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Abstract No.: FrOr-16
Speaker: Anton Amann
Session: Trace Gas Analysis
Presentation date: Fri, Sep 1, 2006
Presentation time: 11:30 – 11:50

Detection of Lung Cancer by Proton Transfer Reaction Mass Spectrometry Analysis of Human Breath

Anton Amann1, Andreas Wehinger1, Alex Schmid1, Maximilian Ledochowski1, Sergei Mechtcheriakov1, Guenther Gastl1

1 Innsbruck Medical University, Innsbruck, Austria

Correspondence address: Anton Amann, Innsbruck Medical University, Anesthesia, Anichstr 35, Innsbruck, 6020 Austria.

Web site: http://www.voc-research.at

Keywords: Biomarkers; Proton Transfer; Trace Analysis; Volatile Organic Analysis.

Novel aspect: Lung cancer detection by exhaled breath analysis is a promising non-invasive diagnostic technique.


Introduction: In developed countries, particularly in North America and Europe, lung cancer is a leading cause of death. European cancer figures for 2004 classified lung cancer as being the commonest form of cancer (13.2%) and of cancer death (20%). Even so, a proper screening method to detect lung cancer in its early stages is not available. A correlation between abnormal concentrations of distinct volatile organic compounds (VOCs) in human breath and primary lung cancer (PLC) has been shown recently by gas chromatography mass spectrometry (GC-MS) and polymer composite sensors.1-3 It was our aim to determine the diagnostic value of volatile compounds in breath for PLC which can be measured using Proton-Transfer-Reaction Mass Spectrometry (PTR-MS). The interesting studies by Michael Phillips and coworkers3 focussed on methylated alkanes.

Experimental Design: By means of PTR-MS, we analysed breath samples from PLC patients (n=17) and compared their VOC concentrations with a control cohort of healthy individuals (n=86). Particular consideration was placed on different subgroups of the control cohort: smokers, non-smokers, hospital personnel and groups of different age. Concentrations were determined using an assumed kinetic reaction rate constant with the primary ion H3O+ of k=2×10-9cm3sec-1, i.e. the results are only semi-quantitative. Concentrations of methylated alkanes, as considered by Michael Phillips, were not determined in our study.

Results: From ~200 different VOCs, we observed significantly higher levels of product ions at m/z=31 and m/z=43 in the PLC group when compared to controls. For ions at m/z=31 (probably protonated formaldehyde) the concentrations determined were 18.2 ± 11.1 ppbv for cancer patients versus 4.7 ± 2.4 ppbv for controls (p < 0.001). For ions at m/z=43 [a characteristic fragment of protonated (iso)propanol has this m/z] concentrations determined were 345.1 ± 226.1 ppbv for cancer patients versus 131.6 ± 206.4 ppbv for controls (p < 0.001). The sensitivity determined over 1-specificity for receiver operating characteristic curves (ROC-curves) yielded integral values of 0.92 for ions at m/z=31 and 0.93 for ions at m/z=43.

Discussion: Ions at m/z=31 and m/z=43 were found to best distinguish between PLC cases and healthy controls. Thus, simple and time-saving breath sample analysis by PTR-MS makes this method attractive for larger clinical evaluation and might offer a new valuable tool for diagnosis of PLC.

1. M. Corradi, et al., Ital. Med. Lav. Ergon. 25 Suppl, 59 (2003).
2. R. F. Machado, et al., Am. J. Respir. Crit. Care Med. 171, 1286 (2005).
3. M. Phillips, et al., Chest 123, 2115 (2003).