The role of mathematical modeling in VOC analysis using isoprene as a prototypic example

Isoprene is one of the most abundant endogenous volatile organic compounds (VOCs) contained in human breath and is considered to be a potentially useful biomarker for diagnostic and monitoring purposes. However, neither the exact biochemical origin of isoprene nor its physiological role is understood in sufficient depth, thus hindering the validation of breath isoprene tests in clinical routine. Exhaled isoprene concentrations are reported to change under different clinical and physiological conditions, especially in response to enhanced cardiovascular and respiratory activity. Investigating isoprene exhalation kinetics under dynamical exercise helps to gather the relevant experimental information for understanding the gas exchange phenomena associated with this important VOC. The first model for isoprene in exhaled breath has been developed by our research group. In this paper, we aim at giving a concise overview of this model and describe its role in providing supportive evidence for a peripheral (extrahepatic) source of isoprene. In this sense, the results presented here may enable a new perspective on the biochemical processes governing isoprene formation in the human body.

[1]  M. Hlastala,et al.  Measuring airway exchange of endogenous acetone using a single-exhalation breathing maneuver. , 2006, Journal of applied physiology.

[2]  G. Teschl,et al.  Isoprene and acetone concentration profiles during exercise on an ergometer , 2009, Journal of breath research.

[3]  Melvin E. Andersen,et al.  Physiologically Based Pharmacokinetic Modeling : Science and Applications , 2005 .

[4]  T. Risby.  Critical issues for breath analysis , 2008 .

[5]  A. Modak.  13C BREATH TESTS: TRANSITION FROM RESEARCH TO CLINICAL PRACTICE , 2005 .

[6]  R. Fall,et al.  Enzymatic synthesis of isoprene from dimethylallyl diphosphate in aspen leaf extracts. , 1991, Plant physiology.

[7]  Albert L. Babb,et al.  Modeling Soluble Gas Exchange in the Airways and Alveoli , 2003, Annals of Biomedical Engineering.

[8]  S. Telser,et al.  EXHALED BREATH GAS AS A BIOCHEMICAL PROBE DURING SLEEP , 2005 .

[9]  Julian King,et al.  A mathematical model for breath gas analysis of volatile organic compounds with special emphasis on acetone , 2010, Journal of mathematical biology.

[10]  J. Futrell,et al.  Detection of isoprene in expired air from human subjects using proton-transfer-reaction mass spectrometry. , 1997, Rapid communications in mass spectrometry : RCM.

[11]  Bradford G. Stone,et al.  Effect of regulating cholesterol biosynthesis on breath isoprene excretion in men , 1993, Lipids.

[12]  Joachim D Pleil,et al.  Role of Exhaled Breath Biomarkers in Environmental Health Science , 2008, Journal of toxicology and environmental health. Part B, Critical reviews.

[13]  M. Phillips,et al.  Metabolic and environmental origins of volatile organic compounds in breath. , 1994, Journal of clinical pathology.

[14]  R. Fall,et al.  Human breath isoprene and its relation to blood cholesterol levels: new measurements and modeling. , 2001, Journal of applied physiology.

[15]  D. B. Milligan,et al.  Quantitative analysis of trace gases of breath during exercise using the new SIFT–MS technique , 2000, Redox report : communications in free radical research.

[16]  F. Frerman,et al.  LOVASTATIN, ISOPRENES, AND MYOPATHY , 1989, The Lancet.

[17]  R. Diasio,et al.  Dihydropyrimidine dehydrogenase deficiency, a pharmacogenetic syndrome associated with potentially life-threatening toxicity following 5-fluorouracil administration. , 2004, Clinical colorectal cancer.

[18]  David Smith,et al.  Breath analysis: the approach towards clinical applications. , 2007, Mini reviews in medicinal chemistry.

[19]  Terence H Risby,et al.  Effects of ventilation on the collection of exhaled breath in humans. , 2004, Journal of applied physiology.

[20]  M. Evans,et al.  The myotoxicity of statins , 2002, Current opinion in lipidology.

[21]  Leiliane Coelho A Amorim,et al.  Breath air analysis and its use as a biomarker in biological monitoring of occupational and environmental exposure to chemical agents. , 2007, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[22]  G. Hobbs,et al.  A simple non-invasive method to detect and monitor hypercapnia: the sodium [13C]bicarbonate breath test , 2007, Isotopes in environmental and health studies.

[23]  W. Kessler,et al.  Toxicokinetics of isoprene in rodents and humans. , 1996, Toxicology.

[24]  T. Sharkey,et al.  Isoprene synthesis by plants and animals. , 1996, Endeavour.

