Interpretation of non-invasive breath tests using 13 C-labeled substrates - a preliminary report with 13 C-methacetin
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december 14, 2009 Eur J Med Res (2009) 14: 547-550
547 © I. Holzapfel Publishers 2009
InTERPRETaTIon of non-InvasIvE BREaTH TEsTs UsInG 13C-laBElEd sUBsTRaTEs – a PRElIMInaRy REPoRT WITH 13C-METHaCETIn J. f. lock 1, P. Taheri 1, s. Bauer 2, H.-G. Holzhütter 3, M. Malinowski 1, P. neuhaus 1, M. stockmann 1 1 department of General, visceral and Transplantation surgery, 2 Institute of Clinical Pharmacology and Toxicology,
3 Institute
of Biochemistry, Charité - Universitätsmedizin Berlin, Germany
Abstract non-invasive breath tests can serve as valuable diagnostic tools in medicine as they can determine particular enzymatic and metabolic functions in vivo. However, methodological pitfalls have limited the actual clinical application of those tests till today. a major challenge of non-invasive breath tests has remained the provision of individually reliable test results. To overcome these limitations, a better understanding of breath kinetics during non-invasive breaths tests is essential. This analysis compares the breath recovery of a 13 C-methacetin breath test with the actual serum kinetics of the substrate. It is shown, that breath and serum kinetics of the same test are significantly different over a period of 60 minutes. The recovery of the tracer 13 Co2 in breath seems to be significantly delayed due to intermediate storage in the bicarbonate pool. This has to be taken into account for the application of non-invasive breath test protocols. otherwise, breath tests might display bicarbonate kinetics despite the metabolic capacity of the particular target enzyme. Key words: liver function, liver function test, 13 C-breath test, methacetin, cytochrome P450 1a2, liMax test Abbreviations: nBT, non-invasive breath tests; doB, delta over baseline; HPlC, high performance liquid chromatography
olism without repeated blood sampling, which makes it more acceptable and comfortable for both physicians and patients. However, 13 Co2 is not directly exhaled from the target enzyme, but needs to be transported from the investigated organ as bicarbonate (H 12 Co3- / H 13 Co3-) into the lung [8]. Methodological studies reported the kinetics of 13 Co2 excretion already in the 1970-80ies [9-13]. It is known that emerging bicarbonate has a relatively long halftime of approx. 60 minutes [14] and that ultimately only 70% of the emerging 13 Co2 is excreted [15]. This could significantly interfere with nBT results [8]. However, these data did neither influence the design of later breath test protocols nor the algorithms of nBT interpretation. different ways for calculation of test readouts have been described in literature: some authors used single time points (fig. 2; # 1-4) - whether at chosen arbitrary points in time like 15, 30 or 60 minutes (fig. 2; # 2-4) [16] or maximal abundance (fig. 2; # 1) [7]. other authors applied area-under-curve analysis (fig. 2; # 5) [17, 18]. However, it remains somehow undefined which way actually provides the most valid and reliable test readout. The aim of this analysis was to explore the correlati
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