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  • Original Article
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Improving the specificity of the [13C]mixed triacylglycerol breath test by estimating carbon dioxide production from heart rate

Abstract

Background:

The [13C]mixed triacylglycerol (MTG) breath test is a non-invasive measure of fat digestion and can be used to assess the need for enzyme replacement therapy in children with cystic fibrosis (CF). However, it lacks specificity. Quantitation of cumulative percent dose recovered (cPDR) requires knowledge of carbon dioxide production rate (VCO2). A resting value is assumed, but children are unlikely to remain at rest during the test.

Objective:

To improve the specificity and therefore the positive predictive value (PPV) of the MTG breath test using calibrated heart rate monitors to estimate non-resting VCO2.

Design:

Proof of concept study.

Subjects:

Six children with CF, 10 healthy children and eight healthy adults performed [13C]MTG breath tests.

Methods:

Heart rate monitors were worn throughout the test. Non-resting VCO2 was estimated continuously from heart rate. Percentage dose recovered was calculated using predicted resting VCO2, measured resting VCO2 and non-resting VCO2 estimated from heart rate. Physical activity level (PAL) was taken as cPDR calculated using non-resting VCO2 divided by cPDR calculated using measured resting VCO2. The cutoff point was determined using two graph-receiver operator characteristics.

Results:

Use of calibrated heart rate monitors to estimate non-resting VCO2 improved the specificity of the test. The PPV increased from 0.67 to 0.99. PAL was 1.3 in adults and children who performed the test in hospital, and 1.7 in children who performed the test at home.

Conclusion:

Individually calibrated heart rate monitors are useful tools to estimate non-resting VCO2 during the [13C]MTG breath test.

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References

  • Ainsworth BE, Haskell WL, Leon AS, Jacobs Jr DR, Montoye HJ, Sallis JF et al. (1993). Compendium of physical activities: classification of energy costs of human physical activities. Med Sci Sports Exerc 25, 71–80.

    Article  CAS  Google Scholar 

  • Ainsworth BE, Haskell WL, Whitt MC, Irwin MA, Swartz AM, Strath SJ et al. (2000). Compendium of physical activities: an update of activity codes and MET intensities. Med Sci Sports Exerc 32, S498–S516.

    Article  CAS  Google Scholar 

  • Amarri S, Coward WA, Harding M, Weaver LT (1998). Importance of measuring CO2-production rate when using 13C-breath tests to measure fat digestion. Br J Nutr 79, 541–545.

    Article  CAS  Google Scholar 

  • Amarri S, Harding M, Coward WA, Evans TJ, Weaver LT (1997). 13Carbon mixed triglyceride breath test and pancreatic enzyme supplementation in CF. Arch Dis Child 76, 349–351.

    Article  CAS  Google Scholar 

  • Amarri S, Weaver LT (1995). 13C-breath tests to measure fat and carbohydrate digestion in clinical practice. Clin Nutr 14, 149–154.

    Article  CAS  Google Scholar 

  • Bland M (1995). An Introduction to Medical Statistics. Oxford University Press: Oxford, p 275.

    Google Scholar 

  • Christian MT, Edwards CA, Preston T, Johnston L, Varley R, Weaver LT (2003). Starch fermentation by faecal bacteria of infants, toddlers and adults: importance for energy salvage. Eur J Clin Nutr 57, 1486–1491.

    Article  CAS  Google Scholar 

  • Cole TJ, Freeman JV, Preece MA (1995). Body mass index reference curves for the UK, 1990. Arch Dis Child 73, 25–29.

    Article  CAS  Google Scholar 

  • Coplen TB (1996). New guidelines for reporting stable hydrogen, carbon, and oxygen isotope-ratio data. Geochim Cosmochim Acta 60, 3359–3360.

    Article  CAS  Google Scholar 

  • de Boeck K, Delbeke I, Eggermont E, Veereman-Wauters G, Ghoos Y (1998). Lipid digestion in cystic fibrosis: comparison of conventional and high lipase enzyme therapy using the mixed-triglyceride breath test. J Pediatr Gastroenterol Nutr 26, 408–411.

    Article  CAS  Google Scholar 

  • Department of Health (1991). Dietary Reference Values for Food Energy and Nutrients for the United Kingdom. Report of the Panel on Dietary Reference Values of the Committee on Medical Aspects of Food Policy, HMSO: London.

  • Dewit O, Prentice A, Coward WA, Weaver LT (1992). Starch digestion in young children with cystic fibrosis measured using a 13C breath test. Pediatr Res 32, 45–49.

