Pancreatic Insufficient Cystic Fibrosis Research Articles

Comprehensive semen examination in patients with cystic fibrosis

Introduction. Cystic fibrosis (CF) is a common genetic disorder associated with male infertility. Almost all men with CF are infertile due to obstructive azoospermia. The objective is to evaluate semen parameters, excretion of seminal fluid, and spermatogenesis in CF patients. Materials and methods . We examined 44 male CF patients with pancreatic sufficiency (n = 20) and pancreatic insufficiency (n = 24). Standard semen analysis, quantitative karyological analysis of immature germ cells from ejaculate sediment, biochemical semen analysis (fructose, α-glucosidase, citric acid) were performed. Results. Semen analysis diagnosed azoospermia in 77.3 % patients, severe oligozoospermia (< 1 million/ml) and other diagnoses (oligozoospermia, asthenozoospermia, normozoospermia) in 13.6 % and 9.1 % patients, respectively. The signs of obstruction of the vas deferens and aplasia of seminal vesicles were observed in 91 % patients. Azoospermia, oligospermia, pH <7.0 and low content of fructose in the semen samples result from bilateral obstruction of the vas deferens and aplasia of the seminal vesicles. Conclusion . Cryptozoospermia and immature germ cells, detected in ejaculate sediment in all azoospermic patients with CF, indicated aplasia, but not congenital absence of the vas deferens. The majority of CF patients presented signs of seminal ducts obstruction and impaired spermatogenesis and seminal fluid secretion. In contrast to pancreatic-sufficient CF male patients, pancreatic-insufficient CF patients can be fertile and have no obstruction of seminal ducts and severe pathozoospermia.

Reduced β-Cell Secretory Capacity in Pancreatic-Insufficient, but Not Pancreatic-Sufficient, Cystic Fibrosis Despite Normal Glucose Tolerance.

Patients with pancreatic-insufficient cystic fibrosis (PI-CF) are at increased risk for developing diabetes. We determined β-cell secretory capacity and insulin secretory rates from glucose-potentiated arginine and mixed-meal tolerance tests (MMTTs), respectively, in pancreatic-sufficient cystic fibrosis (PS-CF), PI-CF, and normal control subjects, all with normal glucose tolerance, in order to identify early pathophysiologic defects. Acute islet cell secretory responses were determined under fasting, 230 mg/dL, and 340 mg/dL hyperglycemia clamp conditions. PI-CF subjects had lower acute insulin, C-peptide, and glucagon responses compared with PS-CF and normal control subjects, indicating reduced β-cell secretory capacity and α-cell function. Fasting proinsulin-to-C-peptide and proinsulin secretory ratios during glucose potentiation were higher in PI-CF, suggesting impaired proinsulin processing. In the first 30 min of the MMTT, insulin secretion was lower in PI-CF compared with PS-CF and normal control subjects, and glucagon-like peptide 1 and gastric inhibitory polypeptide were lower compared with PS-CF, and after 180 min, glucose was higher in PI-CF compared with normal control subjects. These findings indicate that despite “normal” glucose tolerance, adolescents and adults with PI-CF have impairments in functional islet mass and associated early-phase insulin secretion, which with decreased incretin responses likely leads to the early development of postprandial hyperglycemia in CF.

Abdominal Pain in a 17-Year-Old Girl With Pancreatic Insufficient Cystic Fibrosis.

Abdominal Pain in a 17-Year-Old Girl With Pancreatic Insufficient Cystic Fibrosis.

Supplementation of ursodeoxycholic acid improves fat digestion and absorption in cystic fibrosis patients with mild liver involvement.

Ursodeoxycholic acid (UDCA) supplementation is recommended for cystic fibrosis (CF) patients with associated liver disease. However, its effect on fat digestion and absorption is not known. In 23 patients with mild liver involvement, a C-mixed triglyceride breath test was performed on UDCA supplementation (with and without pancreatic enzymes - standard and increased dose) and after 1 month of UDCA withdrawal. Cumulative percentage dose recovery [CPDR; median (interquartile range)] has been considered to reflect lipid digestion and absorption. The enzyme supplementation resulted in a significant CPDR improvement [0% (0-0) vs. 4.6% (0.4-6.0); P<0.00046]. With the increased dose of enzymes in 16 patients with abnormal C-mixed triglyceride breath test results and lipase dose less than 3000 U/g of fat, higher CPDR values [8.6% (5.6-12.7); P<0.000027] were observed. However, a 1-month UDCA withdrawal resulted in a significant reduction in (P<0.000031) fat digestion and absorption [2.9% (0.7-5.8)]. UDCA supplementation seems to enhance lipid digestion and absorption in pancreatic insufficient CF patients with mild liver involvement. This finding points toward the potential impact of UDCA supplementation on nutritional status in CF patients with liver disease and underscores the often overlooked role of factors other than pancreatic enzymes on digestion and absorption of fats in CF.

