The scent of disease: Volatile organic compounds of the human body related to disease and disorder

Journal of Biochemistry

Volumn 150, Issue 3, 2011, Pages 257-266

  Shirasu, Mika ^a   Touhara, Kazushige ^a  

^a UNIVERSITY OF TOKYO   (Japan)

Author keywords

biomarker; disease; disorder; metabolism; odour; olfactory; volatile organic compound

Indexed keywords

VOLATILE ORGANIC COMPOUND;

DIABETES MELLITUS; DIABETIC KETOACIDOSIS; GENETIC DISORDER; HUMAN; INFECTION; INTESTINE OBSTRUCTION; INTOXICATION; KIDNEY FAILURE; METABOLIC DISORDER; NEOPLASM; REVIEW; SCHIZOPHRENIA; UREMIA;

ANIMALS; BIOLOGICAL MARKERS; BREATH TESTS; CLINICAL CHEMISTRY TESTS; COMMUNICABLE DISEASES; DOGS; HUMANS; METABOLIC DISEASES; NEOPLASMS; ODORS; SCHIZOPHRENIA; SKIN; SWEAT; VOLATILE ORGANIC COMPOUNDS;

EID: 80052252876     PISSN: 0021924X     EISSN: 17562651     Source Type: Journal    
DOI: 10.1093/jb/mvr090     Document Type: Review

References (88)

