Skip to main content

Advertisement

SpringerLink
Log in

Significant different volatile biomarker during bronchoscopic ion mobility spectrometry investigation of patients suffering lung carcinoma

  • Original Research
  • Published:
International Journal for Ion Mobility Spectrometry

Abstract

Exhaled breath of patients suffering non-small bronchial carcinoma contains volatile organic compounds (VOC) different from healthy people. VOCs could be detected using ion mobility spectrometry down to the pg/L range even in air directly. To date, the origin of the different VOCs found is insecure. Such VOCs could be a direct product of the metabolism of the tumor or relatable to mostly present co-factors like infections or necrosis or a reaction of the human organism to the tumor (e.g. oxidativ stress). In the present study the breath of 19 patients suffering from confirmed NSCLC (non-small-cell lung carcinoma) with different histological types was investigated. In all cases flexible video-chip bronchoscopy was realized. Before taking samples for histological investigations in the lung on both main bronchi, samples of air were taken using a polytetrafluoroethylene (PTFE or Teflon) tube as catheter directly from the working channel of a bronchoscope and connected directly to the inlet of the ion mobility spectrometer. The measurement was started immediately. In total, 72 common peaks could be identified. 5 Peaks were significantly varying between the tumor site and the collateral lung. Considering adenocarcinoma, one peak separates both sites clearly and was relatable to the dimer of n-Dodecane. Two peaks were found on squamous cell carcinoma and relatable to 2-Butanol or 2-Methylfuran and Nonanal. The sensitivity, specificity, positive and negative predictive values were, for adenocarcinoma 100%, 75%, 80% and 100%, respectively – for squamous cell carcinoma 78%/78%, 67%/78%, 70%/80% and 75%/88%, for 2-Butanol and Nonanal respectively. Therefore, VOCs obtained from bronchoscopic sampling of breath could be detected using ion mobility spectrometry. The present study suggests that lung carcinoma with different histology will be represented by different volatile analytes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Phillips M, Herrera J, Krishnan S, Zain M, Greenberg J, Cataneo RN (1999) Variation in volatile organic compounds in the breath of normal humans. J Chromatogr B Biomed Sci Appl 729:75–88

    Article  CAS  Google Scholar 

  2. Amann A, Corradi M, Mazzone P, Mutti A (2011) Lung cancer biomarkers in exhaled breath. Expert Rev Mol Diagn 11:207–217. doi:10.1586/erm.10.112

    Article  CAS  Google Scholar 

  3. Amann A, Poupart G, Telser S, Ledochowski M, Schmid A, Mechtcheriakov S (2004) Applications of breath gas analysis in medicine. Int J Mass Spectrom 239:227–233

    Article  CAS  Google Scholar 

  4. Barker M, Hengst M, Schmid J, Buers HJ, Mittermaier B, Klemp D, Koppmann R, Barker M, Hengst M, Schmid J, Buers HJ, Mittermaier B, Klemp D, Koppmann R (2006) Volatile organic compounds in the exhaled breath of young patients with cystic fibrosis. Eur Respir J 27:929–936, Epub 2006 Feb 2002

    CAS  Google Scholar 

  5. Basanta M et al (2010) Non-invasive metabolomic analysis of breath using differential mobility spectrometry in patients with chronic obstructive pulmonary disease and healthy smokers. Analyst 135:315–320. doi:10.1039/b916374c

    Article  CAS  Google Scholar 

  6. Bunkowski A, Maddula S, Davies AN, Westhoff M, Litterst P, Bödecker B, Baumbach JI (2010) One-year time series of investigations of analytes within human breath using ion mobility spectrometry. Int J Ion Mobility Spectrom 13:141–148. doi:10.1007/s12127-010-0052-7

    Article  CAS  Google Scholar 

  7. Cho SM, Kim YJ, Heo GS, Shin S-M (2006) Two-step preconcentration for analysis of exhaled gas of human breath with electronic nose. Sensors and Actuators B: Chemical 117:50–57

    Article  Google Scholar 

  8. Fens N, Zwinderman AH, van der Schee MP, de Nijs SB, Dijkers E, Roldaan AC, Cheung D, Bel EH, Sterk PJ (2009) Exhaled Breath Profiling Enables Discrimination of Chronic Obstructive Pulmonary Disease and Asthma. Am J Respir Crit Care Med 180:1076–1082. doi:10.1164/rccm.200906-0939OC

