Continuous Real Time Breath Gas Monitoring in the Clinical Environment by Proton-Transfer-Reaction-Time-of-Flight-Mass Spectrometry

Trefz, Phillip; Schmidt, M.; Oertel, Peter; Obermeier, Juliane; Brock, Beate; Kamysek, Svend; Dunkl, Jürgen; Zimmermann, Ralf; Schubert, Jochen K.; Miekisch, Wolfram

doi:10.1021/ac402298v

Cited by 139 publications

(150 citation statements)

References 51 publications

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“…Exhaled breath, which may change its chemical signature depending on the physiological or pathophysiological state of disease [12][13][14][15][16][17][18][19][20][21][22][23][24], is considered as one of the most fascinating body fluids/sources. Sampling of breath is non-invasive and can be used for screening, at an intensive care unit (ICU) [25,26], during surgery [27][28][29], or monitoring pre-and post-surgery [30]. Volatile compounds that do not appear normally in exhaled breath can be used for detection of bacterial or fungal infection in the lungs [31][32][33][34][35].…”

Section: Introductionmentioning

confidence: 99%

Assessment of the exhalation kinetics of volatile cancer biomarkers based on their physicochemical properties

et al. 2014

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The current review provides an assessment of the exhalation kinetics of volatile organic compounds (VOCs) that have been linked with cancer. Towards this end, we evaluate various physicochemical properties, such as 'breath:air' and 'blood:fat' partition coefficients, of 112 VOCs that have been suggested over the past decade as potential markers of cancer. With these data, we show that the cancer VOC concentrations in the blood and in the fat span over 12 and 8 orders of magnitude, respectively, in order to provide a specific counterpart concentration in the exhaled breath (e.g., 1 ppb). This finding suggests that these 112 different compounds have different storage compartments in the body and that their exhalation kinetics depends on one or a combination of the following factors: (i) the VOC concentrations in different parts of the body; (ii) the VOC synthesis and metabolism rates; (iii) the partition coefficients between tissue(s), blood and air; and (iv) the VOCs' diffusion constants. Based on this analysis, we discuss how this knowledge allows modeling and simulating the behavior of a specific VOC under different sampling protocols (with and without exertion of effort). We end this review by a brief discussion on the potential role of these scenarios in screening and therapeutic monitoring of cancer.

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Section: Introductionmentioning

confidence: 99%

Assessment of the exhalation kinetics of volatile cancer biomarkers based on their physicochemical properties

et al. 2014

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“…[12][13][14][15] Breath sampling can be accomplished either offline using established lab-based techniques such as GC and GCxGC-ToFMS 16 which can be coupled to preconcentration techniques such as thermal desorption to enable high resolution measurements on low concentration breath metabolites. The development of techniques such as proton transfer reaction-mass spectrometry (PTR-MS) 17 and selected ion flow tube -mass spectrometry (SIFT-MS) 18 has enabled monitoring of highly volatile species in real-time, providing diagnostic data in a very short timescale, however these techniques are less useful for the analysis of larger, less volatile species.…”

Section: Introductionmentioning

confidence: 99%

Analysis of human breath samples using a modified thermal desorption: gas chromatography electrospray ionization interface

Reynolds¹,

Jimoh²,

Guallar-Hoyas³

et al. 2014

J. Breath Res.

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A two-stage thermal desorption/secondary electrospray ionization/time-of-flight mass spectrometry for faster targeted breath profiling has been studied. A new secondary electrospray ionization (SESI) source was devised to constrain the thermal desorption plume and promote efficient mixing in the ionization region. Further, a chromatographic pre-separation stage was introduced to suppress interferences from siloxanes associated with thermal desorption profiles of exhaled breath samples. In vitro tests with 5-nonanone indicated an increased sensitivity and a lowered limit-of-detection, both by a factor of ~4, the latter to an on-trap mass of 14.3 ng, equivalent to a sampled breath concentration of 967 pptv. Analysis of the mass spectrometric responses from 20 breath samples acquired sequentially from a single participant indicated enhanced reproducibility (reduced relative standard deviations (RSD) for 5-nonanone, benzaldehyde and 2-butanone were 28 %, 16% and 14% respectively. The corresponding values for an open SESI source were that 5-nonanone was not detected, with %RSD of 39% for benzaldehyde and 31% for 2-butanone). The constrained source with chromatographic pre-separation resulted in an increase in the number of detectable volatile organic compounds (VOCs) from 260 mass spectral peaks with an open SESI source to 541 peaks with the constrained source with pre-separation. Most of the observed VOCs were present at trace levels, at less than 2.5% of the intensity of the base peak. Seventeen 2.5 dm3 distal breath samples were collected from asthma patients and healthy controls respectively, and subjected to comparative high-throughput screening using thermal desorption/SESI/time-of-flight mass spectrometry (TD-SESI-ToFMS). Breath metabolites were detected by using a background siloxane ion (hexamethylcyclotrisiloxane m/z 223.0642) as an internal lockmass. Eleven breath metabolites were selected from the breath research literature and successfully targeted. These data reinforce the proposition that TD-SESI-MS has potential for development as a rapid screening method for disease stratification and targeted metabolism profiling.

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“…Lab based Needle Trap Micro-Extraction Gas Chromatography Mass Spectrometry (NTME-GC-MS) at certain time points was applied to confirm marker identities. Details of analytical Brock et methods and instrumentation have been described before [9,10]. Briefly, breath gas for PTR analysis was continuously drawn from the alveolar tube in side stream mode (20 ml/min) by means of a t-piece.…”

Section: Methodsmentioning

confidence: 99%

O-Toluidine in Breath-Non-Invasive Prilocaine Monitoring

Brock¹,

Kamysek²,

Trefz³

et al. 2017

Clin Exp Pharmacol

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The generation of methaemoglobin is a rare but potential life-threatening side effect in the use of the local anaesthetic prilocaine. It is currently only possible to ensure the diagnosis by means of blood tests. Rapid noninvasive diagnosis is desirable, especially for risk patients.Using a pig model, we induced methaemoglobinemia via application of dimethyl aminophenol and prilocaine (setup I) or natrium nitrite and prilocaine (setup II). Continuous real time breath gas monitoring was performed by proton transfer reaction-time-of-flight-mass spectrometry (PTR-TOF-MS) for non-invasive determination of volatile organic compounds (VOCs).O-Toluidine, the main metabolite of prilocaine, could be detected in alveolar breath gas by means of PTR-TOF-MS and was confirmed by NTME-GC-MS (needle trap micro-extraction gas chromatography-mass spectrometry). The administration of prilocaine intravenously was clearly reflected with a time lag of a few min by the detection of O-Toluidine in the respiratory gas.If reliable correlations between prilocaine and methaemoglobin concentrations in blood and O-Toluidine levels in breath can be established, detection of prilocaine induced methaemoglobinemia and prevention of prilocaine poisoning with potentially life threatening hypoxia might be possible by means of non-invasive O-Toluidine analysis in breath.

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Continuous Real Time Breath Gas Monitoring in the Clinical Environment by Proton-Transfer-Reaction-Time-of-Flight-Mass Spectrometry

Cited by 139 publications

References 51 publications

Assessment of the exhalation kinetics of volatile cancer biomarkers based on their physicochemical properties

Assessment of the exhalation kinetics of volatile cancer biomarkers based on their physicochemical properties

Analysis of human breath samples using a modified thermal desorption: gas chromatography electrospray ionization interface

O-Toluidine in Breath-Non-Invasive Prilocaine Monitoring

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