Sleep and Breathing

, Volume 12, Issue 3, pp 207–215

Exhaled breath markers in patients with obstructive sleep apnoea

  • Marina Petrosyan
  • Eleni Perraki
  • Davina Simoes
  • Ioannis Koutsourelakis
  • Emmanouil Vagiakis
  • Charis Roussos
  • Christina Gratziou
Original Article


The objectives of the present study were to assess the level of exhaled breath markers indicating airway inflammation and oxidative stress in patients with obstructive sleep apnoea syndrome (OSAS) in comparison with non-apnoeic (obese and non-obese) subjects and investigate whether therapy with continuous positive airway pressure (CPAP) can modify them. The design was a retrospective observational study, set in Evgeneidio Hospital. Twenty-six OSAS patients and nine obese and 10 non-obese non-apnoeic subjects participated in this study. We measured nasal nitric oxide (nNO), exhaled nitric oxide (eNO), exhaled carbon monoxide (eCO) in exhaled breath, and 8-isoprostane, leukotriene B4 (LTB4), nitrates, hydrogen peroxide (H2O2), and pH in exhaled breath condensate (EBC) before and after 1 month of CPAP therapy. The levels of eNO and eCO were higher in OSAS patients than in control subjects (p < 0.05). Nasal NO was higher in OSAS patients than in obese controls (p < 0.01). The level of H2O2, 8-isoprostane, LTB4, and nitrates were elevated in OSAS patients in comparison with obese subjects (p < 0.01). Conversely, pH was lower in OSAS patients than in non-apnoeic controls (p < 0.01). One month of CPAP therapy increased pH (p < 0.05) and reduced eNO (p < 0.001) and nNO (p < 0.05). Apnea/hypopnoea index was positively correlated with 8-isoprostane (r = 0.42; p < 0.05), LTB4 (r = 0.35; p < 0.05), nitrates (r = 0.54; p < 0.001), and H2O2 (r = 0.42; p < 0.05). Airway inflammation and oxidative stress are present in the airway of OSAS patients in contrast to non-apnoeic subjects. Exhaled breath markers are positively correlated with the severity of OSAS. One-month administration of CPAP improved airway inflammation and oxidative stress.