1. Snoddy, A.M., Heckathorn, D., and Tessel, R.E. (1985) Cold-restraint stress and urinary endogenous beta-phenylethylamine excretion in rats. Pharmacol. Biochem. Behav. 22, 497-500 (Pubitemid 15140964)
2. Nodari, F., Hsu, F.F., Fu, X., Holekamp, T.F., Kao, L.F., Turk, J., and Holy, T.E. (2008) Sulfated steroids as natural ligands of mouse pheromone-sensing neurons. J. Neurosci. 28, 6407-6418
3. Adams, F. ed. (1994). Hippocratic Writings: Aphorism 4, Web Atomics, New York.
4. Shirasu, M., Nagai, S., Hayashi, R., Ochiai, A., and Touhara, K. (2009) Dimethyl trisulfide as a characteristic odor associated with fungating cancer wounds. Biosci. Biotechnol. Biochem. 73, 2117-2120
5. Manolis, A. (1983) The diagnostic potential of breath analysis. Clin. Chem. 29, 5-15 (Pubitemid 13167610)
6. Phillips, M., Herrera, J., Krishnan, S., Zain, M., Greenberg, J., and Cataneo, R.N. (1999) Variation in volatile organic compounds in the breath of normal humans. J. Chromatogr. B Biomed. Sci. Appl. 729, 75-88 (Pubitemid 29264111)
7. Chen, S., Zieve, L., and Mahadevan, V. (1970) Mercaptans and dimethyl sulfide in the breath of patients with cirrhosis of the liver. Effect of feeding methionine. J. Lab. Clin. Med. 75, 628-635
8. Kaji, H., Hisamura, M., Saito, N., and Murao, M. (1978) Gas chromatographic determination of volatile sulfur compounds in the expired alveolar air in hepatopathic subjects. J. Chromatogr. 145, 464-468 (Pubitemid 8368850)
9. Zlatkis, A., Brazell, R.S., and Poole, C.F. (1981) The role of organic volatile profiles in clinical diagnosis. Clin. Chem. 27, 789-797 (Pubitemid 11042752)
10. Matsumura, K., Opiekun, M., Oka, H., Vachani, A., Albelda, S.M., Yamazaki, K., and Beauchamp, G.K. (2010) Urinary volatile compounds as biomarkers for lung cancer: A proof of principle study using odor signatures in mouse models of lung cancer. PLoS One 5, e8819
11. Pelchat, M.L., Bykowski, C., Duke, F.F., and Reed, D.R. (2011) Excretion and perception of a characteristic odor in urine after asparagus ingestion: A psychophysical and genetic study. Chem. Senses 36, 9-17
12. Horvath, G., Andersson, H., and Paulsson, G. (2010) Characteristic odour in the blood reveals ovarian carcinoma. BMC Cancer 10, 643
13. Deng, C., Zhang, X., and Li, N. (2004) Investigation of volatile biomarkers in lung cancer blood using solid-phase microextraction and capillary gas chromatography-mass spectrometry. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 808, 269-277 (Pubitemid 38952922)
14. Goldberg, E.M., Blendis, L.M., and Sandler, S. (1981) A gas chromatographic-mass spectrometric study of profiles of volatile metabolites in hepatic encephalopathy. J. Chromatogr. 226, 291-299 (Pubitemid 12131998)
15. Garner, C.E., Smith, S., Bardhan, P.K., Ratcliffe, N.M., and Probert, C.S. (2009) A pilot study of faecal volatile organic compounds in faeces from cholera patients in Bangladesh to determine their utility in disease diagnosis. Trans. R. Soc. Trop. Med. Hyg. 103, 1171-1173
16. Garner, C.E., Smith, S., de Lacy Costello, B., White, P., Spencer, R., Probert, C.S., and Ratcliffe, N.M. (2007) Volatile organic compounds from feces and their potential for diagnosis of gastrointestinal disease. FASEB J. 21, 1675-1688 (Pubitemid 46855613)
17. Pavlou, A.K. and Turner, A.P. (2000) Sniffing out the truth: Clinical diagnosis using the electronic nose. Clin. Chem. Lab. Med. 38, 99-112 (Pubitemid 30245777)
18. Liddell, K. (1976) Smell as a diagnostic marker. Postgrad. Med. J. 52, 136-138
19. Stitt, W.Z. and Goldsmith, A. (1995) Scratch and sniff. The dynamic duo. Arch. Dermatol. 131, 997-999
20. Probert, C.S., Ahmed, I., Khalid, T., Johnson, E., Smith, S., and Ratcliffe, N. (2009) Volatile organic compounds as diagnostic biomarkers in gastrointestinal and liver diseases. J. Gastrointestin. Liver Dis. 18, 337-343
21. Seaman, S. (2006) Management of malignant fungating wounds in advanced cancer. Semin. Oncol. Nurs. 22, 185-193 (Pubitemid 44163103)
22. Bowler, P.G. and Davies, B.J. (1999) The microbiology of infected and noninfected leg ulcers. Int. J. Dermatol. 38, 573-578 (Pubitemid 29404785)
