Taking your breath away: metabolomics breathes life in to personalized medicine.

Breath-based metabolomics (breathomics) is an exciting developing area of biotechnology that centers on the capture, identification, and quantification of volatile organic compound (VOC) patterns in human breath and their utilization as tools in the diagnosis of a broad spectrum of medical problems. With the age of personalized medicines demanding rapid bespoke diagnosis and treatment, this area of molecular diagnostics is beginning to see an upsurge in biotechnological advancement. Here, we discuss recent improvements and directions in the development of breath VOC analysis and diagnosis platforms that offer the potential for disease biomarker discovery and disease prognosis.

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

[2]  Joachim D Pleil,et al.  Clinical breath analysis: discriminating between human endogenous compounds and exogenous (environmental) chemical confounders , 2013, Journal of breath research.

[3]  Graham Bothamley,et al.  Breath biomarkers of active pulmonary tuberculosis. , 2010, Tuberculosis.

[4]  Douglas B. Kell,et al.  Proposed minimum reporting standards for data analysis in metabolomics , 2007, Metabolomics.

[5]  Massimo Corradi,et al.  Determination of aldehydes in exhaled breath of patients with lung cancer by means of on-fiber-derivatisation SPME-GC/MS. , 2010, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[6]  Julian King,et al.  Measurement of endogenous acetone and isoprene in exhaled breath during sleep , 2012, Physiological measurement.

[7]  Kevin Gleeson,et al.  Detection of lung cancer with volatile markers in the breath. , 2003, Chest.

[8]  Malcolm Kohler,et al.  Human Breath Analysis May Support the Existence of Individual Metabolic Phenotypes , 2013, PloS one.

[9]  B. Costello,et al.  The human volatilome: volatile organic compounds (VOCs) in exhaled breath, skin emanations, urine, feces and saliva , 2014, Journal of breath research.

[10]  R. Laing,et al.  2-Aminoacetophenone as a potential breath biomarker for Pseudomonas aeruginosa in the cystic fibrosis lung , 2010, BMC pulmonary medicine.

[11]  L. T. Tanoue Detection of Lung Cancer by Sensor Array Analyses of Exhaled Breath , 2007 .

[12]  António S. Barros,et al.  Allergic asthma exhaled breath metabolome: a challenge for comprehensive two-dimensional gas chromatography. , 2012, Journal of chromatography. A.

[13]  J. Lausmaa,et al.  TOF-SIMS analysis of exhaled particles from patients with asthma and healthy controls , 2011, European Respiratory Journal.

[14]  Jamin C. Hoggard,et al.  Recent advancements in comprehensive two-dimensional separations with chemometrics. , 2008, Journal of chromatography. A.

[15]  Bogusław Buszewski,et al.  Chemotherapy control by breath profile with application of SPME-GC/MS method. , 2012, Journal of separation science.

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

[17]  M. Evans,et al.  An exploratory comparative study of volatile compounds in exhaled breath and emitted by skin using selected ion flow tube mass spectrometry. , 2008, Rapid communications in mass spectrometry : RCM.

[18]  Royston Goodacre,et al.  Non-invasive Metabolomic Analysis of Breath Using Differential Mobility Spectrometry in Patients with Chronic Obstructive Pulmonary Disease and Healthy Smokers , 2022 .

[19]  David Smith,et al.  Mass spectrometry for real-time quantitative breath analysis , 2014, Journal of breath research.

[20]  M. O’Hara,et al.  Development of a protocol to measure volatile organic compounds in human breath: a comparison of rebreathing and on-line single exhalations using proton transfer reaction mass spectrometry , 2008, Physiological measurement.

[21]  Ashley Woodcock,et al.  Exhaled volatile organic compounds for phenotyping chronic obstructive pulmonary disease: a cross-sectional study , 2012, Respiratory Research.

[22]  A. Tabesh,et al.  Breath biomarkers and non-alcoholic fatty liver disease: Preliminary observations , 2006, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[23]  U. Tegtbur,et al.  Experimental setup and analytical methods for the non-invasive determination of volatile organic compounds, formaldehyde and NOx in exhaled human breath. , 2010, Analytica chimica acta.

