Advertisement

Somnologie

, Volume 23, Issue 3, pp 164–171 | Cite as

Neues zur Pathophysiologie schlafbezogener Atmungsstörungen

  • S. D. HerkenrathEmail author
  • W. J. Randerath
Übersichten
  • 11 Downloads

Zusammenfassung

Schlafbezogene Atmungsstörungen umfassen die obstruktive und zentrale Schlafapnoe sowie schlafbezogene Hypoventilationssyndrome. Zugrundeliegende pathophysiologische Charakteristika dieser Krankheitsbilder weisen essenzielle Unterschiede auf. Während bei der obstruktiven Schlafapnoe der obere Atemwegskollaps im Vordergrund steht, basiert die zentrale Schlafapnoe vor allem auf einer fehlerhaften Regulation der Ventilation. Eine erhöhte atemmechanische Last und/oder eine fehlerhafte neuronale Signalübertragung/Muskeldystrophie prädisponieren für das Auftreten einer (schlafbezogenen) Hypoventilation. Im Regelfall definieren wir bei Patienten eine dieser Entitäten auf Basis polysomnografischer und kapnometrischer Charakteristika, nicht selten finden wir jedoch eine Koexistenz verschiedener pathophysiologischer Aspekte. Dies trifft insbesondere auf den multimorbiden älteren Patienten zu. Um Krankheitsbilder klar zu definieren und suffiziente Therapiekonzepte zu entwickeln, ist eine differenzierte Betrachtung jedweder zugrundeliegenden Störung essenziell. Nur der integrative Therapieansatz orientiert an der zugrundeliegenden Pathophysiologie supprimiert die schlafbezogene Atmungsstörung effektiv und sichert eine langfristige Therapieadhärenz. Der vorliegende Artikel beschreibt aktuelle pathophysiologische Konzepte schlafbezogener Atmungsstörungen und soll dabei helfen, integrative Therapiestrategien orientiert an der Pathophysiologie zu entwickeln.

Schlüsselwörter

Schlafapnoe Hypoventilation Loop gain Arousalschwelle Adipositas 

Current insights in the pathophysiology of sleep disordered breathing

Abstract

Sleep-related breathing disturbances include obstructive and central sleep apnea as well as sleep-related hypoventilation syndromes. The underlying pathophysiological characteristics of these diseases essentially differ. While obstructive sleep apnea is primarily due to upper airway collapse, central sleep apnea is mainly driven by a disturbed ventilatory control. Increased respiratory mechanical load and/or an impaired neuronal signal transduction/muscle dystrophy promote the occurrence of a (sleep-related) hypoventilation. Usually we diagnose one of these entities based on polysomnographic und capnometric characteristics, but frequently a co-existence of different pathophysiological aspects can be found. This is especially true in the multi-morbid elderly patient. In order to define disease entities more clearly and develop sufficient therapy concepts, a differentiated appraisal of each and every underlying disturbance is needed. Only the integrative therapy approach oriented towards the underlying pathophysiology facilitates effective suppression of sleep-related breathing disturbances and ensures long-term therapy adherence. This article describes current pathophysiological concepts of sleep-related breathing disturbances and is intended to help develop integrative therapy strategies oriented towards pathophysiology.

Keywords

Sleep apnea Hypoventilation Loop gain Arousal threshold Obesity 

Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt

S.D. Herkenrath und W.J. Randerath geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

