TY - JOUR AB - Exhaled breath contains numerous volatile organic compounds (VOCs) known to be related to lung disease like asthma. Its collection is non-invasive, simple to perform and therefore an attractive method for the use even in young children. We analysed breath in children of the multicenter All Age Asthma Cohort (ALLIANCE) to evaluate if ‘breathomics’ have the potential to phenotype patients with asthma and wheeze, and to identify extrinsic risk factors for underlying disease mechanisms. A breath sample was collected from 142 children (asthma: 51, pre-school wheezers: 55, healthy controls: 36) and analysed using gas chromatography-mass spectrometry (GC/MS). Children were diagnosed according to Global Initiative for Asthma guidelines and comprehensively examined each year over up to seven years. Forty children repeated the breath collection after 24 or 48 months. Most breath VOCs differing between groups reflect the exposome of the children. We observed lower levels of lifestyle-related VOCs and higher levels of the environmental pollutants, especially naphthalene, in children with asthma or wheeze. Naphthalene was also higher in symptomatic patients and in wheezers with recent inhaled corticosteroid use. No relationships with lung function or TH2 inflammation were detected. Increased levels of naphthalene in asthmatics and wheezers and the relationship to disease severity could indicate a role of environmental or indoor air pollution for the development or progress of asthma. Breath VOCs might help to elucidate the role of the exposome for the development of asthma. The study was registered at ClinicalTrials.gov (NCT02496468). AU - Shahrokny, P.* AU - Maison, N. AU - Riemann, L.* AU - Ehrmann, M.* AU - Deluca, D.* AU - Schuchardt, S.* AU - Thiele, D.* AU - Weckmann, M.* AU - Dittrich, A.M.* AU - Schaub, B.* AU - Brinkmann, F.* AU - Hansen, G.* AU - Kopp, M.V.* AU - von Mutius, E. AU - Rabe, K.F.* AU - Bahmer, T.* AU - Hohlfeld, J.M.* AU - Grychtol, R.* AU - Holz, O.* C1 - 68819 C2 - 53700 CY - Temple Circus, Temple Way, Bristol Bs1 6be, England TI - Increased breath naphthalene in children with asthma and wheeze of the All Age Asthma Cohort (ALLIANCE). JO - J. Breath Res. VL - 18 IS - 1 PB - Iop Publishing Ltd PY - 2024 SN - 1752-7155 ER - TY - JOUR AB - Volatile organic compounds (VOCs) from breath can successfully be used to diagnose disease-specific pathological alterations in metabolism. However, the exact origin and underlying biochemical pathways that could be mapped to VOC signatures are mainly unknown. There is a knowledge gap regarding the contribution of tissues, organs, the gut microbiome, and exogenous factors to the "sum signal" from breath samples. Animal models for human disease such as mutant mice provide the possibility to reproduce genetic predisposition to disease, thereby allowing the in-depth analysis of metabolic and biochemical functions. We hypothesized that breath VOCs can be traced back to origins and organ-specific metabolic functions by combining breath concentrations with systemic levels detected in different organs and biological media (breath, blood, faeces and urine). For this we fed C57Bl/6N mice a grain-based chow or a purified low-fat diet, thereby modifying the emission of methanol in breath whereas acetone levels were unaffected. We then measured headspace concentrations of both VOCs in ex-vivo samples of several biological media. Especially cecum content was identified as a likely source of systemic methanol, whereas liver showed highest acetone concentrations. Our findings are a first step to the systemic mapping of VOC patterns to metabolic functions in mice because differences between VOCs could be traced to different sources in the body. As a future aim, different levels of so-called omics technologies (genomics, proteomics, metabolomics, and breathomics) could be mapped to metabolic pathways in multiple tissues deepening our understanding of VOC metabolism and possibly leading to early non-invasive biomarkers for human pathologies. AU - Kistler, M. AU - Muntean, A. AU - Höllriegl, V. AU - Matuschek, G. AU - Zimmermann, R. AU - Hoeschen, C.