There is experimental evidence that volatile substances in human breath can reflect presence of neoplasma. Volatile aldehydes were determined in exhaled breath of 12 lung cancer patients, 12 smokers and 12 healthy volunteers. Alveolar breath samples were collected under control of expired CO 2 . Reactive aldehydes were transformed into stable oximes by means of on-fiber-derivatization (SPME-OFD). Aldehyde concentrations in the ppt and ppb level were determined by means of gas chromatography-mass spectrometry (GC-MS). Exhaled concentrations were corrected for inspired values. Exhaled C 1 -C 10 aldehydes could be detected in all healthy volunteers, smokers and lung cancer patients. Concentrations ranged from 7 pmol/ l (161 pptV) for butanal to 71 nmol/l (1,582 ppbV) for formaldehyde. Highest inspired concentrations were found for formaldehyde and acetaldehyde (0-55 nmol/l and 0-13 nmol/l, respectively). Acetaldehyde, propanal, butanal, heptanal and decanal concentrations showed no significant differences for cancer patients, smokers and healthy volunteers. Exhaled pentanal, hexanal, octanal and nonanal concentrations were significantly higher in lung cancer patients than in smokers and healthy controls (p pentanal 5 0.001; p hexanal 5 0.006; p octanal 5 0.014; p nonanal 5 0.025). Sensitivity and specificity of this method were comparable to the diagnostic certitude of conventional serum markers and CT imaging. Lung cancer patients could be identified by means of exhaled pentanal, hexanal, octanal and nonanal concentrations. Exhaled aldehydes reflect aspects of oxidative stress and tumor-specific tissue composition and metabolism. Noninvasive recognition of lung malignancies may be realized if analytical skills, biochemical knowledge and medical expertise are combined into a joint effort.

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This study was intended to evaluate low-volume (20 mL) multibed needle trap (NTD) sampling combined with heart-cut gas chromatography/mass spectrometry (GC/MS) and comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry (GC x GC/TOF-MS) for trace gas analysis under clinical conditions. NTDs, high-throughput automatic desorption and separation systems, were tested in vitro and within a study in 11 patients undergoing cardiac surgery with respect to reproducibility, reliability, and clinical applicability. NTD-heart-cut GC/MS analysis of standard mixtures containing different volatile organic compounds (VOCs) yielded relative standard deviations (RSDs) from 4.0% to 18.5%. Substance adsorption was stable for 1 day if NTDs were closed on both ends and was stable for approximately 7.8 h when NTD tip ends had to be left open during autosampler storage. Even in the presence of high concentrations of contaminants linearity of heart-cut GC/MS was conserved. In patients' breath potential biomarkers could be determined even in the presence of very high concentrations of sevoflurane. Profiles of blood-borne biomarkers, intravenous drugs, and clinical contaminants were characterized. Comprehensive GC x GC/TOF-MS may be used as a screening tool for new biomarkers, if patterns are generated from deconvoluted normalized areas. Needle trap sampling in combination with hyphenated chromatographic techniques can thus be used to provide well-tailored solutions for complex problems occurring in clinical breath analysis.

BackgroundWhile assumed to protect against coronavirus transmission, face-masks may have effects on respiratory-haemodynamic parameters. Within this pilot study, we investigated immediate and progressive effects of FFP2 and surgical masks on exhaled breath constituents and physiological attributes in 30 adults at rest.MethodsWe continuously monitored exhaled breath profiles within mask space in older (age: 60–80 years) and young to mid-aged (age: 20–60 years) adults over the period of 15 and 30 min, respectively by high-resolution real-time mass-spectrometry (PTR-ToF-MS). Peripheral oxygen saturation, respiratory- and haemodynamic parameters were measured (non-invasively) simultaneously.ResultsProfound, consistent and significant (p-value≤0.001) changes in SpO2 (Adults>60_FFP2-15 min: 5.8±1.3%↓, Adults>60_surgical-15 min: 3.6±0.9%↓, Adults<60_FFP2-30 min: 1.9±1.0%↓, Adults<60_surgical-30 min: 0.9±0.6%↓) and pET-CO2 (Adults>60_FFP2-15 min: 19.1±8.0%↑, Adults>60_surgical-15 min: 11.6±7.6%↑, Adults<60_FFP2- 30 min: 12.1±4.5%↑, Adults<60_surgical- 30 min: 9.3±4.1%↑) indicate ascending deoxygenation and hypercarbia. Secondary changes (p-value≤0.005) to hemodynamic parameters (e.g. MAP: Adults>60_FFP2-15 min: 9.8±10.4%↑) were found. Exhalation of blood-borne volatile metabolites e.g. aldehydes, hemiterpene, organosulfur, short-chain fatty acids, alcohols, ketone, aromatics, nitrile and monoterpene mirrored behaviour of cardiac output, MAP, SpO2, respiratory rate and pET-CO2. Exhaled humidity (e.g. Adults>60_FFP2-15 min: 7.1±5.8%↑) and exhaled oxygen (e.g. Adults>60_FFP2-15 min: 6.1±10.0%↓) changed significantly (p-value≤0.005) over time.ConclusionsBreathomics allows unique physio-metabolic insights into immediate and transient effects of face-mask wearing. Physiological parameters and breath profiles of endogenous and/or exogenous volatile metabolites indicated putative cross-talk between transient hypoxemia, oxidative stress, hypercarbia, vasoconstriction, altered systemic microbial activity, energy homeostasis, compartmental storage and washout. FFP2 masks affected more pronouncedly than surgical masks. Older adults were more vulnerable to FFP2 mask induced hypercarbia, arterial oxygen decline, blood pressure fluctuations and concomitant physiological and metabolic effects.

