Pathophysiology & genetics of obstructive sleep apnoea

Indian Journal of Medical Research

Volumn 131, Issue 2, 2010, Pages 176-187

  Campana, Lisa ^a   Eckert, Danny J ^a   Patel, Sanjay R ^a   Malhotra, Atul ^a,b  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b UNIVERSITY HOSPITALS OF CLEVELAND   (United States)

Author keywords

Arousal; Genioglossus; Lung; Obstructive sleep apnoea; Upper airway; Ventilatory control stability

Indexed keywords

ACETAZOLAMIDE; APOLIPOPROTEIN E4; HYPNOTIC AGENT; OXYGEN;

AGING; AROUSAL; CARDIOVASCULAR DISEASE; FUNCTIONAL RESIDUAL CAPACITY; GENETIC LINKAGE; GENETIC PREDISPOSITION; GENETIC RISK; GENETIC TRAIT; HUMAN; LUNG COLLAPSE; NERVE STIMULATION; NEUROLOGIC DISEASE; NONREM SLEEP; OBESITY; PATHOPHYSIOLOGY; POSITIVE END EXPIRATORY PRESSURE; PREVALENCE; REM SLEEP; REVIEW; RISK ASSESSMENT; SEX DIFFERENCE; SLEEP APNEA SYNDROME; BIOLOGICAL MODEL; BIOMECHANICS; BREATHING; GENETICS; LUNG; PATHOLOGY; RESPIRATORY SYSTEM; RISK FACTOR; SLEEP; SLEEP DISORDERED BREATHING; TIME;

BIOMECHANICS; CARDIOVASCULAR DISEASES; HUMANS; LUNG; MODELS, BIOLOGICAL; MODELS, GENETIC; RESPIRATION; RESPIRATORY SYSTEM; RISK FACTORS; SLEEP; SLEEP APNEA, OBSTRUCTIVE; TIME FACTORS; BIOMECHANICAL PHENOMENA;

EID: 77649313120     PISSN: 09715916     EISSN: 09715916     Source Type: Journal    
DOI: None     Document Type: Review

References (160)

1. Malhotra A, White DP. Obstructive sleep apnea. Lancet 2002; 360: 237-45.
2. Badr MS. Pathogenesis of obstructive sleep apnea. Prog Cardiovasc Dis 1999; 41: 323-30.
3. Eckert DJ, Malhotra A. Pathophysiology of adult obstructive sleep apnea. Proc Am Thorac Soc 2008; 5: 144-53.
4. Pack AI. Obstructive sleep apnea. Adv Intern Med 1994; 39 517-67.
5. Eckert DJ, Jordan AS, Merchia P, Malhotra A. Central apnea: Pathophysiology and treatment. Chest 2007; 131: 595-607.
6. Caples SM, Gami AS, Somers VK. Obstructive sleep apnea. Ann Intern Med 2005; 142: 187-97.
7. Caples SM, Garcia-Touchard A, Somers VK. Sleep-disordered breathing and cardiovascular risk. Sleep 2007; 30: 291-303.
8. Rahangdale S, Campana L, Malhotra A. Not so good vibrations. Sleep 2008; 31: 1204-5.
9. Younes M. Role of arousals in the pathogenesis of obstructive sleep apnea. Am J Respir Crit Care Med 2004; 169: 623-33.
10. Douglas NJ, Martin SE. Arousals and the sleep apnea/ hypopnea syndrome. Sleep 1996; 19 (10 Suppl): S196-7.
11. Phillipson EA, Bowes G, Sullivan CE, Woolf GM. The influence of sleep fragmentation on arousal and ventilatory responses to respiratory stimuli. Sleep 1980; 3: 281-8.
12. Malhotra A, Jordan AS. Did fat boy Joe need hormone replacement? Sleep 2006; 29: 16-8.
13. Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 1993; 32: 1230-5.
14. Udwadia ZF, Doshi AV, Lonkar SG, Singh CI. Prevalence of sleep-disordered breathing and sleep apnea in middle-aged urban Indian men. Am J Respir Crit Care Med 2004; 169: 168-73.