    Article  CAS  Google Scholar 

  • Ghoos YF, Vantrappen G, Rutgeerts PJ, Schurmans PC (1981). A mixed-triglyceride breath test for intraluminal fat digestive activity. Digestion 22, 239–247.

    Article  CAS  Google Scholar 

  • Greiner M, Sohr D, Göbel P (1995). A modified ROC analysis for the selection of cut-off values and the definition of intermediate results of serodiagnostic tests. J Immunol Methods 185, 123–132.

    Article  CAS  Google Scholar 

  • Haycock G, Schwartz G, Wisotsky G (1978). Geometric method for measuring body surface area: a height–weight formula validated in infants, children and adults. J Pediatr 93, 62–66.

    Article  CAS  Google Scholar 

  • Holland B, Welch AA, Unwin ID, Buss DH, Paul AA, Southgate DAT (1991). McCance and Widdowson's, The Composition of Foods, 5th edn. The Royal Society of Chemistry: Cambridge.

    Google Scholar 

  • IDECG (1990). Converting carbon dioxide production to energy expenditure. In: Prentice AM (ed). Report by the International Dietary Energy Consultancy Group (IDECG). NAHRES-4. The Doubly-Labelled Water Method for Measuring Energy Expenditure: Technical Recommendations for human use. IAEA: Vienna, p 201.

  • Kalivianakis M, Verkade HJ, Stellaard F, van der Werf M, Elzinga H, Vonk RJ (1997). The 13C-mixed triglyceride breath test in healthy adults: determinants of the 13CO2 response. Eur J Clin Invest 27, 434–442.

    Article  CAS  Google Scholar 

  • Löser C, Brauer C, Aygen S, Hennemann O, Fölsch UR (1998). Comparative clinical evaluation of the 13C-mixed triglyceride breath test as an indirect pancreatic function test. Scand J Gastroenterol 33, 327–334.

    Article  Google Scholar 

  • Montgomery C, Reilly JJ, Jackson DM, Kelly LA, Slater C, Paton JY et al. (2004). Relation between physical activity and energy expenditure in a representative sample of young children. Am J Clin Nutr 80, 591–596.

    Article  CAS  Google Scholar 

  • Morrison DJ, Dodson B, Slater C, Preston T (2000). 13C natural abundance in the British diet: implications for 13C breath tests. Rapid Commun Mass Spectrom 14, 1321–1324.

    Article  CAS  Google Scholar 

  • Motulsky HJ, Ransnas LA (1987). Fitting curves to data using nonlinear regression: a practical and nonmathematical review. FASEB J 1, 365–374.

    Article  CAS  Google Scholar 

  • Parker AC, Preston T, Heaf D, Kitteringham NR, Choonara I (1994). Inhibition of caffeine metabolism by ciprofloxacin in children with cystic fibrosis as measured by the caffeine breath test. Br J Clin Pharmacol 38, 573–576.

    Article  CAS  Google Scholar 

  • Parker AC, Pritchard P, Preston T, Choonara I (1998). Induction of CYP1A2 activity by carbamezepine in children using the caffeine breath test. Br J Clin Pharmacol 45, 176–178.

    Article  CAS  Google Scholar 

  • Parker AC, Pritchard P, Preston T, Dalzell AM, Choonara I (1997). Lack of inhibitory effect of cimetidine on caffeine metabolism in children using the caffeine breath test. Br J Clin Pharmacol 45, 467–470.

    Article  Google Scholar 

  • Prosser SJ, Brookes ST, Linton A, Preston T (1991). Rapid, automated analysis of 13C and 18O of CO2 in gas samples by continuous-flow, isotope ratio mass spectrometry. Biol Mass Spectrom 20, 724–730.

    Article  CAS  Google Scholar 

  • Schoeller DA, Klein PD, Watkins JB, Heim T, MacLean WCJ (1980). 13C abundance of nutrients and the effect of variations in 13C isotopic abundances of test meals formulated for 13CO2 breath tests. Am J Clin Nutr 33, 2375–2385.

    Article  CAS  Google Scholar 

  • Schoenheimer R, Rittenberg D (1939). Studies in protein metabolism I. General considerations in the application of isotopes to the study of protein metabolism. The normal abundance of nitrogen isotopes in amino acids. J Biol Chem 127, 285–289.

    Google Scholar 

  • Schofield WN (1985). Predicting basal metabolic rate, new standards and review of previous work. Hum Nutr: Clin Nutr 39C, 5–41.

    Google Scholar 

  • Schulz S, Westerterp KR, Bruck K (1989). Comparison of energy expenditure by the doubly labeled water technique with energy intake, heart rate, and activity recording in man. Am J Clin Nutr 49, 1146–1154.

