{A pilot study has been carried out to define typical characteristics of the trace gas compounds in exhaled breath of non-smokers and smokers to assist interpretation of breath analysis data from patients who smoke with respiratory diseases and lung cancer. Exhaled breath was analyzed using proton transfer reaction-mass spectrometry (PTR-MS) for 370 volunteers (81 smokers, 210 non-smokers, 79 ex-smokers). Volatile organic compounds corresponding to product ions at seven mass-to-charge ratios (m/z 28, 42, 69, 79, 93, 97, 123) in the PTR-MS spectra differentiated between smokers and non-smokers. The Youden index (= maximum of sensitivity + specificity - 1, YI) as a measure for differentiation between smokers and non-smokers was YI = 0.43 for ions at the m/z values 28 (tentatively identified as HCN)

{Lung 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.Exhaled 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.Isoprene, 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

Gathering information about a subject's physiological and pathophysiological condition from the `smell' of breath is an idea that dates back to antiquity. This intriguing concept of non-invasive diagnosis has been revitalized by `exhaled breath analysis' in recent decades. A main driving force was the development of sensitive and versatile gas-chromatographic and mass-spectrometric instruments for trace gas analysis. Ironically, only non-smelling constituents of breath, such as O(2), CO(2), H(2), and NO have so far been included in routine clinical breath analysis. The `smell' of human breath, on the other hand, arises through a combination of volatile organic compounds (VOCs) of which several hundred have been identified to date. Most of these volatiles are systemic and are released in the gas-exchange between blood and air in the alveoli. The concentration of these compounds in the alveolar breath is related to the respective concentrations in blood. Measuring VOCs in exhaled breath allows for screening of disease markers, studying the uptake and effect of medication (pharmacokinetics), or monitoring physiological processes. There is a range of requirements for instruments for the analysis of a complex matrix, such as human breath. Mass-spectrometric techniques are particularly well suited for this task since they offer the possibility of detecting a large variety of interesting compounds. A further requirement is the ability to measure accurately in the concentration range of breath VOCs, i.e. between parts-per-trillion (pptv) and parts-per-million (ppmv) range. In the mid 1990's proton transfer reaction-mass spectrometry (PTR-MS) was developed as a powerful and promising tool for the analysis of VOCs in gaseous media. Soon thereafter these instruments became commercially available to a still growing user community and have now become standard equipment in many fields including environmental research, food and flavour science, as well as life sciences. Their high sensitivity for VOCs with detection limits down to sub-pptv levels without pre-concentration and their highly linear signal response over seven orders of magnitude make PTR-MS instruments valuable tools for exhaled breath analysis. The `soft' chemical ionization process in PTR-MS largely avoids fragmentation, providing interpretable spectra without pre-separation. This is especially important for complex gas mixtures such as breath. Even more interesting, PTR-MS instruments analyse a gas sample in real-time and do not require any sample pre-treatment. This offers the possibility for online breath analysis with breath-to-breath resolution. This special issue on PTR-MS applications in medical research contains articles exploring different medical applications of PTR-MS. These applications include screening studies, where the breath composition of a large number of patients is investigated to, e.g., determine influences of demographic data on breath concentrations (Schwarz et al 2009 J. Breath Res. 3 027003). In online monitoring studies the breath of one subject is continuously measured, e.g., to study rapid changes in breath volatiles under physical exercise (King et al 2009 J. Breath Res. 3 027006). Other papers address more elementary breath research and discuss the interpretation of exhaled breath composition in the presence of fragmenting and overlapping compounds (Schwarz et al 2009 J. Breath Res. 3 027002), examine the different causes of variability in the measurement of breath samples (Thekedar et al 2009 J. Breath Res. 3 027007), and compare blood and breath concentrations directly (O'Hara et al 2009 J. Breath Res. 3 027005). Potential sources for breath markers are also explored, by analysing the head-space emissions from microbial culture samples (O'Hara and Mayhew 2009 J. Breath Res. 3 027001). Finally, a recent technological advancement in PTR-MS technology promises several advantages especially for breath gas analysis, which is demonstrated by on-line breath sampling with a PTR-time-of-flight (PTR-TOF) instrument (Herbig et al 2009 J. Breath Res. 3 027004).

