Hybrid volatolomics and disease detection.

This Review presents a concise, but not exhaustive, didactic overview of some of the main concepts and approaches related to "volatolomics"-an emerging frontier for fast, risk-free, and potentially inexpensive diagnostics. It attempts to review the source and characteristics of volatolomics through the so-called volatile organic compounds (VOCs) emanating from cells and their microenvironment. It also reviews the existence of VOCs in several bodily fluids, including the cellular environment, blood, breath, skin, feces, urine, and saliva. Finally, the usefulness of volatolomics for diagnosis from a single bodily fluid, as well as ways to improve these diagnostic aspects by "hybrid" approaches that combine VOC profiles collected from two or more bodily fluids, will be discussed. The perspectives of this approach in developing the field of diagnostics to a new level are highlighted.

[1]  M. Ishii,et al.  Sweat, the driving force behind normal skin: an emerging perspective on functional biology and regulatory mechanisms. , 2015, Journal of dermatological science.

[2]  C. Seger,et al.  Non-13CO2 targeted breath tests: a feasibility study , 2014, Journal of breath research.

[3]  W. John,et al.  Cancer Management and Research Dovepress a Comprehensive Review of Nongenetic Prognostic and Predictive Factors Influencing the Heterogeneity of Outcomes in Advanced Non-small-cell Lung Cancer , 2022 .

[4]  K. Unterkofler,et al.  Quantitative analysis of volatile organic compounds released and consumed by rat L6 skeletal muscle cells in vitro , 2014, Journal of breath research.

[5]  K. Hayashi,et al.  Neural, fuzzy and neuro-fuzzy approach for concentration estimation of volatile organic compounds by surface acoustic wave sensor array , 2014 .

[6]  L. Caplan,et al.  Delay in Breast Cancer: Implications for Stage at Diagnosis and Survival , 2014, Front. Public Health.

[7]  H. Haick,et al.  Unique volatolomic signatures of TP53 and KRAS in lung cells , 2014, British Journal of Cancer.

[8]  S. Solga Breath volatile organic compounds for the gut-fatty liver axis: promise, peril, and path forward. , 2014, World journal of gastroenterology.

[9]  Bogusław Buszewski,et al.  Analysis of exhaled breath for disease detection. , 2014, Annual review of analytical chemistry.

[10]  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.

[11]  K. Unterkofler,et al.  Product ion distributions for the reactions of NO+ with some physiologically significant volatile organosulfur and organoselenium compounds obtained using a selective reagent ionization time-of-flight mass spectrometer , 2014, Rapid communications in mass spectrometry : RCM.

[12]  K. Hase,et al.  Gut microbiota-generated metabolites in animal health and disease. , 2014, Nature chemical biology.

[13]  Bettina Zelger,et al.  Comparative analyses of volatile organic compounds (VOCs) from patients, tumors and transformed cell lines for the validation of lung cancer-derived breath markers , 2014, Journal of breath research.

[14]  Raymond A Martino,et al.  Detecting cancer by breath volatile organic compound analysis: a review of array-based sensors , 2014, Journal of breath research.

[15]  Julian King,et al.  Emission rates of selected volatile organic compounds from skin of healthy volunteers , 2014, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[16]  H. Haick,et al.  Detecting active pulmonary tuberculosis with a breath test using nanomaterial-based sensors , 2014, European Respiratory Journal.

[17]  H. Haick,et al.  Combined Volatolomics for Monitoring of Human Body Chemistry , 2014, Scientific Reports.

[18]  Anton Amann,et al.  Monitoring of Selected Skin-Borne Volatile Markers of Entrapped Humans by Selective Reagent Ionization Time of Flight Mass Spectrometry in NO+ Mode , 2014, Analytical chemistry.

[19]  Gert Mayer,et al.  Blood and breath profiles of volatile organic compounds in patients with end-stage renal disease , 2014, BMC Nephrology.

[20]  H. Haick,et al.  Assessment of the exhalation kinetics of volatile cancer biomarkers based on their physicochemical properties , 2014, Journal of breath research.

[21]  Hossam Haick,et al.  Assessment, origin, and implementation of breath volatile cancer markers. , 2014, Chemical Society reviews.

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

[23]  Xiao Zhi,et al.  Identification of Volatile Biomarkers of Gastric Cancer Cells and Ultrasensitive Electrochemical Detection based on Sensing Interface of Au-Ag Alloy coated MWCNTs , 2014, Theranostics.

