3.8　13C-Breath Tests

Several breath tests using 13C-labeled substrates for indirect measurement of pancreatic function have been developed during the recent years.As described above，lipase synthesis and secretion tend to be impaired earlier than those of other pancreatic enzymes in chronic pancreatitis.Therefore，tests using 13C-labeled lipids are most promising and most frequently performed.The labeled lipids are ingested orally together with a test meal and need to be digested to monoglycerides and free fatty acids by pancreatic lipase prior to absorption.Hepatic metabolism of the absorbed lipids via β-oxidation eventually leads to production of 13CO2 which enters the blood stream and is finally exhaled.Accordingly，intestinal lipolysis，the rate limiting step，is reflected by the ratio of breath 13CO2/12CO2 over time（Vantrappen et al.1989）.Apart from diagnosing pancreatic exocrine insufficiency，breath tests using 13C-labeled lipids can also be used to monitor the effect of enzyme replacement therapy（Dominguez-Munoz et al.2007）.(https://www.daowen.com)

Available substrates for breath testing include 1，3 distearyl-2［13C］-octanoate，uniformly labeled Hiolein®（mixture of long chain triglycerides）and cholesteryl-13C-octanoate（Keller et al.2009）.The 13C-mixed triglyceride breath test has several advantages over other lipid markers and is therefore most commonly used.Sensitivity and specificity of certain modifications of this non-invasive test reach 90%in comparison to the reference method（Iglesias-Garcia et al.2003；Keller et al.2011），and have been shown to also detect mild to moderate pancreatic exocrine insufficiency（Keller et al.2011）.For this modified version of the test subjects receive a standardized test meal，consisting of two slices of white bread，20 g butter and 30 g chocolate cream.The chocolate cream is carefully mixed with 250 mg 13C-mixed triglycerides.The meal is ingested within 10 min，together with 200 ml of water.In order to achieve a stable CO2-production rate，it is important that subjects remain seated during the test.Breath samples are collected before ingestion of the test meal and every 30 min thereafter for 6 h（Keller et al.2011）.The breath 13CO2/12CO2 isotope ratio can be determined by mass spectrometry or isotopeselective non-dispersive infrared spectrometry.A cumulative 13C-exhalation below 26.8%of the dose administered is regarded as pathological（Keller et al.2011）.

A major disadvantage of this test version is the need for prolonged breath sampling.However，retrospective comparison of test results in a large group of patients has shown that an abbreviated version requiring breath sampling for 4 h still provides a high accuracy（Keller et al.2014a）.

Furthermore，the test has limitations in terms of specificity，i.e.false positive results have to be expected in non-pancreatic fat malabsorption（Keller et al.2014b）and it is not yet available in several countries.