BackgroundVolatile breath biomarkers provide a non-invasive window to observe physiological and pathological processes in the body. This study was intended to assess the impact of heart surgery with extracorporeal circulation (ECC) onto breath biomarker profiles. Special attention was attributed to oxidative or metabolic stress during surgery and extracorporeal circulation, which can cause organ damage and poor outcome.Methods24 patients undergoing cardiac surgery with extracorporeal circulation were enrolled into this observational study. Alveolar breath samples (10 mL) were taken after induction of anesthesia, after sternotomy, 5 min after end of ECC, and 30, 60, 90, 120 and 150 min after end of surgery. Alveolar gas samples were withdrawn from the circuit under visual control of expired CO2. Inspiratory samples were taken near the ventilator inlet. Volatile substances in breath were preconcentrated by means of solid phase micro extraction, separated by gas chromatography, detected and identified by mass spectrometry.ResultsMean exhaled concentrations of acetone, pentane and isoprene determined in this study were in accordance with results from the literature. Exhaled substance concentrations showed considerable inter-individual variation, and inspired pentane concentrations sometimes had the same order of magnitude than expired values. This is the reason why, concentrations were normalized by the values measured 120 min after surgery. Exhaled acetone concentrations increased slightly after sternotomy and markedly after end of ECC. Exhaled acetone concentrations exhibited positive correlation to serum C-reactive protein concentrations and to serum troponine-T concentrations. Exhaled pentane concentrations increased markedly after sternotomy and dropped below initial values after ECC. Breath pentane concentrations showed correlations with serum creatinine (CK) levels. Patients with an elevated CK-MB (myocardial&brain)/CK ratio had also high concentrations of pentane in exhaled air. Exhaled isoprene concentrations raised significantly after sternotomy and decreased to initial levels at 30 min after end of ECC. Exhaled isoprene concentrations showed a correlation with cardiac output.ConclusionOxidative and metabolic stress during cardiac surgery could be assessed continuously and non-invasively by means of breath analysis. Correlations between breath acetone profiles and clinical conditions underline the potential of breath biomarker monitoring for diagnostics and timely initiation of life saving therapy.

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Breath analysis could offer a non-invasive means of intravenous drug monitoring if robust correlations between drug concentrations in breath and blood can be established. In this study, propofol blood and breath concentrations were determined in an animal model under varying physiological conditions. Propofol concentrations in breath were determined by means of two independently calibrated analytical methods: continuous, real-time proton transfer reaction mass spectrometry (PTR-MS) and discontinuous solid-phase micro-extraction coupled with gas chromatography mass spectrometry (SPME-GC-MS). Blood concentrations were determined by means of SPME-GC-MS. Effects of changes in pulmonary blood flow resulting in a decreased cardiac output (CO) and effects of dobutamine administration resulting in an increased CO on propofol breath concentrations and on the correlation between propofol blood and breath concentrations were investigated in seven acutely instrumented pigs. Discontinuous propofol determination in breath by means of alveolar sampling and SPME-GC-MS showed good agreement (R(2)=0.959) with continuous alveolar real-time measurement by means of PTR-MS. In all investigated animals, increasing cardiac output led to a deterioration of the relationship between breath and blood propofol concentrations (R(2)=0.783 for gas chromatography-mass spectrometry and R(2)=0.795 for PTR-MS). Decreasing pulmonary blood flow and cardiac output through banding of the pulmonary artery did not significantly affect the relationship between propofol breath and blood concentrations (R(2)>0.90). Estimation of propofol blood concentrations from exhaled alveolar concentrations seems possible by means of different analytical methods even when cardiac output is decreased. Increases in cardiac output preclude prediction of blood propofol concentration from exhaled concentrations.

Breath analysis not only holds great potential for the development of new non-invasive diagnostic methods, but also for the identification and follow up of drug levels in breath. This is of interest for both, forensic and medical science. On the one hand, the detection of drugs of abuse in exhaled breath-similar to the well-known breath alcohol tests-would be highly desirable as an alternative to blood or urine analysis in situations such as police controls for drugged driving. The non-invasive detection of drugs and their metabolites is thus of great interest in forensic science, especially since marijuana is becoming legalized in certain parts of the US and the EU. The detection and monitoring of medical drugs in exhaled breath without the need of drawing blood samples on the other hand, is of high relevance in the clinical environment. This could facilitate a more precise medication and enable therapy control without any burden to the patient. Furthermore, it could be a step towards personalized medicine. This review gives an overview of the current state of drug detection in breath, including both volatile and non-volatile substances. The review is divided into two sections. The first section deals with qualitative detection of drugs (drugs of abuse), while the second is related to quantitative drug detection (medical drugs). Chances and limitations are discussed for both aspects. The detection of the intravenous anesthetic propofol is presented as a detailed example that demonstrates the potential, requirements, pitfalls and limitations of therapeutic drug monitoring by means of breath analysis.