Breath Gas Analysis

  • Michael DolchEmail author
  • Siegfried Praun
  • Johannes Villiger
  • Alexander Choukér
  • Gustav Schelling


Exhaled air analyses are an attractive and emerging technology. It is a noninvasive and easy-to-handle method and may especially be suitable for health monitoring under conditions with limited access to standard diagnostic equipment i.e. for extended space missions. Based on the current knowledge together with ongoing and future clinical and space-related—earthbound and on the ISS—research, air analyses might become a suitable tool to monitor the adaption of various physiological systems (immune, organs, metabolism) to the stressful condition in space, thereby helping to assess overall health status as well to establish the diagnosis of diseases. As the concentration of volatile organic and inorganic components in exhaled breath is usually found in the low parts per billion of volume range highly sensitive diagnostic platforms are a prerequisite. These requirements are now met by recent technical improvements leading to an increase in the sensitivity of direct mass spectrometric and gas chromatographic methods. Particular interest is focused to direct mass spectrometric methods as they allow breath-by-breath analyses without evaluation delays. Recent developments in metal oxide sensor technology have awoke the interest in this technology above all due to low energy consumption and maintenance requirements. Furthermore, the recent discoveries of close relationships between specific compounds present in exhaled breath and physiological changes feeds the hope of developing possible noninvasive diagnostic and monitoring tools to diagnose immune dysfunctional states, infections, and cancer. With these recent progresses the technical cornerstone for exhaled breath gas analyses during space missions has been realized. Current research projects focus on the evaluation of exhaled breath gas compound standard values and the impact of stressors in space akin weightlessness, confinement, nutritional changes, hypoxia, and radiation exposure.



Supported in part by the Department of Anaesthesiology of the University of Munich, the European Space Agency, the National Aeronautics and Space Administration (NASA), the Institute for Biomedical Problems (IBMP), the French and Italian Polar institutes (IPEV, PNRA), the German Space and Aeronautics Centre (DLR) & and the German Federal Ministry of Economics and Technology (50WB0523, 50WB0719, 50WB0919, 50WB1317), and the Kompetenzzentrum Medizin in Tirol, project 09A.


  1. Amann A, Spanel P, Smith D (2007) Breath analysis: the approach towards clinical applications. Mini Rev Med Chem 7:115–129CrossRefPubMedPubMedCentralGoogle Scholar
  2. Bond JH, Levitt MD (1976) Quantitative measurement of lactose absorption. Gastroenterology 70:1058–1062CrossRefPubMedPubMedCentralGoogle Scholar
  3. Braden B (2009) Methods and functions: breath tests. Best Pract Res Clin Gastroenterol 23:337–352CrossRefPubMedPubMedCentralGoogle Scholar
  4. Buszewski B, Kesy M, Ligor T et al (2007) Human exhaled air analytics: biomarkers of diseases. Biomed Chromatogr 21:553–566CrossRefPubMedPubMedCentralGoogle Scholar
  5. Buszewski B, Ulanowska A, Ligor T et al (2009) Analysis of exhaled breath from smokers, passive smokers and non-smokers by solid-phase microextraction gas chromatography/mass spectrometry. Biomed Chromatogr 23:551–556CrossRefPubMedPubMedCentralGoogle Scholar