[24]  H. Haick,et al.  Non-invasive Breath Analysis of Pulmonary Nodules , 2012, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[25]  Jens Herbig,et al.  Buffered end-tidal (BET) sampling—a novel method for real-time breath-gas analysis , 2008, Journal of breath research.

[26]  Tai Hyun Park,et al.  Real-time monitoring of odorant-induced cellular reactions using surface plasmon resonance. , 2009, Biosensors & bioelectronics.

[27]  António S. Barros,et al.  Profiling allergic asthma volatile metabolic patterns using a headspace-solid phase microextraction/gas chromatography based methodology. , 2011, Journal of chromatography. A.

[28]  Lucy Fairclough,et al.  Systems biology coupled with label-free high-throughput detection as a novel approach for diagnosis of chronic obstructive pulmonary disease , 2009, Respiratory research.

[29]  H. Haick,et al.  Diagnosing lung cancer in exhaled breath using gold nanoparticles. , 2009, Nature nanotechnology.

[30]  Nigel W. Hardy,et al.  Proposed minimum reporting standards for chemical analysis , 2007, Metabolomics.

[31]  T. Stacewicz,et al.  Ultrasensitive laser spectroscopy for breath analysis , 2012 .

[32]  Hossam Haick,et al.  Sniffing the unique "odor print" of non-small-cell lung cancer with gold nanoparticles. , 2009, Small.

[33]  N. Fens,et al.  Breathomics as a diagnostic tool for pulmonary embolism , 2010, Journal of thrombosis and haemostasis : JTH.

[34]  Bram van Ginneken,et al.  Subphenotypes of Mild-to-Moderate COPD by Factor and Cluster Analysis of Pulmonary Function, CT Imaging and Breathomics in a Population-Based Survey , 2013, COPD.

[35]  Jun Ye,et al.  Cavity-enhanced optical frequency comb spectroscopy: application to human breath analysis. , 2008, Optics express.

[36]  A. Custovic,et al.  Breath metabolomic profiling by nuclear magnetic resonance spectroscopy in asthma , 2013, Allergy.

[37]  B. de Lacy Costello,et al.  A review of the volatiles from the healthy human body , 2014, Journal of breath research.

[38]  W. Miekisch,et al.  Drug detection in breath: effects of pulmonary blood flow and cardiac output on propofol exhalation , 2011, Analytical and bioanalytical chemistry.

[39]  Q. Jöbsis,et al.  Exhaled volatile organic compounds predict exacerbations of childhood asthma in a 1-year prospective study , 2013, European Respiratory Journal.

[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]  Ashley Woodcock,et al.  Non-invasive phenotyping using exhaled volatile organic compounds in asthma , 2011, Thorax.

[42]  D. Kell,et al.  Metabolomics by numbers: acquiring and understanding global metabolite data. , 2004, Trends in biotechnology.

[43]  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.

[44]  Paolo Montuschi,et al.  The Electronic Nose in Respiratory Medicine , 2012, Respiration.

[45]  M P van der Schee,et al.  External validation of exhaled breath profiling using an electronic nose in the discrimination of asthma with fixed airways obstruction and chronic obstructive pulmonary disease , 2011, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[46]  N. Voelkel,et al.  Hypoxia regulates human lung fibroblast proliferation via p53-dependent and -independent pathways , 2009, Respiratory research.

[47]  John Tulip,et al.  Sensitive detection of ammonia and ethylene with a pulsed quantum cascade laser using intra and interpulse spectroscopic techniques , 2009 .

[48]  David Smith,et al.  Detection of volatile compounds emitted by Pseudomonas aeruginosa using selected ion flow tube mass spectrometry , 2005, Pediatric pulmonology.

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

[50]  Douglas B. Kell,et al.  Statistical strategies for avoiding false discoveries in metabolomics and related experiments , 2007, Metabolomics.

[51]  P. Martínez-Lozano,et al.  Electrospray ionization of volatiles in breath , 2007 .

[52]  F. Hughes,et al.  Oral malodour--a review. , 2008, Archives of oral biology.

