Breath Analysis in Disease Diagnosis: Methodological Considerations and Applications

Breath analysis is a promising field with great potential for non-invasive diagnosis of a number of disease states. Analysis of the concentrations of volatile organic compounds (VOCs) in breath with an acceptable accuracy are assessed by means of using analytical techniques with high sensitivity, accuracy, precision, low response time, and low detection limit, which are desirable characteristics for the detection of VOCs in human breath. “Breath fingerprinting”, indicative of a specific clinical status, relies on the use of multivariate statistics methods with powerful in-built algorithms. The need for standardisation of sample collection and analysis is the main issue concerning breath analysis, blocking the introduction of breath tests into clinical practice. This review describes recent scientific developments in basic research and clinical applications, namely issues concerning sampling and biochemistry, highlighting the diagnostic potential of breath analysis for disease diagnosis. Several considerations that need to be taken into account in breath analysis are documented here, including the growing need for metabolomics to deal with breath profiles.

[1]  N. Rogers,et al.  Acetone in breath and blood. , 1977, Transactions of the American Clinical and Climatological Association.

[2]  Rossana Salerno-Kennedy,et al.  Potential applications of breath isoprene as a biomarker in modern medicine: a concise overview , 2005, Wiener klinische Wochenschrift.

[3]  N. Ratcliffe,et al.  The importance of methane breath testing: a review , 2013, Journal of breath research.

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

[5]  C. Mayhew,et al.  Real-time breath monitoring of propofol and its volatile metabolites during surgery using a novel mass spectrometric technique: a feasibility study. , 2003, British journal of anaesthesia.

[6]  J. Herbig,et al.  On the performance of proton-transfer-reaction mass spectrometry for breath-relevant gas matrices , 2013 .

[7]  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.

[8]  P. Boyle,et al.  Diet and oxidative stress in breast, colon and prostate cancer patients: a case-control study. , 1994, European journal of clinical nutrition.

[9]  M. Phillips,et al.  Volatile Markers of Breast Cancer in the Breath , 2003, The breast journal.

[10]  S. Cocozza,et al.  Identification of Candidate Children for Maturity-Onset Diabetes of the Young Type 2 (MODY2) Gene Testing: A Seven-Item Clinical Flowchart (7-iF) , 2013, PloS one.

[11]  Josef Guttmann,et al.  CO2-controlled sampling of alveolar gas in mechanically ventilated patients , 2001 .

[12]  P. J. Barnes,et al.  Exhaled breath condensate: methodological recommendations and unresolved questions , 2005, European Respiratory Journal.

[13]  K. Verbeke,et al.  Relevance of protein fermentation to gut health. , 2012, Molecular nutrition & food research.

[14]  David Smith,et al.  Progress in SIFT-MS: breath analysis and other applications. , 2011, Mass spectrometry reviews.

[15]  Anders Eklund,et al.  Assessing Recent Smoking Status by Measuring Exhaled Carbon Monoxide Levels , 2011, PloS one.

[16]  K. Dubowski Biological aspects of breath-alcohol analysis. , 1974, Clinical chemistry.

[17]  L. Halonen,et al.  Background levels and diurnal variations of hydrogen cyanide in breath and emitted from skin , 2011, Journal of breath research.

[18]  S. Pratsinis,et al.  Correlations between blood glucose and breath components from portable gas sensors and PTR-TOF-MS , 2013, Journal of breath research.

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

[20]  P Rolfe,et al.  The selected ion flow tube (SIFT)--a novel technique for biological monitoring. , 1996, The Annals of occupational hygiene.

[21]  A. Amann,et al.  Suitability of different polymer bags for storage of volatile sulphur compounds relevant to breath analysis. , 2009, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

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

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

[24]  D. Niederseer,et al.  Gender and age specific differences in exhaled isoprene levels , 2006, Respiratory Physiology & Neurobiology.

