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Signals of neutropenia in human breath?

  • Technical Report
  • Published:
International Journal for Ion Mobility Spectrometry

Abstract

Children undergoing systemic chemotherapy often suffer from severe immunosuppression usually associated to severe neutropenia (neutrophils < 0.5 x 109/l). Clinical courses during those periods range from asymptomatic to septic general conditions. Development of septic symptoms can be very fast and life-threatening. Swift detection of risk factors in those patients is therefore needed. So far no early, rapid and reliable marker or tool exists. Ion-Mobility-Spectrometry coupled with a Multi-Capillary-Column (IMS-MCC) can analyze more than 600 volatile components from exhaled air within a few minutes and hence is a potential, rapid detection-tool. As a proof of concept we measured the exhaled breath of 11 patients with neutropenia and 10 healthy controls ranging from 3 to 18 years of age at the time of measurement. Ten milliliters breath samples were taken at the outpatient clinic and analyzed with an onsite IMS-MCC (BreathDiscovery, B&S Analytik, Dortmund, Germany). Dead-space-volume was adapted to two groups (small 250 ml, large 500 ml). Interestingly 59 differing peaks were measured. Eleven were significantly different (p ≤ 0.05), three of which highly significant (p ≤ 0.01) in Mann-Whitney-Rank-Sum-testing. The corresponding analytes used in the decision tree are 2-Propanol, D-Limonene and Acetone. The analytes with the lowest rank sum identified are 2-Hexanone, Iso-Propylamine and 1-Butanol. Eventually we were able to show a three-step-decision-tree, which discerns the 21 samples except one from each group. Sensitivity was 90 % and specificity was 91 %. Naturally these findings need further confirmation within a bigger population. Our pilot-study proves that Ion-Mobility-Spectrometry coupled with a Multi-Capillary-Column is a feasible rapid diagnostic tool in the setting of a pediatric oncology out-patient clinic for patients 3 years and older. Our first results furthermore encourage additional analysis as to whether patients at risk for septic events during immunosuppression can be diagnosed in advance by rapidly assessing risk factors such as Neutropenia in exhaled breath.

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References

  1. Simon A, Ammann RA, Bode U et al (2008) Healthcare-associated infections in pediatric cancer patients: results of a prospective surveillance study from university hospitals in Germany and Switzerland. BMC Infect Dis 8:70

    Article  Google Scholar 

  2. Ammann RA, Tissing WJE, Phillips B (2012) Rationalizing the approach to children with fever in neutropenia. Curr Opin Infect Dis 25:258–265

    Article  Google Scholar 

  3. Agyeman P, Aebi C, Hirt A et al (2011) Predicting bacteremia in children with cancer and fever in chemotherapy-induced neutropenia: results of the prospective multicenter SPOG 2003 FN study. Pediatr Infect Dis J 30:e114–e119

    Article  Google Scholar 

  4. Baumbach JI (2009) Ion mobility spectrometry coupled with multi-capillary columns for metabolic profiling of human breath. J Breath Res 3:034001

    Article  Google Scholar 

  5. Jünger M, Vautz W, Kuhns M et al (2012) Ion mobility spectrometry for microbial volatile organic compounds: a new identification tool for human pathogenic bacteria. Appl Microbiol Biotechnol 93:2603–2614

    Google Scholar 

  6. Maddula S, Blank LM, 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 

  7. Maddula S, Rabis T, Sommerwerck U et al (2011) Correlation analysis on data sets to detect infectious agents in the airways by ion mobility spectrometry of exhaled breath. Int J Ion Mobil Spectrom 14:197–206

    Article  CAS  Google Scholar 

  8. Rabis T, Sommerwerck U, Anhenn O et al (2011) Detection of infectious agents in the airways by ion mobility spectrometry of exhaled breath. Int J Ion Mobil Spectrom 14:187–195

    Article  CAS  Google Scholar 

  9. Fazekas T, Eickhoff P, Lawitschka A, Knotek B, Potschger U, Peters C (2012) Exhaled nitric oxide and pulmonary complications after paediatric stem cell transplantation. Eur J Pediatr 171:1095–1101

