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Cancer detection by analysis of exhaled breath


BAMOD Structure

Cancer is one of the leading causes of death in Europe and the western world. At present, diagnosis of cancer very often happens late in the course of the disease since available diagnostic methods are not sufficiently sensitive and specific. An early diagnosis of cancer would improve prognosis and treatment and could save thousands of lives a year.
There is strong evidence to suggest that certain cancers can be detected by molecular analysis of exhaled air. Breath analysis represents a new diagnostic technique that is without risk for the patient even if repeated frequently and can provide information beyond conventional analysis of blood and urine. Recent results suggest that detection of different kinds of cancer is possible by means of breath analysis in very early stages of the disease.

The project BAMOD is focused on the diagnosis of minimal disease and early stages of lung and oesophageal cancer. The analytical techniques will be:

  • gas chromatography with mass spectrometric detection (GC-MS)
  • proton transfer reaction mass spectrometry (PTR-MS)
  • selected ion flow tube mass spectrometry (SIFT-MS)
  • laser spectrometry
  • ion mobility spectrometry (IMS).

In order to establish a reliable clinical method for the diagnosis of minimal residual cancer diseases clinical expertise, basic research and technical development is necessary.
The objectives of the project are the development of

  • sensitive and specific markers sets for the detection of early cancer stages based on human breath
  • reliable analytical methods to determine these markers in the clinical environment
  • easy-to-use and non-expensive equipment establishing breath analysis as a novel cancer screening tool

The project BAMOD is centred around 5 studies: A lung cancer patient study, an oesophageal cancer study, a study of cancer cell lines, a study of immune-system related cells and a study of bacterial cell lines. The SMEs in our consortium will develop analytical methodology for subsequent use in clinical applications.

Previous studies showed that the project goal is promising [1-6]. Using GC-MS, substances in exhaled breath gas samples can be identified and quantified [7-10]. Nevertheless, online measurements with this technique are impossible. For online measurements with cell cultures and humans, we use PTR-MS [11], SIFT-MS [12-15], laser spectrometry [16-19] and ion mobility spectrometry [20, 21]. An overview on different techniques and clinical applications is presented in ref. [22].
Origin, biochemical pathways and distribution of the most volatile organic marker molecules are still unknown [23, 24]. For the use of breath tests in clinical praxis it is essential to know origins of marker molecules as well as potential confounding variables.

References:

1.         Phillips, M., et al., Volatile organic compounds in breath as markers of lung cancer: a cross-sectional study. Lancet, 1999. 353(9168): p. 1930-3.

2.         Phillips, M., et al., Detection of lung cancer with volatile markers in the breath. Chest, 2003. 123(6): p. 2115-23.

3.         Phillips, M., et al., Volatile markers of breast cancer in the breath. Breast J, 2003. 9(3): p. 184-91.

4.         Di Natale, C., et al., Lung cancer identification by the analysis of breath by means of an array of non-selective gas sensors. Biosens Bioelectron, 2003. 18(10): p. 1209-18.

5.         Machado, R.F., et al., Detection of lung cancer by sensor array analyses of exhaled breath. Am J Respir Crit Care Med, 2005. 171(11): p. 1286-91.

6.         Smith, D., et al., Quantification of acetaldehyde released by lung cancer cells in vitro using selected ion flow tube mass spectrometry. Rapid Commun Mass Spectrom, 2003. 17(8): p. 845-50.

7.         Schubert, J., et al., Impact of inspired substance concentrations onto results of breath analysis in mechanically ventilated patients. Biomarkers, 2005: p. in press.

8.         Schubert, J., W. Miekisch, and G. Nöldge-Schomburg, VOC breath markers in critically ill patients: potentials and limitations, in Breath Analysis for Clinical Diagnosis and Therapeutic Monitoring, A. Amann and D. Smith, Editors. 2005, World Scientific: Singapore.

9.         Schubert, J., W. Miekisch, and K. Geiger, Exhaled breath markers in ARDS, in Lung Biology in Health and Disease. Disease Markers in Exhaled Breath, N. Marczin and S. Kharitonov, Editors. 2003, Marcel Dekker: New York. p. 363 - 380.