[25]  N. Stickland,et al.  Feed allowance and maternal backfat levels during gestation influence maternal cortisol levels, milk fat composition and offspring growth , 2013, Journal of Nutritional Science.

[26]  A. Hansel,et al.  On-line monitoring of volatile organic compounds at pptv levels by means of proton-transfer-reaction mass spectrometry (PTR-MS) medical applications, food control and environmental research , 1998 .

[27]  D. de Freitas,et al.  [Alcohol and cancer]. , 1997, Acta medica portuguesa.

[28]  Gordon G. Wallace,et al.  Development of an electronic nose , 1997, Smart Materials, Nano-, and Micro- Smart Systems.

[29]  C. Ager,et al.  Optimization of sampling parameters for collection and preconcentration of alveolar air by needle traps , 2012, Journal of breath research.

[30]  A. P. van Harreveld Odor concentration decay and stability in gas sampling bags. , 2003, Journal of the Air & Waste Management Association.

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

[32]  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.

[33]  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.

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

[35]  S Lenzi,et al.  Monitoring breath during oral glucose tolerance tests , 2013, Journal of breath research.

[36]  A. Hansel,et al.  Endogenous production of methanol after the consumption of fruit. , 1997, Alcoholism, clinical and experimental research.

[37]  P. Span,et al.  Selected ion flow tube mass spectrometry for on-line trace gas analysis in biology and medicine , 2007 .

[38]  G. Teschl,et al.  A modeling-based evaluation of isothermal rebreathing for breath gas analyses of highly soluble volatile organic compounds , 2011, Journal of breath research.

[39]  P. Španěl,et al.  Volatile metabolites in the exhaled breath of healthy volunteers: their levels and distributions , 2007, Journal of breath research.

[40]  Simone Meinardi,et al.  Noninvasive measurement of plasma glucose from exhaled breath in healthy and type 1 diabetic subjects. , 2011, American journal of physiology. Endocrinology and metabolism.

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

[42]  A. Ziegler,et al.  Human breath gas analysis in the screening of gestational diabetes mellitus. , 2012, Diabetes Technology & Therapeutics.

[43]  D. Osborne,et al.  Gas-chromatographic and mass-spectrometric analysis of the odor of human feces. , 1987, Gastroenterology.

[44]  G. Ferns,et al.  Effects of dietary nutrients on volatile breath metabolites , 2013, Journal of Nutritional Science.

[45]  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.

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

[47]  L. Trizio,et al.  Exhaled volatile organic compounds identify patients with colorectal cancer , 2013, The British journal of surgery.

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

[49]  Metabolic monitoring and assessment of anaerobic threshold by means of breath biomarkers , 2012, Metabolomics.

[50]  Anton Amann,et al.  Proton Transfer Reaction-Mass Spectrometry Applications in Medical Research , 2009, Journal of breath research.

[51]  P. Španěl,et al.  A study of sulfur-containing compounds in mouth- and nose-exhaled breath and in the oral cavity using selected ion flow tube mass spectrometry , 2008, Journal of breath research.

[52]  Bogusław Buszewski,et al.  Human exhaled air analytics: biomarkers of diseases. , 2007, Biomedical chromatography : BMC.

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

[54]  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.

[55]  F. Biasioli,et al.  Rapid “Breath-Print” of Liver Cirrhosis by Proton Transfer Reaction Time-of-Flight Mass Spectrometry. A Pilot Study. , 2013, PloS one.

[56]  C. N. Hewitt,et al.  The application of proton transfer reaction-mass spectrometry (PTR-MS) to the monitoring and analysis of volatile organic compounds in the atmosphere. , 2003, Journal of environmental monitoring : JEM.

[57]  David Zhang,et al.  Diabetes Identification and Classification by Means of a Breath Analysis System , 2010, ICMB.

[58]  A. Manolis,et al.  The diagnostic potential of breath analysis. , 1983, Clinical chemistry.

[59]  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.

[60]  W. S. Fowler Lung function studies; the respiratory dead space. , 1948, The American journal of physiology.