15. McTigue K, Larson JC, Valoski A, Burke G, Kotchen J, Lewis CE, et al. Mortality and cardiac and vascular outcomes in extremely obese women. JAMA 2006; 296: 79-86.
16. Hosselet JJ, Norman RG, Ayappa I, Rapoport DM. Detection of flow limitation with a nasal cannula/pressure transducer. Am J Respir Crit Care Med 1998; 157: 1461-7.
17. Barbe F, Mayoralas LR, Duran J, Masa JF. Treatment with continuous positive airway pressure is not effective in patients with sleep apnea but no daytime sleepiness. A randomized, controlled trial. Ann Intern Med 2001; 134: 1065-7.
18. Davies RJ, Ali NJ, Stradling JR. Neck circumference and other clinical features in the diagnosis of the obstructive sleep apnea syndrome. Thorax 1992; 47: 101-5.
19. Jordan A, McEvoy D. Gender differences in sleep apnea: epidemiology, clinical presentation and pathogenic mechanisms. Sleep Med Rev 2003; 7: 377-89.
20. Young T. Menopause, hormone replacement therapy, and sleep-disordered breathing: are we ready for the heat. Am J Respir Crit Care Med 2001; 163: 597-8.
21. Peppard PE, Szklo-Coxe M, Hla KM, Young T. Longitudinal association of sleep-related breathing disorder and depression. Arch Intern Med 2006; 166: 1709-15.
22. Johns MW. Daytime sleepiness, snoring, and obstructive sleep apnea. The Epworth Sleepiness Scale. Chest 1993; 103: 30-6.
23. Jenkinson C, Davies RJ, Mullins R, Stradling JR. Comparison of therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnea: a randomized prospective parallel trial. Lancet 1999; 353: 2100-5.
24. Teran-Santos J, Jimenez-Gomez A, Cordero-Guevara J. The association between sleep apnea and the risk of traffic accidents. Cooperative Group Burgos-Santander. N Engl JMed 1999; 340: 847-51.
25. Jenkinson C, Davies RJ, Mullins R, Stradling JR. Long-term benefits in self-reported health status of nasal continuous positive airway pressure therapy for obstructive sleep apnea. QJM 2001; 94: 95-9.
26. Wright J, Johns R, Watt I, Melville A, Sheldon T. Health effects of obstructive sleep apnoea and the effectiveness of contnous positive airways pressure: a systematic review of the research evidence. BMJ 1997; 314: 851-60.
27. Marshall NS, Wong KK, Liu PY, Cullen SR, Knuiman MW, Grunstein RR. Sleep apnea as an independent risk factor for all-cause mortality: the Busselton Health Study. Sleep 2008; 31: 1079-85.
28. Young T, Finn L, Peppard PE, Szklo-Coxe M, Austin D, Nieto FJ, et al. Sleep disordered breathing and mortality: eighteen-year follow-up of the Wisconsin sleep cohort. Sleep 2008; 31: 1071-8.
29. Shahar E, Whitney CW, Redline S, Lee ET, Newman AB, Javier Nieto F, et al. Sleep-disordered breathing and cardiovascular disease. Cross-sectional results of the sleep heart health study. Am J Respir Crit Care Med 2001; 163: 19-25.
30. Arzt M, Young T, Finn L, Skatrud JB, Bradley TD. Association of sleep-disordered breathing and the occurrence of stroke. Am J Respir Crit Care Med 2005; 172: 1447-51.
31. Yaggi HK, Concato J, Kernan WN, Lichtman JH, Brass LM, Mohsenin V. Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med 2005; 353: 2034-41.
32. Brooks D, Horner RL, Kozar LF, Render-Teixeira CL, Phillipson EA. Obstructive sleep apnea as a cause of systemic hypertension. Evidence from a canine model. J Clin Invest 1997; 99: 106-9.
33. Nieto F, Young TB, Lind BK, Shahar E, Samet JM, Redline S, et al. Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study. JAMA 2000; 283: 1829-36.
34. Lavie P, Here P, Hoffstein V. Obstructive sleep apnea syndrome as a risk factor for hypertension. Br Med J 2000; 320: 479-82.