    Article  CAS  Google Scholar 

  10. Schneider T et al (2013) An integrative clinical database and diagnostics platform for biomarker identification and analysis in ion mobility spectra of human exhaled air. J Integr Bioinforma 10(2):218

    Google Scholar 

  11. Hauschild A-C et al (2013) Peak detection method evaluation for ion mobility spectrometry by using machine learning approaches. Metabolites 3:277–293

    Article  CAS  Google Scholar 

  12. Hauschild A-C et al (2012) Computational methods for metabolomic data analysis of ion mobility spectrometry data—reviewing the state of the art. Metabolites 2:733–755

    Article  CAS  Google Scholar 

  13. Hauschild A-C, Baumbach JI, Baumbach JI (2012) Integrated statistical learning of metabolic ion mobility spectrometry profiles for pulmonary disease identification. Genet Mol Res 11(3):2733–2744

    Article  CAS  Google Scholar 

  14. Westhoff M et al (2011) Statistical and bioinformatical methods to differentiate chronic obstructive pulmonary disease (COPD) including lung cancer from healthy control by breath analysis using ion mobility spectrometr. Int J Ion Mobil Spectrom 11(4):139–149

    Article  Google Scholar 

  15. Rabis T et al (2011) Detection of infectious agents in the airways by ion mobility spectrometry of exhaled breath. Int J Ion Mobil Spectrom 11(4):187–195

    Article  Google Scholar 

  16. Vogtland D, Baumbach JI (2009) Breit-Wigner-function and IMS-signals. Int J Ion Mobil Spectrom 12:109–114

    Article  CAS  Google Scholar 

  17. Bödeker B, Baumbach JI (2009) Analytical description of IMS-signals. Int J Ion Mobil Spectrom 12:103–108

    Article  Google Scholar 

  18. Westhoff M, Litterst P, Freitag L, Urfer W, Bader S, Baumbach J (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

    Article  CAS  Google Scholar 

  19. Westhoff M, Litterst P, Maddula S et al (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 Mobil Spectrom 13:131–139

    Article  CAS  Google Scholar 

  20. Westhoff M, Litterst P, Maddula S, Bödeker B, Baumbach JI (2011) Statistical and bioinformatical methods to differentiate chronic obstructive pulmonary disease (COPD) including lung cancer from healthy control by breath analysis using ion mobility spectrometry. Int J Ion Mobil Spectrom 14:139–149

    Article  CAS  Google Scholar 

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Acknowledgments

We thank Prof. N. Graf and the Elterninitiative krebskranker Kinder im Saarland e.V. for their financial support of this study. The data analysis part of the work of this paper (JIBB) has been supported by Deutsche Forschungsgemeinschaft (DFG, Germany) within the Collaborative Research Center (Sonderforschungsbereich) SFB 876 “Providing Information by Resource-Constrained Analysis”, project TB1 “Resource-Constrained Analysis of Spectrometry Data”.

Conflict of interest

JIBB is a shareholder of, BB and SM are employed at B&S Analytik GmbH, the manufacturer of BreathDiscovery.

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Authors and Affiliations

  1. Pediatric Hematology and Oncology, Saarland University Hospital, Building 9, 66421, Homburg, Germany

    R. Furtwängler, J. Hübel, H. Rakicioglou & A. Simon

  2. Max Planck Institut for Informatics, Im Stadtwald, 66123, Saarbrücken, Germany

    A.-C. Hauschild

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

    B. Bödeker, S. Maddula & J. I. Baumbach

  4. Faculty Applied Chemistry, Reutlingen University, Alteburgstraße 150, 72762, Reutlingen, Germany

    J. I. Baumbach

Authors
  1. R. Furtwängler
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  2. A.-C. Hauschild
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  3. J. Hübel
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  4. H. Rakicioglou
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  5. B. Bödeker
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  6. S. Maddula
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  7. A. Simon
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  8. J. I. Baumbach
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Correspondence to R. Furtwängler.

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Furtwängler, R., Hauschild, AC., Hübel, J. et al. Signals of neutropenia in human breath?. Int. J. Ion Mobil. Spec. 17, 19–23 (2014). https://doi.org/10.1007/s12127-014-0145-9

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  • DOI: https://doi.org/10.1007/s12127-014-0145-9

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