[61]  Recommendations for Standardized Procedures for the Online and Offline Measurement of Exhaled Lower Respiratory Nitric Oxide and Nasal Nitric Oxide in Adults and Children — 1999 , 1999 .

[62]  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.

[63]  M. Phillips,et al.  Volatile biomarkers in the breath of women with breast cancer , 2010, Journal of breath research.

[64]  P. Åman,et al.  Proliferation of Ewing sarcoma cell lines is suppressed by the receptor tyrosine kinase inhibitors gefitinib and vandetanib , 2008, Cancer Cell International.

[65]  J. Beauchamp,et al.  On the use of Tedlar® bags for breath-gas sampling and analysis , 2008, Journal of breath research.

[66]  Anton Amann,et al.  Ion mobility spectrometry for detection of skin volatiles , 2012, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

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

[68]  Y. Henderson,et al.  THE RESPIRATORY DEAD SPACE , 1915 .

[69]  Christopher Walton,et al.  Breath acetone concentration decreases with blood glucose concentration in type I diabetes mellitus patients during hypoglycaemic clamps , 2009, Journal of breath research.

[70]  David Smith,et al.  Time variation of ammonia, acetone, isoprene and ethanol in breath: a quantitative SIFT-MS study over 30 days. , 2003, Physiological measurement.

[71]  K. Unterkofler,et al.  Breath acetone—aspects of normal physiology related to age and gender as determined in a PTR-MS study , 2009, Journal of breath research.

[72]  Helko Borsdorf,et al.  Ion Mobility Spectrometry: Principles and Applications , 2006 .

[73]  P. Španěl,et al.  A selected ion flow tube study of the reactions of H3O+, NO+ and O2+• with seven isomers of hexanol in support of SIFT-MS , 2012 .

[74]  L. Freitag,et al.  Ion mobility spectrometry for the detection of volatile organic compounds in exhaled breath of patients with lung cancer: results of a pilot study , 2009, Thorax.

[75]  B. Buszewski,et al.  Analysis of exhaled breath from smokers, passive smokers and non-smokers by solid-phase microextraction gas chromatography/mass spectrometry. , 2009, Biomedical chromatography : BMC.

[76]  P. Smith,et al.  Advances in On-line Absolute Trace Gas Analysis by SIFT-MS , 2013 .

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

[78]  Anton Amann,et al.  Volatile Biomarkers : Non-Invasive Diagnosis in Physiology and Medicine , 2013 .

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

[80]  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.

[81]  R. Hoeldtke,et al.  Acetone Metabolism in Humans During Diabetic Ketoacidosis , 1986, Diabetes.

[82]  Patrik Španěl,et al.  Application of ion chemistry and the SIFT technique to the quantitative analysis of trace gases in air and on breath , 1996 .

[83]  David Smith,et al.  A quantitative study of the influence of inhaled compounds on their concentrations in exhaled breath , 2013, Journal of breath research.

[84]  Philipp Sulzer,et al.  An online ultra-high sensitivity Proton-transfer-reaction mass-spectrometer combined with switchable reagent ion capability (PTR + SRI − MS) , 2009 .

[85]  P. Španěl,et al.  Hydrogen cyanide, a volatile biomarker of Pseudomonas aeruginosa infection , 2013, Journal of breath research.

[86]  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.

[87]  W. Miekisch,et al.  A novel visually CO2 controlled alveolar breath sampling technique. , 2006, Technology and health care : official journal of the European Society for Engineering and Medicine.

[88]  T. Karl,et al.  Quantification of passive smoking using proton-transfer-reaction mass spectrometry , 1998 .

[89]  P. Španěl,et al.  SIFT-MS Analysis of Nose-Exhaled Breath; Mouth Contamination and the Influence of Exercise , 2013 .

[90]  A. Hansel,et al.  Acetonitrile and benzene in the breath of smokers and non-smokers investigated by proton transfer reaction mass spectrometry (PTR-MS) , 1995 .