[25]  D. Harris,et al.  The physiology of respiration , 1994, Perfusion.

[26]  J. Mead,et al.  Acid-catalyzed formation of isoprene from a mevalonate-derived product using a rat liver cytosolic fraction. , 1985, The Journal of biological chemistry.

[27]  Julian King,et al.  Physiological modeling of isoprene dynamics in exhaled breath. , 2010, Journal of theoretical biology.

[28]  J. Herbig,et al.  On-line breath analysis with PTR-TOF , 2009, Journal of breath research.

[29]  M. Fiegl,et al.  Noninvasive detection of lung cancer by analysis of exhaled breath , 2009, BMC Cancer.

[30]  S. Telser,et al.  Applications of breath gas analysis in medicine , 2004 .

[31]  A. B. Robinson,et al.  Quantitative analysis of urine vapor and breath by gas-liquid partition chromatography. , 1971, Proceedings of the National Academy of Sciences of the United States of America.

[32]  M. Kouwaki,et al.  [Dihydropyrimidine dehydrogenase deficiency]. , 1998, Ryoikibetsu shokogun shirizu.

[33]  John F. Nunn,et al.  Respiratory Physiology—the essentials , 1975 .

[34]  Doktor Rerum Naturalium,et al.  A Global Model for the Cardiovascular and Respiratory System , 1998 .

[35]  Editors , 1986, Brain Research Bulletin.

[36]  F. Gabreëls,et al.  Dihydropyrimidine dehydrogenase deficiency Neurological aspects , 1987, Journal of the Neurological Sciences.

[37]  K. Unterkofler,et al.  Breath isoprene – aspects of normal physiology related to age, gender and cholesterol profile as determined in a proton transfer reaction mass spectrometry study , 2008, Clinical chemistry and laboratory medicine.

[38]  R. Cherniack,et al.  Pulmonary Physiology , 1975, Advances in Psychosomatic Medicine.

[39]  Martin R. Johnson,et al.  Rapid Identification of Dihydropyrimidine Dehydrogenase Deficiency by Using a Novel 2-13C-Uracil Breath Test , 2004, Clinical Cancer Research.

[40]  H. Hinterhuber,et al.  Dynamic profiles of volatile organic compounds in exhaled breath as determined by a coupled PTR-MS/GC-MS study , 2010, Physiological measurement.

[41]  Anton Amann,et al.  Methodological issues of sample collection and analysis of exhaled breath , 2010 .

[42]  J B West,et al.  Measurement of continuous distributions of ventilation-perfusion ratios: theory. , 1974, Journal of applied physiology.

[43]  Barbara Silvestri,et al.  Physiology of Respiration 2nd ed , 1975 .

[44]  A. Modak.  Single time point diagnostic breath tests: a review , 2010, Journal of breath research.

[45]  J. Farmer.  Statins and myotoxicity , 2003, Current atherosclerosis reports.

[46]  P. Barnes,et al.  Biomarkers of some pulmonary diseases in exhaled breath , 2002, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[47]  David Smith,et al.  Isoprene levels in the exhaled breath of 200 healthy pupils within the age range 7–18 years studied using SIFT-MS , 2010, Journal of breath research.

[48]  Werner Lindinger,et al.  Proton-transfer-reaction mass spectrometry (PTR–MS): on-line monitoring of volatile organic compounds at pptv levels , 1998 .

[49]  R. Fall,et al.  Characterization of Aspen Isoprene Synthase, an Enzyme Responsible for Leaf Isoprene Emission to the Atmosphere (*) , 1995, The Journal of Biological Chemistry.

[50]  H. Hinterhuber,et al.  Exhaled breath analysis - quantifying the storage of lipophilic compounds in the human body , 2009 .

[51]  L. Farhi.  Elimination of inert gas by the lung. , 1967, Respiration physiology.

[52]  A. Modak.  Stable isotope breath tests in clinical medicine: a review , 2007, Journal of breath research.

[53]  Konrad Schwarz,et al.  Compounds enhanced in a mass spectrometric profile of smokers' exhaled breath versus non-smokers as determined in a pilot study using PTR-MS , 2008, Journal of breath research.

[54]  P. Španěl,et al.  The challenge of breath analysis for clinical diagnosis and therapeutic monitoring. , 2007, The Analyst.

[55]  A. Dzien,et al.  The analysis of healthy volunteers' exhaled breath by the use of solid-phase microextraction and GC-MS , 2008, Journal of breath research.

[56]  W. Miekisch,et al.  Diagnostic potential of breath analysis--focus on volatile organic compounds. , 2004, Clinica chimica acta; international journal of clinical chemistry.