[24]  Patricia Kennedy,et al.  Impact of Delayed Diagnosis and Treatment in Clinically Isolated Syndrome and Multiple Sclerosis , 2013, The Journal of neuroscience nursing : journal of the American Association of Neuroscience Nurses.

[25]  V. Ruzsányi Ion mobility spectrometry for pharmacokinetic studies-–exemplary application , 2013, Journal of breath research.

[26]  M. Schivo,et al.  Diabetes and the Metabolic Syndrome: Possibilities of a New Breath Test in a Dolphin Model , 2013, Front. Endocrinol..

[27]  Sung Soo Kim,et al.  Cancer cell metabolism: implications for therapeutic targets , 2013, Experimental & Molecular Medicine.

[28]  Heather D. Bean,et al.  Robust detection of P. aeruginosa and S. aureus acute lung infections by secondary electrospray ionization-mass spectrometry (SESI-MS) breathprinting: from initial infection to clearance , 2013, Journal of breath research.

[29]  Radu Ionescu,et al.  Volatile fingerprints of cancer specific genetic mutations. , 2013, Nanomedicine : nanotechnology, biology, and medicine.

[30]  Markus Grammel,et al.  Chemical reporters for biological discovery. , 2013, Nature chemical biology.

[31]  Willem Takken,et al.  Relation between HLA genes, human skin volatiles and attractiveness of humans to malaria mosquitoes. , 2013, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[32]  Michelle Gallagher,et al.  Volatile biomarkers from human melanoma cells. , 2013, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[33]  M. Trivella,et al.  Post-operative elimination of sevoflurane anesthetic and hexafluoroisopropanol metabolite in exhaled breath: pharmacokinetic models for assessing liver function , 2013, Journal of breath research.

[34]  H. Haick,et al.  Nanomaterial-based sensors for detection of disease by volatile organic compounds. , 2013, Nanomedicine.

[35]  Olof Beck,et al.  Detection of drugs of abuse in exhaled breath using a device for rapid collection: comparison with plasma, urine and self-reporting in 47 drug users , 2013, Journal of breath research.

[36]  Laurent Dormont,et al.  Human Skin Volatiles: A Review , 2013, Journal of Chemical Ecology.

[37]  Comparative analysis of volatile metabolomics signals from melanoma and benign skin: a pilot study , 2013, Metabolomics.

[38]  Julian King,et al.  Blood and breath levels of selected volatile organic compounds in healthy volunteers. , 2013, The Analyst.

[39]  N De Giovanni,et al.  The current status of sweat testing for drugs of abuse: a review. , 2013, Current medicinal chemistry.

[40]  Ulrike Tisch,et al.  A nanomaterial-based breath test for short-term follow-up after lung tumor resection. , 2013, Nanomedicine : nanotechnology, biology, and medicine.

[41]  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.

[42]  Hossam Haick,et al.  Volatile organic compounds of lung cancer and possible biochemical pathways. , 2012, Chemical reviews.

[43]  C. L. Thomas,et al.  Sampling and characterisation of volatile organic compound profiles in human saliva using a polydimethylsiloxane coupon placed within the oral cavity. , 2012, The Analyst.

[44]  G. Teschl,et al.  Breath isoprene: muscle dystrophy patients support the concept of a pool of isoprene in the periphery of the human body. , 2012, Biochemical and biophysical research communications.

[45]  Ulrike Tisch,et al.  Classification of lung cancer histology by gold nanoparticle sensors. , 2012, Nanomedicine : nanotechnology, biology, and medicine.

[46]  I. Brune,et al.  The transcriptional regulatory network of Corynebacterium jeikeium K411 and its interaction with metabolic routes contributing to human body odor formation. , 2012, Journal of biotechnology.

[47]  J. Nicholson,et al.  Host-Gut Microbiota Metabolic Interactions , 2012, Science.

[48]  P. Mazzone,et al.  Exhaled breath volatile organic compound biomarkers in lung cancer , 2012, Journal of breath research.

[49]  K. Unterkofler,et al.  Human Blood and Plasma Partition Coefficients for C4-C8 n-alkanes, Isoalkanes, and 1-alkenes , 2012, International journal of toxicology.

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

[51]  H. Haick,et al.  Gold nanoparticle sensors for detecting chronic kidney disease and disease progression. , 2012, Nanomedicine.

[52]  Katherine H. Huang,et al.  Structure, Function and Diversity of the Healthy Human Microbiome , 2012, Nature.

[53]  Joshua T. Morgan,et al.  Characterization of Volatile Organic Compounds in Human Leukocyte Antigen Heterologous Expression Systems: a Cell's “Chemical Odor Fingerprint” , 2012, Chembiochem : a European journal of chemical biology.