[91]  David Smith,et al.  On-line, simultaneous quantification of ethanol, some metabolites and water vapour in breath following the ingestion of alcohol. , 2002, Physiological measurement.

[92]  M. Phillips,et al.  Alveolar gradient of pentane in normal human breath. , 1994, Free radical research.

[93]  M. Hlastala,et al.  Breath tests and airway gas exchange. , 2007, Pulmonary pharmacology & therapeutics.

[94]  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.

[95]  ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005. , 2005, American journal of respiratory and critical care medicine.

[96]  A. I. Smith,et al.  Age-Dependent Changes in the Proteome Following Complete Spinal Cord Transection in a Postnatal South American Opossum (Monodelphis domestica) , 2011, PloS one.

[97]  H. Flint,et al.  The microbiology of butyrate formation in the human colon. , 2002, FEMS microbiology letters.

[98]  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.

[99]  H. Garewal,et al.  Cigarette smoking and ethane exhalation in humans. , 1995, American journal of respiratory and critical care medicine.

[100]  M. Phillips,et al.  Pilot study of a breath test for volatile organic compounds associated with oral malodor: evidence for the role of oxidative stress. , 2005, Oral diseases.

[101]  P. Španěl,et al.  Kinetics of ethanol decay in mouth- and nose-exhaled breath measured on-line by selected ion flow tube mass spectrometry following varying doses of alcohol. , 2010, Rapid communications in mass spectrometry : RCM.

[102]  M. Kalapos,et al.  On the mammalian acetone metabolism: from chemistry to clinical implications. , 2003, Biochimica et biophysica acta.

[103]  J D Pleil,et al.  Simply breath-taking? Developing a strategy for consistent breath sampling , 2013, Journal of breath research.

[104]  J. V. van Amsterdam,et al.  A simple method to sample exhaled NO not contaminated by ambient NO from children and adults in epidemiological studies. , 2000, Nitric oxide : biology and chemistry.

[105]  F. Nagengast,et al.  The role of carbohydrate fermentation in colon cancer prevention. , 1993, Scandinavian journal of gastroenterology. Supplement.

[106]  N. Adams,et al.  The selected ion flow tube (SIFT); A technique for studying ion-neutral reactions , 1976 .

[107]  P. Spanĕl,et al.  Concentrations of some metabolites in the breath of healthy children aged 7–18 years measured using selected ion flow tube mass spectrometry (SIFT-MS) , 2009, Journal of breath research.

[108]  J. Herbig,et al.  Real-time metabolic monitoring with proton transfer reaction mass spectrometry , 2013, Journal of breath research.

[109]  David Smith,et al.  Acetone, ammonia and hydrogen cyanide in exhaled breath of several volunteers aged 4–83 years , 2007, Journal of breath research.

[110]  A. Neugut,et al.  IGHMBP2 Thr671Ala polymorphism might be a modifier for the effects of cigarette smoking and PAH–DNA adducts to breast cancer risk , 2006, Breast Cancer Research and Treatment.

[111]  Patrik Španěl,et al.  Quantification of pentane in exhaled breath, a potential biomarker of bowel disease, using selected ion flow tube mass spectrometry. , 2013, Rapid communications in mass spectrometry : RCM.

[112]  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.

[113]  Bogusław Buszewski,et al.  Determination of volatile organic compounds in human breath for Helicobacter pylori detection by SPME-GC/MS. , 2011, Biomedical chromatography : BMC.

[114]  S. Cunnane,et al.  Breath acetone is a reliable indicator of ketosis in adults consuming ketogenic meals. , 2002, The American journal of clinical nutrition.

[115]  G. Pioggia,et al.  Implementation of Fowler's method for end-tidal air sampling , 2008, Journal of breath research.

[116]  N. Adams,et al.  The Selected Ion Flow Tube (Sift): Studies of Ion-Neutral Reactions , 1988 .

