Fluorescein dilaurate test of exocrine pancreatic function in cystic fibrosis.

The fluorescein dilaurate test, a non-invasive test of exocrine pancreatic function, was carried out on 21 children with cystic fibrosis and pancreatic exocrine insufficiency, and 12 healthy siblings. The test clearly discriminated between the patients with cystic fibrosis and severe exocrine pancreatic insufficiency and the normal control subjects.     

Diagnosis of exocrine pancreatic insufficiency in cystic fibrosis by use of fluorescein dilaurate test.

In the fluorescein dilaurate test fluorescein dilaurate is cleaved by the pancreas specific cholesterol ester hydrolase activity and the liberated fluorescein is absorbed and excreted in the urine. Fluorescein recovery is a reflection of exocrine pancreatic function. The test was evaluated in 14 patients with cystic fibrosis and 16 healthy volunteers. The test was well tolerated by patients, was easy to perform, and gave significantly lower values in the patients suffering from cystic fibrosis. The result of the pancreolauryl test was also correlated with the result of the faecal chymotrypsin test in 11 of the patients suffering from cystic fibrosis. A positive correlation was found between the two test results. The test is a practical and reliable index of pancreatic exocrine function and may have a useful role as a screening procedure.     

Decline of exocrine pancreatic function in cystic fibrosis patients with pancreatic sufficiency.

Patients with cystic fibrosis and pancreatic sufficiency were investigated for evidence of progressive pancreatic disease. From a cohort of 630 patients, 20 pancreatic-sufficient patients became pancreatic insufficient after an average duration of 5.6 y (range 0.6-20.6 y) from diagnosis. Among 54 patients documented to be pancreatic sufficient by direct pancreatic stimulation test, 47 remained pancreatic sufficient and seven developed pancreatic insufficiency. The patients who ultimately developed pancreatic insufficiency were younger and had greatly reduced outputs of enzyme, fluid, and electrolytes. Those who remained pancreatic sufficient showed enzyme secretion close to or within the non-cystic fibrosis control range. Twenty of these patients underwent a second pancreatic stimulation test after an average interval of 4 y (range 1.3-6.2 y). No significant alteration in enzyme, fluid, or electrolyte output was seen in the patients who remained pancreatic sufficient, but there was further reduction in enzyme and fluid output in the patients who developed pancreatic failure. In conclusion, the majority of pancreatic-sufficient patients with pancreatic enzyme secretion within the control range showed no deterioration of function over an extended time period. However, a small number of pancreatic-sufficient patients with reduced enzyme and fluid secretion are at risk of pancreatic failure.     

Longitudinal follow-up of exocrine pancreatic function in pancreatic sufficient cystic fibrosis patients using the fecal elastase-1 test

BACKGROUND: A progressive decline in pancreatic function is possible in cystic fibrosis (CF) patients with exocrine pancreatic sufficiency. The secretin-cholecystokinin test is invasive and not acceptable as a repeatable procedure for children. Steatorrhea, conversely, has low sensitivity. Therefore, the aim of the present study was to evaluate the usefulness of the noninvasive fecal elastase-1 (E1) test for the longitudinal assessment of exocrine pancreatic function (EPF) in pancreatic-sufficient (PS) CF patients. METHODS: One hundred eighty-four CF patients were included in the study. In all subjects, E1 concentrations and fecal fat excretion were measured. PS patients were followed for 5 years. RESULTS: At the beginning of the study, 35 (19.0%) CF patients were PS, and 32 (17.4%) had normal E1 concentrations. Longitudinal measurements of E1 concentrations in PS patients with CF demonstrated stable enzyme output in 27 and gradual decrease in 8. The decrease was rapid in five infant patients and gradual in three older patients. The decrease of E1 concentrations preceded the appearance of steatorrhea in all eight subjects. CONCLUSIONS: The decline of EPF in patients with CF appears more frequently during the first months and years of life. However, late PS to pancreatic-insufficient (PI) conversion is also possible. The appearance of maldigestion is preceded by the decrease of fecal E1 concentration. Thus, the fecal E1 test is a helpful screening tool for the longitudinal assessment of declining EPF in PS patients with CF to demonstrate pancreatic deterioration. In suspected patients, fecal fat excretion should be assessed.     

