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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.

References:
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).