[54]  J. Greenman,et al.  Microbial volatile compounds in health and disease conditions , 2012, Journal of breath research.

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

[56]  Tarek Mekhail,et al.  Exhaled Breath Analysis with a Colorimetric Sensor Array for the Identification and Characterization of Lung Cancer , 2012, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[57]  Ping Wang,et al.  The analysis of volatile organic compounds biomarkers for lung cancer in exhaled breath, tissues and cell lines. , 2012, Cancer biomarkers : section A of Disease markers.

[58]  K. Unterkofler,et al.  Measurement of isoprene solubility in water, human blood and plasma by multiple headspace extraction gas chromatography coupled with solid phase microextraction , 2011, Journal of breath research.

[59]  B. Bouchikhi,et al.  Novel e-nose for the discrimination of volatile organic biomarkers with an array of carbon nanotubes (CNT) conductive polymer nanocomposites (CPC) sensors , 2011 .

[60]  Kazushige Touhara,et al.  The scent of disease: volatile organic compounds of the human body related to disease and disorder. , 2011, Journal of biochemistry.

[61]  Peter Beyerlein,et al.  Diagnostic potential of saliva: current state and future applications. , 2011, Clinical chemistry.

[62]  Kenneth G Furton,et al.  Development of headspace SPME method for analysis of volatile organic compounds present in human biological specimens , 2011, Analytical and bioanalytical chemistry.

[63]  C. Proctor,et al.  Reduction of aldehydes and hydrogen cyanide yields in mainstream cigarette smoke using an amine functionalised ion exchange resin , 2011, Chemistry Central journal.

[64]  Massimo Corradi,et al.  Lung cancer biomarkers in exhaled breath , 2011, Expert review of molecular diagnostics.

[65]  S. Cristoni,et al.  Secondary electrospray ionization-mass spectrometry: breath study on a control group , 2011, Journal of breath research.

[66]  G. Teschl,et al.  The role of mathematical modeling in VOC analysis using isoprene as a prototypic example , 2011, Journal of breath research.

[67]  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.

[68]  Anton Amann,et al.  Analysis of volatile organic compounds (VOCs) in the headspace of NCI-H1666 lung cancer cells. , 2011, Cancer biomarkers : section A of Disease markers.

[69]  Thomas Peyret,et al.  A unified algorithm for predicting partition coefficients for PBPK modeling of drugs and environmental chemicals. , 2010, Toxicology and applied pharmacology.

[70]  W. Miekisch,et al.  Analysis of exhaled breath for screening of lung cancer patients , 2010 .

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

[72]  Richard G. Brereton,et al.  Analysis of Volatile Organic Compounds in Human Saliva by a Static Sorptive Extraction Method and Gas Chromatography-Mass Spectrometry , 2010, Journal of Chemical Ecology.

[73]  H. Haick,et al.  Detection of lung, breast, colorectal, and prostate cancers from exhaled breath using a single array of nanosensors , 2010, British Journal of Cancer.

[74]  Q. Jöbsis,et al.  Metabolomics of Volatile Organic Compounds in Cystic Fibrosis Patients and Controls , 2010, Pediatric Research.

[75]  G. Archunan,et al.  Biochemical evaluation in human saliva with special reference to ovulation detection. , 2010, Indian journal of dental research : official publication of Indian Society for Dental Research.

[76]  A. Tangerman,et al.  Extra-oral halitosis: an overview , 2010, Journal of breath research.

[77]  Suzely Adas Saliba Moimaz,et al.  Saliva: reflection of the body. , 2010, International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases.

[78]  Allison M. Curran,et al.  The Differentiation of the Volatile Organic Signatures of Individuals Through SPME‐GC/MS of Characteristic Human Scent Compounds , 2010, Journal of forensic sciences.

[79]  Anton Amann,et al.  TD-GC-MS Analysis of Volatile Metabolites of Human Lung Cancer and Normal Cells In vitro , 2010, Cancer Epidemiology, Biomarkers & Prevention.

[80]  David Smith,et al.  Quantification of acetaldehyde and carbon dioxide in the headspace of malignant and non-malignant lung cells in vitro by SIFT-MS. , 2009, The Analyst.

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

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

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

[84]  M. Jakubowski,et al.  Calculating the retention of volatile organic compounds in the lung on the basis of their physicochemical properties. , 2009, Environmental toxicology and pharmacology.