Effect of exocrine pancreatic function on resting energy expenditure in cystic fibrosis

AIM: To prove the hypothesis that exocrine pancreatic function determines resting energy expenditure (REE) in cystic fibrosis (CF). METHOD: Thirty-eight CF individuals, 9-34 (19.98 +/- 1.0) years, were divided into three groups: Six pancreatic sufficient patients (PS; group A), 21 pancreatic insufficient patients (PI), whose pulmonary function was comparable to that of group A (group B1) and 11 PI patients, whose pulmonary function was significantly worse than that of group A (group B2). REE was estimated by indirect calorimetry. Predicted REE was based on Schofield equations. Measured REE was expressed as % of the predicted. BMI, BMI z-scores, serum albumin, cholesterol and triglycerides levels were related to REE. Results were expressed as mean +/- standard error. RESULTS: Groups B1 and B2 had significantly higher REE% (111.7 +/- 2.75% and 119.94 +/- 3.8, respectively) as opposed to group A (98.9 +/- 3.81%; p = 0.022 and 0.035, respectively) whose REE% was similar to that predicted. REE% between group B1 and B2 was not statistically significant. In groups A, B1 and B, mean FEV1% was 86.33 +/- 10.1%, 90.24 +/- 4.39%, 44.54 +/- 3.47%, respectively, mean BMI was 25.6 +/- 2.06, 19.48 +/- 0.64 and 20.09 +/- 8.8, respectively, BMI z-scores were 0.75 +/- 0.51, -0.52 +/- 0.24 and -1.07 +/- 0.37, respectively. Significant correlation was demonstrated between REE%, BMI z-scores and cholesterol levels in group A. CONCLUSION: Clinically stable CF patients, who had comparable pulmonary function, exhibited increased REE% only in the presence of exocrine pancreatic insufficiency. REE% strongly correlated with BMI z-scores in pancreatic sufficiency. These findings support the hypothesis that pancreatic rather than pulmonary function may determine nutritional status as well as REE in CF.     

Carbohydrate tolerance in cystic fibrosis is closely linked to pancreatic exocrine function

We evaluated carbohydrate tolerance in nine thin cystic fibrosis (CF) patients and in six controls, measuring responsiveness to the following insulinotropic secretagogues: oral glucose, IV glucose, and IV tolbutamide. Glucose responses segregated patients into two groups: Group I with normal carbohydrate tolerance associated with normal to slightly increased insulin responses, and Group II with impaired carbohydrate tolerance associated with insulinopenia. This latter group included one patient with frank diabetes. The CF patients demonstrated a significant positive correlation between insulin secretion, in response to each secretagogue, and pancreatic exocrine function as measured by serum pancreatic amylase isoenzyme concentration. Pancreatic alpha-cell function, as reflected by basal plasma glucagon concentrations, also correlated well with exocrine function in the CF patients, excluding the diabetic individual. The enteroinsular axis of the CF group was intact as reflected by normal plasma gastric inhibitory polypeptide concentrations in Group I and by elevated levels, basally and in response to oral glucose, in the insulinopenic Group II patients. Furthermore, those patients with impaired tolerance demonstrated a greater magnitude of insulinopenia compared to controls following IV glucose and possibly IV tolbutamide, than following oral glucose. Thus, these data suggest that loss of carbohydrate tolerance in patients with CF, like that seen with classical chronic pancreatitis, 1) parallels the loss of exocrine function, 2) is associated with appropriate enteroinsular signaling, and 3) can be detected earlier or more easily following testing with direct IV secretagogues than following oral glucose stimulation.     

Faecal elastase-1 test is superior to faecal lipase test in the assessment of exocrine pancreatic function in cystic fibrosis

BACKGROUND AND AIMS: Direct tests are characterized by the highest sensitivity and specificity. However, their practical use, especially in children, is limited. Among the indirect tests, the highest sensitivity and specificity was documented for faecal elastase-1 test, yet the value of faecal lipase test in cystic fibrosis (CF) has not been defined. Therefore, the aim of the present study was to compare the sensitivity and the specificity of the faecal lipase test to the faecal elastase-1 test in the assessment of exocrine pancreatic function in children with CF. METHODS: The study comprised 90 CF patients and 95 healthy subjects (HS). In all subjects, faecal elastase-1 concentrations (ELISA) and lipase activities (ELISA) were measured. The presence of pancreatic insufficiency was documented by the determination of faecal fat excretion in 78 pancreatic insufficient and by the secretin-cholecystokinin test in 12 CF patients without steatorrhoea. Sensitivity and specificity of the faecal elastase-1 test and faecal lipase test were analysed and, in 50 HS, sample-to-sample and day-to-day variations were determined. RESULTS: With cut-off levels providing the same specificity for both tests (95.8%), the sensitivity of the faecal elastase-1 test (91.1%) was significantly higher (p < 0.0036) than that of the faecal lipase test (76.7%). Sample-to-sample (mean +/- SEM: 13.2 +/- 1.2% vs 23.4 +/- 2.2%) and day-to-day variations (mean +/- SEM: 16.3 +/- 1.2% vs 32.5 +/- 2.6%) were significantly lower (p < 0.0001) for elastase-1 than for lipase measurements. CONCLUSION: Among indirect tests, faecal elastase-1 test is superior to faecal lipase test in the assessment of exocrine pancreatic function in cystic fibrosis.     

