Lung cancer detection by proton transfer reaction mass-spectrometric analysis of human breath gas

• Published in: International journal of mass spectrometry 2007-08, Vol.265 (1), p.49-59
• Main Authors: Wehinger, Andreas, Schmid, Alex, Mechtcheriakov, Sergei, Ledochowski, Maximilian, Grabmer, Christoph, Gastl, Guenther A., Amann, Anton
• Format: Article
• Language: English
• Subjects: Exhaled breath; Primary lung cancer; Proton transfer reaction mass spectrometry; Receiver operating characteristic curve; Volatile organic compound
• ISSN: 1387-3806; 1873-2798
• DOI: 10.1016/j.ijms.2007.05.012

Determination of the diagnostic usefulness of proton transfer reaction mass spectrometry (PTR-MS) for detecting primary lung cancer through analysis of volatile organic compounds (VOCs) in exhaled human breath was demonstrated in this investigation. Unlike, for example, gas-chromatographic analyses, PTR-MS can be used without time-consuming preconcentration of the gas samples. By means of PTR-MS, exhaled breath samples from primary lung cancer patients ( n = 17) were analyzed and compared with both an overall control collective (controls total, n = 170) and three sub-collectives: hospital personnel (controls hospital, n = 35), age-matched persons (controls age, n = 25), and smokers (controls s, n = 60), respectively. Among the VOCs present at reasonably high concentrations, the ones leading to the product ion at m/ z = 31 (VOC-31, tentatively protonated formaldehyde) and m/ z = 43 (VOC-43, tentatively a fragment of protonated iso-propanol), were found at significantly higher concentrations in the breath gas of the primary lung cancer patients as compared to the healthy controls at the following median concentrations (with interquartile distance, iqr): For VOC-31 the median concentrations were 7.0 ppb (iqr, 15.5 ppb) versus 3.0 ppb (iqr, 1.9 ppb) with P < 10 −4. For VOC-43 the median concentrations were 244.1 ppb (iqr, 236.2 ppb) versus 94.1 ppb (iqr, 55.2 ppb) with P < 10 −6. The discriminative power between the two collectives was further assessed by ROC-curves obtained upon variation of the chosen threshold concentration and by Fisher's Quadratic Discriminant Method. Within the limits of pilot study, VOC-31 and -43 were found to best discriminate between exhaled breath of primary lung cancer cases and healthy controls. Simple and time-saving breath gas analysis by PTR-MS makes this method attractive for a larger clinical evaluation. It may become a new valuable tool for diagnosing primary lung cancer.