Literatur

  1. 1.
    Amatoury J, Azarbarzin A, Younes M et al (2016) Arousal intensity is a distinct pathophysiological trait in obstructive sleep apnea. Sleep 39:2091–2100.  https://doi.org/10.5665/sleep.6304 CrossRefGoogle Scholar
  2. 2.
    American Academy of Sleep Medicine (2014) Diagnostic and coding manual, international classification of sleep disorders, 3. Aufl. American Academy of Sleep Medicine, WestchesterGoogle Scholar
  3. 3.
    Bailey EF, Janssen PL, Fregosi RF (2005) PO2-dependent changes in intrinsic and extrinsic tongue muscle activities in the rat. Am J Respir Crit Care Med 171:1403–1407.  https://doi.org/10.1164/rccm.200411-1550OC CrossRefGoogle Scholar
  4. 4.
    Bilici S, Yigit O, Celebi OO et al (2018) Relations between hyoid-related cephalometric measurements and severity of obstructive sleep apnea. J Craniofac Surg 29:1276–1281.  https://doi.org/10.1097/SCS.0000000000004483 Google Scholar
  5. 5.
    Carberry JC, Amatoury J, Eckert DJ (2018) Personalized management approach for OSA. Chest 153:744–755.  https://doi.org/10.1016/j.chest.2017.06.011 CrossRefGoogle Scholar
  6. 6.
    Carberry JC, Hensen H, Fisher LP et al (2015) Mechanisms contributing to the response of upper-airway muscles to changes in airway pressure. J Appl Physiol 118:1221–1228.  https://doi.org/10.1152/japplphysiol.01103.2014 CrossRefGoogle Scholar
  7. 7.
    Chi L, Comyn F‑L, Mitra N et al (2011) Identification of craniofacial risk factors for obstructive sleep apnea using three-dimensional MRI. Eur Respir J 38:348–358.  https://doi.org/10.1183/09031936.00119210 CrossRefGoogle Scholar
  8. 8.
    Considine RV, Sinha MK, Heiman ML et al (1996) Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 334:292–295.  https://doi.org/10.1056/NEJM199602013340503 CrossRefGoogle Scholar
  9. 9.
    Deacon NL, Catcheside PG (2015) The role of high loop gain induced by intermittent hypoxia in the pathophysiology of obstructive sleep apnoea. Sleep Med Rev 22:3–14.  https://doi.org/10.1016/j.smrv.2014.10.003 CrossRefGoogle Scholar
  10. 10.
    Degache F, Sforza E, Dauphinot V et al (2013) Relation of central fat mass to obstructive sleep apnea in the elderly. Sleep 36:501–507.  https://doi.org/10.5665/sleep.2532 CrossRefGoogle Scholar
  11. 11.
    DeLorey DS, Wyrick BL, Babb TG (2005) Mild-to-moderate obesity: Implications for respiratory mechanics at rest and during exercise in young men. Int J Obes (Lond) 29:1039–1047.  https://doi.org/10.1038/sj.ijo.0803003 CrossRefGoogle Scholar
  12. 12.
    Eckert DJ, Malhotra A, Jordan AS (2009) Mechanisms of apnea. Prog Cardiovasc Dis 51:313–323.  https://doi.org/10.1016/j.pcad.2008.02.003 CrossRefGoogle Scholar
  13. 13.
    Eckert DJ, Wellman A (2015) Physiological phenotypes. In: Sleep apnoea. European Respiratory Society monograph. ERS, Plymouth, S 9–23Google Scholar
  14. 14.
    Eckert DJ, White DP, Jordan AS et al (2013) Defining phenotypic causes of obstructive sleep apnea. Identification of novel therapeutic targets. Am J Respir Crit Care Med 188:996–1004.  https://doi.org/10.1164/rccm.201303-0448OC CrossRefGoogle Scholar
  15. 15.
    Elias RM, Bradley TD, Kasai T et al (2012) Rostral overnight fluid shift in end-stage renal disease: Relationship with obstructive sleep apnea. Nephrol Dial Transplant 27:1569–1573.  https://doi.org/10.1093/ndt/gfr605 CrossRefGoogle Scholar
  16. 16.
