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Non-(13)CO2 targeted breath tests: a feasibility study.

Veronika Ruzsanyi1, Wolfgang Lederer, Christoph Seger

  • 1Department of Anesthesiology and Critical Care Medicine, Innsbruck Medical University, Anichstr 35, A-6020 Innsbruck, Austria. Breath Research Institute of the University of Innsbruck, Rathausplatz 4, A-6850 Dornbirn, Austria.

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This study introduces a novel breath test using deuterated 2-propanol to measure alcohol dehydrogenase activity. The test non-invasively assesses enzyme function, with ethanol consumption showing a notable impact on results.

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Area of Science:

  • Biochemistry
  • Pharmacology
  • Analytical Chemistry

Background:

  • Breath tests offer non-invasive diagnostics for enzyme phenotypic functionality.
  • 13C-breath tests are established, with 13C-urea breath test FDA/EMA approved.
  • Advanced analytical techniques enable real-time detection of volatile compounds in exhaled breath.

Purpose of the Study:

  • To develop and validate a novel breath test for assessing alcohol dehydrogenase (ADH) activity.
  • To investigate the impact of ethanol consumption on ADH-mediated metabolism.
  • To demonstrate the utility of volatile metabolite analysis in exhaled breath for enzyme phenotyping.

Main Methods:

  • Volunteers ingested deuterated 2-propanol (0.8 mg).
  • Metabolism to d3-acetone was monitored in exhaled breath using high-sensitivity mass spectrometry (proton-transfer reaction time-of-flight).
  • Breath samples were analyzed in real-time to quantify d3-acetone concentrations (ppb range).

Main Results:

  • Deuterated 2-propanol was converted to d3-acetone, detectable in breath up to 30 ppb.
  • Co-administration of ethanol reduced d3-acetone production by approximately 15-30%.
  • This indicates ethanol's inhibitory effect on alcohol dehydrogenase activity.

Conclusions:

  • A novel, non-invasive breath test using deuterated 2-propanol effectively measures alcohol dehydrogenase activity.
  • The test can detect metabolic changes influenced by factors like ethanol consumption.
  • Breath analysis of volatile metabolites provides a sensitive method for enzyme phenotyping, crucial for understanding physiological variations.