Human exhaled air analytics: biomarkers of diseases.

Over the last few years, breath analysis for the routine monitoring of metabolic disorders has attracted a considerable amount of scientific interest, especially since breath sampling is a non-invasive technique, totally painless and agreeable to patients. The investigation of human breath samples with various analytical methods has shown a correlation between the concentration patterns of volatile organic compounds (VOCs) and the occurrence of certain diseases. It has been demonstrated that modern analytical instruments allow the determination of many compounds found in human breath both in normal and anomalous concentrations. The composition of exhaled breath in patients with, for example, lung cancer, inflammatory lung disease, hepatic or renal dysfunction and diabetes contains valuable information. Furthermore, the detection and quantification of oxidative stress, and its monitoring during surgery based on composition of exhaled breath, have made considerable progress. This paper gives an overview of the analytical techniques used for sample collection, preconcentration and analysis of human breath composition. The diagnostic potential of different disease-marking substances in human breath for a selection of diseases and the clinical applications of breath analysis are discussed.

[1]  X. Zhang,et al.  Investigation of volatile biomarkers in lung cancer blood using solid-phase microextraction and capillary gas chromatography-mass spectrometry. , 2004, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[2]  R. Cataneo,et al.  Volatile organic compounds in breath as markers of lung cancer: a cross-sectional study , 1999, The Lancet.

[3]  A. Berg,et al.  Ammonia sensors and their applications - a review , 2005 .

[4]  A. Bacher,et al.  Biosynthesis of isoprenoids via the non-mevalonate pathway , 2004, Cellular and Molecular Life Sciences CMLS.

[5]  J. Trottier,et al.  Book Review: Mass Spectrometry: Principles and Applications. E. de Hoffman, J. Charette and W. Stroobant. Wiley, Chichester 1996. ISBN 0 471 96697 5 , 1997 .

[6]  Anton Amann,et al.  Lung cancer detection by proton transfer reaction mass-spectrometric analysis of human breath gas , 2007 .

[7]  R. Dweik NITRIC OXIDE IN EXHALED BREATH: A WINDOW ON LUNG PHYSIOLOGY AND PULMONARY DISEASE , 2005 .

[8]  Y. D. Kim,et al.  Breath pentane concentrations during labor and the effect of epidural analgesia on the pentane concentration. , 1997, International journal of obstetric anesthesia.

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

[10]  P. Montuschi,et al.  Ozone-induced increase in exhaled 8-isoprostane in healthy subjects is resistant to inhaled budesonide. , 2002, Free radical biology & medicine.

[11]  D. Fuchs,et al.  Fructose malabsorption is associated with decreased plasma tryptophan. , 1999, Advances in experimental medicine and biology.

[12]  Daniel Halmer,et al.  Online recording of ethane traces in human breath via infrared laser spectroscopy. , 2003, Journal of applied physiology.

[13]  H. K. Wilson,et al.  New technologies in the use of exhaled breath analysis for biological monitoring. , 1999, Occupational and environmental medicine.

[14]  Andrew M Ellis,et al.  Demonstration of proton-transfer reaction time-of-flight mass spectrometry for real-time analysis of trace volatile organic compounds. , 2004, Analytical chemistry.

[15]  P. Scheepers,et al.  On-line monitoring of UV-induced lipid peroxidation products from human skin in vivo using proton-transfer reaction mass spectrometry , 2006 .

[16]  Olaf Tietje,et al.  Prediction of breast cancer using volatile biomarkers in the breath , 2006, Breast Cancer Research and Treatment.

[17]  Gerard Wysocki,et al.  Pulsed quantum-cascade laser-based sensor for trace-gas detection of carbonyl sulfide. , 2004, Applied optics.

[18]  J. F. Periago,et al.  Application of solid-phase microextraction and gas chromatography-mass spectrometry to the determination of volatile organic compounds in end-exhaled breath samples. , 2003, Journal of chromatography. A.

