C mixed triglyceride breath test

There is no easy and reliable test universally accepted in clinical practice to measure fat digestion. Fat balance studies are insensitive and unpleasant for regular clinical assessment, direct measures of pancreatic function are impractical for repeated use, the “steatocrit” method is not quantitative; tubeless tests have not proved to be eVective substitutes; and clinical measures, such as stool frequency, appearance, and consistency, are subjective. In 1981 an isotope breath test named the “mixed triglyceride (MTG) breath test” was described by Ghoos et al to measure intraduodenal lipase activity as an index of exocrine pancreatic function in adults. It was later modified by the substitution of C for C. The labelled carbon, originating from the labelled fat as a result of digestion, absorption, and oxidation, can be detected in exhaled carbon dioxide and the amount recovered in the breath is an indirect measure of lipolysis within the small intestine. The MTG breath test derives its name from the presence in the test molecule of both long and medium chain fatty acids. The labelled substrate consists of a triglyceride with two molecules of stearic acid at the Sn-1 and three positions and C octanoic acid in the Sn-2 position (1,3-distearyl [C octanoyl] glycerol). The MTG has a number of advantages over other triglycerides, such as trioctanoin and triolein, which have been used as substrates with which to measure fat digestion in adults and children. 5 Although the MTG is not representative of a naturally occurring dietary fat, the rate limiting step in its digestion is hydrolysis of the two stearyl groups by pancreatic lipase. Normal diet contains little octanoate, and the labelled tracer is not therefore diluted by unlabelled substrate. Octanoic acid, as a medium chain fatty acid, is rapidly and completely absorbed and is also speedily oxidised in the liver. 7 The appearance rate of the tracer in the breath correlates well with lipase secretion and when compared with an invasive direct function test was found to have a sensitivity of 89% and a specificity of 81% in adults. The MTG breath test has been the interest of a number of the partners in this BIOMED programme, and the abstracts summarising their work reflect current issues surrounding its use, directions for its further development, and its validation for clinical purposes. In most of the studies described, results have been expressed as “percentage dose recovered” (PDR) of the C taken by mouth as MTG over five or six hours. In abstract 1 a comparison was made of fat digestion in normal children with that in children with cystic fibrosis (CF) and small intestinal mucosal disease. The normal range of PDR was 22–41%. Unsupplemented children with CF had a median PDR of 3%, which increased significantly to within the normal range with pancreatic enzyme supplementation. Children with diseases of the small intestine had PDRs within the normal range. No relation was found between units of lipase taken and C recovery in the breath. The eVects of enteric coated enzyme supplements on fat digestion in children with CF were investigated (abstract 2). Equivalent amounts of lipase from conventional and high dose preparations caused comparable improvements in lipid digestion. Furthermore, a study to determine whether high strength lipase supplements might be responsible for the colonopathy of CF found no diVerence in intestinal transit rate or site of maximal lipolysis between children taking standard and high strength enzymes (abstract 3). Abstract 4 describes a study of children with untreated coeliac disease to investigate whether mucosal disease might aVect the results. PDR ranged from 10 to 44%, and two children whose results were in the abnormal range improved with treatment, with PDRs returning to the normal range after one year of gluten free diet, suggesting that mucosal damage may be a rate limiting factor in the MTG breath test. A comparison was made of the MTG breath test with fat balance measurements in adults with exocrine pancreatic disease (abstract 5). There was an exponential relation between the results of the two tests, and—excluding four patients with mucosal defects—a sensitivity of 81% and specificity of 75% was found. It is argued in abstract 6 that the MTG breath test is a more sensitive method for detecting defects in lipase activity than the assessment of fat malabsorption by 72 hour faecal fat measurement in children with CF, whose PDRs ranged from 3–31%. In abstract 7 the eVects of physical exercise and composition of diet before the test were studied. Foods that were naturally enriched with C resulted in too low a PDR, but there was no substantial eVect of exercise on the results. Gastric acid suppression caused some improvement in PDR in adults with CF. The MTG breath test was compared with the secretin-pancreozymin test (abstract 8). Patients with mild, moderate, and severe pancreatic disease, and patients with nonpancreatic gastrointestinal disease and controls were studied. The sensitivity and specificity of the test was best (63% and 85% respectively) when the PDR over 150 minutes was used to discriminate between groups, and a significant relation between PDR and duodenal enzyme concentrations was found. Abstract 9 describes the application of the MTG to study the ontogeny of fat digestion in infancy. There was an increase in the capacity Gut 1998;43 (suppl 3):S13–S19 S13