    Article  CAS  Google Scholar 

  9. Jünger M, Bödeker B, Baumbach JI (2010) Peak assignment in multi-capillary column - ion mobility spectrometry using comparative studies with gas chromatography - mass spectrometry for exhalred breath analysis. Anal Bioanal Chem 396:471–482. doi:10.1007/s00216-009-3168-z

    Article  Google Scholar 

  10. Machado RF et al (2005) Detection of lung cancer by sensor array analyses of exhaled breath. Am J Respir Crit Care Med 171:1286–1291. doi:10.1164/rccm.200409-1184OC

    Article  Google Scholar 

  11. Machado Roberto F et al (2005) Detection of lung cancer by sensor array analyses of exhaled breath. Am J Respir Crit Care Med 171:1286–1291

    Article  CAS  Google Scholar 

  12. Martin AN, Farquar GR, Jones AD, Frank M (2010) Human breath analysis: methods for sample collection and reduction of localized background effects. Anal Bioanal Chem 396:739–750

    Article  CAS  Google Scholar 

  13. Mazzone PJ, Hammel J, Dweik R, Na J, Czich C, Laskowski D, Mekhail T (2007) Diagnosis of lung cancer by the analysis of exhaled breath with a colorimetric sensor array. Thorax 62:565–568. doi:10.1136/thx.2006.072892

    Article  Google Scholar 

  14. Miekisch W, Hengstenberg A, Kischkel S, Beckmann U, Mieth M, Schubert JK (2010) Construction and Evaluation of a Versatile CO2 Controlled Breath Collection Device. IEEE Sens J 10:211–215. doi:10.1109/jsen.2009.2035757

    Article  CAS  Google Scholar 

  15. Mieth M, Kischkel S, Schubert JK, Hein D, Miekisch W (2009) Multibed Needle Trap Devices for on Site Sampling and Preconcentration of Volatile Breath Biomarkers. Anal Chem 81:5851–5857. doi:10.1021/ac9009269

    Article  CAS  Google Scholar 

  16. Mieth M, Schubert JK, Groger T, Sabel B, Kischkel S, Fuchs P, Hein D, Zimmermann R, Miekisch W (2010) Automated Needle Trap Heart-Cut GC/MS and Needle Trap Comprehensive Two-Dimensional GC/TOF-MS for Breath Gas Analysis in the Clinical Environment. Anal Chem 82:2541–2551. doi:10.1021/ac100061k

    Article  CAS  Google Scholar 

  17. Moretti M, Phillips M, Abouzeid A, Cataneo RN, Greenberg J (2004) Increased breath markers of oxidative stress in normal pregnancy and in preeclampsia. Am J of Obstetics and Gynecology 190:1184–1190

    Article  CAS  Google Scholar 

  18. Phillips M, Cataneo RN, Cheema T, Greenberg J (2004) Increased breath biomarkers of oxidative stress in diabetes mellitus. Clin Chim Acta 344:189–194

    Article  CAS  Google Scholar 

  19. Phillips M, Cataneo RN, Greenberg J, Munawar M, Nachnani S, Samtani S (2005) Pilot study of a breath test for volatile organic compounds associated with oral malodor: evidence for the role of oxidative stress. Oral Dis 11(Suppl 1):32–34

    Article  Google Scholar 

  20. Pleil JD, Lindstrom AB (1997) Exhaled Human Breath Measurement Method for Assessing Exposure to Halogenated Volatile Organic Compounds. Clin Chem 43:723–730

    CAS  Google Scholar 

  21. Van Berkel J, Dallinga JW, Moller GM, Godschalk RWL, Moonen EJ, Wouters EFM, Van Schooten FJ (2010) A profile of volatile organic compounds in breath discriminates COPD patients from controls. Respir Med 104:557–563. doi:10.1016/j.rmed.2009.10.018

    Article  Google Scholar 

  22. Westhoff M, Litterst P, Freitag L, Urfer W, Bader S, Baumbach JI (2009) Ion mobility spectrometry for the detection of volatile organic compounds in exhaled breath of patients with lung cancer: results of a pilot study. Thorax 64:744–748. doi:10.1136/thx.2008.099465

    Article  CAS  Google Scholar 

  23. Buszewski B, Kesy M, Ligor T, Amann A (2007) Human exhaled air analytics: biomarker of diseases. Biomed Chromatogr 21:553–566

    Article  CAS  Google Scholar 

  24. Horvath I, Lazar Z, Gyulai N, Kollai M, Losonczy G (2009) Exhaled biomarkers in lung cancer. Eur Respir J 34:261–275. doi:10.1183/09031936.00142508