Restoration of exocrine pancreatic function in older children with cystic fibrosis on ivacaftor

Prior to the use of cystic fibrosis (CF) modulator therapy, exocrine pancreatic insufficiency in CF was thought to be irreversible. Improvement in pancreatic function on ivacaftor has been reported in open label studies in 1–5 year olds. The mechanism by which ivacaftor might improve exocrine pancreatic function is unclear. Although the effect of ivacaftor on pancreatic function may be more significant in younger children, evidence is mounting that there may still be potential for improvement in older children on long term therapy.     

The effect of exocrine pancreatic function on chloramphenicol pharmacokinetics in patients with cystic fibrosis

The effect of exocrine pancreatic function on the pharmacokinetics of the choramphenicol oral capsule (CAP-base), chloramphenicol palmitate oral liquid (CAP-P), and chloramphenicol succinate intravenous (CAP-S) formulations was evaluated in 10 patients, aged 16-30 yr, with cystic fibrosis. Pancreatic insufficiency was assessed in each patient by measuring the absorption of p-amino-benzoic acid after oral administration of N-benzoyl-L-tyrosyl-p-aminobenzoic acid which requires chymotrypsin to cleave p-aminobenzoic from the parent molecule. In a controlled cross-over design, the overall biodisposition of each formulation was assessed in each patient with or without concurrent administration of oral pancreatic enzymes. The relative amounts of active chloramphenicol available in systemic circulation was CAP-base greater than CAP-S greater than CAP-P. Pancreatic enzyme replacement had little effect on the biodisposition parameters for the CAP-base and CAP-S formulation, but significantly increased the peak concentration and bioavailability of the CAP-P formulation. Although pancreatic enzyme replacement improved the absorption characteristics of the CAP-P formulation, absorption remained prolonged and unreliable. Serum concentration-time profiles for either CAP-base or CAP-S consistently exceeded the MIC of important nonpseudomonal pathogens. This finding was not observed after CAP-P administration independent of pancreatic enzyme replacement. The results of this study support the continued clinical use of either CAP-base or CAP-S, but the cautious use of CAP-P formulations in CF patients with concurrent pancreatic insufficiency.     

Cystic fibrosis serum pancreatic amylase. Useful discriminator of exocrine function

To develop a simple test for pancreatic exocrine function in patients with cystic fibrosis, we compared serum pancreatic amylase isoenzyme (P isoamylase) activity with the more complex standard tests of pancreatic function. Twenty-seven patients with cystic fibrosis, newborn to 46 years of age, were studied. All patients over 17 months old with evidence of pancreatic exocrine insufficiency, as manifested by abnormal duodenal secretions and/or abnormal 72-hour fecal fat absorption, had serum P isoamylase activity below the age-matched normal range; patients with adequate pancreatic function (aged 2 to 46 years) had P isoamylase activity in or above the normal range. Although both normal neonates and neonates with cystic fibrosis have very low levels of serum P isoamylase activity, in patients over 1 1/2 years of age serum P isoamylase activity may serve as a simple and useful discriminator of pancreatic exocrine function in patients with cystic fibrosis.     

BT-Paba test in the diagnosis of pancreatic exocrine insufficiency in cystic fibrosis: urinary and serum determinations compared

Urinary recovery and serum determination of Paba were carried out in 48 control children (C) and 53 paediatric patients with cystic fibrosis (CF) divided into three classes by age. Ninety and 120 min after the ingestion of 15 mg/kg of BT-Paba and of a standard meal, serum Paba was determined. In the same subjects the percentage Paba recovery was measured in the urine collected during an 8 h period after the same administration of BT-Paba. Correlation between urinary and serum Paba values was higher in the older children in respect to the 0–2-year-old infants. A urinary Paba test was less sensitive and specific than a serum Paba test in the evaluation of exocrine pancreatic function. The best discrimination between C and children with CF, using the maximal value of serum Paba at 90 or 120 min (peak), was obtained in the younger infants (0–2 years old). BT-Paba test with serum Paba peak determination is recommended as a substitute for the classical urinary Paba test in the evaluation of exocrine pancreatic function in paediatric patients, especially in the younger infants.Abbreviations C control - CF cystic fibrosis     

Serum immunoreactive pancreatic lipase and cationic trypsinogen for the assessment of exocrine pancreatic function in older patients with cystic fibrosis