* AU - Hrabě de Angelis, M. AU - Rozman, J. C1 - 51801 C2 - 43474 CY - Bristol TI - A systemic view on the distribution of diet-derived methanol and hepatic acetone in mice. JO - J. Breath Res. VL - 12 IS - 1 PB - Iop Publishing Ltd PY - 2018 SN - 1752-7155 ER - TY - JOUR AB - Breath gas profiles, which reflect metabolic disorders like diabetes, are the subject of scientific focus. Nevertheless, profiling is still a challenging task that requires complex and standardized methods. This study was carried out to verify breath gas patterns that were obtained in previous proton-transfer reaction-quadrupole mass spectrometry (PTR-QMS) studies and that can be linked to glucose metabolism. An experimental setup using simultaneous PTR-QMS and complementary highly time-resolved needle trap micro extraction (NTME) combined with comprehensive 2D gas chromatography-time-of-flight mass spectrometry (GC×GC-TOFMS) was established for the analysis of highly polar volatile organic compounds (VOCs). The method was applied to the breath gas analysis of three volunteers during a glucose challenge, whereby subjects ingested a glucose solution orally. Challenge responsive PTR-QMS target VOCs could be linked to small n-carbonic (C2-C4) alcohols and short chain fatty acids (SCFA). Specific isomers could be identified by simultaneously applied NTME-GC×GC-TOFMS and further verified by their characteristic time profiles and concentrations. The identified VOCs potentially originate from bacteria that are found in the oral cavity and gastrointestinal tract. In this study breath gas monitoring enabled the identification of potential VOC metabolites that can be linked to glucose metabolism. AU - Gruber, B. AU - Keller, S. AU - Gröger, T.M. AU - Matuschek, G. AU - Szymczak, W. AU - Zimmermann, R. C1 - 48883 C2 - 41480 CY - Bristol TI - Breath gas monitoring during a glucose challenge by a combined PTR-QMS/GC×GC-TOFMS approach for the verification of potential volatile biomarkers. JO - J. Breath Res. VL - 10 IS - 3 PB - Iop Publishing Ltd PY - 2016 SN - 1752-7155 ER - TY - JOUR AB - The prevalence of obesity is still rising in many countries, resulting in an increased risk of associated metabolic diseases. In this study we aimed to describe the volatile organic compound (VOC) patterns symptomatic for obesity. We analyzed high fat diet (HFD) induced obese and mono-genetic obese mice (global knock-in mutation in melanocortin-4 receptor MC4R-ki). The source strengths of 208 VOCs were analyzed in ad libitum fed mice and after overnight food restriction. Volatiles relevant for a random forest-based separation of obese mice were detected (26 in MC4R-ki, 22 in HFD mice). Eight volatiles were found to be important in both obesity models. Interestingly, by creating a partial correlation network of the volatile metabolites, the chemical and metabolic origins of several volatiles were identified. HFD-induced obese mice showed an elevation in the ketone body acetone and acrolein, a marker of lipid peroxidation, and several unidentified volatiles. In MC4R-ki mice, several yet-unidentified VOCs were found to be altered. Remarkably, the pheromone (methylthio)methanethiol was found to be reduced, linking metabolic dysfunction and reproduction. The signature of volatile metabolites can be instrumental in identifying and monitoring metabolic disease states, as shown in the screening of the two obese mouse models in this study. Our findings show the potential of breath gas analysis to non-invasively assess metabolic alterations for personalized diagnosis. AU - Kistler, M. AU - Muntean, A. AU - Szymczak, W. AU - Rink, N.* AU - Fuchs, H. AU - Gailus-Durner, V. AU - Wurst, W. AU - Hoeschen, C. AU - Klingenspor, M.* AU - Hrabě de Angelis, M. AU - Rozman, J. C1 - 47864 C2 - 39629 CY - Bristol TI - Diet-induced and mono-genetic obesity alter volatile organic compound signature in mice. JO - J. Breath Res. VL - 10 IS - 1 PB - Iop Publishing Ltd PY - 2016 SN - 1752-7155 ER - TY - JOUR AB - � 2016 IOP Publishing Ltd. The persistence of aroma compounds in breath after swallowing is an important attribute of the overall aroma experience during eating and drinking. It is mainly related to the coating of the oral tract with food residues and the interaction between volatile compounds and airway mucosa. We have studied the persistence of eight compounds (2,5-dimethylpyrazine, guaiacol, 4-methylguaiacol, phenylethylalcohol, ethylbutanoate, ethyloctanoate, isoamylacetate and 2-heptanone) both in-nose and in-mouth after administration of volatiles in gas phase (vapor) to five different panelists. By using volatiles in the gas phase, only the interaction with the mucosa is highlighted and the formation of a liquid coating in the oral and tracheal airway is avoided. The physicochemical properties of the compounds, mainly polarity and vapor pressure, determine the interactions of the volatiles with the airway mucosa. The use of different breathing protocols allowed the study of the differences between nasal and oral mucosa in volatile retention, with higher persistence of volatiles obtained in-mouth. Initial concentration also affected persistence, but only for compounds with high volatility and at low concentration. AU - Sánchez-López, J.A.