23. Dankert, J., Holloway, Y., Bouma, J., van der Werf, J., and Wolthers, B.G. (1981) Metronidazole in smelly gynaecological tumours. Lancet 2, 1295 (Pubitemid 12227428)
24. Kuge, S., Tokuda, Y., Ohta, M., Okumura, A., Kubota, M., Ninomiya, S., Sawamura, S., Makuuchi, H., Tajima, T., and Mitomi, T. (1996) Use of metronidazole gel to control malodor in advanced and recurrent breast cancer. Jpn J. Clin. Oncol. 26, 207-210 (Pubitemid 126474680)
25. Labows, J.N., McGinley, K.J., Webster, G.F., and Leyden, J.J. (1980) Headspace analysis of volatile metabolites of Pseudomonas aeruginosa and related species by gas chromatography-mass spectrometry. J. Clin. Microbiol. 12, 521-526 (Pubitemid 10012768)
26. Honig, P.J., Frieden, I.J., Kim, H.J., and Yan, A.C. (2003) Streptococcal intertrigo: An underrecognized condition in children. Pediatrics 112, 1427-1429 (Pubitemid 37523434)
27. Tucker, J.B. (2001) The Once and Future Threat of Smallpox. 1 edn., Grove/Atlantic Inc., New York, NY, USA
28. Turck, M. (1985) Foul breath and a productive cough. Hosp. Pract. 20, 50
29. Syhre, M. and Chambers, S.T. (2008) The scent of Mycobacterium tuberculosis. Tuberculosis 88, 317-323
30. Phillips, M., Cataneo, R.N., Condos, R., Ring Erickson, G.A., Greenberg, J., La Bombardi, V., Munawar, M.I., and Tietje, O. (2007) Volatile biomarkers of pulmonary tuberculosis in the breath. Tuberculosis 87, 44-52 (Pubitemid 44960164)
31. Fend, R., Kolk, A.H., Bessant, C., Buijtels, P., Klatser, P.R., and Woodman, A.C. (2006) Prospects for clinical application of electronic-nose technology to early detection of Mycobacterium tuberculosis in culture and sputum. J. Clin. Microbiol. 44, 2039-2045 (Pubitemid 43902150)
32. Burke, D.G., Halpern, B., Malegan, D., McCairns, E., Danks, D., Schlesinger, P., and Wilken, B. (1983) Profiles of urinary volatiles from metabolic disorders characterized by unusual odors. Clin. Chem. 29, 1834-1838 (Pubitemid 13018329)
33. Centerwall, S.A. and Centerwall, W.R. (2000) The discovery of phenylketonuria: The story of a young couple, two retarded children, and a scientist. Pediatrics 105, 89-103 (Pubitemid 30035724)
34. Vockley, J. and Ensenauer, R. (2006) Isovaleric acidemia: New aspects of genetic and phenotypic heterogeneity. Am. J. Med. Genet. C Semin. Med. Genet. 142C, 95-103
35. Tanaka, K. (1990) Isovaleric acidemia: Personal history, clinical survey and study of the molecular basis. Prog. Clin. Biol. Res. 321, 273-290
36. Tanaka, K., Budd, M.A., Efron, M.L., and Isselbacher, K.J. (1966) Isovaleric acidemia: A new genetic defect of leucine metabolism. Proc. Natl Acad, Sci. USA 56, 236-242
37. Tanaka, K. and Isselbacher, K.J. (1967) The isolation and identification of N-isovalerylglycine from urine of patients with isovaleric acidemia. J. Biol. Chem. 242, 2966-2972
38. Tanaka, K., Orr, J.C., and Isselbacher, K.J. (1968) Identification of beta-hydroxyisovaleric acid in the urine of a patient with isovaleric acidemia. Biochim. Biophys. Acta 152, 638-641
39. Liebich, H.M. (1983) Analysis of Acidic metabolites by capillary column GC and GC/MS. J. High Resolut. Chromatogr. Chromatogr. Commun. 6, 640-650
40. Smith, A.J. and Strang, L.B. (1958) An inborn error of metabolism with the urinary excretion of alpha-hydroxy-butyric acid and phenylpyruvic acid. Arch. Dis. Child 33, 109-113
41. Chamberlin, M.E., Ubagai, T., Mudd, S.H., Wilson, W.G., Leonard, J.V., and Chou, J.Y. (1996) Demyelination of the brain is associated with methionine adenosyltransferase I/III deficiency. J. Clin. Invest. 98, 1021-1027 (Pubitemid 26293321)
42. Gahl, W.A., Bernardini, I., Finkelstein, J.D., Tangerman, A., Martin, J.J., Blom, H.J., Mullen, K.D., and Mudd, S.H. (1988) Transsulfuration in an adult with hepatic methionine adenosyltransferase deficiency. J. Clin. Invest. 81, 390-397 (Pubitemid 18075230)
43. Ubagai, T., Lei, K.J., Huang, S., Mudd, S.H., Levy, H.L., and Chou, J.Y. (1995) Molecular mechanisms of an inborn error of methionine pathway. Methionine adenosyltransferase deficiency. J. Clin. Invest. 96, 1943-1947