  6. Choukèr A, Kaufmann I, Dolch M et al (2007) Stress responses during parabolic flight maneuvers are reflected by changes in expiratory air. In: (Iabr) SMOTIaOBR (ed) Breath analysis summit 2007: clinical applications of breath testings, Cleveland, 1–3 Nov 2007Google Scholar
  7. Christl SU, Murgatroyd PR, Gibson GR et al (1992) Production, metabolism, and excretion of hydrogen in the large intestine. Gastroenterology 102:1269–1277CrossRefPubMedPubMedCentralGoogle Scholar
  8. Davies S, Spanel P, Smith D (1997) Quantitative analysis of ammonia on the breath of patients in end-stage renal failure. Kidney Int 52:223–228CrossRefPubMedPubMedCentralGoogle Scholar
  9. De Lacy Costello B, Amann A, Al-Kateb H et al (2014) A review of the volatiles from the healthy human body. J Breath Res 8(1):014001CrossRefPubMedPubMedCentralGoogle Scholar
  10. Dolch M, Frey L, Hornuss C et al (2008) Molecular breath-gas analysis by online mass spectrometry in mechanically ventilated patients: a new software-based method of CO2-controlled alveolar gas monitoring. J Breath Res 2(3):037010CrossRefPubMedPubMedCentralGoogle Scholar
  11. Dolch ME, Choukèr A, Hornuss C et al (2015) Quantification ofpropionaldehydeinbreathofpatientsafter lung transplantation. Free Radic Biol Med 85:157–164CrossRefPubMedPubMedCentralGoogle Scholar
  12. Dolch ME, Hummel T, Fetter V et al (2017) Electronic nose functionality for breath gas analysis during parabolic flight. Microgravity Sci Technol 29:201–207CrossRefGoogle Scholar
  13. Endre ZH, Pickering JW, Storer MK et al (2011) Breath ammonia and trimethylamine allow real-time monitoring of haemodialysis efficacy. Physiol Meas 32:115–130CrossRefPubMedPubMedCentralGoogle Scholar
  14. Gelmont D, Stein RA, Mead JF (1981) Isoprene-the main hydrocarbon in human breath. Biochem Biophys Res Commun 99:1456–1460CrossRefPubMedPubMedCentralGoogle Scholar
  15. Graham DY, Klein PD, Evans DJ Jr et al (1987) Campylobacter pylori detected noninvasively by the 13C-urea breath test. Lancet 1:1174–1177CrossRefPubMedPubMedCentralGoogle Scholar
  16. Guo L, Wang C, Chi C et al (2015) Exhaled breath volatile biomarker analysis for thyroid cancer. Transl Res 166:188–195CrossRefPubMedPubMedCentralGoogle Scholar
  17. Hornuss C, Praun S, Villinger J et al (2007) Real-time monitoring of propofol in expired air in humans undergoing total intravenous anesthesia. Anesthesiology 106:665–674CrossRefPubMedPubMedCentralGoogle Scholar
  18. Karl T, Prazeller P, Mayr D et al (2001) Human breath isoprene and its relation to blood cholesterol levels: new measurements and modeling. J Appl Physiol 91:762–770CrossRefPubMedPubMedCentralGoogle Scholar
  19. Karlsson LL, Kerckx Y, Gustafsson LE et al (2009) Microgravity decreases and hypergravity increases exhaled nitric oxide. J Appl Physiol 107:1431–1437CrossRefPubMedPubMedCentralGoogle Scholar
  20. Kazui M, Andreoni KA, Williams GM et al (1994) Visceral lipid peroxidation occurs at reperfusion after supraceliac aortic cross-clamping. J Vasc Surg 19:473–477CrossRefPubMedPubMedCentralGoogle Scholar
  21. Kövesi TS, Royston D, Yacoub MH et al (2003) Exhaled nitric oxide in human lung ischemia-reperfusion. In: Marczin N, Kharitonov SA, Yacoub MH et al (eds) Disease markers in exhaled breath. Marcel Dekker, Inc, New York/BaselGoogle Scholar
  22. Kramer A, Below H, Bieber N et al (2007) Quantity of ethanol absorption after excessive hand disinfection using three commercially available hand rubs is minimal and below toxic levels for humans. BMC Infect Dis 7:117CrossRefPubMedPubMedCentralGoogle Scholar