Preliminary report of the 13C-mixed triglyceride breath test to assess timing of pancreatic enzyme replacement therapy in children with cystic fibrosis

BackgroundDespite guidelines suggesting pancreatic enzyme replacement therapy (PERT) should be taken before or during a meal, it is currently unknown whether this has benefits over administration after a meal in individuals with cystic fibrosis (CF). Methods18 children with pancreatic insufficient CF were randomised to two 13C-mixed triglyceride (13C-MTG) breath tests to assess lipase activity with PERT administered 10min before and 10min after a meal. Results were expressed as percentage cumulative dose recovered (PCDR) of 13CO2 and were compared with established values in healthy subjects. Gastric half emptying time (T½) was also assessed by a 13C-octanoate breath test. ResultsThere was no difference in mean PCDR of 13CO2 between taking PERT before versus after the meal (p=0.68). Eleven subjects had a greater PCDR when PERT was taken before and 7 when PERT was taken after the meal. 6/8 subjects (75%) with a lower than normal PCDR at one time point normalised PCDR when PERT timing was changed. When PERT was taken after the meal, PCDR was higher in normal vs. fast T½ (p=0.04). ConclusionsChanging PERT timing can result in normalised lipase activity. Gastric emptying rate may influence optimal timing of PERT.Clinical Trial Registration Number — This study was undertaken prior to the registration process being a commonly required practice.

EPS01.3 Genotype–phenotype correlation in Russian cystic fibrosis patients with S466X–R1070Q complex allele

In the databases of CFTR mutations (CFTR1 and CFTR2) mutations S466X and R1070Q are described as separate ones: mutation S466X (p.Ser466X, c.1397C>G) – CF causing mutation (refers to mutations of class I); mutation R1070Q (p.Arg1070Gln, c.3208C>A) is considered as a mutation with variable clinical CF manifestations (mutation of class IV). Objectives To study genotype–phenotype correlations in Russian CF patients with S466X–R1070Q complex allele. Methods Sequencing of the coding region of CFTR gene and adjacent regions in 69 CF patients (with at least one unidentified mutation after standard analysis on 28 mutations) and clinical observation. Results In five unrelated patients we detected S466X–R1070Q complex allele. In all cases mutation S466X (p.Ser466X) was a substitution c.1397C>G. In three cases, DNA was available from the parents and the analysis confirmed that mutation S466X and R1070Q are in cis . Since S466X mutation leads to disruption of the CFTR protein synthesis, we can assume that the consequences of allele S466X–R1070Q are determined by mutation S466X. In all the patients a second mutant allele was identified. One patient without pancreatic insufficiency had class V mutation – 3849+10kbC>T (c.3717 + 12191C>T). Four were pancreatic insufficient: two had class I mutations [2143delT (p.Leu671X, c.2012delT) and R785X (p.Arg785X; c.2353C>T)] and the other two had class II mutation: F508del (p.Phe508del, c.1521_1523delCTT) and N1303K (p.Asp1303Lys, c.3909C>G). Conclusion Complex allele S466X–R1070Q violates protein synthesis and can be referred to severe mutations. It is associated with pancreatic-insufficient CF when paired with a known severe CF mutation.

