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'''Breath gas analysis''' is a method for gaining non-invasive information on the clinical state of an individual by monitoring [[volatile organic compound]]s present in the exhaled [[breath]]. Breath gas concentration can then be related to [[blood]] concentrations via [[mathematical modeling]] as for example in [[blood alcohol]] testing.
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==History==
 
The area of modern breath testing commenced in 1971, when [[Nobel Prize]] winner [[Linus Pauling]] demonstrated that human breath is a complex gas, containing more than 200 different volatile organic compounds. However, physicians have used breath analysis since the days of [[Hippocrates]].<ref>Anil S. Modak:  ''Single time point diagnostic breath tests: a review'', J. Breath Res. 4 (2010), 017002 [http://dx.doi.org/10.1088/1752-7155/4/1/017002]</ref>
 
==Overview==
 
[[Endogenous]] volatile organic compounds (VOCs) are released within the human organism as a result of normal [[metabolism|metabolic]] activity or due to pathological disorders. They enter the blood stream and are eventually metabolized or excreted via [[exhalation]], [[skin]] emission, [[urine]], etc.
 
Breath sampling is non-invasive and breath samples can be extracted as often as desired.<ref>H. Koc, K. Unterkofler, S. Teschl, and J. King: "Mathematical modeling for breath gas analysis," 3. Forschungsforum der Österreichischen Fachhochschulen, Wien 2011. [http://www.esi.ac.at/~susanne/FFOeFH2011_KUTK.pdf]</ref>
 
Identification and quantification of potential disease [[biomarker]]s 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 strongly be 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 this 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<ref>Leon E. Farhi: ''Elimination of inert gas by the lung,'' Respiration Physiology 3 (1967) 1–11 [http://dx.doi.org/10.1016/0034-5687(67)90018-7]</ref>
: <math>
C_A = \frac{C_{\bar v}}{\lambda_\text{b:air} + \dot V_A/\dot Q_c},
</math>
where <math> C_A </math> 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  <math>C_{\bar v} </math>, the substance-specific blood:air [[partition coefficient]] <math>\lambda_\text{b:air} </math>, and the [[ventilation-perfusion ratio]]  <math>\dot V_A/\dot Q_c </math>.
But this model fails when two prototypical substances like [[acetone]] (partition coefficient  <math>\lambda_\text{b:air} = 340 </math>) or [[isoprene]] (partition coefficient  <math>\lambda_\text{b:air} = 0.75  </math> ) are measured.<ref>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) [http://iopscience.iop.org/1752-7163/3/2/027006]</ref>
 
E.g., multiplying the proposed population mean of approximately <math> 1 \mu g/l </math> acetone  in end-tidal breath by the partition coefficient <math>\lambda_\text{b:air} = 340 </math> at body temperature  grossly underestimates observed (arterial) blood levels spreading around  <math> 1 mg/l </math>. 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 recently.<ref>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, [http://arxiv.org/abs/1010.2145]</ref><ref>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, [http://dx.doi.org/10.1007/s00285-010-0398-9]</ref>
 
==Applications==
 
Breath gas analysis is used in a number of [[breath test]]s.
 
* [[Asthma]] detection by [[exhaled nitric oxide]]
* [[Blood alcohol]] testing <ref>"[http://www.mphlastala.com/abtreview.pdf]" Michael P. Hlastala: ''The alcohol breath test—a review'', Journal of Applied Physiology (1998) vol. 84 no. 2, 401–408.</ref>
* [[Lung cancer]] detection<ref>"[http://technology.newscientist.com/channel/tech/mg19926715.200-nasas-electronic-nose-could-sniff-out-cancer.html NASA's electronic nose could sniff out cancer]", [[New Scientist]], 27 Aug. 2008.</ref>
* [[Diabetes]] detection
* Fructose malabsorption with [[hydrogen breath test]]
* [[Helicobacter pylori]] with [[urea breath test]]
* [[Halitosis#Diagnosis|Diagnosis of bad breath]]
* Organ rejection
 
==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]].
 
* Gas chromatography-mass spectrometry [[GC-MS]]
* Proton transfer reaction mass spectrometry [[PTR-MS]] and [[Time-of-flight mass spectrometry|PTR-TOF]]
* Selected ion flow tube mass spectrometry [[SIFT-MS]]
* Ion mobility spectrometry [[Ion mobility spectrometry|IMS]]
* Fourier transform infrared spectroscopy [[FTIR]]
* Laser spectrometry [[Spectroscopy]]
* [[Chemical sensors]] resp. [[Electronic nose]]
 
==References==
{{reflist}}
 
==External links==
*[http://iabr.voc-research.at/ International Association for Breath Research (IABR)]
*[http://iopscience.iop.org/1752-7163/ Journal of Breath Research]
 
{{DEFAULTSORT:Breath Gas Analysis}}
[[Category:Breath tests]]
[[Category:Mathematical and theoretical biology]]
[[Category:Mathematical modeling]]

Revision as of 14:42, 23 February 2014

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