[117]  Tianshu Wang,et al.  A selected ion flow tube mass spectrometry study of ammonia in mouth- and nose-exhaled breath and in the oral cavity. , 2008, Rapid communications in mass spectrometry : RCM.

[118]  K Geiger,et al.  Impact of inspired substance concentrations on the results of breath analysis in mechanically ventilated patients , 2005, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[119]  Julian King,et al.  Stability of selected volatile breath constituents in Tedlar, Kynar and Flexfilm sampling bags. , 2013, The Analyst.

[120]  T. Clutton-Brock,et al.  Endogenous volatile organic compounds in breath and blood of healthy volunteers: examining breath analysis as a surrogate for blood measurements , 2009, Journal of breath research.

[121]  P. Španěl,et al.  The novel selected-ion flow tube approach to trace gas analysis of air and breath. , 1996, Rapid communications in mass spectrometry : RCM.

[122]  P. Gibson,et al.  Butyrate production from dietary fibre and protection against large bowel cancer in a rat model. , 1993, Gut.

[123]  Sotiris E Pratsinis,et al.  Breath acetone monitoring by portable Si:WO3 gas sensors. , 2012, Analytica chimica acta.

[124]  Lauri Halonen,et al.  Exhaled breath biomonitoring using laser spectroscopy , 2013 .

[125]  W. Vautz,et al.  Determination of serum propofol concentrations by breath analysis using ion mobility spectrometry. , 2009, British journal of anaesthesia.

[126]  S. Bingham,et al.  Dietary fibre, fermentation and large bowel cancer. , 1987, Cancer surveys.

[127]  M. Eastwood,et al.  Methane excretion in man--a study of breath, flatus, and faeces. , 1985, Gut.

[128]  Tianshu Wang,et al.  Generation of volatile compounds on mouth exposure to urea and sucrose: implications for exhaled breath analysis , 2006, Physiological measurement.

[129]  Bo Li,et al.  Volatile organic compound detection using nanostructured copolymers. , 2006, Nano letters.

[130]  J. Greenman,et al.  Volatiles from oral anaerobes confounding breath biomarker discovery , 2013, Journal of breath research.

[131]  F. Biasioli,et al.  Application of PTR-TOF-MS to investigate metabolites in exhaled breath of patients affected by coeliac disease under gluten free diet. , 2014, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[132]  Philipp Sulzer,et al.  A high resolution and high sensitivity proton-transfer-reaction time-of-flight mass spectrometer (PTR-TOF-MS) , 2009 .

[133]  Investigation of organic vapor losses to condensed water vapor in Tedlar bags used for exhaled-breath sampling. , 1996, American Industrial Hygiene Association journal.

[134]  David Smith,et al.  Breath acetone concentration; biological variability and the influence of diet , 2011, Physiological measurement.

[135]  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.

[136]  Olaf Tietje,et al.  Volatile biomarkers of pulmonary tuberculosis in the breath. , 2007, Tuberculosis.

[137]  David Smith,et al.  Increase of acetone and ammonia in urine headspace and breath during ovulation quantified using selected ion flow tube mass spectrometry. , 2003, Physiological measurement.

[138]  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.

[139]  Herbert Tilg,et al.  Headspace screening of fluid obtained from the gut during colonoscopy and breath analysis by proton transfer reaction-mass spectrometry: A novel approach in the diagnosis of gastro-intestinal diseases , 2005 .

[140]  J Guttmann,et al.  CO(2)-controlled sampling of alveolar gas in mechanically ventilated patients. , 2001, Journal of applied physiology.

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

[142]  Tomas Mikoviny,et al.  Release of volatile organic compounds (VOCs) from the lung cancer cell line CALU-1 in vitro , 2008, Cancer Cell International.

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

[144]  J. Furne,et al.  Influence of Method of Alveolar Air Collection on Results of Breath Tests , 1998, Digestive Diseases and Sciences.

[145]  Josep Sulé-Suso,et al.  Quantification by SIFT-MS of acetaldehyde released by lung cells in a 3D model. , 2013, The Analyst.