239 Intake of pancreatic enzymes: Consistent with the guidelines?

Objectives Pancreatic enzyme (PE) replacement therapy is required in pancreatic insufficient CF patients to prevent malnutrition, nutrient deficiency and control abdominal maldigestion symptoms. This study evaluates and compares the actual PE intake with current expert recommendations (ER). Methods The dietary intake, measured by a 3-day dietary diary with PE intake (Creon® 10000, 25000 and 40000) for each meal was reviewed during a dietary consult. Intake is compared to the ER expressed as lipase units (IU)/g fat, /kg body-weight (BW)/day and /kgBW/meal. Results are presented as median (range). Results 54 patients [age 12.8 y (1, 50); 27 males] with BMI z-score –0.3 (–1.9, 1.5) and FEV1% 85.7 (31.8,114.1) (n = 43) were included. Results are presented in the table. TableComparison of PE intake with expert recommendationsGuidelineNumber of patientsTotalIntake greater than advised intakeIn accordance with advised intaken (%)Intake, median (range)n (%)Intake, median (range)Child: 400–800 IU/g fat2424 (100%)5,885 (1,106–13,875)–Adolescent-adult: 4,000 IU/g fat3026 (87%)7,316 (3,220–16,888)4 (13%)2,983 (2,857–3,135)10,000 IU/kgBW/d5440 (74%)18,753 (10,110–36,194)14 (26%)6,996 (2,455–9,711)2,000 IU/kgBW/meal5442 (78%)4,445 (2,210–8,691)12 (22%)1,398 (1,052–1,973) Conclusion The majority of our patients has a pancreatic enzyme intake above the current recommendations without known side effects. Research is needed to formulate recommendations based on achieving optimal digestion rather than using a protective dosing strategy.

Vitamin A intake and serum retinol levels in children and adolescents with cystic fibrosis

Pancreatic insufficient cystic fibrosis (CF) patients receive vitamin A supplementation according to CF-specific recommendations to prevent deficiencies. Whether current recommendations are optimal for preventing both deficiency and toxicity is a subject of debate. We assessed the longitudinal relation between serum retinol levels and appropriate variables. We studied vitamin A intake, and the long-term effects of vitamin A intake, coefficient of fat absorption (CFA) and immunoglobulin G (IgG) on serum retinol levels in 221 paediatrics CF patients during a seven-year follow up period. Total vitamin A intake, derived from 862 dietary assessments, exceeded the tolerable upper intake level in 30% of the assessments, mainly up to age six. Although CF patients failed to meet the CF-specific recommendations, serum retinol deficiency was found in only 17/862 (2%) of the measurements. Longitudinally, we observed no association to serum retinol levels for total vitamin A intake, CFA, gender or age but serum retinol levels were associated with serum IgG levels. Each g/L increase in serum IgG level would result in a 2.49% (95% CI -3.60 to-1.36%) reduction in serum retinol levels. In this large sample of children and adolescents with CF, serum retinol deficiency was rare despite lower than the CF-specific recommendations. However, the TUL was commonly exceeded. A reduction in CF-specific vitamin A supplementation recommendations should therefore be considered. Moreover, serum retinol levels were not associated with vitamin A intake, CFA, gender or age, although a decreased serum retinol was associated with an increased serum IgG.

Vitamin E intake, α-tocopherol levels and pulmonary function in children and adolescents with cystic fibrosis.

Pancreatic insufficiency cystic fibrosis (CF) patients receive vitamin E supplementation according to CF-specific recommendations in order to prevent deficiencies. It has been suggested that higher serum α-tocopherol levels could have protective effects on pulmonary function (PF) in patients with CF. Whether current recommendations are indeed optimal for preventing deficiency and whether vitamin E has therapeutic benefits are subjects of debate. Therefore, we studied vitamin E intake as well as the long-term effects of vitamin E intake, the coefficient of fat absorption (CFA) and IgG on α-tocopherol levels. We also examined the long-term effects of serum α-tocopherol and serum IgG on forced expiratory volume in 1 s expressed as percentage of predicted (FEV₁% pred.) in paediatric CF patients during a 7-year follow-up period. We found that CF patients failed to meet the CF-specific vitamin E recommendations, but serum α-tocopherol below the 2·5th percentile was found in only twenty-three of the 1022 measurements (2 %). Furthermore, no clear effect of vitamin E intake or the CFA on serum α-tocopherol was found (both P≥ 0·103). FEV₁% pred. was longitudinally inversely associated with age (P< 0·001) and serum IgG (P= 0·003), but it was not related to serum α-tocopherol levels. We concluded that in the present large sample of children and adolescents with CF, vitamin E intake was lower than recommended, but serum α-tocopherol deficiency was rare. We found no evidence that higher serum α-tocopherol levels had protective effects on PF. Adjustment of the recommendations to the real-life intake of these patients may be considered.