44. Humbert, J.A., Hammond, K.B., and Hathaway, W.E. (1970) Trimethylaminuria: The fish-odour syndrome. Lancet 2, 770-771
45. Whittle, C.L., Fakharzadeh, S., Eades, J., and Preti, G. (2007) Human breath odors and their use in diagnosis. Ann. NY Acad. Sci. 1098, 252-266 (Pubitemid 47092532)
46. Cashman, J.R. and Zhang, J. (2002) Interindividual differences of human flavin-containing monooxygenase 3: Genetic polymorphisms and functional variation. Drug Metab. Dispos. 30, 1043-1052
47. Zhang, J., Tran, Q., Lattard, V., and Cashman, J.R. (2003) Deleterious mutations in the flavin-containing monooxygenase 3 (FMO3) gene causing trimethylaminuria. Pharmacogenetics 13, 495-500 (Pubitemid 37034591)
48. Leopold, D.A., Preti, G., Mozell, M.M., Youngentob, S.L., and Wright, H.N. (1990) Fish-odor syndrome presenting as dysosmia. Arch. Otolaryngol. Head Neck Surg. 116, 354-355 (Pubitemid 20100615)
49. Zschocke, J., Kohlmueller, D., Quak, E., Meissner, T., Hoffmann, G.F., and Mayatepek, E. (1999) Mild trimethylaminuria caused by common variants in FMO3 gene. Lancet 354, 834-835 (Pubitemid 29415594)
50. Rosenblatt, Y., Phan, P., Desandre, P., Lobon, L., and Hsu, C. (2000) Diagnostic odor recognition. Acad. Emerg. Med. 7, 1168-1169
51. Behrman, A.D. and Goertemoeller, S. (2009) What is that smell? J. Emerg. Nurs. 35, 263-264, quiz 271
52. Rooth, G. and Ostenson, S. (1966) Acetone in alveolar air, and the control of diabetes. Lancet 2, 1102-1105
53. Buszewski, B., Kesy, M., Ligor, T., and Amann, A. (2007) Human exhaled air analytics: Biomarkers of diseases. Biomed. Chromatogr. 21, 553-566 (Pubitemid 46937852)
54. Simenhoff, M.L., Burke, J.F., Saukkonen, J.J., Ordinario, A.T., and Doty, R. (1977) Biochemical profile or uremic breath. N. Engl. J. Med. 297, 132-135
55. Ludwig, J.A. and Weinstein, J.N. (2005) Biomarkers in cancer staging, prognosis and treatment selection. Nat. Rev. Cancer 5, 845-856 (Pubitemid 41746029)
56. Phillips, M., Cataneo, R.N., Ditkoff, B.A., Fisher, P., Greenberg, J., Gunawardena, R., Kwon, C.S., Rahbari-Oskoui, F., and Wong, C. (2003) Volatile markers of breast cancer in the breath. Breast J. 9, 184-191 (Pubitemid 36627163)
57. Phillips, M., Cataneo, R.N., Ditkoff, B.A., Fisher, P., Greenberg, J., Gunawardena, R., Kwon, C.S., Tietje, O., and Wong, C. (2006) Prediction of breast cancer using volatile biomarkers in the breath. Breast Cancer Res. Treat. 99, 19-21 (Pubitemid 44168599)
58. Phillips, M., Gleeson, K., Hughes, J.M., Greenberg, J., Cataneo, R.N., Baker, L., and McVay, W.P. (1999) Volatile organic compounds in breath as markers of lung cancer: A cross-sectional study. Lancet 353, 1930-1933 (Pubitemid 29255706)
59. Gendron, K.B., Hockstein, N.G., Thaler, E.R., Vachani, A., and Hanson, C.W. (2007) In vitro discrimination of tumor cell lines with an electronic nose. Otolaryngol. Head Neck Surg. 137, 269-273 (Pubitemid 47102434)
60. Chen, X., Xu, F., Wang, Y., Pan, Y., Lu, D., Wang, P., Ying, K., Chen, E., and Zhang, W. (2007) A study of the volatile organic compounds exhaled by lung cancer cells in vitro for breath diagnosis. Cancer 110, 835-844 (Pubitemid 47257662)
61. Filipiak, W., Sponring, A., Mikoviny, T., Ager, C., Schubert, J., Miekisch, W., Amann, A., and Troppmair, J. (2008) Release of volatile organic compounds (VOCs) from the lung cancer cell line CALU-1 in vitro. Cancer Cell Int. 8, 17
62. Sponring, A., Filipiak, W., Mikoviny, T., Ager, C., Schubert, J., Miekisch, W., Amann, A., and Troppmair, J. (2009) Release of volatile organic compounds from the lung cancer cell line NCI-H2087 in vitro. Anticancer Res. 29, 419-426
63. McCulloch, M., Jezierski, T., Broffman, M., Hubbard, A., Turner, K., and Janecki, T. (2006) Diagnostic accuracy of canine scent detection in early-And late-stage lung and breast cancers. Integr. Cancer Ther. 5, 30-39 (Pubitemid 43260792)
64. Pickel, D.P., Manucy, G.P., Walker, D.B., Hall, S.B., and Walker, J.C. (2004) Evidence for canine olfactory detection of melanoma. Appl. Anim. Behav. Sci. 89, 107
