body resection in patients with chronic obstructive pulmonary disease. Chest. 1992;101(3):656–61.PubMedCrossRefGoogle Scholar
  192. 192.
    Sullivan CE. Bilateral carotid body resection in asthma: vulnerability to hypoxic death in sleep. Chest. 1980;78(2):354.PubMedCrossRefGoogle Scholar
  193. 193.
    Zikk D, Shanon E, Rapoport Y, Samuel J. Sleep apnea following bilateral excision of carotid body tumors. Laryngoscope. 1983;93(11 Pt 1):1470–2.PubMedGoogle Scholar
  194. 194.
    Parisi RA, Croce SA, Edelman NH, Santiago TV. Obstructive sleep apnea following bilateral carotid body resection. Chest. 1987;91(6):922–4.PubMedCrossRefGoogle Scholar
  195. 195.
    Patel AV, Hwang D, Masdeu MJ, Chen GM, Rapoport DM, Ayappa I. 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 JCSM Off Publ Am Acad Sleep Med. 2011;7(1):13–22.Google Scholar
  196. 196.
    Avidan AY. The development of central sleep apnea with an oral appliance. Sleep Med. 2006;7(1):85–6.PubMedCrossRefGoogle Scholar
  197. 197.
    Denbar MA. A case study involving the combination treatment of an oral appliance and auto-titrating CPAP unit. Sleep Breath Schlaf Atm. 2002;6(3):125–8.CrossRefGoogle Scholar
  198. 198.
    El-Solh AA, Moitheennazima B, Akinnusi ME, Churder PM, Lafornara AM. Combined oral appliance and positive airway pressure therapy for obstructive sleep apnea: a pilot study. Sleep Breath Schlaf Atm. 2011;15(2):203–8.CrossRefGoogle Scholar
  199. 199.
    Szollosi I, Roebuck T, Thompson B, Naughton MT. Lateral sleeping position reduces severity of central sleep apnea/Cheyne-Stokes respiration. Sleep. 2006;29(8):1045–51.PubMedGoogle Scholar
  200. 200.
    Joho S, Oda Y, Hirai T, Inoue H. Impact of sleeping position on central sleep apnea/Cheyne-Stokes respiration in patients with heart failure. Sleep Med. 2010;11(2):143–8.PubMedCrossRefGoogle Scholar
  201. 201.
    White LH, Bradley TD. Role of nocturnal rostral fluid shift in the pathogenesis of obstructive and central sleep apnoea. J Physiol. 2013;591(Pt 5):1179–93.PubMedCentralPubMedCrossRefGoogle Scholar
  202. 202.
    Redolfi S, Yumino D, Ruttanaumpawan P, et al. Relationship between overnight rostral fluid shift and Obstructive Sleep Apnea in nonobese men. Am J Respir Crit Care Med. 2009;179(3):241–6.PubMedCrossRefGoogle Scholar
  203. 203.
    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;5(4):467–74.PubMedCrossRefGoogle Scholar
  204. 204.
    Friedman O, Bradley TD, Chan CT, Parkes R, Logan AG. Relationship between overnight rostral fluid shift and obstructive sleep apnea in drug-resistant hypertension. Hypertension. 2010;56(6):1077–82.PubMedCrossRefGoogle Scholar
  205. 205.
    Elias RM, Bradley TD, Kasai T, Motwani SS, Chan CT. Rostral overnight fluid shift in end-stage renal disease: relationship with obstructive sleep apnea. Nephrol Dial Transplant Off Publ Eur Dial Transplant Assoc Eur Renal Assoc. 2012;27(4):1569–73.Google Scholar
  206. 206.
    Ponikowski P, Javaheri S, Michalkiewicz D, et al. Transvenous phrenic nerve stimulation for the treatment of central sleep apnoea in heart failure. Eur Heart J. 2012;33(7):889–94.PubMedCentralPubMedCrossRefGoogle Scholar
  207. 207.
    Schwab RJ, Badr SM, Epstein LJ, et al. An official American Thoracic Society statement: continuous positive airway pressure adherence tracking systems. The optimal monitoring strategies and outcome measures in adults. Am J Respir Crit Care Med. 2013;188(5):613–20.PubMedCrossRefGoogle Scholar
  208. 208.
    Ekkernkamp E, Storre JH, Windisch W, Dreher M. Impact of Intelligent Volume-Assured Pressure Support on Sleep Quality in Stable Hypercapnic Chronic Obstructive Pulmonary Disease Patients: A Randomized, Crossover Study. Respir Internatl Rev Thorac Dis. 22 2014.Google Scholar
  209. 209.
    Storre JH, Seuthe B, Fiechter R, et al. Average volume-assured pressure support in obesity hypoventilation: A randomized crossover trial. Chest. 2006;130(3):815–21.PubMedCrossRefGoogle Scholar
  210. 210.
    Oscroft NS, Chadwick R, Davies MG, Quinnell TG, Smith IE. Volume assured versus pressure preset non-invasive ventilation for compensated ventilatory failure in COPD. Respir Med. 2014;108(10):1508–15.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Department of Medicine, Division of Pulmonary, Critical Care & SleepBeth Israel Deaconess Medical CenterBostonUSA

Personalised recommendations