* AU - Ziere, A.* AU - Martins, S.I.F.S.* AU - Zimmermann, R. AU - Yeretzian, C.* C1 - 49136 C2 - 41654 CY - Bristol TI - Persistence of aroma volatiles in the oral and nasal cavities: Real-time monitoring of decay rate in air exhaled through the nose and mouth. JO - J. Breath Res. VL - 10 IS - 3 PB - Iop Publishing Ltd PY - 2016 SN - 1752-7155 ER - TY - JOUR AB - Breath analysis is commonly understood to target gaseous or volatile organic compounds (VOCs) for the characterization of different pathologies. Targeted analysis is most effective if a working hypothesis can be based on a plethora of data. The recently published volatilome builds an optimal basis for organizing powerful target sets. However, the origin and pathways of biosynthesis of many VOCs are not known, which complicates the formulation of useful hypotheses. To find the missing link between VOCs and their origin, it is necessary to analyze their precursor fluids themselves. In order to provide condensation nuclei for the generation of future hypotheses, we provide the compositional space over 23 samples of the unperturbed human exhaled breath condensate (EBC) metabolome. We propose a way to connect the compositional spaces of both VOCs and EBC so as to gain insight into the most probable form of VOC precursors. In a way analogous to tandem MS it is possible to create a mass difference network over compositional data by linking compositions with mass differences that are designed to mimic biochemical reactions. We propose to use mass difference enrichment analysis (MDEA) in order to mine probable relations between VOCs and their precursor fluids. We have found 2691 EBC compositions and linked them to 235 breath VOC compositions that correspond to 848 individual compounds. We found that VOCs are likely to be found as hexose conjugates or as amino acid conjugates with Glutamine or Asparagine playing a major role. Furthermore, we found that dicarboxylic acid mass differences may be more indicative for oxidative stress than oxygenation-hydrogenation sequences. AU - Moritz, F. AU - Janicka, M.* AU - Zygler, A.* AU - Forcisi, S. AU - Kot-Wasik, A.* AU - Kot, J.* AU - Gebefügi, I.L. AU - Namiesnik, J.* AU - Schmitt-Kopplin, P. C1 - 44698 C2 - 36992 CY - Bristol TI - The compositional space of exhaled breath condensate and its link to the human breath volatilome. JO - J. Breath Res. VL - 9 IS - 2 PB - Iop Publishing Ltd PY - 2015 SN - 1752-7155 ER - TY - JOUR AB - Breath gas analysis in humans proved successful in identifying disease states and assessing metabolic functions in a non-invasive way. While many studies report diagnostic capability using volatile organic compounds (VOC) in breath, the inter-individual variability even in healthy human cohorts is rather large and not completely understood in its biochemical origin. Laboratory mice are the predominant animal model system for human disorders and are analysed under highly standardized and controlled conditions. We established a novel setup to monitor VOCs as biomarkers for disease in the breath gas of non-anesthetized, non-restrained mice using a proton transfer reaction mass spectrometer with time of flight detection. In this study, we implemented breath gas analysis in a dietary intervention study in C57BL/6J mice with the aim to assess the variability in VOC signatures due to a change in the diet matrix. Mice were fed a standard laboratory chow and then exposed to four semi-purified low- or high-fat diets for four weeks. Random forest (RF++) was used to identify VOCs that specifically respond to the diet matrix change. Interestingly, we found that the change from a chow diet to semi-purified diets resulted in a considerable drop of several VOC levels. Our results suggest that the diet matrix impacts VOC signatures and the underlying metabolic functions and may be one source of variability in exhaled volatiles. AU - Kistler, M. AU - Szymczak, W. AU - Fedrigo, M. AU - Fiamoncini, J.