65. Willis, C.M., Church, S.M., Guest, C.M., Cook, W.A., McCarthy, N., Bransbury, A.J., Church, M.R., and Church, J.C. (2004) Olfactory detection of human bladder cancer by dogs: Proof of principle study. BMJ 329, 712
66. Horvath, G., Jarverud, G.A., Jarverud, S., and Horvath, I. (2008) Human ovarian carcinomas detected by specific odor. Integr. Cancer Ther. 7, 76-80 (Pubitemid 351806533)
67. Sonoda, H., Kohnoe, S., Yamazato, T., Satoh, Y., Morizono, G., Shikata, K., Morita, M., Watanabe, A., Kakeji, Y., Inoue, F., and Maehara, Y. (2011) Colorectal cancer screening with odour material by canine scent detection. Gut 60, 814-819
68. D'Amico, A., Bono, R., Pennazza, G., Santonico, M., Mantini, G., Bernabei, M., Zarlenga, M., Roscioni, C., Martinelli, E., Paolesse, R., and Di Natale, C. (2008) Identification of melanoma with a gas sensor array. Skin Res. Technol. 14, 226-236 (Pubitemid 351560383)
69. Mitchell, K.J. and Porteous, D.J. (2011) Rethinking the genetic architecture of schizophrenia. Psychol. Med. 41, 19-32
70. Arai, M., Yuzawa, H., Nohara, I., Ohnishi, T., Obata, N., Iwayama, Y., Haga, S., Toyota, T., Ujike, H., Ichikawa, T., Nishida, A., Tanaka, Y., Furukawa, A., Aikawa, Y., Kuroda, O., Niizato, K., Izawa, R., Nakamura, K., Mori, N., Matsuzawa, D., Hashimoto, K., Iyo, M., Sora, I., Matsushita, M., Okazaki, Y., Yoshikawa, T., Miyata, T., and Itokawa, M. (2010) Enhanced carbonyl stress in a subpopulation of schizophrenia. Arch. Gen. Psychiatry 67, 589-597
71. Singh, I. and Rose, N. (2009) Biomarkers in psychiatry. Nature 460, 202-207
72. Hutton, T.J. (1878) The value of clinical odors. New York M.J. 28, 268-272
73. Hammond, W.A. (1877) The odor of the human body, as developed by certain affilications of nervous system. Transac. Amer. Neurol. Assoc. 2, 17-23
74. Melancon, S.B. (1970) (The peculiar odor of schizophrenics). Union Med. Can. 99, 1445-1446
75. Smith, K. and Sines, J.O. (1960) Demonstration of a peculiar odor in the sweat of schizophrenic patients. Arch. Gen. Psychiatry 2, 184-188
76. Smith, K., Thompson, G.F., and Koster, H.D. (1969) Sweat in schizophrenic patients: Identification of the odorous substance. Science 166, 398-399
77. Gordon, S.G., Smith, K., Rabinowitz, J.L., and Vagelos, P.R. (1973) Studies of trans-3-methyl-2-hexenoic acid in normal and schizophrenic humans. J. Lipid. Res. 14, 495-503
78. Phillips, M., Sabas, M., and Greenberg, J. (1993) Increased pentane and carbon disulfide in the breath of patients with schizophrenia. J. Clin. Pathol. 46, 861-864 (Pubitemid 23287353)
79. Phillips, M., Erickson, G.A., Sabas, M., Smith, J.P., and Greenberg, J. (1995) Volatile organic compounds in the breath of patients with schizophrenia. J. Clin. Pathol. 48, 466-469
80. Turner, A.P. and Magan, N. (2004) Electronic noses and disease diagnostics. Nat. Rev. Microbiol. 2, 161-166
81. Bondy, P.K. and Rosenberg, L.E. (1980) Metabolic Control and Disease., W.B. Saunders, Philadelphia, PA
82. Pearson, M.A., Aleck, K.A., and Heidenreich, R.A. (1995) Benign clinical presentation of 3-methylcrotonylglycinuria. J. Inherit. Metab. Dis. 18, 640-641
83. Wilson, A.D. and Baietto, M. (2011) Advances in electronic-nose technologies developed for biomedical applications. Sensors 11, 1105-1176
84. Daughaday, W.H. (1968) The Textbook of Endocrinology, (Williams, R.H., ed.), W.B. Saunders, Philadelphia, PA, USA
85. Olopade, C.O., Zakkar, M., Swedler, W.I., and Rubinstein, I. (1997) Exhaled pentane levels in acute asthma. Chest 111, 862-865 (Pubitemid 27171453)
86. Paredi, P., Kharitonov, S.A., and Barnes, P.J. (2000) Elevation of exhaled ethane concentration in asthma. Am. J. Respir. Crit. Care Med. 162, 1450-1454
87. Montuschi, P., Corradi, M., Ciabattoni, G., Nightingale, J., Kharitonov, S.A., and Barnes, P.J. (1999) Increased 8-isoprostane, a marker of oxidative stress, in exhaled condensate of asthma patients. Am. J. Respir. Crit. Care Med. 160, 216-220 (Pubitemid 29326091)
88. Blackburn, E.K. (1957) The breath in acute leukaemia. Br. Med. J. 1, 146-147