Breath Analysis and VOC’s

More than 99% of a person’s exhaled breath consists of gases already present in the atmosphere. But the remaining 1% consists of volatile organic compounds, some of which rise and fall depending on the person’s health, metabolic processes and environmental exposures.
More than 99% of a person’s exhaled breath consists of gases already present in the atmosphere. But the remaining 1% consists of volatile organic compounds, some of which rise and fall depending on the person’s health, metabolic processes and environmental exposures.

Breath consists primarily of N2, CO2, O2, water vapour, and a mixture of acetone, isoprene, pentane, and hundreds of other compounds. The composition of VOCs in breath varies widely from person to person, both qualitatively and quantitatively. Although the amount of VOCs found in everyone’s breath is in the high hundreds (872 identified compounds[1]), only a small fraction are common to everyone. These common VOCs, which include ethane, acetone, and methanol, are products of core metabolic processes. A person’s physiological state is not the only source of VOCs in breath. Objects like trees, gas stoves, gasoline pumps, and household cleaning products release VOCs into the air, and these exogenous VOCs get inhaled and eliminated from the body by exhalation[2].

The complexity of biological processes only now begins to be matched by similarly complex methodological advances for their analysis. Most recently VOCs have gained considerable interest, to: (i) to obtain insight into underlying mechanisms of physiological and pathophysiological processes, and (ii) to exploit concentration profiles of VOCs in exhaled breath and other sources for disease detection and/or therapeutic monitoring of treatment regimens[3],[4]. Up to 1840 biogenic VOCs have been assigned from breath (872), saliva (359), blood (154), milk (256), skin secretions (532) urine (279), and faeces (381) in apparently healthy individuals[1].

As a biochemical probe, VOCs in breath are unique in the sense that they can provide both non-invasive and continuous information on the metabolic/physiological state of an individual. Apart from diagnostics and therapy control[3], this information might potentially be used for dynamic assessments of normal physiological function (e.g., by a stress test on a stationary bicycle[5],[6], in an intra-operative setting[7], or in a sleep lab[8]), pharmacodynamics[9] or for quantifying environmental exposure[10]. It has also been used for online-monitoring of drug levels in a patient undergoing anesthesia[11],[12].

In humans, volatile organic compounds are found in exhaled breath[13],[14] and a variety of tissues and specimens like skin emanations[15],[16], urine[17],[18], blood[19],[20], saliva[21],[22],[23] and feces[4]. Detection and confirmation of VOCs as biomarkers may be additionally complicated by the fact that VOC levels are linked to metabolic processes, which may undergo large fluctuations, e.g. in response to food intake or physical activity[3],[4]. Moreover, different sources for generation of the same volatile compound are possible in the human body, and the individual VOC signature may be shaped by genes controlling the human immune response[24].

Contributions:

  • Breathe Free Consortium http://www.breathe-free.org/. Joint effort to develop an open source breath sampler that can be used with a range of analytical instrument.
  • Coupling a branch enclosure with differential Mobility Spectrometry to isolate and measure plant volatiles in contained greenhouse settings. M.M.McCartney, S.L.Spitulski, A.Pasamontes, D.J.Peirano, M.J.Schirle, R.Cumeras, J.D.Simmons, J.L.Ware, J.F.Brown, A.J.Y.Poh, S.C.Dike, E.K.Foster, K.E.Godfrey, C.E.Davis. Talanta, 2016, 146: 148-54. http://dx.doi.org/10.1016/j.talanta.2015.08.039.
  • Using Skin Volatile Compounds to Detect Early-Stage Pressure Ulcers. M. Schivo, A.A. Aksenov, A. Pasamontes, A.M. Oberbauer, R. Cumeras, R. Fink, R. Johnson, C.E. Davis. American Thoracic Society 2015 International Conference, in A43. Evolving Technologies in Critical Care, p. A1651.
  • Chemical analysis of whale breath volatiles: a case study for non-invasive field health diagnostics of marine mammals. R.Cumeras†, W.HK.Cheung†, F.Gulland, D.Goley, C.E.Davis. († joint first authors) Metabolites, 2014, 4 :790-806. DOI:10.3390/metabo4030790
  • Online-monitoring of drugs with ion mobility spectrometry in patients under anesthesia. R. Cumeras, P. Favrod, H. Buchinger, S. Kreuer, Th. Volk, E. Figueras, I. Gràcia, S. Maddula, J.I. Baumbach. In Abstracts of the Breath Summit 2013: International Conference of Breath Research, Page 118. Saarbrücken/Wallerfangen, Germany, June 9-12th 2013.
  • Gastric Interferences in Breath Analysis: Sweets case. R. Cumeras. In Abstracts of the Breath Summit 2013: International Conference of Breath Research, Pages 21-23. Workshop III: Ion Mobility Spectrometry. Saarbrücken/Wallerfangen, Germany, June 9th 2013.
  • What is a good Control Group?, R.Cumeras, E.Figueras, I.Gràcia, S.Maddula, J.I.Baumbach. Int. J. Ion Mobil. Spec., 2013, 16 (3): 191-198. DOI: 10.1007/s12127-012-0116-y.
  • Influence of Operational Background Emissions on Breath Analysis using MCC/IMS devices.,  R. Cumeras, P. Favrod, K. Rupp, E. Figueras, I. Gràcia, S. Maddula, J.I.Baumbach. Int. J. Ion Mobil. Spec., 2012, 15 (2): 69-78. DOI: 10.1007/s12127-012-0094-0.