    Genta PR, Schorr F, Eckert DJ et al (2014) Upper airway collapsibility is associated with obesity and hyoid position. Sleep 37:1673–1678.  https://doi.org/10.5665/sleep.4078 CrossRefGoogle Scholar
  17. 17.
    Gleeson K, Zwillich CW, White DP (1990) The influence of increasing ventilatory effort on arousal from sleep. Am Rev Respir Dis 142:295–300.  https://doi.org/10.1164/ajrccm/142.2.295 CrossRefGoogle Scholar
  18. 18.
    Heidbreder A, Spießhöfer J, Stypmann J et al (2018) Microstructural cerebral lesions are associated with the severity of central sleep apnea with Cheyne-Stokes-respiration in heart failure and are modified by PAP-therapy. Respir Physiol Neurobiol 247:181–187.  https://doi.org/10.1016/j.resp.2017.10.010 CrossRefGoogle Scholar
  19. 19.
    Heinzer R, Vat S, Marques-Vidal P et al (2015) Prevalence of sleep-disordered breathing in the general population: The HypnoLaus study. Lancet Respir Med 3:310–318.  https://doi.org/10.1016/S2213-2600(15)00043-0 CrossRefGoogle Scholar
  20. 20.
    Herkenrath SD, Randerath WJ (2019) More than heart failure: Central sleep apnea and sleep-related hypoventilation. Respiration:1–16.  https://doi.org/10.1159/000500728 Google Scholar
  21. 21.
    Javaheri S, Simbartl LA (2014) Respiratory determinants of diurnal hypercapnia in obesity hypoventilation syndrome. What does weight have to do with it? Ann Am Thorac Soc 11:945–950.  https://doi.org/10.1513/AnnalsATS.201403-099OC CrossRefGoogle Scholar
  22. 22.
    Kasai T, Motwani SS, Yumino D et al (2012) Differing relationship of nocturnal fluid shifts to sleep apnea in men and women with heart. Circ Heart Fail 5:467–474.  https://doi.org/10.1161/CIRCHEARTFAILURE.111.965814 CrossRefGoogle Scholar
  23. 23.
    Khoo MC, Kronauer RE, Strohl KP, Slutsky AS (1982) Factors inducing periodic breathing in humans: A general model. J Appl Physiol Respir Environ Exerc Physiol 53:644–659.  https://doi.org/10.1152/jappl.1982.53.3.644 Google Scholar
  24. 24.
    Kim AM, Keenan BT, Jackson N et al (2014) Tongue fat and its relationship to obstructive sleep apnea. Sleep 37:1639–1648.  https://doi.org/10.5665/sleep.4072 CrossRefGoogle Scholar
  25. 25.
    Lalley PM (2008) Opiodergic and dopaminergic modulation of respiration. Respir Physiol Neurobiol 164:160–167.  https://doi.org/10.1016/j.resp.2008.02.004 CrossRefGoogle Scholar
  26. 26.
    Landry SA, Andara C, Terrill PI et al (2018) Ventilatory control sensitivity in patients with obstructive sleep apnea is sleep stage dependent. Sleep.  https://doi.org/10.1093/sleep/zsy040 Google Scholar
  27. 27.
    Lorenzi-Filho G, Azevedo ER, Parker JD, Bradley TD (2002) Relationship of carbon dioxide tension in arterial blood to pulmonary wedge pressure in heart failure. Eur Respir J 19:37–40.  https://doi.org/10.1183/09031936.02.00214502 CrossRefGoogle Scholar
  28. 28.
    Mallampati SR, Gatt SP, Gugino LD et al (1985) A clinical sign to predict difficult tracheal intubation: A prospective study. Can Anaesth Soc J 32:429–434CrossRefGoogle Scholar
  29. 29.
    Mokhlesi B (2010) Obesity Hypoventilation syndrome: A state-of-the-Art review. Respir Care 55:1347–1365Google Scholar
  30. 30.
    Mokhlesi B, Kryger MH, Grunstein RR (2008) Assessment and management of patients with obesity hypoventilation syndrome. Proc Am Thorac Soc 5:218–225.  https://doi.org/10.1513/pats.200708-122MG CrossRefGoogle Scholar
  31. 31.
    Oliven R, Cohen G, Somri M et al (2019) Spectral analysis of peri-pharyngeal muscles’ EMG in patients with OSA and healthy subjects. Respir Physiol Neurobiol 260:53–57.  https://doi.org/10.1016/j.resp.2018.12.002 CrossRefGoogle Scholar