[146]  M. Epton,et al.  Measurement of breath acetone concentrations by selected ion flow tube mass spectrometry in type 2 Diabetes , 2011, Journal of breath research.

[147]  Lauren E. Manning,et al.  The scent of Mycobacterium tuberculosis--part II breath. , 2009, Tuberculosis.

[148]  Karin Greiner,et al.  Elective haemodialysis increases exhaled isoprene. , 2003, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[149]  David Smith,et al.  Selected ion flow tube mass spectrometry (SIFT-MS) for on-line trace gas analysis. , 2005, Mass spectrometry reviews.

[150]  P. Španěl,et al.  Selected ion flow tube: a technique for quantitative trace gas analysis of air and breath , 1996, Medical and Biological Engineering and Computing.

[151]  David Smith,et al.  An investigation of suitable bag materials for the collection and storage of breath samples containing hydrogen cyanide , 2012, Journal of breath research.

[152]  J. Bond,et al.  Use of pulmonary hydrogen (H 2 ) measurements to quantitate carbohydrate absorption. Study of partially gastrectomized patients. , 1972, The Journal of clinical investigation.

[153]  B. Ross,et al.  A preliminary investigation of exhaled breath from patients with celiac disease using selected ion flow tube mass spectrometry. , 2010, Journal of gastrointestinal and liver diseases : JGLD.

[154]  Breath volatile analysis from patients diagnosed with harmful drinking, cirrhosis and hepatic encephalopathy: a pilot study , 2013, Metabolomics.

[155]  Patrik Španěl,et al.  Selected ion flow tube – mass spectrometry: detection and real-time monitoring of flavours released by food products , 1999 .

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

[157]  Michael Hill,et al.  Public policy and private provisions: changes in residential care from 1991 to 2001. , 2006, Health & social care in the community.

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

[159]  J. Beauchamp,et al.  Inhaled today, not gone tomorrow: pharmacokinetics and environmental exposure of volatiles in exhaled breath , 2011, Journal of breath research.

[160]  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.

[161]  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.

[162]  David Smith,et al.  Can volatile compounds in exhaled breath be used to monitor control in diabetes mellitus? , 2011, Journal of breath research.

[163]  Alicja Wolk,et al.  Meat consumption and risk of colorectal cancer: A meta‐analysis of prospective studies , 2006, International journal of cancer.

[164]  P. Hellström,et al.  Pancreaticobiliary juice releases motilin during phase I of the migrating motor complex in man. , 1993, Scandinavian journal of gastroenterology.

[165]  David Smith The Ion Chemistry of Interstellar Clouds , 1992 .

[166]  P. Španěl,et al.  On-line measurement of the absolute humidity of air, breath and liquid headspace samples by selected ion flow tube mass spectrometry. , 2001, Rapid communications in mass spectrometry : RCM.

[167]  Shaun W. Lawson,et al.  Canine responses to hypoglycemia in patients with type 1 diabetes. , 2008, Journal of alternative and complementary medicine.

[168]  J G Hamilton,et al.  Needle phobia: a neglected diagnosis. , 1995, The Journal of family practice.

[169]  David Smith,et al.  Increase of acetone emitted by urine in relation to ovulation , 2006, Acta obstetricia et gynecologica Scandinavica.

[170]  Werner Lindinger,et al.  Analysis of Compounds in Human Breath after Ingestion of Garlic Using Proton-Transfer-Reaction Mass Spectrometry , 1996 .

[171]  J D Pleil,et al.  Sample Timing and Mathematical Considerations for Modeling Breath Elimination of Volatile Organic Compounds , 1998, Risk analysis : an official publication of the Society for Risk Analysis.

[172]  Tianshu Wang,et al.  Analysis of breath, exhaled via the mouth and nose, and the air in the oral cavity , 2008, Journal of breath research.

[173]  P. Wagner Pulmonary gas exchange , 2007, American journal of respiratory and critical care medicine.

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