Evaluation of ¹³C Mixed Triglyceride Breath Testing and Fecal Elastase 1 assays for the assessment of pancreatic function in babies with cystic fibrosis

Abstract

Evaluation of ¹³C Mixed Triglyceride Breath Testing and Fecal Elastase 1 assays for the assessment of pancreatic function in babies with cystic fibrosis (Including an assessment of healthy babies to establish the range of normal for the ¹³C Breath test) Background and aims The 'gold standard' test for the indirect determination of pancreatic function status in infants with cystic fibrosis (CF), the 72-hour fecal fat excretion test, is likely to become obsolete in the near future. Alternative indirect pancreatic function tests with sufficient sensitivity and specificity to determine pancreatic phenotype need further evaluation in infants with CF and healthy controls. The first aim of this thesis was the evaluation of the clinical utility of both the non-invasive, non-radioactive ¹³C-mixed triglyceride (MTG) breath test and fecal elastase-1 (FE1) in comparison with the 72-hour fecal fat assessment in infants with CF. The second aim of this thesis was the longitudinal assessment of the ¹³C MTG breath test to measure pancreatic function in healthy babies less than two years of age. Methods and patients ¹³C MTG breath test with non-dispersive infrared spectrometry (NDIRS) and the monoclonal and polyclonal FE1 assessment in stool was compared with the 72-hour fecal fat assessment in 24 infants with CF and ¹³C MTG breath testing was also performed longitudinally in a group of 53 babies during their first two years of life with at least three consecutive breath tests. Babies were divided into 4 consecutive age groups: first ¹³C breath test on babies less than 5 months of age, second breath test between 6-9 months of age, third breath test between 9-12 months and fourth breath test between 9-24 months and with a different test meal (of yoghurt). Results Sensitivity rates between 82-100% for CF patients with pancreatic insufficiency assessed by both the ¹³C MTG breath test and the FE1 tests proved to be high and promising. However, the ¹³C MTG breath test (31-38%), as well as both FE1 tests assessed by the monoclonal (46-54%) and the polyclonal (45%) ELISA-kits showed unacceptably low sensitivity rates for the detection of pancreatic sufficient CF patients in the current study. In healthy babies a percentage of between 39% (9-24 months old) to 56% (9-12 months old) of individual results were found lower compared to the minimum reference point in all age groups. Intra-individual variation of the ¹³CO₂ response, in which no rate-limiting variation in pancreatic exocrine function was expected, was also assessed and showed that out of the 53 longitudinally assessed babies with three to four consecutive MTG breath tests, only 6 babies (3%) had consistent results above the minimum ¹³C cut-off point during the three to four breath test assessments with NDIRS technique<br /> Conclusion The ¹³C MTG breath test with NDIRS technique, as well as both FE1 tests, are not alternatives to the fecal fat balance test for the evaluation of pancreatic function in CF infants. NDIRS technique proved also to be too insensitive to determine pancreatic function status in healthy babies within the first two years of life and therefore the fecal fat balance test remains the gold standard test in assessing CF patient's pancreatic function in the first two years of life.