Diagnostic accuracy of secretin-stimulated ultrasonography of the pancreas assessing exocrine pancreatic failure in cystic fibrosis and chronic pancreatitis

Objective. Volume output failure is a feature of decreasing exocrine pancreatic function. This parameter is assessed by secretin-stimulated MRI in several studies. Our purpose was to evaluate ultrasonography of the fluid in the descending duodenum and Wirsung duct (WD) after secretin stimulation as a measure of pancreatic fluid flow in patients expected to have severe output failure. Material and methods. We included subjects with chronic pancreatitis (CP), cystic fibrosis (CF) and a group of healthy controls in a prospective observation study. Transabdominal ultrasonography was performed before and during 15 min after secretin i.v. duodenal juice was collected by endoscopic short test (EST), and bicarbonate concentration measured. Patient groups were classified according to exocrine pancreatic function. Results. Pancreatic insufficient CF (CFI) patients and CP insufficient (CPI) patients showed less duodenal fluid filling compared to other groups (p < 0.001). Measures of the WD diameter could only identify the most severe failure in the CFI group (p < 0.001). Conclusion. Secretin-stimulated ultrasonography can be used to assess pancreatic fluid flow and may be combined with EST in the evaluation of exocrine pancreatic function. Fluid filling in the descending part of duodenum was the most accurate predictor of pancreatic insufficiency in both patient groups. The test demonstrated better diagnostic accuracy diagnosing exocrine pancreatic failure in the CF patients than in CP patients.

Body composition and pulmonary function in cystic fibrosis.

Background: Lower body mass index (BMI) is associated with worse pulmonary function in cystic fibrosis (CF). Hypothesis: lean body mass (LBM) is more strongly associated with pulmonary function than BMI is.Methods: Anthropometrics, body composition by dual x-ray absorptiometry, and pulmonary function were determined in pancreatic insufficient CF (PI-CF) youth. Sex and age-adjusted Z-scores (BMI-Z, LBMI-Z, FMI-Z) were generated for CF and controls. (1) Associations of BMI-Z with LBMI-Z and FMI-Z and (2) age-adjusted associations of BMI-Z, LBMI-Z, and FMI-Z with FEV1%-predicted were tested.Results: Two hundred eight PI-CF subjects had lower BMI-Z, LBMI-Z, and FMI-Z compared to 390 controls. BMI-Z was associated with lower LBMI-Z (p < 0.0001) in PI-CF. In females, LBMI-Z and BMI-Z were positively associated with FEV1%-predicted; this relationship did not persist for FMI-Z after adjustment for LBMI-Z. In males, only LBMI-Z and BMI-Z were associated with FEV1%-predicted.Conclusion: In PI-CF youth, deficits in LBM were apparent. At lower BMI percentiles, BMI may not accurately depict LBM in PI-CF. In under-nourished PI-CF youth, this preservation of FM in preference to LBM is relevant since LBMI-Z, but not FMI-Z, is positively associated with FEV1%-predicted. Lean body mass index is more strongly associated with lung function compared to BMI, especially in the under-nourished child and adolescent with PI-CF.

Pancreatic Enzyme Supplementation Improves the Incretin Hormone Response and Attenuates Postprandial Glycemia in Adolescents With Cystic Fibrosis: A Randomized Crossover Trial

Cystic fibrosis-related diabetes is characterized by postprandial, rather than fasting, hyperglycemia. Gastric emptying and the release of the incretin hormones [glucagon-like peptide-1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP)] are central to postprandial glycemic control. Lipolysis is required for fat to slow gastric emptying and stimulate incretin release. We aimed to determine the effect of pancreatic enzyme replacement therapy (PERT) on postprandial glycemia in adolescents with cystic fibrosis (CF). This was a double-blinded randomized crossover trial. Subjects consumed a high-fat pancake, with either PERT (50 000 IU lipase) or placebo. Gastric emptying was measured by a breath test and blood sampled frequently for plasma blood glucose, insulin, glucagon, GLP-1, and GIP. Data were also compared with seven healthy subjects. Fourteen adolescents (13.1 ± 2.7 y) with pancreatic-insufficient CF and seven healthy age-matched controls participated in the study. Postprandial hyperglycemia was measured as peak glucose and area under the curve for blood glucose at 240 minutes. CF subjects had postprandial hyperglycemia compared with controls (area under the curve, P < .0001). PERT reduced postprandial hyperglycemia (P = .0002), slowed gastric emptying (P = .003), and normalized GLP-1 and GIP secretion (P < .001 for each) when compared with placebo, without affecting insulin. In young people with pancreatic insufficient CF, PERT markedly attenuates postprandial hyperglycemia by slowing gastric emptying and augmenting incretin hormone secretion.