    Article  CAS  Google Scholar 

  • Shreeve VW, Cerasi E, Luft R (1970). Metabolism of [2-14C]pyruvate in normal, acromegalic and HGH-treated human subjects. Acta Endocrinol 65, 155–169.

    Article  CAS  Google Scholar 

  • Slater C (2004). Improvements to the [13C]MTG breath test for measuring fat digestion. PhD thesis, University of Glasgow, https://dspace.gla.ac.uk/handle/1905/449, pp 97, 117, 144, 159, 161, 162.

  • Slater C, Ling SC, Preston T, Weaver LT (2002a). Bulk and compound specific analysis of stool lipid confirm that the ‘missing’ 13C in mixed triacylglycerol breath test is not in the stool. Food Nutr Bul 23 (Suppl), 48–52.

    Article  Google Scholar 

  • Slater C, Preston T, Morrison DJ, Weaver LT (2002b). A shelf-stable, palatable test meal suitable for use with hydrophilic and lipophilic tracers in 13C breath tests. Proc Nutr Soc 61, 66A (abstract).

    Google Scholar 

  • Slater C, Preston T, Weaver LT (2001). Stable isotopes and the International System of Units. Rapid Commun Mass Spectrom 15, 1270–1273.

    Article  CAS  Google Scholar 

  • Slater C, Preston T, Weaver LT (2004). Is there an advantage in normalising the results of the Helicobacter pylori [13C]urea breath test for CO2 production rate in children? Isotopes Environ Health Stud 40, 89–98.

    Article  CAS  Google Scholar 

  • Slater C, Preston T, Weaver LT (2006). Comparison of accuracy and precision of heart rate calibration methods to estimate CO2 production during breath tests. Eur J Clin Nutr 60, 69–76.

    Article  CAS  Google Scholar 

  • Swart GR, Baartman EA, Wattimena JL, Rietveld T, Overbeek SE, Van den Berg JW (1997). Evaluation studies of the 13C-mixed triglyceride breath test in healthy controls and adult cystic fibrosis patients with exocrine pancreatic insufficiency. Digestion 58, 415–420.

    Article  CAS  Google Scholar 

  • van Dijk-van Aalst K, Van Den Driessche M, van der Schoor S, Schiffelers S, van't Westeinde T, Ghoos Y et al. (2001). 13C mixed triglyceride breath test: a noninvasive method to assess lipase activity in children. J Pediatr Gastroenterol Nutr 32, 579–585.

    Article  CAS  Google Scholar 

  • Vantrappen GR, Rutgeerts PJ, Ghoos YF, Schurmans PC (1989). Mixed triglyceride breath test: a noninvasive test of pancreatic lipase activity in the duodenum. Gastroenterology 96, 1126–1134.

    Article  CAS  Google Scholar 

  • Walsh S, Diamond D (1995). Non-linear curve fitting using Microsoft Excel Solver. Talanta 42, 561–572.

    Article  CAS  Google Scholar 

  • Weaver LT, Dibba B, Sonko B, Bohane TD, Hoare S (1995). Measurement of starch digestion of naturally 13C-enriched weaning foods, before and after partial digestion with amylase-rich flour, using a 13C breath test. Br J Nutr 74, 531–537.

    Article  CAS  Google Scholar 

  • Wutzke KD, Radke M, Breuel K, Gurk S, Lafrenz J-D, Heine WE (1999). Triglyceride oxidation in cystic fibrosis: a comparison between different 13C-labeled tracer substances. J Pediatr Gastroenterol Nutr 29, 148–154.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We acknowledge financial support from the UK Medical Research Council Joint Research Equipment Initiative and the University of Glasgow, and thank Cambridge Isotopes Laboratory Inc, Andover, MA, USA for donating the [13C]MTG used in this study. We thank Dr Simon Ling, formerly consultant gastroenterologist, Royal Hospital for Sick Children (RHSC), Glasgow, for assistance in recruiting children with CF.

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Correspondence to C Slater.

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Guarantor: C Slater.

Contributors: CS performed the study, analysed the data, wrote the first draft and refined the manuscript. TP conceived the original idea, advised on study design and data analysis and critically appraised the manuscript. LTW cosupervised the project and critically appraised the manuscript.

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Slater, C., Preston, T. & Weaver, L. Improving the specificity of the [13C]mixed triacylglycerol breath test by estimating carbon dioxide production from heart rate. Eur J Clin Nutr 60, 1245–1252 (2006). https://doi.org/10.1038/sj.ejcn.1602444

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