    Article  CAS  Google Scholar 

  25. Bunkowski A, Boedeker B, Bader S, Westhoff M, Litterst P, Baumbach JI (2009) MCC/IMS signals in human breath related to sarcoidosis-results of a feasibility study using an automated peak finding procedure. J Breath Res 3, 046001/046001-046001/046010

  26. Westhoff M, Litterst P, Freitag L, Baumbach JI (2007) Ion mobility spectrometry in the diagnosis of Sarcoidosis: Results of a feasibility study. J Physiol Pharmacol 58:739–751

    Google Scholar 

  27. Baumbach JI, Westhoff M (2006) Ion mobility spectrometry to detect lung cancer and airway infections. Spectroscopy Europe 18:22–27

    CAS  Google Scholar 

  28. Baumbach JI (2006) Process analysis using ion mobility spectrometry. Anal Bioanal Chem 384:1059–1070

    Article  CAS  Google Scholar 

  29. Westhoff M, Litterst P, Maddula S, Bödecker B, Rahmann S, Davies AN, Baumbach JI (2010) Differentiation of chronic obstructive pulmonary disease (COPD) including lung cancer from healthy control group by breath analysis using ion mobility spectrometry Int. J Ion Mobility Spectrom 13:131–139

    Article  CAS  Google Scholar 

  30. Bödecker B, Davies AN, Maddula S, Baumbach JI (2010) Biomarker validation—room air variation during human breath investigations. Int J Ion Mobility Spectrom 13:177–184. doi:10.1007/s12127-010-0044-7

    Article  Google Scholar 

  31. Maddula S, Blank L, Schmid A, Baumbach JI (2009) Detection of volatile metabolites of Escherichia coli by multi capillary column coupled ion mobility spectrometry. Anal Bioanal Chem 394:791–800

    Article  CAS  Google Scholar 

  32. Bödeker B, Baumbach JI (2009) Analytical Description of IMS-Signals. Int J Ion Mobility Spectrom 12:103–108. doi:10.1007/s12127-009-0024-y

    Article  Google Scholar 

  33. Bödeker B, Vautz W, Baumbach JI (2008) Peak Finding and Referencing in MCC/IMS - Data. Int J Ion Mobility Spectrom 11:83–88

    Article  Google Scholar 

  34. Bödeker B, Vautz W, Baumbach JI (2008) Peak Comparison in MCC/IMS – Data – Searching for potential biomarkers in human breath data. Int J Ion Mobility Spectrom 11:89–93

    Article  Google Scholar 

  35. Bödeker B, Vautz W, Baumbach JI (2008) Visualisation of MCC/IMS – Data. Int J Ion Mobility Spectrom 11:77–82

    Article  Google Scholar 

  36. Hu Y, Qiu Y, Chen E, Ying K, Yu J, Wang P (2010) Determination of volatile organic compounds in lung cancer cell lines and lung cancer tissue. Zhejiang Daxue Xuebao, Yixueban 39:278–284. doi:10.3785/j.issn.1008-9292.2010.03.011

    CAS  Google Scholar 

  37. Gaspar EM, Lucena AF, Duro dCJ, Chaves dNH (2009) Organic metabolites in exhaled human breath - A multivariate approach for identification of biomarkers in lung disorders. J. Chromatogr., A 1216, 2749–2756, doi:10.1016/j.chroma.2008.10.125

  38. Phillips M, Cataneo RN, Sounders C, Hope P, Schmitt P, Wai J (2010) Volatile biomarkers in the breath of women with breast cancer. J Breath Res 4. doi:10.1088/1752-7155/4/2/026003

  39. Van Berkel JJBN, Dallinga JW, Moeller GM, Godschalk RWL, Moonen E, Wouters EFM, Van Schooten FJ (2008) Development of accurate classification method based on the analysis of volatile organic compounds from human exhaled air. J Chromatogr B: Anal Technol Biomed Life Sci 861:101–107

    Article  Google Scholar 

  40. Sanchez JM, Sacks RD (2006) Development of a Multibed Sorption Trap, Comprehensive Two-Dimensional Gas Chromatography, and Time-of-Flight Mass Spectrometry System for the Analysis of Volatile Organic Compounds in Human Breath. Anal Chem 78:3046–3054

    Article  CAS  Google Scholar 

  41. Muehlberger F, Streibel T, Wieser J, Ulrich A, Zimmermann R (2005) Single Photon Ionization Time-of-Flight Mass Spectrometry with a Pulsed Electron Beam Pumped Excimer VUV Lamp for On-Line Gas Analysis: Setup and First Results on Cigarette Smoke and Human Breath. Anal Chem 77:7408–7414