35. Pepperell JC, Ramdassingh-Dow S, Crosthwaite N, Mullins R, Jenkinson C, Stradling JR, et al. Ambulatory blood pressure after therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnea: a randomized parallel trial. Lancet 2002; 359: 204-10.
36. Becker HF, Jerrentrup A, Ploch T, Grote L, Penzel T, Sullivan CE, et al. Effect of nasal continuous positive airway pressure treatment on blood pressure in patients with obstructive sleep apnea. Circulation 2003; 107: 68-73.
37. Logan AG, Tkacova R, Perlikowski SM, Leung RS, Tisler A, Floras JS, et al. Refractory hypertension and sleep apnea: effect of CPAP on blood pressure and baroreflex. Eur Respir J 2003; 21: 241-7.
38. Schwab RJ. Upper airway imaging. Clin Chest Med 1998; 19: 33-54.
39. Schwab RJ, Pasirstein M, Pierson R, Mackley A, Hachadoorian R, Arens R, et al. Identification of upper airway anatomic risk factors for obstructive sleep apnea with volumetric magnetic resonance imaging. Am J Respir Crit Care Med 2003; 168: 522-30.
40. Malhotra A, Trinder J, Fogel R, Stanchina M, Patel SR, Schory K, et al. Postural effects on pharyngeal protective reflex mechanisms. Sleep 2004; 27: 1105-12.
41. Malhotra A, Pillar G, Fogel RB, Beauregard J, Edwards JK, Slamowitz DI, et al. Genioglossal but not palatal muscle activity relates closely to pharyngeal pressure. Am J Respir Crit Care Med 2000; 162: 1058-62.
42. Malhotra A, Pillar G, Fogel RB, Edwards JK, Ayas N, Akahoshi T, et al. Pharyngeal pressure and flow effects on genioglossus activation in normal subjects. Am J Respir Crit Care Med 2002; 165: 71-7.
43. Malhotra A, Pillar G, Fogel R, Beauregard J, Edwards J, White DP. Upper-airway collapsibility: measurements and sleep effects. Chest 2001; 120: 156-61.
44. Berry RB, Gleeson K. Respiratory arousal from sleep: mechanisms and significance. Sleep 1997; 20: 654-75.
45. Berry RB, Light RW. Effect of hyperoxia on the arousal response to airway occlusion during sleep in normal subjects. Am Rev Respir Dis 1992; 146: 330-4.
46. Khoo M. Determinants of ventilatory instability and variability. Respir Physiol 2000; 122: 167-82.
47. 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: 1181-90.
48. Cherniack NS. Respiratory dysrhythmias during sleep. N Engl J Med 1981; 305: 325-30.
49. Begle RL, Badr S, Skatrud JB, Dempsey JA. Effect of lung inflation on pulmonary resistance during NREM sleep. Am Rev Respir Dis 1990; 141: 854-60.
50. Van de Graaff WB. Thoracic influence on upper airway patency. J Appl Physiol 1988; 65: 2124-31.
51. Van de Graaff WB. Thoracic traction on the trachea: mechanisms and magnitude. J Appl Physiol 1991; 70: 1328-63.
52. Stanchina ML, Malhotra A, Fogel RB, Trinder J, Edwards JK, Schory K, et al. The influence of lung volume on pharyngeal mechanics, collapsibility, and genioglossus muscle activation during sleep. Sleep 2003; 26: 851-6.
53. White DP. Pathogenesis of obstructive and central sleep apnea. Am J Respir Crit Care Med 2005; 172: 1363-70.
54. Malhotra A, Huang Y, Fogel RB, Pillar G, Edwards JK, Kikinis R, et al. The male predisposition to pharyngeal collapse: importance of airway length. Am J Respir Crit Care Med 2002; 166: 1388-95.
55. Haponik E, Smith P, Bohlman M, Allan R, Goldman S, Bleecker E. Computerized tomography in obstructive sleep apnea: correlation of airway size with physiology during sleep and wakefulness. Am Rev Respir Dis 1983; 127: 221-6.
56. 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; 127: 487-92.