  23. Lewis JM, Savage RS, Beeching NJ et al (2017) Identifying volatile metabolite signatures for the diagnosis of bacterial respiratory tract infection using electronic nose technology: a pilot study. PLoS One 12:e0188879CrossRefPubMedPubMedCentralGoogle Scholar
  24. Li P, Xu G, Wang C et al (2009) Breath pentane: an indicator for early and continuous monitoring of lipid peroxidation in hepatic ischaemia-reperfusion injury. Eur J Anaesthesiol 26:513–519CrossRefPubMedPubMedCentralGoogle Scholar
  25. Lindinger W, Hansel A, Jordan A (1998) On-line monitoring of volatile organic compounds at pptv levels by means of proton-transfer-reaction mass spectrometry (PTR-MS) medical applications, food control and environmental research. Int J Mass Spectrom Ion Process 173:191–241CrossRefGoogle Scholar
  26. Markar SR, Brodie B, Chin ST et al (2018) Profile of exhaled-breath volatile organic compounds to diagnose pancreatic cancer. Br J Surg 105:1493–1500CrossRefPubMedPubMedCentralGoogle Scholar
  27. Miekisch W, Schubert JK, Noeldge-Schomburg GFE (2004) Diagnostic potential of breath analysis - focus on volatile organic compounds. Clin Chim Acta 347:25–39CrossRefPubMedPubMedCentralGoogle Scholar
  28. Modak AS (2007) Stable isotope breath tests in clinical medicine: a review. J Breath Res 1:014003CrossRefPubMedPubMedCentralGoogle Scholar
  29. Moeskops BW, Steeghs MM, Van Swam K et al (2006) Real-time trace gas sensing of ethylene, propanal and acetaldehyde from human skin in vivo. Physiol Meas 27:1187–1196CrossRefPubMedPubMedCentralGoogle Scholar
  30. Pauling L, Robinson AB, Teranish R et al (1971) Quantitative analysis of urine vapor and breath by gas-liquid partition chromatography. Proc Natl Acad Sci U S A 68:2374–2376CrossRefPubMedPubMedCentralGoogle Scholar
  31. Pedrosa M, Cancelliere N, Barranco P et al (2010) Usefulness of exhaled nitric oxide for diagnosing asthma. J Asthma 47:817–821CrossRefPubMedPubMedCentralGoogle Scholar
  32. Phillips M, Boehmer JP, Cataneo RN et al (2004) Heart allograft rejection: detection with breath alkanes in low levels (the HARDBALL study). J Heart Lung Transplant 23:701–708CrossRefPubMedPubMedCentralGoogle Scholar
  33. Phillips M, Bauer TL, Cataneo RN et al (2015) Blinded validation of breath biomarkers of lung cancer, a potential ancillary to chest CT screening. PLoS One 10:e0142484CrossRefPubMedPubMedCentralGoogle Scholar
  34. Phillips M, Cataneo RN, Cruz-Ramos JA et al (2018) Prediction of breast cancer risk with volatile biomarkers in breath. Breast Cancer Res Treat 170:343–350CrossRefPubMedPubMedCentralGoogle Scholar
  35. Pinggera GM, Lirk P, Bodogri F et al (2005) Urinary acetonitrile concentrations correlate with recent smoking behaviour. BJU Int 95:306–309CrossRefPubMedPubMedCentralGoogle Scholar
  36. Reidt U, Helwig A, Müller G et al (2017) Detection of microorganisms onboard the international Space Station using an electronic nose. Gravit Space Res 5:89–111Google Scholar
  37. Risby TH (2005) Current status of clinical breath analysis. In: Amann A, Smith D (eds) Breath analysis for clinical diagnosis and therapeutic monitoring. World Scientific Publishing, SingaporeGoogle Scholar
  38. Risby TH, Sehnert SS (1999) Clinical application of breath biomarkers of oxidative stress status. Free Radic Biol Med 27:1182–1192CrossRefPubMedPubMedCentralGoogle Scholar
  39. Roccarina D, Lauritano EC, Gabrielli M et al (2010) The role of methane in intestinal diseases. Am J Gastroenterol 105:1250–1256CrossRefPubMedPubMedCentralGoogle Scholar