Obstructive sleep apnoea Exhaled breath Exhaled breath condensate CPAP 


  1. 1.
    Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S (1993) The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 328:1230–1235PubMedCrossRefGoogle Scholar
  2. 2.
    Peker Y, Hedner J, Norum J, Kraiczi H, Carlson J (2002) Increased incidence of cardiovascular disease in middle-aged men with obstructive sleep apnea. A 7-year follow-up. Am J Respir Crit Care Med 166:159–165PubMedCrossRefGoogle Scholar
  3. 3.
    Peppard PE, Young T, Palta M, Skatrud J (2000) Prospective study of the association between sleep disordered breathing and hypertension. N Engl J Med 342:1378–1384PubMedCrossRefGoogle Scholar
  4. 4.
    Mathur S, Devaraj S, Jialal I (2002) Accelerated atherosclerosis, dyslipidemia, and oxidative stress in end-stage renal disease. Curr Opin Nephrol Hypertens 11:141–147PubMedCrossRefGoogle Scholar
  5. 5.
    Lavie L (2003) Obstructive sleep apnoea—an oxidative stress disorder. Sleep Med Rev 7:35–51PubMedCrossRefGoogle Scholar
  6. 6.
    Svatikova A, Wolk R, Lerman L, Juncos L, Greene E, Mc Connell J, Somers V (2005) Oxidative stress in obstructive sleep apnoea. Eur Heart J 26:2435–2439PubMedCrossRefGoogle Scholar
  7. 7.
    Carpagnano G, Kharitonov S, Resta O, Foschino-Barbaro M, Gramiccioni E, Barnes P (2002) Increased 8-isoprostane and Interleukin-6 in breath condensate of obstructive sleep apnoea patients. Chest 122:1162–1167PubMedCrossRefGoogle Scholar
  8. 8.
    Schulz R, Mahmoudi S, Hattar K, Sibelius U, Olschewski H, Mayer K, Seeger W, Grimminger F (2000) Enhanced release of superoxide from polymorphonuclear neutrophils in obstructive sleep apnea. Impact of continuous positive airway pressure therapy. Am J Respir Crit Care Med 162:566–570PubMedGoogle Scholar
  9. 9.
    Wali S, Bahammam A, Massaeli H, Pierce G, Iliskovic N, Singal P, Kryger M (1998) Susceptibility of LDL to oxidative stress in obstructive sleep apnea. Sleep 21:290–296PubMedGoogle Scholar
  10. 10.
    Muns G, Rubistein I, Bergmann K (1995) Phagocytosis and oxidative burst of blood phagocytes in chronic obstructive airway disease. Scand J Infect Dis 27:369–373PubMedCrossRefGoogle Scholar
  11. 11.
    Dyugovskaya L, Lavie P, Lavie L (2002) Increased adhesion molecules expression and production of reactive oxygen species in leykocytes of sleep apnea patients. Am J Respir Crit Care Med 165:934–939PubMedGoogle Scholar
  12. 12.
    Olopade C, Christon J, Zakkar M, Hua C, Swedler W, Scheff P, Rubinstein I (1997) Exhaled pentane and nitric oxide levels in patients with obstructive sleep apnea. Chest 111:1500–1504PubMedCrossRefGoogle Scholar
  13. 13.
    Agusti AG, Barbe F, Togores B (1999) Exhaled nitric oxide in patients with sleep apnea. Sleep 22:231–235PubMedGoogle Scholar
  14. 14.
    Kharitonov S, Barnes P (2001) Exhaled markers of inflammation. Curr Opin Allergy Clin Immunol 1:217–224PubMedGoogle Scholar
  15. 15.
    Rechtschaffen A, Kales A (eds) (1968) A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects. National Institutes of Health, BethesdaGoogle Scholar
  16. 16.
    American Academy of Sleep Medicine Task Force (1999) Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. Sleep 22:667–689Google Scholar
  17. 17.
    ATS/ERS Task Force on Exhaled Breath Condensate (2005) Exhaled breath condensate: methodological recommendations and unresolved questions. Eur Respir J 26:523–548CrossRefGoogle Scholar
  18. 18.
    Hunt JF, Fang K, Malik R, Snyder A, Malhotra N, Platts-Mills TAE, Gaston B (2000) Endogenous airway acidification: implications for asthma pathology. Am J Respir Crit Care Med 161:694–699PubMedGoogle Scholar
  19. 19.
    Gallati H, Pracht I (1985) Horseradish peroxidase: kinetic studies and optimization of peroxidase activity determination using the substrates H2O2 and 3,3,5,5-tetramethylbenzidine. J Clin Chem Clin Biochem 23:453–460PubMedGoogle Scholar
  20. 20.
    Kharitonov S, Barnes P (2001) Exhaled markers of pulmonary disease. Am J Respir Crit Care Med 163:1693–1722PubMedGoogle Scholar
  21. 21.
    Janssen-Heininger Y, Persinger R, Korn S, Pantano C, McElhinney B, Reynaert N, Langen R, Ckless K, Shrivastava P, Poynter M (2002) Reactive nitrogen species and cell signaling: implications for death or survival of lung epithelium. Am J Respir Crit Care Med 166:S9–S16PubMedCrossRefGoogle Scholar
  22. 22.
    Struben V, Wieringa M, Feenstra L, De Jongste J (2006) Nasal nitric oxide and nasal allergy. Allergy 61:665–670PubMedCrossRefGoogle Scholar
  23. 23.
    Kharitonov S, Barnes P (2006) Exhaled biomarkers. Chest 130:1541–1546PubMedCrossRefGoogle Scholar
  24. 24.
    Predi P, Kharitonov S, Barnes P (2002) Analysis of expired air for oxidation products. Am J Respir Crit Care Med 166:S31–S37CrossRefGoogle Scholar
  25. 25.
    Montuschi P, Ciabattoni G, Paredi P, Pantelidis P, du Bois RM, Kharitonov S, Barnes P (1998) 8-Isoprostane as a biomarker of oxidative stress in interstitial lung diseases. Am J Respir Crit Care Med 158:1524–1527PubMedGoogle Scholar
  26. 26.
    Carpagnano GE, Kharitonov SA, Resta O, Foschino-Barbaro M, Gramiccioni E, Barnes P (2003) 8-Isoprostane, a marker of oxidative stress, is increased in exhaled breath condensate of patients with obstructive sleep apnea after night and is reduced by continuous positive airway pressure therapy. Chest 124:1386–1392PubMedCrossRefGoogle Scholar
  27. 27.
    Vgontzas A, Papanicolaou D, Bixler E Kales A, Tyson K, Chrousos G (1997) Elevation of plasma cytokines in disorders of excessive daytime sleepiness: role of sleep disturbance and obesity. Clin Endocrinol Metab 82:1313–1316CrossRefGoogle Scholar
  28. 28.
    Nicosia S, Capra V, Rovati G (2001) Leukotriens as mediators of asthma. Pulm Pharmacol Ther 14:3–19PubMedCrossRefGoogle Scholar
  29. 29.
    Montuschi P, Barnes P (2002) Analysis of exhaled breath condensate for monitoring airway inflammation. Trends Pharmacol Sci 23:232–237PubMedCrossRefGoogle Scholar
  30. 30.
    Kostikas K, Papatheodorou G, Ganas K, Psathakis K, Panagou P, Loukides S (2002) pH in expired breath condensate of patients with inflammatory airway diseases. Am J Respir Crit Care Med 165:1364–1370PubMedCrossRefGoogle Scholar
  31. 31.
    Leung T, Li C, Lam C, Au C, Yung E, Chan I, Wong G, Fok T (2004) The relationship between obesity and asthmatic airway inflammation. Pediatr Allergy Immunol 15:344–350PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Marina Petrosyan
    • 1
    • 2
  • Eleni Perraki
    • 1
    • 2
  • Davina Simoes
    • 1
    • 2
  • Ioannis Koutsourelakis
    • 1
    • 2
  • Emmanouil Vagiakis
    • 1
    • 2
  • Charis Roussos
    • 1
    • 2
  • Christina Gratziou
    • 1
    • 2
  1. 1.Center of Sleep DisordersMedical School of Athens UniversityAthensGreece
  2. 2.Department of Critical Care and Pulmonary ServicesEvgeneidio HospitalAthensGreece

Personalised recommendations