57. Horner RL, Mohiaddin RH, Lowell DG, Shea SA, Burman ED, Longmore DB, et al. Sites and sizes of fat deposits around the pharynx in obese patients with obstructive sleep apnea and weight matched controls. Eur Respir J 1989; 2: 613-22.
58. Ciscar MA, Juan G, Martínez V, Ramón M, Lloret T, Mínguez J, et al. Magnetic resonance imaging of the pharynx in OSA patients and healthy subjects. Eur Respir J 2001; 17: 79-86.
59. Mezzanotte WS, Tangel DJ, White DP. Waking genioglossal EMG in sleep apnea patients versus normal controls (a neuromuscular compensatory mechanisms). J Clin Invest 1992; 89: 1571-9.
60. Schwartz AR, Smith PL, Wise RA, Gold AR, Permutt S. Induction of upper airway occlusion in sleeping individuals with subatmospheric nasal pressure. J Appl Physiol 1988; 64: 535-42.
61. Patil SP, Schneider H, Marx JJ, Gladmon E, Schwartz AR, Smith PL. Neuromechanical control of upper airway patency during sleep. J Appl Physiol 2007; 102: 547-56.
62. Patil SP, Punjabi NM, Schneider H, O'Donnell CP, Smith PL, Schwartz AR. A simplified method for measuring critical pressures during sleep in the clinical setting. Am J Respir Crit Care Med 2004; 170: 86-93.
63. Isono S, Remmers JE, Tanaka A, Sho Y, Sato J, Nishino T. Anatomy of pharynx in patients with obstructive sleep apnea and in normal subjects. J Appl Physiol 1997; 82: 1319-26.
64. Eastwood P, Szollosi I, Platt P, Hillman D. Comparison of upper airway collapse during general anaesthesia and sleep. Lancet 2002; 359: 1207-9.
65. Malhotra A, Fogel RB, Edwards JK, Shea SA, White DP. Local mechanisms drive genioglossus activation in obstructive sleep apnea. Am J Respir Crit Care Med 2000; 161: 1746-9.
66. Worsnop C, Kay A, Pierce R, Kim Y, Trinder J. Activity of respiratory pump and upper airway muscles during sleep onset. J Appl Physiol 1998; 85: 908-20.
67. Skatrud JB, Henke KG, Dempsey J. A sleep-induced apneic threshold. Prog Clin Biol Res 1990; 345: 191-9.
68. Basner RC, Ringler J, Schwartzstein RM, Weinberger SE, Weiss JW. Phasic electromyographic activity of the genioglossus increases in normals during slow-wave sleep. Respir Physiol 1991; 83: 189-200.
69. Pillar G, Malhotra A, Fogel RB, Beauregard J, Slamowitz DI, Shea SA, et al. Upper airway muscle responsiveness to rising PCO2 during NREM sleep. J Appl Physiol 2000; 89:1275-82.
70. Horner RL. The neuropharmacology of upper airway motor control in the awake and asleep states: implications for obstructive sleep apnea. Respir Res 2001; 2: 286-94.
71. Horner RL. Motor control of the pharyngeal musculature and implications for the pathogenesis of obstructive sleep apnea. Sleep 1996; 19: 827-53.
72. Horner RL, Bradley TD. Update in sleep and control of ventilation 2006. Am J Respir Crit Care Med 2007; 175: 426-31.
73. Kubin L, Tojima H, Reignier C, Pack AI, Davies RO. Interaction of serotonergic excitatory drive to hypoglossal motoneurons with carbachol-induced, REM sleep-like atonia. Sleep 1996; 19: 187-95.
74. Kubin L, Kimura H, Tojima H, Davies RO, Pack AI. Suppression of hypoglossal motoneurons during the carbachol-induced atonia of REM sleep is not caused by fast synaptic inhibition. Brain Res 1993; 611: 300-12.
75. Kubin L, Tojima H, Davies RO, Pack AI. Serotonergic excitatory drive to hypoglossal motoneuron in the decerebrate cat. Neurosci Lett 1992; 139: 243-8.
76. Berger AJ, Bayliss DA, Viana F. Modulation of neonatal rat hypoglossal motoneuron excitability by serotonin. Neurosci Lett 1992; 143: 164-8.