[85]  Norman Ratcliffe,et al.  Volatile organic compounds as diagnostic biomarkers in gastrointestinal and liver diseases. , 2009, Journal of gastrointestinal and liver diseases : JGLD.

[86]  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.

[87]  K. Rostásy,et al.  3-Heptanone as a potential new marker for valproic acid therapy , 2009, Journal of breath research.

[88]  K. Hiraoka,et al.  Rapid detection of drugs in biofluids using atmospheric pressure chemi/chemical ionization mass spectrometry. , 2009, Rapid communications in mass spectrometry : RCM.

[89]  Tomas Mikoviny,et al.  Release of volatile organic compounds from the lung cancer cell line NCI-H2087 in vitro. , 2009, Anticancer research.

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

[91]  C. Wysocki,et al.  Analyses of volatile organic compounds from human skin , 2008, The British journal of dermatology.

[92]  Wolfram Miekisch,et al.  Assessment of propofol concentrations in human breath and blood by means of HS-SPME-GC-MS. , 2008, Clinica chimica acta; international journal of clinical chemistry.

[93]  J. Austin,et al.  Detection of lung cancer using weighted digital analysis of breath biomarkers. , 2008, Clinica chimica acta; international journal of clinical chemistry.

[94]  C Di Natale,et al.  Identification of melanoma with a gas sensor array , 2008, Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging.

[95]  D. Blake,et al.  Exhaled methyl nitrate as a noninvasive marker of hyperglycemia in type 1 diabetes , 2007, Proceedings of the National Academy of Sciences.

[96]  Ping Wang,et al.  A study of the volatile organic compounds exhaled by lung cancer cells in vitro for breath diagnosis , 2007, Cancer.

[97]  Giorgia Antonelli,et al.  Saliva specimen: a new laboratory tool for diagnostic and basic investigation. , 2007, Clinica chimica acta; international journal of clinical chemistry.

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

[99]  D. Penn,et al.  Individual and gender fingerprints in human body odour , 2007, Journal of The Royal Society Interface.

[100]  J. Minna,et al.  Multiple oncogenic changes (K-RAS(V12), p53 knockdown, mutant EGFRs, p16 bypass, telomerase) are not sufficient to confer a full malignant phenotype on human bronchial epithelial cells. , 2006, Cancer research.

[101]  J. Schmid,et al.  A Broad Diversity of Volatile Carboxylic Acids, Released by a Bacterial Aminoacylase from Axilla Secretions, as Candidate Molecules for the Determination of Human‐Body Odor Type , 2006, Chemistry & biodiversity.

[102]  H. Lührs,et al.  Effect of isomalt consumption on faecal microflora and colonic metabolism in healthy volunteers , 2006, British Journal of Nutrition.

[103]  Allison M. Curran,et al.  Comparison of the Volatile Organic Compounds Present in Human Odor Using Spme-GC/MS , 2005, Journal of Chemical Ecology.

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

[105]  Andrew I. Spielman,et al.  Analysis of characteristic human female axillary odors: Qualitative comparison to males , 1996, Journal of Chemical Ecology.

[106]  J. Pollack,et al.  Immortalization of Human Bronchial Epithelial Cells in the Absence of Viral Oncoproteins , 2004, Cancer Research.

[107]  Dianne B. Walker,et al.  Evidence for canine olfactory detection of melanoma , 2004 .

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

[109]  Denise Mills,et al.  Predicting blood:air partition coefficients using theoretical molecular descriptors. , 2004, Environmental toxicology and pharmacology.

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

[111]  Xinxin Ding,et al.  Human extrahepatic cytochromes P450: function in xenobiotic metabolism and tissue-selective chemical toxicity in the respiratory and gastrointestinal tracts. , 2003, Annual review of pharmacology and toxicology.

[112]  Pierre P Massion,et al.  The molecular basis of lung cancer: molecular abnormalities and therapeutic implications , 2003, Respiratory research.

[113]  G. Theodoridis,et al.  Determination of amphetamines in human urine by headspace solid-phase microextraction and gas chromatography. , 2003, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[114]  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.

[115]  R. Nagler,et al.  Saliva Analysis in the Clinical Setting: Revisiting an Underused Diagnostic Tool , 2002, Journal of Investigative Medicine.

[116]  I. Lamster,et al.  The diagnostic applications of saliva--a review. , 2002, Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists.

[117]  N. Homann Alcohol and upper gastrointestinal tract cancer: the role of local acetaldehyde production , 2001, Addiction biology.

[118]  G. Mills,et al.  Headspace solid-phase microextraction profiling of volatile compounds in urine: application to metabolic investigations. , 2001, Journal of chromatography. B, Biomedical sciences and applications.