254 The prognostic significance of hypoglycaemia on oral glucose tolerance tests in adults with cystic fibrosis (CF): A prospective clinical study

Objectives: In normal individuals, the shape of the OGTT curve (monophasic or biphasic) is influenced not only by the glucose load but also the patient’s metabolic response. This has not been studied in CF and may give an insight into the abnormal glucose handling even in those without CFRD. Method: We compared the area under the curve (AUC) for glucose, insulin, C-Peptide and glucagon following a 2-hour OGTT in 13 pancreatic insufficient adult CF (without known CFRD) and 10 healthy subjects, classified according to the OGTT curve shape. Results: See table. Biphasic curves were more common in CF (Chi2 = 4.97, p< 0.03), and these patients also had higher glucagon levels (p = 0.01) compared to their healthy counterparts, whilst CF patients with monophasic curves had reduced C-peptide levels (p = 0.04). Conclusions: This study shows that the shape of the OGTT curve in CF is related to pancreatic alpha and beta-cell function, as well as glucose load. The OGTT shape index may be a useful screening tool to make an early diagnosis of diabetes in CF.

256 The diagnostic utility of continuous glucose monitoring (CGM) in cystic fibrosis related diabetes (CFRD)

Objectives: In normal individuals, the shape of the OGTT curve (monophasic or biphasic) is influenced not only by the glucose load but also the patient’s metabolic response. This has not been studied in CF and may give an insight into the abnormal glucose handling even in those without CFRD. Method: We compared the area under the curve (AUC) for glucose, insulin, C-Peptide and glucagon following a 2-hour OGTT in 13 pancreatic insufficient adult CF (without known CFRD) and 10 healthy subjects, classified according to the OGTT curve shape. Results: See table. Biphasic curves were more common in CF (Chi2 = 4.97, p< 0.03), and these patients also had higher glucagon levels (p = 0.01) compared to their healthy counterparts, whilst CF patients with monophasic curves had reduced C-peptide levels (p = 0.04). Conclusions: This study shows that the shape of the OGTT curve in CF is related to pancreatic alpha and beta-cell function, as well as glucose load. The OGTT shape index may be a useful screening tool to make an early diagnosis of diabetes in CF.

253 The shape and relevance of the oral glucose tolerance test (OGTT) curve in CF

Objectives: In normal individuals, the shape of the OGTT curve (monophasic or biphasic) is influenced not only by the glucose load but also the patient’s metabolic response. This has not been studied in CF and may give an insight into the abnormal glucose handling even in those without CFRD. Method: We compared the area under the curve (AUC) for glucose, insulin, C-Peptide and glucagon following a 2-hour OGTT in 13 pancreatic insufficient adult CF (without known CFRD) and 10 healthy subjects, classified according to the OGTT curve shape. Results: See table. Biphasic curves were more common in CF (Chi2 = 4.97, p< 0.03), and these patients also had higher glucagon levels (p = 0.01) compared to their healthy counterparts, whilst CF patients with monophasic curves had reduced C-peptide levels (p = 0.04). Conclusions: This study shows that the shape of the OGTT curve in CF is related to pancreatic alpha and beta-cell function, as well as glucose load. The OGTT shape index may be a useful screening tool to make an early diagnosis of diabetes in CF.

WS1.6 The need of an appropriate diagnosis of gastroesophageal reflux disease in cystic fibrosis patients: impact on clinical management

Objectives: The gastric emptying rate (GER) may be delayed in CF, but its assessment is problematic and previous CF studies have employed scintigraphic techniques which are expensive and unsuitable for routine use. We wished to assess the use of ultrasonography for this purpose, which has been validated in a non-CF population using a 3.5-MHz abdominal transducer probe measuring gastric antral size [1]. Methods: After an overnight fast, in the supine position we looked at 12 nondiabetic subjects (mean age 26 [SD 4] years, 9 male) comparing the GER in 8 pancreatic insufficient CF patients with 4 healthy controls. Subjects consumed 113mls (made up to 200mls with water) of Polycal®, a liquid energy supplement. Ultrasound measurements were made regularly over 2 hours and gastric emptying >63% at 90 minutes was considered normal. Results: There was a significant decrease in GER at 90 minutes (p = 0.04) and 120 minutes (p = 0.02) in the CF group (see table). Conclusions: Delayed gastric emptying occurs in pancreatic insufficient patients with CF and without known cystic-fibrosis related diabetes. The novel use of bedside ultrasound in this patient group will allow timely management of patients with gastro-paresis by dietary manipulation or prokinetic therapy.