77. Guyenet PG, Stornetta RL, Bayliss DA, Mulkey DK. Retrotrapezoid nucleus: a litmus test for the identification of central chemoreceptors. Exp Physiol 2005; 90: 247-53.
78. Smith JC, Ellenberger HH, Ballanyi K, Richter DW, Feldman JL. Pre-Botzinger complex: a brainstem region that may generate respiratory rhythm in mammals. Science 1991; 254: 726-9.
79. Mathew OP. Upper airway negative pressure effects on respiratory activity of upper airway muscles. J Appl Physiol 1984; 56: 500-5.
80. Mathew OP. Maintenance of upper airway patency. J Pediatr 1985; 106: 863-9.
81. Mathew OP, Abu-Osba YK, Thach BT. Genioglossus muscle response to upper airway pressure changes: afferent pathways. J Appl Physiol 1982; 52: 445-50.
82. Horner RL, Innes, JA, Murphy, K, Guz A. Evidence for reflex upper airway dilator muscle activation by sudden negative airway pressure in man. J Physiol 1991; 436: 15-29.
83. Wheatley J, Mezzanotte W, Tangel D, White D. Influence of sleep on genioglossus muscle activation by negative pressure in normal men. Am Rev Respir Dis 1993; 148: 597-605.
84. Wheatley J, Tangel D, Mezzanotte W, White D. Influence of sleep on response to negative airway pressure of tensor palatini muscle and retropalatal airway. J Appl Physiol 1993; 75: 2117-24.
85. Ryan S, Nolan P. Superior laryngeal and hypoglossal afferents tonically influence upper airway motor excitability in anesthetized rats. J Appl Physiol 2005; 99: 1019-28.
86. Doherty LS, Nolan P, McNicholas WT. Effects of topical anesthesia on upper airway resistance during wake-sleep transitions. J Appl Physiol 2005; 99: 549-55.
87. Ryan S, McNicholas WT, O'Regan RG, Nolan P. Upper airway muscle paralysis reduces reflex upper airway motor response to negative transmural pressure in rat. J Appl Physiol 2003; 94: 1307-16.
88. Malhotra A, Pillar G, Fogel R, Beauregard J, White D. Genioglossal but not palatal muscle activity relates closely to pharyngeal pressure. Am J Respir Crit Care Med 2000; 162: 1058-62.
89. Chamberlin NL, Eikermann M, Fassbender P, White DP, Malhotra A. Genioglossus premotoneurons and the negative pressure reflex in rats. J Physiol 2007; 579: 515-26.
90. Shea S, Edwards J, White D. Effect of wake-sleep transitions and rapid eye movement sleep on pharyngeal muscle response to negative pressure in humans. J Physiol 1999; 520: 897-908.
91. Stanchina ML, Malhotra A, Fogel RB, Ayas N, Edwards JK, Schory K, et al. Genioglossus muscle responsiveness to chemical and mechanical stimuli during non-rapid eye movement sleep. Am J Respir Crit Care Med 2002; 165: 945-9.
92. Jordan AS, Wellman A, Heinzer RC, Lo YL, 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.
93. 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.
94. Younes M. Contributions of upper airway mechanics and control mechanisms to severity of obstructive apnea. Am J Respir Crit Care Med 2003; 168: 645-58.
95. Younes M. Role of respiratory control mechanisms in the pathogenesis of obstructive sleep disorders. J Appl Physiol 2008; 105: 1389-405.
96. Gleeson K, Zwillich CW, White DP. The influence of increasing ventilatory effort on arousal from sleep. Am Rev Respir Dis 1990; 142: 295-300.
97. Horner RL, Innes JA, Holden HB, Guz A. Afferent pathway(s) for pharyngeal dilator reflex to negative pressure in man: a study using upper airway anaesthesia. J Physiol 1991; 436:31-44.
98. Berry RB, McNellis MI, Kouchi K, Light RW. Upper airway anesthesia reduces phasic genioglossus activity during sleep apnea. Am J Respir Crit Care Med 1997; 156: 127-32.