  32. 32.
    Omobomi O, Quan SF (2018) Positional therapy in the management of positional obstructive sleep apnea—A review of the current literature. Sleep Breath 22:297–304.  https://doi.org/10.1007/s11325-017-1561-y CrossRefGoogle Scholar
  33. 33.
    Pankow W, Podszus T, Gutheil T et al (1998) Expiratory flow limitation and intrinsic positive end-expiratory pressure in obesity. J Appl Physiol 85:1236–1243.  https://doi.org/10.1152/jappl.1998.85.4.1236 CrossRefGoogle Scholar
  34. 34.
    Patel JA, Ray BJ, Fernandez-Salvador C et al (2018) Neuromuscular function of the soft palate and uvula in snoring and obstructive sleep apnea: A systematic review. Am J Otolaryngol 39:327–337.  https://doi.org/10.1016/j.amjoto.2018.03.006 CrossRefGoogle Scholar
  35. 35.
    Pattinson KTS (2008) Opioids and the control of respiration. Br J Anaesth 100:747–758.  https://doi.org/10.1093/bja/aen094 CrossRefGoogle Scholar
  36. 36.
    Pépin JL, Bailly S, Tamisier R (2018) Incorporating polysomnography into obstructive sleep apnoea phenotyping: Moving towards personalised medicine for OSA. Thorax 73:409–411.  https://doi.org/10.1136/thoraxjnl-2017-210943 CrossRefGoogle Scholar
  37. 37.
    Peppard PE, Young T, Barnet JH et al (2013) Increased prevalence of sleep-disordered breathing in adults. Am J Epidemiol 177:1006–1014.  https://doi.org/10.1093/aje/kws342 CrossRefGoogle Scholar
  38. 38.
    Phillipson EA (1978) Control of breathing during sleep. Am Rev Respir Dis 118:909–939.  https://doi.org/10.1164/arrd.1978.118.5.909 Google Scholar
  39. 39.
    Ratnavadivel R, Stadler D, Windler S et al (2010) Upper airway function and arousability to ventilatory challenge in slow wave versus stage 2 sleep in obstructive sleep apnoea. Thorax 65:107–112.  https://doi.org/10.1136/thx.2008.112953 CrossRefGoogle Scholar
  40. 40.
    Rubinstein I, Zamel N, DuBarry L, Hoffstein V (1990) Airflow limitation in morbidly obese, nonsmoking men. Ann Intern Med 112:828–832CrossRefGoogle Scholar
  41. 41.
    Saboisky JP, Butler JE, Fogel RB et al (2006) Tonic and phasic respiratory drives to human genioglossus motoneurons during breathing. J Neurophysiol 95:2213–2221.  https://doi.org/10.1152/jn.00940.2005 CrossRefGoogle Scholar
  42. 42.
    Saboisky JP, Butler JE, Gandevia SC, Eckert DJ (2012) Functional role of neural injury in obstructive sleep apnea. Front Neurol 3:95.  https://doi.org/10.3389/fneur.2012.00095 CrossRefGoogle Scholar
  43. 43.
    Sands SA, Edwards BA, Terrill PI et al (2018) Phenotyping pharyngeal pathophysiology using polysomnography in patients with obstructive sleep apnea. Am J Respir Crit Care Med 197:1187–1197.  https://doi.org/10.1164/rccm.201707-1435OC CrossRefGoogle Scholar
  44. 44.
    Santarnecchi E, Sicilia I, Richiardi J et al (2013) Altered cortical and subcortical local coherence in obstructive sleep apnea: A functional magnetic resonance imaging study. J Sleep Res 22:337–347.  https://doi.org/10.1111/jsr.12006 CrossRefGoogle Scholar
  45. 45.
    Schorr F, Kayamori F, Hirata RP et al (2016) Different craniofacial characteristics predict upper airway collapsibility in Japanese-Brazilian and white men. Chest 149:737–746.  https://doi.org/10.1378/chest.15-0638 CrossRefGoogle Scholar
  46. 46.
    Schwartz AR, O’donnell CP, Baron J et al (1998) The hypotonic upper airway in obstructive sleep apnea. Am J Respir Crit Care Med 157:1051–1057.  https://doi.org/10.1164/ajrccm.157.4.9706067 CrossRefGoogle Scholar