Indirect and qualitative tests of pancreatic function are commonly used to screen patients with cystic fibrosis for pancreatic insufficiency. In an attempt to develop a more quantitative assessment, we compared the usefulness of measuring serum pancreatic lipase using a newly developed enzyme-linked immunosorbent immunoassay with that of cationic trypsinogen using a radioimmunoassay in the assessment of exocrine pancreatic function in patients with cystic fibrosis. Previously, we have shown neither lipase nor trypsinogen to be of use in assessing pancreatic function prior to 5 years of age because the majority of patients with cystic fibrosis in early infancy have elevated serum levels regardless of pancreatic function. Therefore, we studied 77 patients with cystic fibrosis older than 5 years of age, 41 with steatorrhea and 36 without steatorrhea. In addition, 28 of 77 patients consented to undergo a quantitative pancreatic stimulation test. There was a significant difference between the steatorrheic and nonsteatorrheic patients with the steatorrheic group having lower lipase and trypsinogen values than the nonsteatorrheic group (P less than .001). Sensitivities and specificities in detecting steatorrhea were 95% and 86%, respectively, for lipase and 93% and 92%, respectively, for trypsinogen. No correlations were found between the serum levels of lipase and trypsinogen and their respective duodenal concentrations because of abnormally high serum levels of both enzymes found in some nonsteatorrheic patients. We conclude from this study that both serum lipase and trypsinogen levels accurately detect steatorrhea in patients with cystic fibrosis who are older than 5 years but are imprecise indicators of specific pancreatic exocrine function above the level needed for normal fat absorption.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diagnosis of exocrine pancreatic insufficiency in cystic fibrosis by the synthetic peptide N-benzoyl-L-tyrosyl-p-aminobenzoic acid.

The synthetic peptide N-benzoyl-L-tyrosyl-p-aminobenzoic acid is specifically cleaved by chymotrypsin to Bz-Ty and PABA. The liberated PABA is absorbed and excreted in the urine. Accordingly, PABA recovery reflects intraluminal chymotrypsin activity and is an index of exocrine pancreatic function. This test was evaluated in 24 patients with cystic fibrosis to determine its role in the diagnosis of exocrine pancreatic insufficiency. Cumulative percent PABA recovery in six hours was significantly lower in CF patients compared with the control group. No overlap was noted between the two groups. There was good correlation between PABA recovery, fecal chymotrypsin activity, and coefficient of fat absorption. These findings indicate that PABA recovery is significantly reduced in patients with CF and steatorrhea and may prove a practical and reliable test of pancreatic insufficiency.     

PABA screening test for exocrine pancreatic function in infants and children.

P-Amino-benzoic acid (PABA) is split specifically by pancreatic chymotrypsin from the synthetic tripeptide N-benzoyl-L-tyrosyl-PABA. The urinary excretion of absorbed PABA serves as an index for exocrine pancreatic function. The peptide (0.015 g/kg) was administered orally to 20 controls (aged between 5 months and 16 years), 6 patients with exocrine pancreatic insufficiency caused by cystic fibrosis (CF), and 9 newborn infants. In the controls the mean 6-hour PABA recovery was 58.5% (+/- 11.2 SD). Recovery in patients with CF was lower (P less than 0.001) with no overlap. In newborn infants the mean 6-hour PABA recovery was 23.4 (+/- 17.7 SD); overlapping in 3 instances with the results in CF patients. This simple, noninvasive test thus appears promising and merits further investigation in younger infants, especially newborns.     

Serum pancreatic lipase as a screening test for cystic fibrosis.

Pancreatic lipase catalyses the hydrolysis of emulsified triglycerides to form a transparent solution of monoglycerides and fatty acids. Levels of serum pancreatic lipase were measured in neonates known to have cystic fibrosis and compared with levels in control infants. During the first weeks of life infants with cystic fibrosis had raised serum pancreatic lipase values in parallel with raised serum trypsin values. A simple and specific turbidimetric dried blood spot assay for serum pancreatic lipase was used as a screening test fo cystic fibrosis in the neonate.     

Ontogeny of pancreatic exocrine function.

Exocrine pancreatic proteolytic activity, determined by serial measurement of faecal chymotrypsin concentration, was investigated in 21 preterm infants (23-32 weeks'' gestation) during the first 28 days of life. The overall chymotrypsin concentration range was similar to that already described in term infants showing that pancreatic chymotrypsin secretion is equally well developed at birth in the preterm infant. A chymotrypsin concentration peak, seen in term infants at 4 days, did not occur in this study until day 8, suggesting a slower initiation of pancreatic exocrine function in the preterm infant. Median faecal chymotrypsin concentrations, calculated for each baby using data from stools passed between day 2 and day 12 of life, were significantly lower in infants who were small for gestational age when compared with those who were an appropriate size for gestational age. The lower chymotrypsin concentration in infants who were small for gestational age suggests a deleterious effect of intrauterine growth retardation on pancreatic exocrine function which may be a factor in limiting postnatal catch up growth.