[119]  D. Grant,et al.  Variation in enzymes of arylamine procarcinogen biotransformation among bladder cancer patients and control subjects. , 2001, Pharmacogenetics.

[120]  G I Murray,et al.  The role of cytochrome P450 in tumour development and progression and its potential in therapy , 2000, The Journal of pathology.

[121]  I B Lamster,et al.  Analysis of saliva for periodontal diagnosis--a review. , 2000, Journal of clinical periodontology.

[122]  C. Meulenberg,et al.  Empirical relations predicting human and rat tissue:air partition coefficients of volatile organic compounds. , 2000, Toxicology and applied pharmacology.

[123]  Christian A. Rees,et al.  Systematic variation in gene expression patterns in human cancer cell lines , 2000, Nature Genetics.

[124]  S. A. Centerwall,et al.  The Discovery of Phenylketonuria: The Story of a Young Couple, Two Retarded Children, and a Scientist , 2000, Pediatrics.

[125]  L. Laffel Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes , 1999, Diabetes/metabolism research and reviews.

[126]  D. Ingram,et al.  Breath ethane as a marker of reactive oxygen species during manipulation of diet and oxygen tension in rats. , 1999, Journal of applied physiology.

[127]  Minro Watanabe,et al.  Polymorphic CYP genes and disease predisposition--what have the studies shown so far? , 1998, Toxicology letters.

[128]  S. Chen,et al.  Aromatase and breast cancer. , 1998, Frontiers in bioscience : a journal and virtual library.

[129]  D. Kidwell,et al.  Testing for drugs of abuse in saliva and sweat. , 1998, Journal of chromatography. B, Biomedical sciences and applications.

[130]  J. Tayek A review of cancer cachexia and abnormal glucose metabolism in humans with cancer. , 1992, Journal of the American College of Nutrition.

[131]  C. Cross,et al.  Free radicals, antioxidants, and human disease: where are we now? , 1992, The Journal of laboratory and clinical medicine.

[132]  T. Shimada,et al.  Oxidation of toxic and carcinogenic chemicals by human cytochrome P-450 enzymes. , 1991, Chemical research in toxicology.

[133]  D Mackay,et al.  Correlation of tissue, blood, and air partition coefficients of volatile organic chemicals. , 1989, British journal of industrial medicine.

[134]  G. Cohen,et al.  Production of ethane by rats treated with the colon carcinogen, 1,2-dimethylhydrazine. , 1988, Biochemical pharmacology.

[135]  K. T. Holland,et al.  A comparative study of the cutaneous microflora of normal feet with low and high levels of odour. , 1988, The Journal of applied bacteriology.

[136]  J. Mead,et al.  Small hydrocarbons formed by the peroxidation of squalene. , 1988, Chemistry and physics of lipids.

[137]  G. Gercken,et al.  Simultaneous determination of C2-C22 non-esterified fatty acids and other metabolically relevant carboxylic acids in biological material by gas chromatography of their benzyl esters. , 1988, Journal of chromatography.

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

[139]  H. Bartsch,et al.  Rapid oxidative stress induced by N-nitrosamines. , 1987, Biochemical and biophysical research communications.

[140]  M. J. Coon,et al.  Hydrocarbon formation in the reductive cleavage of hydroperoxides by cytochrome P-450. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[141]  Ortiz de Montellano,et al.  Cytochrome P-450: Structure, Mechanism, and Biochemistry , 1986 .

[142]  J. Stradling,et al.  Changes in ventilation and its components in normal subjects during sleep. , 1985, Thorax.

[143]  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.

[144]  Gas chromatographic--mass spectrometric determination of total 4-heptanone, a new marker in diabetes mellitus. , 1983, Journal of chromatography.

[145]  J. Cummings Short chain fatty acids in the human colon. , 1981, Gut.

[146]  G. Preti,et al.  Quantitative differences in volatiles from healthy mouths and mouths with periodontitis. , 1981, Clinical chemistry.

[147]  M. Yokoyama,et al.  Microbial metabolites of tryptophan in the intestinal tract with special reference to skatole. , 1979, The American journal of clinical nutrition.

[148]  O. Korhonen,et al.  Lung retention and clearance of shipyard arc welders , 1978, International archives of occupational and environmental health.

[149]  D. Calloway,et al.  Respiratory hydrogen and methane as affected by consumption of gas-forming foods. , 1966, Gastroenterology.

[150]  A. Guyton,et al.  Textbook of Medical Physiology , 1961 .