  47. 47.
    Schwartz AR, Smith PL, Wise RA et al (1988) Induction of upper airway occlusion in sleeping individuals with subatmospheric nasal pressure. J Appl Physiol 64:535–542.  https://doi.org/10.1152/jappl.1988.64.2.535 CrossRefGoogle Scholar
  48. 48.
    Sforza E, Petiau C, Weiss T et al (1999) Pharyngeal critical pressure in patients with obstructive sleep apnea syndrome. Clinical implications. Am J Respir Crit Care Med 159:149–157.  https://doi.org/10.1164/ajrccm.159.1.9804140 CrossRefGoogle Scholar
  49. 49.
    Shea SA, Edwards JK, White DP (1999) Effect of wake-sleep transitions and rapid eye movement sleep on pharyngeal muscle response to negative pressure in humans. J Physiol (Lond) 520(3):897–908CrossRefGoogle Scholar
  50. 50.
    Shimura R, Tatsumi K, Nakamura A et al (2005) Fat accumulation, leptin, and hypercapnia in obstructive sleep apnea-hypopnea syndrome. Chest 127:543–549.  https://doi.org/10.1378/chest.127.2.543 CrossRefGoogle Scholar
  51. 51.
    Smith PL, Wise RA, Gold AR et al (1988) Upper airway pressure-flow relationships in obstructive sleep apnea. J Appl Physiol 64:789–795.  https://doi.org/10.1152/jappl.1988.64.2.789 CrossRefGoogle Scholar
  52. 52.
    Solin P, Bergin P, Richardson M et al (1999) Influence of pulmonary capillary wedge pressure on central apnea in heart failure. Circulation 99:1574–1579.  https://doi.org/10.1161/01.CIR.99.12.1574 CrossRefGoogle Scholar
  53. 53.
    Taranto-Montemurro L, Messineo L, Sands SA et al (2018) The combination of atomoxetine and oxybutynin greatly reduces obstructive sleep apnea severity: A randomized, placebo-controlled, double-blind crossover trial. Am J Respir Crit Care Med.  https://doi.org/10.1164/rccm.201808-1493OC Google Scholar
  54. 54.
    Wellman A, Malhotra A, Fogel RB et al (2003) Respiratory system loop gain in normal men and women measured with proportional-assist ventilation. J Appl Physiol 94:205–212.  https://doi.org/10.1152/japplphysiol.00585.2002 CrossRefGoogle Scholar
  55. 55.
    White LH, Bradley TD (2013) Role of nocturnal rostral fluid shift in the pathogenesis of obstructive and central sleep apnoea. J Physiol 591:1179–1193.  https://doi.org/10.1113/jphysiol.2012.245159 CrossRefGoogle Scholar
  56. 56.
    Xie A, Skatrud JB, Puleo DS et al (2002) Apnea–hypopnea threshold for CO2 in patients with congestive heart failure. Am J Respir Crit Care Med 165:1245–1250.  https://doi.org/10.1164/rccm.200110-022OC CrossRefGoogle Scholar
  57. 57.
    Younes M (2004) Role of arousals in the pathogenesis of obstructive sleep apnea. Am J Respir Crit Care Med 169:623–633.  https://doi.org/10.1164/rccm.200307-1023OC CrossRefGoogle Scholar
  58. 58.
    Younes M, Ostrowski M, Thompson W et al (2001) Chemical control stability in patients with obstructive sleep apnea. Am J Respir Crit Care Med 163:1181–1190.  https://doi.org/10.1164/ajrccm.163.5.2007013 CrossRefGoogle Scholar
  59. 59.
    Yu J, Zhang JF, Fletcher EC (1998) Stimulation of breathing by activation of pulmonary peripheral afferents in rabbits. J Appl Physiol 85:1485–1492.  https://doi.org/10.1152/jappl.1998.85.4.1485 CrossRefGoogle Scholar

Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2019

Authors and Affiliations

  1. 1.Institut für Pneumologie an der Universität zu KölnKrankenhaus BethanienSolingenDeutschland

Personalised recommendations