  40. Romagnuolo J, Schiller D, Bailey RJ (2002) Using breath tests wisely in a gastroenterology practice: an evidence-based review of indications and pitfalls in interpretation. Am J Gastroenterol 97:1113–1126CrossRefPubMedPubMedCentralGoogle Scholar
  41. Schmoelz M, Praun S, Schmoeckel M et al (2007) Online measurement of acetone in expiratory air by mass spectrometry during cardiac surgery. In: Annual meeting of the American Society of Anesthesiologists, San Francisco, 16 Oct, A1426Google Scholar
  42. Scholpp J, Schubert JK, Miekisch W et al (2002) Breath markers and soluble lipid peroxidation markers in critically ill patients. Clin Chem Lab Med 40:587–594CrossRefPubMedPubMedCentralGoogle Scholar
  43. Schubert JK, Müller WPE, Benzing A et al (1998) Application of a new method for analysis of exhaled gas in critically ill patients. Intensive Care Med 24:415–421CrossRefPubMedPubMedCentralGoogle Scholar
  44. Schubert JK, Miekisch W, Birken T et al (2005) Impact of inspired substance concentrations on the results of breath analysis in mechanically ventilated patients. Biomarkers 10:138–152CrossRefPubMedPubMedCentralGoogle Scholar
  45. Smith D, Wang T, Spanel P (2002) On-line, simultaneous quantification of ethanol, some metabolites and water vapour in breath following the ingestion of alcohol. Physiol Meas 23:477–489CrossRefPubMedPubMedCentralGoogle Scholar
  46. Smolinska A, Tedjo DI, Blanchet L et al (2018) Volatile metabolites in breath strongly correlate with gut microbiome in CD patients. Anal Chim Acta 1025:1–11CrossRefPubMedPubMedCentralGoogle Scholar
  47. Steeghs MM, Moeskops BW, Van Swam K et al (2006) On-line monitoring of UV-induced lipid peroxidation products, from human skin in vivo using proton-transfer reaction mass spectrometry. Int J Mass Spectrom 253:58–64Google Scholar
  48. Stenseth R, Nilsen T, Haaverstad R et al (2007) Frequent sampling allows detection of short and rapid surges of exhaled ethane during cardiac surgery. Perfusion 22:391–396CrossRefPubMedPubMedCentralGoogle Scholar
  49. Szulejko JE, Mcculloch M, Jackson J et al (2010) Evidence for cancer biomarkers in exhaled breath. IEEE Sensors J 10:25CrossRefGoogle Scholar
  50. Turner S (2007) The role of exhaled nitric oxide in the diagnosis, management and treatment of asthma. Mini Rev Med Chem 7:539–542PubMedPubMedCentralGoogle Scholar
  51. Turner C, Spanel P, Smith D (2006a) A longitudinal study of ammonia, acetone and propanol in the exhaled breath of 30 subjects using selected ion flow tube mass spectrometry, SIFT-MS. Physiol Meas 27:321–337CrossRefPubMedPubMedCentralGoogle Scholar
  52. Turner C, Spanel P, Smith D (2006b) A longitudinal study of breath isoprene in healthy volunteers using selected ion flow tube mass spectrometry (SIFT-MS). Physiol Meas 27:13–22CrossRefPubMedPubMedCentralGoogle Scholar
  53. Van Den Velde S, Nevens F, Van Hee P et al (2008) GC-MS analysis of breath odor compounds in liver patients. J Chromatogr B Analyt Technol Biomed Life Sci 875:344–348CrossRefPubMedPubMedCentralGoogle Scholar
  54. Wang C, Sun B, Guo L et al (2014) Volatile organic metabolites identify patients with breast cancer, cyclomastopathy, and mammary gland fibroma. Sci Rep 4:5383CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Michael Dolch
    • 1
    Email author
  • Siegfried Praun
    • 2
  • Johannes Villiger
    • 2
  • Alexander Choukér
    • 1
  • Gustav Schelling
    • 1
  1. 1.Department of AnaesthesiologyHospital of the University of Munich (LMU)MunichGermany
  2. 2.V&F Analyse- und Messtechnik GmbHAbsamAustria

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