Defining phenotypic causes of obstructive sleep apnea: Identification of novel therapeutic targets

American Journal of Respiratory and Critical Care Medicine

Volumn 188, Issue 8, 2013, Pages 996-1004

  Eckert, Danny J ^a,b   White, David P ^a   Jordan, Amy S ^a,c   Malhotra, Atul ^a   Wellman, Andrew ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b UNIVERSITY OF NEW SOUTH WALES   (Australia)

^c UNIVERSITY OF MELBOURNE   (Australia)

Author keywords

Arousal; Muscle; Respiratory physiology; Sleep disordered breathing; Upper airway pathophysiology

Indexed keywords

ARTICLE; PHENOTYPE; PRIORITY JOURNAL; SLEEP DISORDERED BREATHING;

ADULT; AGED; CASE-CONTROL STUDIES; FEMALE; HUMANS; MALE; MIDDLE AGED; PHENOTYPE; POLYSOMNOGRAPHY; RESPIRATORY MUSCLES; RESPIRATORY SYSTEM; SLEEP APNEA, OBSTRUCTIVE; YOUNG ADULT;

EID: 84886382900     PISSN: 1073449X     EISSN: 15354970     Source Type: Journal    
DOI: 10.1164/rccm.201303-0448OC     Document Type: Article

References (58)

1. Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults.NEngl JMed 1993;328:1230-1235.
2. 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;353:2034-2041.
3. Kribbs NB, Pack AI, Kline LR, Smith PL, Schwartz AR, Schubert NM, Redline S, Henry JN, Getsy JE, Dinges DF. Objective measurement of patterns of nasal CPAP use by patients with obstructive sleep apnea. Am Rev Respir Dis 1993;147:887-895.
4. White DP. Pathogenesis of obstructive and central sleep apnea. Am J Respir Crit Care Med 2005;172:1363-1370.
5. Eckert DJ, Malhotra A. Pathophysiology of adult obstructive sleep apnea. Proc Am Thorac Soc 2008;5:144-153.
6. Gleadhill IC, Schwartz AR, Schubert N, Wise RA, Permutt S, Smith PL. Upper airway collapsibility in snorers and in patients with obstructive hypopnea and apnea. Am Rev Respir Dis 1991;143:1300-1303.
7. 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;62:861-867.
8. Loewen AH, Ostrowski M, Laprairie J, Maturino F, Hanly PJ, Younes M. Response of genioglossus muscle to increasing chemical drive in sleeping obstructive apnea patients. Sleep 2011;34:1061-1073.
9. 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 (Lond) 2011;120:505-514. (accelerated publication).
10. Younes M. Role of arousals in the pathogenesis of obstructive sleep apnea. Am J Respir Crit Care Med 2004;169:623-633.
11. 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;103:1929-1941.
12. Longobardo GS, Evangelisti CJ, Cherniack NS. Analysis of the interplay between neurochemical control of respiration and upper airway mechanics producing upper airway obstruction during sleep in humans. Exp Physiol 2008;93:271-287.
13. Younes M. Role of respiratory control mechanisms in the pathogenesis of obstructive sleep disorders. J Appl Physiol 2008;105:1389-1405.
14. Younes M, Ostrowski M, Thompson W, Leslie C, ShewchukW. Chemical control stability in patients with obstructive sleep apnea. Am J Respir Crit Care Med 2001;163:1181-1190.
15. 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.AmJ Respir Crit CareMed 2004;170:1225-1232.
16. Schwartz AR, Gold AR, Schubert N, Stryzak A, Wise RA, Permutt S, Smith PL. Effect of weight loss on upper airway collapsibility in obstructive sleep apnea. Am Rev Respir Dis 1991;144:494-498.
17. Schwartz AR, Schubert N, Rothman W, Godley F, Marsh B, Eisele D, Nadeau J, Permutt L, Gleadhill I, Smith PL. Effect of uvulopalatopharyngoplasty on upper airway collapsibility in obstructive sleep apnea. Am Rev Respir Dis 1992;145:527-532.
18. Ng AT, Gotsopoulos H, Qian J, Cistulli PA. Effect of oral appliance therapy on upper airway collapsibility in obstructive sleep apnea. Am J Respir Crit Care Med 2003;168:238-241.
19. Eastwood PR, BarnesM, 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;34:1479-1486.
20. Schwartz AR, Barnes M, Hillman D, Malhotra A, Kezirian E, Smith PL, Hoegh T, Parrish D, Eastwood PR. Acute upper airway responses to hypoglossal nerve stimulation during sleep in obstructive sleep apnea. Am J Respir Crit Care Med 2012;185:420-426.
21. 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;590:1199-1211.
22. 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;162:144-151.
23. Eckert DJ, Jordan AS, Malhotra A, White DP, Wellman A. Variability in the pathophysiological phenotypic causes of obstructive sleep apnea: targets for novel therapeutic approaches. Sleep 2011;34:A159. (abstract).
24. EckertDJ, JordanAS,MalhotraA,WhiteDP,WellmanA. Characterization of pathophysiological phenotypic traits in obstructive sleep apnea: avenues for novel treatment strategies. Am J Respir Crit Care Med 2011;183:A3690. (abstract).
25. Eckert DJ, Jordan AS, Malhotra A, White DP, Wellman A. Defining phenotypic causes of obstructive sleep apnea: identification of novel therapeutic targets. Am J Respir Crit Care Med 2013;187:A6120. (abstract).
26. Jordan AS, Eckert DJ, Wellman A, Trinder JA, Malhotra A, White DP. Termination of respiratory events with and without cortical arousal in obstructive sleep apnea. Am J Respir Crit Care Med 2011;184:1183-1191.
27. Wellman A, Eckert DJ, Jordan AS, Edwards BA, Passaglia CL, Jackson AC, Gautam S, Owens RL, Malhotra A, White DP. A method for measuring and modeling the physiological traits causing obstructive sleep apnea. J Appl Physiol 2011;110:1627-1637.
28. Rechtschaffen A, Kales A. A manual of standardized terminology, techniques, and scoring system for sleep stages of human subjects. Los Angeles: Brain Information Service/ Brain Research Institute, UCLA; 1968.
29. American Sleep Disorders Association. EEG arousals: Scoring rules and examples: a preliminary report from the sleep disorders atlas task force of the American Sleep Disorders Association. Sleep 1992;15: 173-184.
30. AASM. Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The report of an American Academy of Sleep Medicine task force. Sleep 1999;22:667-689.
31. MezzanotteWS, Tangel DJ,White DP.Waking genioglossal electromyogram in sleep apnea patients versus normal controls (a neuromuscular compensatory mechanism). J Clin Invest 1992;89:1571-1579.
32. Heinzer RC, White DP, Jordan AS, Lo YL, Dover L, Stevenson K, Malhotra A. Trazodone increases arousal threshold in obstructive sleep apnoea. Eur Respir J 2008;31:1308-1312.
33. Jordan AS, Wellman A, Edwards JK, Schory K, Dover L, MacDonald M, Patel SR, Fogel RB, Malhotra A, White DP. Respiratory control stability and upper airway collapsibility in men and women with obstructive sleep apnea. J Appl Physiol 2005;99:2020-2027.
34. Kirkness JP, Schwartz AR, Schneider H, Punjabi NM, Maly JJ, Laffan AM, McGinley BM, Magnuson T, Schweitzer M, Smith PL, et al. Contribution of male sex, age, and obesity to mechanical instability of the upper airway during sleep. J Appl Physiol 2008;104:1618-1624.
35. 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;82:1319-1326.
36. Eastwood PR, Szollosi I, Platt PR, Hillman DR. Comparison of upper airway collapse during general anaesthesia and sleep. Lancet 2002; 359:1207-1209.
37. Eckert DJ, Lo YL, Saboisky JP, Jordan AS, White DP, Malhotra A. Sensorimotor function of the upper-airway muscles and respiratory sensory processing in untreated obstructive sleep apnea. J Appl Physiol 2011;111:1644-1653.
38. 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;94:1875-1882.
39. Patil SP, Schneider H, Marx JJ, Gladmon E, Schwartz AR, Smith PL. Neuromechanical control of upper airway patency during sleep. J Appl Physiol 2007;102:547-556.
40. Dantas DA, Mauad T, Silva LF, Lorenzi-Filho G, Formigoni GG, Cahali MB. The extracellular matrix of the lateral pharyngeal wall in obstructive sleep apnea. Sleep 2012;35:483-490.
41. Brown EC, Cheng S, McKenzie DK, Butler JE, Gandevia SC, Bilston LE. Respiratory movement of upper airway tissue in obstructive sleep apnea. Sleep 2013;36:1069-1076.
42. Berry RB, Kouchi KG, Der DE, DickelMJ, Light RW. Sleep apnea impairs the arousal response to airway occlusion. Chest 1996;109:1490-1496.
43. Loewen A, Ostrowski M, Laprairie J, Atkar R, Gnitecki J, Hanly P, Younes M. Determinants of ventilatory instability in obstructive sleep apnea: inherent or acquired? Sleep 2009;32:1355-1365.
44. Boudewyns A, Sforza E, Zamagni M, Krieger J. Respiratory effort during sleep apneas after interruption of long-term CPAP treatment in patients with obstructive sleep apnea. Chest 1996;110:120-127.
45. 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;9:12-19.
46. 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;20: 533-537.
47. Xie A, Teodorescu M, Pegelow DF, Teodorescu MC, Gong Y, Fedie JE, Dempsey JA. Effects of stabilizing or increasing respiratory motor outputs on obstructive sleep apnea. J Appl Physiol 2013;115:22-33.
48. Jordan AS, White DP, Owens RL, Eckert DJ, Rahangdale S, Yim-Yeh S, Malhotra A. The effect of increased genioglossus activity and endexpiratory lung volume on pharyngeal collapse. J Appl Physiol 2010; 109:469-475.
49. White DP, Douglas NJ, Pickett CK, Zwillich CW, Weil JV. Sleep deprivation and the control of ventilation. Am Rev Respir Dis 1983; 128:984-986.
50. 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;95:1761-1766.
51. Stadler DL, McEvoy RD, Sprecher KE, Thomson KJ, Ryan MK, Thompson CC, Catcheside PG. Abdominal compression increases upper airway collapsibility during sleep in obese male obstructive sleep apnea patients. Sleep 2009;32:1579-1587.
52. Redolfi S, Arnulf I, Pottier M, Lajou J, Koskas I, Bradley TD, Similowski T. Attenuation of obstructive sleep apnea by compression stockings in subjects with venous insufficiency. Am J Respir Crit CareMed 2011;184: 1062-1066.
53. 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;179:241-246.
54. Walsh JH, Maddison KJ, Platt PR, Hillman DR, Eastwood PR. Influence of head extension, flexion, and rotation on collapsibility of the passive upper airway. Sleep 2008;31:1440-1447.
55. 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.
56. Killick R,Wang D, Hoyos CM, Yee BJ, Grunstein RR, Liu PY. The effects of testosterone on ventilatory responses in men with obstructive sleep apnea: a randomised, placebo-controlled trial. J Sleep Res 2013;22:331-336.
57. 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;168:1512-1519.
58. 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 2013;114:911-922.