Breath gas analysis

Breath gas analysis is a method for gaining non-invasive information on the clinical state of an individual by monitoring volatile organic compounds 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.

’’Physicians have diagnosed what is ailing the patient from the breath since the days of Hippocrates. The modern era of breath testing commenced in 1971, when Nobel Prize winner Linus Pauling demonstrated that human breath is a complex gas, containing well over 200 different volatile organic compounds (VOCs) in picomolar concentrations.’’^[1]

The simplest model relating breath gas concentration to blood concentrations was developed by Farhi^[2]

${\displaystyle C_{A}={\frac {C_{\bar {v}}}{\lambda _{\text{b:air}}+{\dot {V}}_{A}/{\dot {Q}}_{c}}},}$

where ${\displaystyle C_{A}}$ 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 ${\displaystyle C_{\bar {v}}}$, the substance-specific blood:air partition coefficient ${\displaystyle \lambda _{\text{b:air}}}$, and the ventilation-perfusion ratio ${\displaystyle {\dot {V}}_{A}/{\dot {Q}}_{c}}$. But this model fails when two prototypical substances like acetone (partition coefficient ${\displaystyle \lambda _{\text{b:air}}=340}$) or isoprene (partition coefficient ${\displaystyle \lambda _{\text{b:air}}=0.75}$ ) are measured^[3].

E.g., multiplying the proposed population mean of approximately ${\displaystyle 1\mu g/l}$ acetone in end-tidal breath by the partition coefficient ${\displaystyle \lambda _{\text{b:air}}=340}$ at body temperature grossly underestimates observed (arterial) blood levels spreading around ${\displaystyle 1mg/l}$. 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^[4][5].

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

• Asthma detection by exhaled nitric oxide
• Blood alcohol testing ^[6]
• Lung cancer detection^[7]
• Diabetes detection
• Fructose malabsorption with hydrogen breath test
• Helicobacter pylori
• Diagnosis of bad breath
• Organ rejection

Breath analysis can be done with selected ion flow tube mass spectrometry or gas chromatography, 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 PTR-TOF
• Selected ion flow tube mass spectrometry SIFT-MS
• Ion mobility spectrometry IMS
• Fourier transform infrared spectroscopy FTIR
• Laser spectrometry Spectroscopy
• Electronic nose

• International Association for Breath Research (IABR)
• Journal of Breath Research