* AU - Höllriegl, V. AU - Hoeschen, C. AU - Klingenspor, M. AU - Hrabě de Angelis, M. AU - Rozman, J. C1 - 30662 C2 - 33780 CY - Bristol TI - Effects of diet-matrix on volatile organic compounds in breath in diet-induced obese mice. JO - J. Breath Res. VL - 8 IS - 1 PB - IOP Publishing PY - 2014 SN - 1752-7155 ER - TY - JOUR AB - Breath gas analysis is a promising technology for medical applications. By identifying disease-specific biomarkers in the breath of patients, a non-invasive and easy method for early diagnosis or therapy monitoring can be developed. In order to achieve this goal, one essential prerequisite is the reproducibility of the method applied, i.e. the quantification of exhaled volatile organic compounds (VOCs). The variability of breath gas VOC measurements can be affected by many factors. In this respect, sampling-specific parameters like flow rate and volume of exhalation, exhalation with or without breath holding, exhalation in single or multiple breathing and volume of air inhaled before breath gas exhalation can play a vital role. These factors affecting the measurements must be controlled by optimizing the sampling procedure. For such an optimization, it is important to know how exactly the different parameters affect the exhaled VOC concentrations. Therefore, a study has been undertaken in order to identify some effects of different breath sampling-specific parameters on the exhaled VOC profile using the mixed expired breath sampling technique. It was found that parameters such as filling the sampling bag with high or low flow rate of exhalation, with multiple or single exhalations, in different volumes of exhalation, with breath holding and under different surrounding air conditions significantly affect the concentrations of the exhaled VOCs. Therefore, the specific results of this work should be taken into account before planning new breath gas studies or developing new breath gas collection systems in order to minimize the number of artefacts affecting the concentration of exhaled VOCs. AU - Thekedar, B. AU - Oeh, U. AU - Szymczak, W. AU - Hoeschen, C. AU - Paretzke, H.G. C1 - 6374 C2 - 28097 TI - Influences of mixed expiratory sampling parameters on exhaled volatile organic compound concentrations. JO - J. Breath Res. VL - 5 IS - 1 PB - IOP PUBLISHING PY - 2011 SN - 1752-7155 ER - TY - JOUR AB - Breath gas analysis is a promising technology in the frame of medical diagnostics. By identifying disease-specific biomarkers in the breath of patients, a non-invasive and easy method for early diagnosis or therapy monitoring might be developed. However, to verify this potential and develop diagnostic tools based on breath gas analysis one essential prerequisite is a low variability in measurement of exhaled volatile organic compounds. Therefore, a study has been undertaken in order to identify possible artefacts within the application of a breath gas test in practice, for which the breath gas is analysed by proton transfer reaction-mass spectrometry (PTR-MS). After validating the low instrumental variability by repeatedly measuring standard gas, the variability of breath gas sampling has been evaluated. The latter has been carried out by measuring single breath gas samples (mixed expiratory breath) collected over different periods of time such as 1 min (10 volunteers, 4 breath gas samples each), 1 h (10 volunteers, 11 breath gas samples each) and several days (11 volunteers, 10 breath gas samples each). The breath gas samples were collected in Teflon bags and consecutively measured with PTR-MS. It was found that those samples collected within 1 min and 1 h show a low variability. This was, however, not the case for samples being collected over longer periods of time (15–70 days). Under these circumstances, many volatile organic compounds (VOCs) showed significant day-to-day variation in concentration, although the breath collection had been performed under the same conditions (similar sampling time, sampling technique, sample storage time, measurement conditions, etc). This large variation might be assigned to the influence of room air VOCs, which have been investigated in this work, or with other parameters which will be discussed. It was also found that the variability in the measurement of exhaled concentrations of methanol, acetone and isoprene within different individuals (inter individual variability) is much higher than differences in the same volunteer (intra individual variability) measured over a longer time interval. AU - Thekedar, B. AU - Szymczak, W. AU - Höllriegl, V. AU - Hoeschen, C. AU - Oeh, U. C1 - 1467 C2 - 27106 TI - Investigations on the variability of breath gas sampling using PTR-MS. JO - J. Breath Res. VL - 3 IS - 2 PB - IOP Publishing Ltd. PY - 2009 SN - 1752-7155 ER -