    Article  CAS  Google Scholar 

  42. Buszewski B, Ulanowska A, Ligor T, Denderz N, Amann A (2009) Analysis of exhaled breath from smokers, passive smokers and non-smokers by solid-phase microextraction gas chromatography/mass spectrometry. Biomed Chromatogr 23:551–556

    Article  CAS  Google Scholar 

  43. Zechman JM, Aldinger S, Labows JN Jr (1986) Characterization of pathogenic bacteria by automated headspace concentration-gas chromatography. J Chromatogr 377:49–57

    Article  CAS  Google Scholar 

  44. Ruzsanyi V, Baumbach JI, Eiceman GA (2003) Detection of the mold markers using ion mobility spectrometry. Int J Ion Mobility Spectrom 6:53–57

    CAS  Google Scholar 

  45. Bajtarevic A et al (2009) Noninvasive detection of lung cancer by analysis of exhaled breath. BMC Cancer 9, doi:10.1186/1471-2407-9-348

  46. Ulanowska A, Ligor M, Amann A, Buszewski B (2008) Determination of volatile organic compounds in exhaled breath by ion mobility spectrometry. Chem Anal (Warsaw, Pol) 53:953–965

    CAS  Google Scholar 

  47. Basanta M, Koimtzis T, Singh D, Wilson I, Thomas CLP (2007) An adaptive breath sampler for use with human subjects with an impaired respiratory function. Analyst (Cambridge, U K 132:153–163

    Article  CAS  Google Scholar 

  48. Fuchs P, Loeseken C, Schubert JK, Miekisch W (2010) Breath gas aldehydes as biomarkers of lung cancer. Int J Cancer 126:2663–2670

    CAS  Google Scholar 

  49. O’Neill HJ, Gordon SM, O'Neill MH, Gibbons RD, Szidon JP (1988) A computerized classification technique for screening for the presence of breath biomarkers in lung cancer. Clin Chem 34:1613–1618

    Google Scholar 

  50. Corradi M, Rubinstein I, Andreoli R, Manini P, Caglieri A, Poli D, Alinovi R, Mutti A (2003) Aldehydes in exhaled breath condensate of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 167:1380–1386

    Article  Google Scholar 

Download references

Acknowledgements

The authors want to acknowledge the helpful discussions and cooperation with the following colleagues O. Anhenn (Clinic of the Ruhr, West German Lung Center at Essen University Hospital -University Clinic-), G. Becher (BecherConsult GmbH), U. Costabel, G. Kentrat, T. Rabis, G. Stamatis (all Ruhrlandklinik Essen), D. Theegarten (Pathology, University Clinic Essen), G. Weinreich and S. Welter (both Clinic of the Ruhr, West German Lung Center at Essen University Hospital -University Clinic-). The instrumentation was funded by the Clinic of the Ruhr, West German Lung Center at Essen University Hospital -University Clinic-.

The financial support of the Ministry of Education, Science and Technology (MEST) of the Republic Korea is acknowledged thankfully. Part of the work on this paper has been supported by Deutsche Forschungsgemeinschaft (DFG) within the Collaborative Research Center (Sonderforschungsbereich) SFB 876 “Providing Information by Resource-Constrained Analysis”, project TB1 “Resource-Constrained Analysis of Spectrometry Data”.

Author information

Authors and Affiliations

  1. KIST Europe, Department Microfluidics and Clinical Diagnostics, Campus E 71, 66123, Saarbrücken, Germany

    J. I. Baumbach & S. Maddula

  2. Clinic of the Ruhr, West German Lung Center at Essen University Hospital -University Clinic-, Tüschener Weg 40, 45239, Essen, Germany

    U. Sommerwerck, V. Besa, I. Kurth, H. Teschler, L. Freitag & K. Darwiche

  3. B&S Analytik, BioMedicalCenter, Otto-Hahn-Str. 15, 44227, Dortmund, Germany

    B. Bödeker

Authors
  1. J. I. Baumbach
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Maddula
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. U. Sommerwerck
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. V. Besa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. I. Kurth
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. B. Bödeker
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. H. Teschler
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. L. Freitag
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. K. Darwiche
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. I. Baumbach.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Baumbach, J.I., Maddula, S., Sommerwerck, U. et al. Significant different volatile biomarker during bronchoscopic ion mobility spectrometry investigation of patients suffering lung carcinoma. Int. J. Ion Mobil. Spec. 14, 159–166 (2011). https://doi.org/10.1007/s12127-011-0078-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12127-011-0078-5

Keywords

Search

Navigation