Real-time, Non-invasive Breath Gas Analysis

In recent years, breath gas analysis of volatile organic compounds (VOCs) has become a growing field of research. It is a non-invasive method and hence could possibly be used for drug testing, screening disease biomarkers, monitoring metabolic processes, and studying pharmacokinetics.

Benefits of IONICON PTR-TOFMS

IONICON PTR-MS systems are considered to be powerful tools for breath gas analysis: While the systems’ detection limits and linearity range match the concentrations of breath VOCs, their high sensitivity and fast response time also enable the analysis of breath both online and in real-time. IONICON PTR-TOFMS can rapidly record the complete spectra. This together with a high mass resolving power, the system can detect several hundred compounds from a single exhalation.

BET-med Breath Sampling Inlet

IONICON has developed a specialized breath sampling inlet for PTR-MS. The Buffered End-Tidal Breath sampler (BET-med) uses inert and heated surfaces to prevent condensation, and can be used with commercially available single-use mouthpieces. It is also certified for medical use (ISO 60601) and enables real-time breath analysis in a clinical setting.

Screening for Breath Markers

The search for breath biomarkers is the standard application. In such screening studies, the breath spectra of healthy volunteers are compared to patients/subjects with a certain condition. IONICON PTR-TOFMS instruments are especially suitable for this application, as the entire spectrum is analyzed at once [1].

Since the most important breath markers are those for smoking, they can be used to standardize the technique. With the help of the PTR-MS, a cross-validate accuracy (AUROC) of 99% was achieved which represents the best value published to date for a large study [2].

Screening for Breath Markers

Figure 1. Analyzing the breath of more than 200 subjects, several markers for smoking can be isolated. Most prominently acetonitrile, which leads to an almost perfect separation of smokers and non-smokers.

Lung Cancer Markers

In a multi-centric clinical study, biomarkers could be identified to detect lung cancer. By integrating just two markers, a cross-validated AUROC value of > 83% was reached for the detection of bronchial adeno-carcinoma [3].

Lung Cancer Markers

Figure 2. Breath markers for lung cancer require a careful analysis of the data. We found two robust markers that give an AUROC value of > 83% (cross-validated).

Monitoring Studies

Real-time breath analysis allowed for new types of studies, where a person’s breath is monitored to follow the variation of one or several marker compounds in time. In such monitoring studies, the patients act as their won control, which greatly facilitates data interpretation.

Pharmacokinetics

Pharmacokinetics is the study of distribution and elimination of drugs in the body. With breath analysis, the blood concentration of a drug can be monitored in a non-invasive way and is updated with every exhalation. In the figure, the drug concentration shows a sharp increase and a slow decay from which pharmacokinetic models can be derived. This behavior needs a high sampling frequency, which would be next to impossible with blood tests or offline analysis [4].

Pharmacokinetics

Figure 3. Pharmacokinetical study: full exhalations, recorded every 15 minutes, which depicts the concentration of a drug in the exhaled breath after ingestion (t=0).

Monitoring Metabolic Effect

Most volatile breath compounds influence several metabolic processes. By administering isotopically labeled educts, their metabolic products will also be labeled and can clearly be differentiated in a mass spectrum. This enables probing and studying specific metabolic processes and deficiencies, paving the way to personalized medicine [5].

Isotopically- labelled metabolites

Figure 4. Two isotopically labeled metabolites (green, blue) with individual variations over time, which arise as a result of the ingestion of a labeled compound (red).

Sources:

[1]: Herbig J, J Breath Res, vol. 3, no. 2, IOP, pp. 027004 (2009)

[2]: Herbig J, 4th Int. Conf. on PTR-MS, IUP Conf. Series, pp. 46-50 (2009)

[3]: Herbig J, 5th Int. Conf. on PTR-MS, IUP Conf. Series, pp. 31-33 (2011)

[4]: Beauchamp J, J Breath Res, vol. 4, no. 2, IOP, pp. 026006 (2010)

[5]: Winkler K, J Breath Res, vol. 7, no. 3, IOP, pp. 036006 (2013)

IONICON Analytik

This information has been sourced, reviewed and adapted from materials provided by IONICON Analytik.

For more information on this source, please visit IONICON Analytik.

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