99. Eckert D, Jordan AS, Wellman A, Smith S, Stevenson K, Malhotra A, et al. The respiratory arousal threshold in obstructive sleep apnea. Am J Respir Crit Care Med 2008; 177: A594.
100. Saboisky JP, Butler JE, Fogel RB, Taylor JL, Trinder JA, White DP, et al. Tonic and phasic respiratory drives to human genioglossus motoneurons during breathing. J Neurophysiol 2006; 95: 2213-21.
101. Saboisky JP, Butler JE, McKenzie DK, Gorman RB, Trinder JA, White DP, et al. Neural drive to human genioglossus in obstructive sleep apnea. J Physiol 2007; 585: 135-46.
102. Wilkinson V, Malhotra A, Nicholas CL, Worsnop C, Jordan AS, Butler JE, et al. Discharge patterns of human genioglossus motor units during sleep onset. Sleep 2008; 31: 525-33.
103. Bailey EF, Rice AD, Fuglevand AJ. Firing patterns of human genioglossus motor units during voluntary tongue movement. J Neurophysiol 2007; 97: 933-6.
104. Phillipson EA, Sullivan CE. Arousal: the forgotten response to respiratory stimuli. Am Rev Respir Dis 1978; 118: 807-9.
105. Younes M, Park E, Horner RL. Pentobarbital sedation increases genioglossus respiratory activity in sleeping rats. Sleep 2007; 30: 478-88.
106. Heinzer RC, White DP, Jordan AS, Lo YL, Dover L, Stevenson K, et al. Trazodone increases arousal threshold in obstructive sleep apnea. Eur Respir J 2008; 31: 1308-12.
107. Berry RB, Kouchi KG, Der DE, Dickel MJ, Light RW. Sleep apnea impairs the arousal response to airway occlusion. Chest 1996; 109: 1490-6.
108. Haba-Rubio J, Sforza E, Weiss T, Schroder C, Krieger J. Effect of CPAP treatment on inspiratory arousal threshold during NREM sleep in OSAS. Sleep Breath 2005; 9: 12-9.
109. 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: 1512-9.
110. Rowley JA, Zhou XS, Diamond MP, Badr MS. The determinants of the apnea threshold during NREM sleep in normal subjects. Sleep 2006; 29: 95-103.
111. Dempsey J. Crossing the apnoeic threshold: causes and consequences. Exp Physiol 2004; 90: 13-24.
112. Dempsey J, Skatrud J, Smith C. Powerful stabilizing effects of CO2 during CPAP treatment. Sleep 2005; 28: 12-3.
113. Khoo MC. Using loop gain to assess ventilatory control in obstructive sleep apnea. Am J Respir Crit Care Med 2001; 163: 1044-5.
114. Khoo M. Theoretical models of periodic breathing. New York: Marcel Dekker; 2000.
115. Khoo MC, Kronauer RE, Strohl KP, Slutsky AS. Factors inducing periodic breathing in humans: a general model. J Appl Physiol 1982; 53: 644-59.
116. Younes M. Proportional assist ventilation. In: Mancebo J, Net A, Brochard L, editors. Update in intensive care and emergency medicine. New York: Springer; 2002. p. 39-73.
117. 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.
118. Wellman A, Malhotra A, Fogel RB, Edwards JK, Schory K, White DP. Respiratory system loop gain in normal men and women measured with proportional-assist ventilation. J Appl Physiol 2003; 94: 205-12.
119. Wellman A, Malhotra A, Jordan AS, Schory K, Gautam S, White DP. Chemical control stability in the elderly. J Physiol 2007; 581: 291-8.
120. 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.
121. Dempsey JA. CO2 response: stimulus definition and limitations. Chest 1976; 70 (1 Suppl): 114-8.
122. Stanchina ML, Ellison K, Malhotra A, Anderson M, Kirk M, Benser ME, et al. The impact of cardiac resynchronization therapy on obstructive sleep apnea in heart failure patients: a pilot study. Chest 2007; 132: 433-9.
123. Sinha AM, Skobel EC, Breithardt OA, Norra C, Markus KU, Breuer C, et al. Cardiac resynchronization therapy improves central sleep apnea and Cheyne-Stokes respiration in patients with chronic heart failure. J Am Coll Cardiol 2004; 44: 68-71.