10.       Schubert, J., W. Miekisch, and G. Nöldge-Schomburg, VOC breath markers in critically ill patients: potentials and limitations, in Breath Analysis for Clinical Diagnosis and Therapeutic Monitoring, A. Amann and D. Smith, Editors. 2005, World Scientific: Singapore. p. 267 - 292.

11.       Amann, A., et al., Exhaled breath as a biochemical probe during sleep, in Breath Analysis for Clinical Diagnosis and Therapeutic Monitoring, A. Amann and D. Smith, Editors. 2005, World Scientific: Singapore. p. 305 - 316.

12.       Smith, D. and P. Spanel, Selected ion flow tube mass spectrometry (SIFT-MS) for on-line trace gas analysis. Mass Spectrom Rev, 2005: p. Published on-line 2004: http://dx.doi.org/10.1002/mas.20033.

13.       Spanel, P. and D. Smith, Flowing afterglow mass spectrometry (FA-MS) for the determination of the deuterium abundance in breath water vapour and aqueous liquid headspace, in Breath Analysis for Clinical Diagnosis and Therapeutic Monitoring, A. Amann and D. Smith, Editors. 2005, World Scientific: Singapore.

14.       Spanel, P., T. Wang, and D. Smith, Parallel FA-MS and SIFT-MS analyses for the variation of HDO and ethanol in breath after oral administration; total body water dispersal and ethanol metabolism. Physiol Meas, 2005: p. in press.

15.       Spanel, P. and D. Smith, Selected Ion Flow Tube Mass Spectrometry (SIFT-MS) and Flowing Afterglow Mass Spectrometry (FA-MS) for the Determination of the Deuterium Abundance in Water Vapour, in Handbook of Stable Isotope Analytical Techniques (Volume I), P. de Groot, Editor. 2004, Elsevier: Amsterdam.

16.       von Basum, G., et al., Parts per trillion sensitivity for ethane in air with an optical parametric oscillator cavity leak-out spectrometer. Opt Lett, 2004. 29(8): p. 797-9.

17.       Wysocki, G., et al., Pulsed quantum-cascade laser-based sensor for trace-gas detection of carbonyl sulfide. Appl Opt, 2004. 43(32): p. 6040-6.

18.       Wysocki, G., et al., Exhaled human breath analysis with quantum cascade laser-based gas sensors, in Breath Analysis for Clinical Diagnosis and Therapeutic Monitoring, A. Amann and D. Smith, Editors. 2005, World Scientific: Singapore. p. 75 - 84.

19.       von Basum, G., et al., Laser spectroscopic on-line monitoring of exhaled trace gases, in Breath Analysis for Clinical Diagnosis and Therapeutic Monitoring, A. Amann and D. Smith, Editors. 2005, World Scientific: Singapore. p. 67 - 74.

20.       Ruzsanyi, V., S. Sielemann, and J. Baumbach, Determination of VOCs in human breath using IMS. Int J Ion Mobility Spectrometry, 2002. 5: p. 45 - 48.

21.       Baumbach, J., et al., Metabolites in human breath: ion mobility spectrometers as diagnostic tools for lung diseases, in Breath Analysis for Clinical Diagnosis and Therapeutic Monitoring, A. Amann and D. Smith, Editors. 2005, World Scientific: Singapore. p. 53 - 66.

22.       Amann, A. and D. Smith, Breath Analysis for Clinical Diagnosis and Therapeutic Monitoring. 2005, Singapore: World Scientific.

23.       Risby, T., Current status of clinical breath analysis, in Breath Analysis for Clinical Diagnosis and Therapeutic Monitoring, A. Amann and D. Smith, Editors. 2005, World Scientific: Singapore. p. 251 - 265.

24.       Risby, T., In vivo assessment of injury and disease based on breath., in Breath Gas For Medical Diagnostics, A. Amann and D. Smith, Editors. 2004, World Scientific: Singapore.