Stable isotope breath tests in clinical medicine: a review

Abstract

Diagnostic (13)C-stable isotope probes are currently being expanded in their scope, to provide precise evaluations of the presence or absence of etiologically significant changes in metabolism due to a specific disease or the lack of a specific enzyme. The salient features of the (13)C-breath test are that they are non-invasive, non-radioactive, safe, simple, and effective. The simplicity of the (13)C-breath test makes it very applicable in a clinical setting: the physician can obtain valuable diagnostic information by distinguishing between two groups or populations on the basis of the recovery of (13)CO(2) from the ingested (13)C-substrate. The breath tests can also be used to monitor the progress of disease severity or to evaluate the efficacy of medications. This review concentrates on current research in the medical field dedicated to the metabolite (13)C-labelled carbon dioxide in exhaled air following ingestion of (13)C-labelled substrates.

ICL-based TDLAS sensor for real-time breath gas analysis of carbon monoxide isotopes

“…The main advantages compared to traditional clinical methods, such as blood sampling and tissue biopsy, are (i) completely non-invasive approach, (ii) unlimited sample volume and (iii) fast response time. Applications range from early disease detection, treatment monitoring and stable isotope tests to breathomics and validation of physiological models [1][2][3].…”

Breath biomarkers in toxicology

“…In fact, in some individuals, the treatment could prove fatal. Rather than inferring metabolism paths from detailed genetic testing, the patient is given a benign surrogate that is isotopically labeled, and then, the metabolism pathway is directly monitored via an exhaled gas, typically 13 C-labeled CO 2 (Modak 2007). For example, cancer patients are treated with 13 C-labeled methionine to assess mitochondrial toxicity of antiretroviral drugs (Milazzo et al 2005), or with [ 13 C]-dextromethorphan to assess breast cancer therapy with tamoxifen (Opdam et al 2015 …”

13C-methacetin breath test reproducibility study reveals persistent CYP1A2 stimulation on repeat examinations

“…Continuous research work has brought about considerable progress and nowadays it is possible to assess by means of 13 C breath tests the microsomal, the cytosolic, and the mitochondrial function of the liver [1][2][3][4] . A look at pertinent literature shows that during the past decade, from among the compounds applied for microsomal 13 C breath tests, 13 C-methacetin has steadily been making its way to be recognized as the most frequently used substrate.…”

“…A look at pertinent literature shows that during the past decade, from among the compounds applied for microsomal 13 C breath tests, 13 C-methacetin has steadily been making its way to be recognized as the most frequently used substrate. A number of features support its usefulness as a functional liver probe: a fast metabolism to acetaminophen and 13 CO2 by cytochrome P450 1A2 (CYP 1A2), safety at low doses applied for a breath test, and a low cost [1][2][3][4] . Accordingly very promising results on its diagnostic usefulness were obtained in patients with chronic hepatitis C virus infection [5,6] , primary biliary cirrhosis [7,8] , non-alcoholic steatohepatitis [9] , and various stages of liver cirrhosis [10][11][12][13][14] , including those awaiting a liver transplantation [15] .…”