124. Meza S, Giannouli E, Younes M. Control of breathing during sleep assessed by proportional assist ventilation. J Appl Physiol 1998; 84: 3-12.
125. Younes M. Proportional assist ventilation, a new approach to ventilatory support. Theory. Am Rev Respir Dis 1992; 145: 114-20.
126. Jordan AS, McEvoy RD, Edwards JK, Schory K, Yang CK, Catcheside PG, et al. The influence of gender and upper airway resistance on the ventilatory response to arousal in obstructive sleep apnea in humans. J Physiol 2004; 558: 993-1004.
127. Jordan AS, Wellman A, Edwards JK, Schory K, Dover L, MacDonald M, et al. Respiratory control stability and upper airway collapsibility in men and women with obstructive sleep apnea. J Appl Physiol 2005; 99: 2020-7.
128. Hoffstein V, Fredberg JJ. The acoustic reflection technique for non-invasive assessment of upper airway area. Eur Respir J 1991; 4: 602-11.
129. Hoffstein V, Zamel N, Phillipson EA. Lung volume dependence of pharyngeal cross-sectional area in patients with obstructive sleep apnea. Am Rev Respir Dis 1984; 130:175-8.
130. Heinzer R, White DP, Malhotra A, Lo YL, Dover L, Stevenson KE, et al. Effect of expiratory positive airway pressure on sleep disordered breathing. Sleep 2008; 31: 429-32.
131. Heinzer RC, Stanchina ML, Malhotra A, Fogel RB, Patel SR, Jordan AS, et al. Lung volume and continuous positive airway pressure requirements in obstructive sleep apnea. Am J Respir Crit Care Med 2005; 172: 114-7.
132. Heinzer RC, Stanchina ML, Malhotra A, Jordan AS, Patel SR, Lo YL, et al. Effect of increased lung volume on sleep disordered breathing in patients with sleep apnea. Thorax 2006; 61: 435-9.
133. Strohl KP, Saunders NA, Feldman NT, Hallett M. Obstructive sleep apnea in family members. N Engl J Med 1978; 299: 969-73.
134. Pillar G, Lavie P. Assessment of the role of inheritance in sleep apnea syndrome. Am J Respir Crit Care Med 1995; 151: 688-91.
135. Mathur R, Douglas NJ. Family studies in patients with the sleep apnea-hypopnea syndrome. Ann Intern Med 1995; 122: 174-8.
136. Redline S, Tishler PV, Tosteson TD, Williamson J, Kump K, Browner I, et al. The familial aggregation of obstructive sleep apnea. Am J Respir Crit Care Med 1995; 151: 682-7.
137. Palmer LJ, Buxbaum SG, Larkin E, Patel SR, Elston RC, Tishler PV, et al. A whole-genome scan for obstructive sleep apnea and obesity. Am J Hum Genet 2003; 72: 340-50.
138. Palmer LJ, Buxbaum SG, Larkin E, Patel SR, Elston RC, Tishler PV, et al. Whole genome scan for obstructive sleep apnea and obesity in African-American families. Am J Respir Crit Care Med 2004; 169: 1314-21.
139. Carmelli D, Colrain IM, Swan GE, Bliwise DL. Genetic and environmental influences in sleep-disordered breathing in older male twins. Sleep 2004; 27: 917-22.
140. Koeppen-Schomerus G, Wardle J, Plomin R. A genetic analysis of weight and overweight in 4-year-old twin pairs. Int J Obes Relat Metab Disord 2001; 25: 838-44.
141. Pietiläinen KH, Kaprio J, Rissanen A, Winter T, Rimpelä A, Viken RJ, et al. Distribution and heritability of BMI in Finnish adolescents aged 16y and 17y: a study of 4884 twins and 2509 singletons. Int J Obes Relat Metab Disord 1999; 23: 107-15.
142. Patel SR, Larkin EK, Redline S. Shared genetic basis for obstructive sleep apnea and adiposity measures. Int J Obes 2008; 32: 795-800.
