BackgroundLung cancer is one of the leading causes of death in Europe and the western world. At present, diagnosis of lung cancer very often happens late in the course of the disease since inexpensive, non-invasive and sufficiently sensitive and specific screening methods are not available. Even though the CT diagnostic methods are good, it must be assured that "screening benefit outweighs risk, across all individuals screened, not only those with lung cancer". An early non-invasive diagnosis of lung cancer would improve prognosis and enlarge treatment options. Analysis of exhaled breath would be an ideal diagnostic method, since it is non-invasive and totally painless.MethodsExhaled breath and inhaled room air samples were analyzed using proton transfer reaction mass spectrometry (PTR-MS) and solid phase microextraction with subsequent gas chromatography mass spectrometry (SPME-GCMS). For the PTR-MS measurements, 220 lung cancer patients and 441 healthy volunteers were recruited. For the GCMS measurements, we collected samples from 65 lung cancer patients and 31 healthy volunteers. Lung cancer patients were in different disease stages and under treatment with different regimes. Mixed expiratory and indoor air samples were collected in Tedlar bags, and either analyzed directly by PTR-MS or transferred to glass vials and analyzed by gas chromatography mass spectrometry (GCMS). Only those measurements of compounds were considered, which showed at least a 15% higher concentration in exhaled breath than in indoor air. Compounds related to smoking behavior such as acetonitrile and benzene were not used to differentiate between lung cancer patients and healthy volunteers.ResultsIsoprene, acetone and methanol are compounds appearing in everybody's exhaled breath. These three main compounds of exhaled breath show slightly lower concentrations in lung cancer patients as compared to healthy volunteers (p < 0.01 for isoprene and acetone, p = 0.011 for methanol; PTR-MS measurements). A comparison of the GCMS-results of 65 lung cancer patients with those of 31 healthy volunteers revealed differences in concentration for more than 50 compounds. Sensitivity for detection of lung cancer patients based on presence of (one of) 4 different compounds not arising in exhaled breath of healthy volunteers was 52% with a specificity of 100%. Using 15 (or 21) different compounds for distinction, sensitivity was 71% (80%) with a specificity of 100%. Potential marker compounds are alcohols, aldehydes, ketones and hydrocarbons.ConclusionGCMS-SPME is a relatively insensitive method. Hence compounds not appearing in exhaled breath of healthy volunteers may be below the limit of detection (LOD). PTR-MS, on the other hand, does not need preconcentration and gives much more reliable quantitative results then GCMS-SPME. The shortcoming of PTR-MS is that it cannot identify compounds with certainty. Hence SPME-GCMS and PTR-MS complement each other, each method having its particular advantages and disadvantages. Exhaled breath analysis is promising t...

Isoprene concentrations in exhaled breath showed gender-specific correlations with respect to age. Further investigations are necessary to clarify the relation between isoprene concentrations in exhaled breath and cholesterol levels and synthesis rates in blood.

Proton-transfer-reaction mass spectrometry (PTR-MS) is a convenient technique for fast analysis of exhaled breath without prior sample preparation. Since compounds are not separated prior to analysis as in gas chromatography mass spectrometry (GC-MS), and since protonated molecules may fragment, relatively complex spectra may arise, which are not easily interpreted in a quantitative way. We calibrated 21 different compounds of importance for exhaled breath analysis, based on the respective pure standards diluted with nitrogen. These calibration measurements included determination of the fragmentation pattern of each compound under dry conditions and in the absence of CO(2). Even though the fragmentation pattern may be predicted in a qualitative manner, the quantitative details may depend on water and CO(2) content. This is exemplarily shown for isoprene. Out of the selected 21 compounds, 11 compounds showed substantial fragmentation (fragments proportion > 10%). Fragmentation of several volatile organic compounds (VOCs) in the drift tube of PTR-MS has been previously observed (Buhr et al 2002 Int. J. Mass Spectrom. 221 1-7; Taipale et al 2008 Atmos. Chem. Phys. Discuss. 8 9435-75; Hewitt et al 2003 J. Environ. Monit. 51-7; Warneke et al 2003 Environ. Sci. Technol. 37 2494-501; de Gouw and Warneke 2007 Mass Spectrom. Rev. 26 223-57; Pozo-Bayon et al 2008 J. Agric. Food Chem. 56 5278-84) and calibration factors for several compounds at corresponding mass-to-charge ratios have been calculated. In this paper, besides the calibration factors, the proportions of substantial fragments are also taken into account for a correct quantification in the case of overlapping signals. The spectrum of a mixture of the considered 21 compounds may be simulated. Conversely, the determination of concentrations from the spectrum of such a mixture is a linear optimization problem, whose solution is determined here using the simplex algorithm.