All Case Studies

Breath Analysis for Medical Applications

Real-time breath analysis is particularly well suited to monitor the concentrations of breath VOCs over time and in response to a stimulus. This offers intriguing possibilities to study exercise, pharmacokinetics, and to monitor metabolic processes.

Real-time breath analysis has also facilitated new types of studies, where the breath of a subject is monitored to follow the variation of one or several marker compounds in time.

Pharmacokinetics

Pharmacokinetics is the study of distribution and elimination of drugs in the body. With breath analysis, the blood concentrations of a drug can be monitored non-invasively and can be updated with every exhalation.

In the figure to the right we show full exhalations, recorded every 15 minutes, which depicts the concentration of a drug in the exhaled breath after ingestion (t=0) of a capsule that dissolves in the intestinal tract after a few hours. Only through real-time breath analysis the sharp increase and a slow decay can be resolved, from which accurate pharmacokinetic models can be derived. This would not be possible with a slower sampling frequency, which makes such studies tedious with offline breath sampling methods and renders it next to impossible with invasive blood analysis (Beauchamp et al.).

Liver Function Test

Liver disease is stealthy: by the time symptoms appear, the condition of the patient is already critical. A simple test that can detect early-stage liver disease could therefore safe many lives. Fernández del Río et al. have monitored the breath of liver transplant patients pre- and post-transplant. They found several compounds that were elevated for patients with an impaired liver. Most notably, the elevated concentrations of limonene decreased when the implanted organ started to work. Limonene, an exogenous compounds, is consumed with many food and beverages, and is cleared by the liver. This can therefore serve as a non-invasive test for liver function. Learn more.

Exercise Stress Tests

Volatile metabolites such as acetone and ammonia have been linked to dextrose, fat, and protein metabolism. Non-invasive breath analysis, therefore, may be used for metabolic monitoring and the identification of fuel sources actually used for energy production. Schubert et al. have conducted a study with 21 volunteers and monitored their breath VOCs during controlled ergometric exercise. A major outcome of this study was the ability to determine the anaerobic threshold from breath VOCs, where the metabolism produces energy from glucose without using oxygen. The determination of this threshold is a in important measure for deciding exercise intensity in endurance sports.

The anaerobic threshold was determined from serum lactate and by means of respiratory exchange rate. They found that exhaled acetone concentrations mirrored exercise induced changes of dextrose metabolism and lipolysis. Furthermore, they found that exhaled ammonia concentration seemed to be linked to protein metabolism and changes of pH under exercise. Isoprene concentrations showed a close correlation to cardiac output and minute ventilation. They conclude that breath biomarkers represent a promising alternative for metabolic monitoring under exercise as they can be determined non-invasively and continuously. In addition, these markers may add complementary information on biochemistry, energy production and fuel consumption.

Fig. 2: Isotopically-labelled Metabolites

Monitoring metabolic processes

The human volatile metabolome can be monitored in exhaled breath. However, most volatile metabolites, such as acetone, isoprene, methanol, etc. play a role in several metabolic processes. A direct interpretation is thus rarely possible.

By administering isotopically labelled educts, the metabolic products will also be labelled and can clearly be distinguished from the metabolic background.

In figure 2 we show two isotopically labelled metabolites with individual variations over time, which arise as a result of the ingestion of a labelled compound. This allows to probe and study specific metabolic processes and deficiencies, and opens the door to personalized medicine. Metabolic monitoring with PTR-MS has been demonstrated in a pilot study by Winkler et al..