References
[1] de Lacy Costello B. et al. A review of the volatiles from the healthy human body. J. Breath Res. (2014) 8: 014001.
[2] Pleil J.D., Stiegel M.A. and Risby T.H. Clinical breath analysis: discriminating between human endogenous compounds and exogenous (environmental) chemical confounders J. Breath Res. (2013) 7: 017107.
[3] Amann A. and Smith D., eds. Breath Analysis for Clinical Diagnosis and Therapeutic Monitoring. 2005, World Scientific: Singapore.
[4] Amann A. and Smith D., eds. Volatile Biomarkers: Non-invasive Diagnosis in Physiology and Medicine. 2013, Elsevier: Amsterdam.
[5] King J. et al. Isoprene and acetone concentration profiles during exercise on an ergometer, J. Breath Res. (2009) 3: 027006.
[6] King J. et al. A mathematical model for breath gas analysis of volatile organic compounds with special emphasis on acetone, J.Math.Biol. (2011) 63: 959-999.
[7] Kamysek S. et al. Drug detection in breath: effects of pulmonary blood flow and cardiac output on propofol exhalation, Anal.Bioanal.Chem.(2011) 401:2093.
[8] King, J. et al. Measurement of endogenous acetone and isoprene in exhaled breath during sleep, Physiol. Meas. (2012) 33: 413–428.
[9] Beauchamp J., Kirsch F. and Buettner A. Real-time breath gas analysis for pharmacokinetics: monitoring exhaled breath by on-line proton-transferreaction mass spectrometry after ingestion of eucalyptol-containing capsules, J. Breath Res. (2010) 4: 026006.
[10] Pleil J.D. Role of exhaled breath biomarkers in environmental health science, J. Toxicol. Environ. Health B Crit. Rev. (2008) 11: 613–629.
[11] Kreuder, A.E., et al. Characterization of propofol in human breath of patients undergoing anesthesia, Int. J. Ion Mobil. Spectr. (2011) 14(4):167-175.
[12] Cumeras R. et al. 2013 On-line monitoring study of exhaled anesthetic drugs Breath’13: Int. Conf. on Breath Research (Wallerfangen, Germany, 9–12 June) p 11.
[13] Miekisch W. et al. Diagnostic potential of breath analysis—focus on volatile organic compounds Clin. Chim. Acta (2004) 347: 25–39.
[14] Amann A. et al. Analysis of exhaled breath for screening of lung cancer patients. Mag. Eur. Med. Oncol. (2010) 3 106–112.
[15] Gallagher M. et al. Analyses of volatile organic compounds from human skin. Br. J. Dermatol. (2008) 159: 780–91.
[16] Ruzsanyi V. et al. Ion mobility spectrometry for detection of skin volatiles J. Chromatogr. B (2012) 911: 84–92.
[17] Mills G.A. & Walker V. Headspace SPME profiling of volatile compounds in urine: application to metabolic investigations J.Chromatogr.B.(2001)753:259.
[18] Wagenstaller M. and Buettner A. Characterization of odorants in human urine using a combined chemoanalytical and human-sensory approach: a potential diagnostic strategy. Metabolomics. (2013) 9: 9–20.
[19] Mochalski, P., et al., Blood and breath profiles of volatile organic compounds in patients with end-stage renal disease. BMC Nephrol, (2014) 15(1): 43.
[20] Miekisch W. et al. Analysis of volatile disease markers in blood. Clin. Chem. (2001) 47: 1053–60.
[21] Lochner A. et al. Gas chromatographic-mass spectrometric analysis of volatile constituents in saliva. J. Chromatogr. (1986) 378: 267–82.
[22] Soini H.A. et al. Analysis of VOC in human saliva by a static sorptive extraction method and GC-MS J. Chem. Ecol. (2010) 36: 1035–42.
[23] Al-Kateb H. et al. An investigation of VOCs from the saliva of healthy individuals using headspace-trap/GC-MS. J. Breath Res. (2013) 7: 036004.
[24] Aksenov A.A. et al. Characterization of volatile organic compounds in human leukocyte antigen heterologous expression systems: a cell’s “chemical odor fingerprint”. ChemBioChem., (2012) 13(7): 1053-9.

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