[19]  Z. Zadák,et al.  Determination of isoprene in human expired breath using solid-phase microextraction and gas chromatography-mass spectrometry. , 2000, Journal of chromatography. B, Biomedical sciences and applications.

[20]  David Smith,et al.  Quantification of acetonitrile in exhaled breath and urinary headspace using selected ion flow tube mass spectrometry , 2003 .

[21]  P. Španěl,et al.  Quantitative selected ion flow tube mass spectrometry: The influence of ionic diffusion and mass discrimination , 2001, Journal of the American Society for Mass Spectrometry.

[22]  J. Orens,et al.  Patterns and significance of exhaled-breath biomarkers in lung transplant recipients with acute allograft rejection. , 2001, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[23]  J. Pawliszyn,et al.  Analysis of human breath with micro extraction techniques and continuous monitoring of carbon dioxide concentration , 2006, Analytical and bioanalytical chemistry.

[24]  McGrath Lawrence T.,et al.  Breath isoprene in patients with heart failure , 2001 .

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

[26]  J. Schubert,et al.  Method for analysis of exhaled air by microwave energy desorption coupled with gas chromatography-flame ionization detection-mass spectrometry. , 1998, Journal of chromatography. B, Biomedical sciences and applications.

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

[28]  D. Karall,et al.  BREATH GAS ANALYSIS IN PATIENTS SUFFERING FROM PROPIONIC ACIDAEMIA , 2005 .

[29]  David Smith,et al.  A general method for the calculation of absolute trace gas concentrations in air and breath from selected ion flow tube mass spectrometry data , 2006 .

[30]  T. Risby,et al.  Clinical application of breath biomarkers of oxidative stress status. , 1999, Free radical biology & medicine.

[31]  Mark Libardoni,et al.  Analysis of human breath samples with a multi-bed sorption trap and comprehensive two-dimensional gas chromatography (GCxGC). , 2006, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[32]  M. Phillips,et al.  Effect of age on the breath methylated alkane contour, a display of apparent new markers of oxidative stress. , 2000, The Journal of laboratory and clinical medicine.

[33]  Milton L. Lee,et al.  Porous layer solid phase microextraction using silica bonded phases , 1997 .

[34]  Klaus Geiger,et al.  Breath analysis in critically ill patients: potential and limitations , 2004, Expert review of molecular diagnostics.

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

[36]  Z. Zeng,et al.  Analysis of fatty acids in lung tissues using gas chromatography-mass spectrometry preceded by derivatization-solid-phase microextraction with a novel fiber. , 2006, Analytica chimica acta.

[37]  Robert G. Hahn,et al.  Role of Variability in Explaining Ethanol Pharmacokinetics , 2003, Clinical pharmacokinetics.

[38]  P. Hering,et al.  LASER SPECTROSCOPIC ON-LINE MONITORING OF EXHALED TRACE GASES , 2005 .

[39]  L. Bianchi,et al.  Exhaled volatile organic compounds in patients with non-small cell lung cancer: cross sectional and nested short-term follow-up study , 2005, Respiratory research.

[40]  David Smith,et al.  A longitudinal study of ethanol and acetaldehyde in the exhaled breath of healthy volunteers using selected-ion flow-tube mass spectrometry. , 2006, Rapid communications in mass spectrometry : RCM.

[41]  M. Harper,et al.  Sorbent trapping of volatile organic compounds from air. , 2000, Journal of chromatography. A.

[42]  W. Eisenreich,et al.  Terpenoid biosynthesis from 1-deoxy-D-xylulose in higher plants by intramolecular skeletal rearrangement. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[43]  P. Barnes,et al.  Exhaled markers of pulmonary disease. , 2001, American journal of respiratory and critical care medicine.

[44]  David Smith,et al.  A longitudinal study of ammonia, acetone and propanol in the exhaled breath of 30 subjects using selected ion flow tube mass spectrometry, SIFT-MS , 2006, Physiological measurement.

