Breath gas analysis

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Breath gas analysis
Purposegaining information on the clinical state of an individual by monitoring
volatile organic compounds
present in the exhaled breath

Breath gas analysis is a method for gaining information on the clinical state of an individual by monitoring

blood alcohol testing.[2] There are various techniques that can be employed to collect and analyze exhaled breath. Research on exhaled breath started many years ago, there is currently limited clinical application of it for disease diagnosis.[3] However, this might change in the near future as currently large implementation studies are starting globally.[4]

History

Lavoiser in his laboratory studying human respiration.

It is known that since the times of

COPD and head and neck cancer[9] are among the diseases that have been considered for biomarker detection. Even though exhaled breath analysis started many years ago, there is still no clinical application of it for disease diagnosis. This is mainly due to a lack of standardization of the clinical tests, both for breath collection procedures and their analysis.[10][11][12]
Though the use of so-called breath-prints, determined by electronic noses, are promising and seem to be able to distinguish between lung cancer, COPD, and asthma.[13] They also seem capable of detecting the various phenotypes of asthma and COPD[14] and other diseases[15]

Overview

Endogenous volatile organic compounds (VOCs) are released within the human organism as a result of normal metabolic activity or due to pathological disorders. They enter the blood stream and are eventually metabolized or excreted via exhalation, skin emission, urine
, etc.

Identification and quantification of potential disease biomarkers can be seen as the driving force for the analysis of exhaled breath. Moreover, future applications for medical diagnosis and therapy control with dynamic assessments of normal physiological function or pharmacodynamics are intended.

Exogenous VOCs penetrating the body as a result of environmental exposure can be used to quantify body burden. Also breath tests are often based on the ingestion of isotopically labeled precursors, producing isotopically labeled carbon dioxide
and potentially many other metabolites.

However, breath sampling is far from being a standardized procedure due to the numerous confounding factors biasing the concentrations of volatiles in breath. These factors are related to both the breath sampling protocols as well as the complex physiological mechanisms underlying

pulmonary gas exchange
. Even under resting conditions exhaled breath concentrations of VOCs can be strongly influenced by specific physiological parameters such as cardiac output and breathing patterns, depending on the physico-chemical properties of the compound under study.

Understanding the influence of all the factors and their control is necessary for achieving an accurate standardization of breath sample collection and for the correct deduction of the corresponding blood concentration levels.

The simplest model relating breath gas concentration to blood concentrations was developed by Farhi[16]

where denotes the alveolar concentration which is assumed to be equal to the measured concentration. It expresses the fact that the concentration of an inert gas in the alveolar air depends on the mixed venous concentration , the substance-specific blood:air partition coefficient , and the

ventilation-perfusion ratio
. But this model fails when two prototypical substances like acetone (partition coefficient ) or isoprene (partition coefficient ) are measured.[17]

E.g., multiplying the proposed population mean of approximately acetone in end-tidal breath by the partition coefficient at body temperature grossly underestimates observed (arterial) blood levels spreading around . Furthermore, breath profiles of acetone (and other highly soluble volatile compounds such as 2-pentanone or methyl acetate) associated with moderate workload ergometer challenges of normal healthy volunteers drastically depart from the trend suggested by the equation above; hence some more refined models are necessary. Such models have been developed.[18][19]

Applications

Breath gas analysis is used in a number of breath tests.

Breath collectors

Breath can be collected using a variety of home-made and commercially available devices. Some examples of breath collection tools used across the research industry for VOC analysis are:

  • Coated stainless steel canister
  • End tidal air collector
  • Tedlar bag

These devices can be used as a vehicle for direct introduction of a gas sample into an appropriate analytical instrument, or serve as a reservoir of breath gas into which an absorption device such as an SPME fiber is placed to collect specific compounds.

Online analysis

Breath can also be analyzed online, which allows for insight into a person's metabolism without the need for sample preparation or sample collection.[26] Technologies that enable real-time analysis of breath include:

Breath analysis is very vulnerable to confounding factors. Analyzing breath in real-time has the advantage that potential confounding factors associated with sample handling and manipulation are eliminated. Recent efforts have focused on standardizing online breath analysis procedures based on SESI-MS, and to systematically study and reduce other confounding sources of variability.[28]

Analytical instruments

Breath analysis can be done with various forms of mass spectrometry, but there are also simpler methods for specific purposes, such as the Halimeter and the breathalyzer.

References

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  4. ^ "Inzet SpiroNose stappen dichterbij gekomen". Longfonds. Feb 26, 2020. Retrieved Aug 14, 2020.
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  15. ^ https://www.ed.ac.uk/files/atoms/files/easl_posters_rs_0.pdf [bare URL PDF]
  16. ^ Leon E. Farhi: Elimination of inert gas by the lung, Respiration Physiology 3 (1967) 1–11
  17. ^ Julian King, Alexander Kupferthaler, Karl Unterkofler, Helin Koc, Susanne Teschl, Gerald Teschl, Wolfram Miekisch, Jochen Schubert, Hartmann Hinterhuber, and Anton Amann: Isoprene and acetone concentration profiles during exercise at an ergometer, J. Breath Research 3, (2009) 027006 (16 pp) [1]
  18. ^ Julian King, Helin Koc, Karl Unterkofler, Pawel Mochalski, Alexander Kupferthaler, Gerald Teschl, Susanne Teschl, Hartmann Hinterhuber, and Anton Amann: Physiological modeling of isoprene dynamics in exhaled breath, J. Theoret. Biol. 267 (2010), 626–637, [2]
  19. ^ Julian King, Karl Unterkofler, Gerald Teschl, Susanne Teschl, Helin Koc, Hartmann Hinterhuber, and Anton Amann: A mathematical model for breath gas analysis of volatile organic compounds with special emphasis on acetone, J. Math. Biol. 63 (2011), 959-999, [3]
  20. S2CID 210946966
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  21. ^ Michael P. Hlastala: The alcohol breath test—a review Archived 2011-06-26 at the Wayback Machine, Journal of Applied Physiology (1998) vol. 84 no. 2, 401–408.
  22. ^ Tarik Saidi, Omar Zaim, Mohammed Moufid, Nezha El Bari, Radu Ionescu, Benachir Bouchikhi: Exhaled breath analysis using electronic nose and gas chromatography–mass spectrometry for non-invasive diagnosis of chronic kidney disease, diabetes mellitus and healthy subjects, Sensors and Actuators B: Chemical 257 (2018) 178-188.
  23. ^ NASA's electronic nose could sniff out cancer, New Scientist, 27 Aug. 2008.
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  27. ^ "Fossiliontech - Breath Analysis". Fossil Ion Technology - Breath Research Instrumentation. Retrieved 2019-05-29.
  28. PMID 30989265
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External links