143. Nance WE, Nakata M, Paul TD, Yu PI. The use of twin studies in the analysis of phenotypic traits in man. In: Janerich DT, Skalko RG, Porter IH, editors. Congenital defects new directions in research. New York: Academic Press; 1974. p. 23-49.
144. Osborne RH, De George FV. Genetic basis of morphologic variation: An evaluation and application of the twin study method. Cambridge: Harvard University Press; 1959.
145. Schwab RJ, Pasirstein M, Kaplan L, Pierson R, Mackley A, Hachadoorian R, et al. Family aggregation of upper airway soft tissue structures in normal subjects and patients with sleep apnea. Am J Respir Crit Care Med 2006; 173: 453-63.
146. Bayadi S, Millman RP, Tishler PV, Rosenberg C, Saliski W, Boucher MA, et al. A family study of sleep apnea. Anatomic and physiologic interactions. Chest 1990; 98: 554-9.
147. 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: 155-60.
148. Lavie P, Rubin AE. Effects of nasal occlusion on respiration in sleep. Evidence of inheritability of sleep apnea proneness. Acta Otolaryngol 1984; 97: 127-30.
149. Mathur R, Douglas NJ. Relation between sudden infant death syndrome and adult sleep apnea/hypopnoea syndrome. Lancet 1994; 344: 819-20.
150. Gislason T, Johannsson JH, Haraldsson A, Olafsdottir BR, Jonsdottir H, Kong A, et al. Familial predisposition and cosegregation analysis of adult obstructive sleep apnea and the sudden infant death syndrome. Am J Respir Crit Care Med 2002; 166: 833-8.
151. Tishler PV, Redline S, Ferrette V, Hans MG, Altose MD. The association of sudden unexpected infant death with obstructive sleep apnea. Am J Respir Crit Care Med 1996; 153: 1857-63.
152. Gottlieb DJ, O'Connor GT, Wilk JB. Genome-wide association of sleep and circadian phenotypes. BMC Med Genet 2007; 8 (Suppl 1): S9.
153. Riha RL, Brander P, Vennelle M, McArdle N, Kerr SM, Anderson NH, et al. Tumour necrosis factor-alpha (-308) gene polymorphism in obstructive sleep apnea-hypopnoea syndrome. Eur Respir J 2005; 26: 673-8.
154. Bayazit YA, Yilmaz M, Ciftci T, Erdal E, Kokturk O, Gokdogan T, et al. Association of the -1438G/A polymorphism of the 5-HT(2A) receptor gene with obstructive sleep apnea syndrome. ORL J Otorhinolaryngol Relat Spec 2006; 68:123-8.
155. Ylmaz M, Bayazit YA, Ciftci TU, Erdal ME, Urhan M, Kokturk O, et al. Association of serotonin transporter gene polymorphism with obstructive sleep apnea syndrome. Laryngoscope 2005; 115: 832-6.
156. Zhang LQ, Yao WZ, He QY, Wang YZ, Ren B, Lin YP. Polymorphisms in the beta2 and beta3 adrenergic receptor genes in obstructive sleep apnea/hypopnea syndrome. Zhonghua Nei Ke Za Zhi 2005; 44: 333-6.
157. Kadotani H, Kadotani T, Young T, Peppard PE, Finn L, Colrain IM, et al. Association between apolipoprotein E epsilon4 and sleep-disordered breathing in adults. JAMA 2001; 285: 2888-90.
158. Gottlieb DJ, DeStefano AL, Foley DJ, Mignot E, Redline S, Givelber RJ, et al. APOE epsilon4 is associated with obstructive sleep apnea/hypopnea: the Sleep Heart Health Study. Neurology 2004; 63: 664-8.
159. Foley DJ, Masaki K, White L, Redline S. Relationship between apolipoprotein E epsilon4 and sleep-disordered breathing at different ages. JAMA 2001; 286: 1447-8.
160. Larkin EK, Patel SR, Redline S, Mignot E, Elston RC, Hallmayer J. Apolipoprotein E and obstructive sleep apnea: evaluating whether a candidate gene explains a linkage peak. Genet Epidemiol 2006; 30: 101-10.