[53]  J. V. van Amsterdam,et al.  Exhaled nitric oxide monitoring by quantum cascade laser: comparison with chemiluminescent and electrochemical sensors. , 2012, Journal of biomedical optics.

[54]  G. Hanna,et al.  Selected ion flow tube mass spectrometry analysis of exhaled breath for volatile organic compound profiling of esophago-gastric cancer. , 2013, Analytical chemistry.

[55]  J. Wu,et al.  Posttreatment 13C-urea breath test is predictive of antimicrobial resistance to H. pylori after failed therapy , 2005, Journal of General Internal Medicine.

[56]  Wolfram Miekisch,et al.  Data interpretation in breath biomarker research: pitfalls and directions , 2012, Journal of breath research.

[57]  Robert S Plumb,et al.  Global metabolic profiling of animal and human tissues via UPLC-MS , 2012, Nature Protocols.

[58]  Joshua D. Knowles,et al.  Procedures for large-scale metabolic profiling of serum and plasma using gas chromatography and liquid chromatography coupled to mass spectrometry , 2011, Nature Protocols.

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

[60]  D. C. Dumitras,et al.  The level of ethylene biomarker in the renal failure of elderly patients analyzed by photoacoustic spectroscopy , 2013 .

[61]  Xiang Zhang,et al.  Detection of an Extended Human Volatome with Comprehensive Two-Dimensional Gas Chromatography Time-of-Flight Mass Spectrometry , 2013, PloS one.

[62]  R. Zenobi,et al.  Evaluation of extractive electrospray ionization and atmospheric pressure chemical ionization for the detection of narcotics in breath , 2011 .

[63]  F H Krouwels,et al.  Exhaled air molecular profiling in relation to inflammatory subtype and activity in COPD , 2011, European Respiratory Journal.

[64]  Malina K. Storer,et al.  Breath ammonia and trimethylamine allow real-time monitoring of haemodialysis efficacy , 2011, Physiological measurement.

[65]  M. Phillips,et al.  Increased breath biomarkers of oxidative stress in diabetes mellitus. , 2004, Clinica chimica acta; international journal of clinical chemistry.

[66]  F. McLafferty,et al.  Early gas chromatography/mass spectrometry , 1993, Journal of the American Society for Mass Spectrometry.

[67]  Chunsheng Wu,et al.  Recent advances in olfactory receptor-based biosensors. , 2013, Biosensors & bioelectronics.

[68]  W. Vautz,et al.  Detection of metabolites of trapped humans using ion mobility spectrometry coupled with gas chromatography. , 2013, Analytical chemistry.

[69]  Bogusław Buszewski,et al.  Near real-time VOCs analysis using an aspiration ion mobility spectrometer , 2013, Journal of breath research.

[70]  Royston Goodacre Water, water, every where, but rarely any drop to drink , 2013, Metabolomics.

[71]  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.

[72]  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.

[73]  Wolfram Miekisch,et al.  Evaluation of needle trap micro-extraction and automatic alveolar sampling for point-of-care breath analysis , 2013, Analytical and Bioanalytical Chemistry.

[74]  Chuji Wang,et al.  Measurements of the Weak UV Absorptions of Isoprene and Acetone at 261–275 nm Using Cavity Ringdown Spectroscopy for Evaluation of a Potential Portable Ringdown Breath Analyzer , 2013, Sensors.

[75]  M. Quirynen,et al.  GC-MS analysis of breath odor compounds in liver patients. , 2008, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[76]  Onofrio Resta,et al.  An electronic nose in the discrimination of patients with non-small cell lung cancer and COPD. , 2009, Lung cancer.

[77]  Christoph Steinbeck,et al.  MetaboLights—an open-access general-purpose repository for metabolomics studies and associated meta-data , 2012, Nucleic Acids Res..

[78]  E. Wouters,et al.  Volatile organic compounds in exhaled breath as a diagnostic tool for asthma in children , 2009, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[79]  F. V. van Schooten,et al.  The versatile use of exhaled volatile organic compounds in human health and disease , 2012, Journal of breath research.