Breath analysis has the potential for early stage detection and monitoring of illnesses to drastically reduce the corresponding medical diagnostic costs and improve the quality of life of patients suffering from chronic illnesses. In particular, the detection of acetone in the human breath is promising for non-invasive diagnosis and painless monitoring of diabetes (no finger pricking). Here, a portable acetone sensor consisting of flame-deposited and in situ annealed, Si-doped epsilon-WO(3) nanostructured films was developed. The chamber volume was miniaturized while reaction-limited and transport-limited gas flow rates were identified and sensing temperatures were optimized resulting in a low detection limit of acetone (?20ppb) with short response (10-15s) and recovery times (35-70s). Furthermore, the sensor signal (response) was robust against variations of the exhaled breath flow rate facilitating application of these sensors at realistic relative humidities (80-90%) as in the human breath. The acetone content in the breath of test persons was monitored continuously and compared to that of state-of-the-art proton transfer reaction mass spectrometry (PTR-MS). Such portable devices can accurately track breath acetone concentration to become an alternative to more elaborate breath analysis techniques.

Isothermal rebreathing has been proposed as an experimental technique for estimating the alveolar levels of hydrophilic volatile organic compounds (VOCs) in exhaled breath. Using the prototypic test compounds acetone and methanol, we demonstrate that the end-tidal breath profiles of such substances during isothermal rebreathing show a characteristic increase that contradicts the conventional pulmonary inert gas elimination theory due to Farhi. On the other hand, these profiles can reliably be captured by virtue of a previously developed mathematical model for the general exhalation kinetics of highly soluble, blood-borne VOCs, which explicitly takes into account airway gas exchange as a major determinant of the observable breath output. This model allows for a mechanistic analysis of various rebreathing protocols suggested in the literature. In particular, it predicts that the end-exhaled levels of acetone and methanol measured during free tidal breathing will underestimate the underlying alveolar concentration by a factor of up to 1.5. Moreover, it clarifies the discrepancies between in vitro and in vivo blood–breath ratios of hydrophilic VOCs and yields further quantitative insights into the physiological components of isothermal rebreathing and highly soluble gas exchange in general.

<p>Proton-transfer-reaction time-of-flight mass-spectrometry (PTR-TOFMS) exhibits high selectivity with a resolution of around 5000m/Δm. While isobars can be separated with this resolution, discrimination of isomeric compounds is usually not possible. The coupling of a multi-capillary column (MCC) with a PTR-TOFMS overcomes these problems as demonstrated in this paper for the ketone isomers 3-heptanone and 2-methyl-3-hexanone and for different aldehydes. Moreover, fragmentation of compounds can be studied in detail which might even improve the identification. LODs for compounds tested are in the range of low ppbv and peak positions of the respective separated substances show good repeatability (RSD of the peak positions &lt;3.2%). Due to its special characteristics, such as isothermal operation, compact size, the MCC setup is suitable to be installed inside the instrument and the overall retention time for a complete spectrum is only a few minutes: this allows near real-time measurements in the optional MCC mode. In contrast to other methods that yield additional separation, such as the use of pre-cursor ions other than H3O(+), this method yields additional information without increasing complexity.</p>

<p>Product ion distributions for the reactions of NO(+) with 22 aldehydes involved in human physiology have been determined under the prevailing conditions of a selective reagent ionization time of flight mass spectrometry (SRI-TOF-MS) at an E/N in the flow/drift tube reactor of 130 Td. The chosen aldehydes were fourteen alkanals (the C2-C11 n-alkanals, 2-methyl propanal, 2-methyl butanal, 3-methyl butanal, and 2-ethyl hexanal), six alkenals (2-propenal, 2-methyl 2-propenal, 2-butenal, 3-methyl 2-butenal, 2-methyl 2-butenal, and 2-undecenal), benzaldehyde, and furfural. The product ion fragmentations patterns were determined for both dry air and humid air (3.5% absolute humidity) used as the matrix buffer/carrier gas in the drift tube of the SRI-TOF-MS instrument. Hydride ion transfer was seen to be a common ionization mechanism in all these aldehydes, thus generating (M-H)(+) ions. Small fractions of the adduct ion, NO(+)M, were also seen for some of the unsaturated alkenals, in particular 2-undecenal, and heterocyclic furfural for which the major reactive channel was non-dissociative charge transfer generating the M(+) parent ion. Almost all of the reactions resulted in partial fragmentation of the aldehyde molecules generating hydrocarbon ions; specifically, the alkanal reactions resulted in multiple product ions, whereas, the alkenals reactions produced only two or three product ions, dissociation of the nascent excited product ion occurring preferentially at the 2-position. The findings of this study are of particular importance for data interpretation in studies of aldehydes reactions employing SRI-TOF-MS in the NO(+) mode.</p>