Significant different volatile biomarker during bronchoscopic ion mobility spectrometry investigation of patients suffering lung carcinoma
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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.
KeywordsExhaled breath Bronchoscopic ion mobility spectrometry Lung carcinoma Volatile biomarker Adeno carconoma Squamous cell carcinoma
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”.
- 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 2002Google 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 CrossRefGoogle 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 CrossRefGoogle Scholar
- 20.Pleil JD, Lindstrom AB (1997) Exhaled Human Breath Measurement Method for Assessing Exposure to Halogenated Volatile Organic Compounds. Clin Chem 43:723–730Google 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, 046001/046001-046001/046010Google Scholar
- 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 58:739–751Google Scholar
- 27.Baumbach JI, Westhoff M (2006) Ion mobility spectrometry to detect lung cancer and airway infections. Spectroscopy Europe 18:22–27Google 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 13:131–139CrossRefGoogle 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 861:101–107CrossRefGoogle 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 77:7408–7414CrossRefGoogle Scholar
- 44.Ruzsanyi V, Baumbach JI, Eiceman GA (2003) Detection of the mold markers using ion mobility spectrometry. Int J Ion Mobility Spectrom 6:53–57Google 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) 53:953–965Google Scholar
- 48.Fuchs P, Loeseken C, Schubert JK, Miekisch W (2010) Breath gas aldehydes as biomarkers of lung cancer. Int J Cancer 126:2663–2670Google 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 34:1613–1618Google Scholar