[45]  Yu. A. Zolotov Breath Analysis , 2005 .

[46]  M. Kinter Analytical technologies for lipid oxidation products analysis. , 1995, Journal of chromatography. B, Biomedical applications.

[47]  H. Baltussen New concepts in sorption based sample preparation for chromatography , 2000 .

[48]  Kohji Mitsubayashi,et al.  Bioelectronic sniffers for ethanol and acetaldehyde in breath air after drinking. , 2005, Biosensors & bioelectronics.

[49]  Jacek A. Koziel,et al.  A Device for Non-invasive On-site Sampling of Cattle Breath with Solid-Phase Microextraction , 2003 .

[50]  M. Phillips,et al.  Increased breath markers of oxidative stress in normal pregnancy and in preeclampsia. , 2004, American journal of obstetrics and gynecology.

[51]  H. J. O’neill,et al.  A computerized classification technique for screening for the presence of breath biomarkers in lung cancer. , 1988, Clinical chemistry.

[52]  T. H. Risby CURRENT STATUS OF CLINICAL BREATH ANALYSIS , 2005 .

[53]  G. Preti,et al.  Analysis of lung air from patients with bronchogenic carcinoma and controls using gas chromatography-mass spectrometry. , 1988, Journal of chromatography.

[54]  X. Zhang,et al.  Determination of acetone in human breath by gas chromatography-mass spectrometry and solid-phase microextraction with on-fiber derivatization. , 2004, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[55]  G. Mills,et al.  Headspace solid-phase microextraction procedures for gas chromatographic analysis of biological fluids and materials. , 2000, Journal of chromatography. A.

[56]  Frederick E. Petry,et al.  Principles and Applications , 1997 .

[57]  M. Takino,et al.  Analysis of volatile sulphur compounds in breath by gas chromatography-mass spectrometry using a three-stage cryogenic trapping preconcentration system. , 2001, Journal of chromatography. B, Biomedical sciences and applications.

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

[59]  David Smith,et al.  Quantification of acetaldehyde released by lung cancer cells in vitro using selected ion flow tube mass spectrometry. , 2003, Rapid communications in mass spectrometry : RCM.

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

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

[62]  Solid phase microextraction for analysis of alkanes and aromatic hydrocarbons in human breath. , 2005, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[63]  A. Ceccarini,et al.  Breath analysis: trends in techniques and clinical applications , 2005 .

[64]  Jianzhong Li,et al.  Determination of acetone in breath , 2005 .

[65]  K. Dettmer,et al.  Adsorbent materials commonly used in air analysis for adsorptive enrichment and thermal desorption of volatile organic compounds , 2002, Analytical and bioanalytical chemistry.

[66]  J. Allard,et al.  Breath alkanes as a marker of oxidative stress in different clinical conditions. , 2000, Free radical biology & medicine.

[67]  Wolfram Miekisch,et al.  From highly sophisticated analytical techniques to life-saving diagnostics: Technical developments in breath analysis , 2006 .

[68]  David Smith,et al.  A longitudinal study of methanol in the exhaled breath of 30 healthy volunteers using selected ion flow tube mass spectrometry, SIFT-MS , 2006, Physiological measurement.

[69]  P. Španěl,et al.  A longitudinal study of breath isoprene in healthy volunteers using selected ion flow tube mass spectrometry (SIFT-MS) , 2006, Physiological measurement.

[70]  Claudio Ronco,et al.  Breath ethane in dialysis patients and control subjects. , 2003, Free radical biology & medicine.

[71]  M. Phillips,et al.  Variation in volatile organic compounds in the breath of normal humans. , 1999, Journal of chromatography. B, Biomedical sciences and applications.

[72]  M D Knutson,et al.  Methods for measuring ethane and pentane in expired air from rats and humans. , 2000, Free radical biology & medicine.