WS1.5 The use of bedside ultrasonography to identify delayed gastric emptying in cystic fibrosis

Objectives: The gastric emptying rate (GER) may be delayed in CF, but its assessment is problematic and previous CF studies have employed scintigraphic techniques which are expensive and unsuitable for routine use. We wished to assess the use of ultrasonography for this purpose, which has been validated in a non-CF population using a 3.5-MHz abdominal transducer probe measuring gastric antral size [1]. Methods: After an overnight fast, in the supine position we looked at 12 nondiabetic subjects (mean age 26 [SD 4] years, 9 male) comparing the GER in 8 pancreatic insufficient CF patients with 4 healthy controls. Subjects consumed 113mls (made up to 200mls with water) of Polycal®, a liquid energy supplement. Ultrasound measurements were made regularly over 2 hours and gastric emptying >63% at 90 minutes was considered normal. Results: There was a significant decrease in GER at 90 minutes (p = 0.04) and 120 minutes (p = 0.02) in the CF group (see table). Conclusions: Delayed gastric emptying occurs in pancreatic insufficient patients with CF and without known cystic-fibrosis related diabetes. The novel use of bedside ultrasound in this patient group will allow timely management of patients with gastro-paresis by dietary manipulation or prokinetic therapy.

Lactose malabsorption is a risk factor for decreased bone mineral density in pancreatic insufficient cystic fibrosis patients

As decreased bone mineral density (BMD) is a common problem in cystic fibrosis (CF) and milk products may have pivotal dietary role affecting BMD, we aimed to assess the potential influence of adult-type hypolactasia (ATH) and lactose malabsorption (LM) on BMD in adolescent and young adult patients. In 95 CF pancreatic-insufficient patients aged 10-25 years (without liver cirrhosis, steatosis and cholestasis, diabetes mellitus, systemic glucocorticoid therapy), lumbar BMD, the nutritional status, pulmonary function, vitamin D3 concentration, calcium intake and single-nucleotide polymorphism upstream of the lactase gene were assessed. In subjects with the -13910 C/C genotype predisposing to ATH, the presence of LM was determined with the use of a hydrogen-methane breath test (BT). BMD and calcium intake were significantly lower in patients with the C/C genotype (P<0.028 and P<0.043, respectively). The abnormal BMD was stated more frequently in patients with the C/C genotype (P<0.042) and with LM (P<0.007). BMD, daily calcium intake and serum vitamin D concentration were significantly lower in LM subjects than in the other patients (P<0.037, P<0.000004 and P<0.0038, respectively). In logistic regression analysis, the relationship between examined parameters and BMD, was found to be statistically significant (P<0.001). However, only standardized body weight and LM were documented to influence BMD (P<0.025 and P<0.044, respectively). In conclusion, LM seems to be an independent risk factor for decreased BMD in CF patients.

International phase III trial of liprotamase efficacy and safety in pancreatic-insufficient cystic fibrosis patients

Background Most cystic fibrosis (CF) patients have exocrine pancreatic insufficiency (EPI) and need supplementation with pancreatic enzyme replacement therapy (PERT). Liprotamase, a novel non-porcine PERT containing highly purified biotechnology-derived lipase, protease, and amylase, has successfully undergone initial efficacy and safety testing. Methods In this international phase III parallel-group, randomized-withdrawal, double-blind placebo-controlled trial, CF patients with EPI 7 years and older, including nutritionally and functionally compromised individuals, underwent baseline testing for coefficients of fat and nitrogen absorption (CFA and CNA) and stool weight and frequency while off PERT. After an open-label treatment period with liprotamase, subjects were randomized 1:1 to one liprotamase or placebo capsule taken with 3 meals and 2 snacks per day. The dose was fixed and increases were not allowed. The same measurements were obtained again after treatment with double-blind study drug or placebo. Results 138 subjects were randomized. The adjusted least squares mean (LSM) difference between the treatment and placebo groups for change in CFA was 15.1% ( p = 0.001) for the subgroup with baseline CFA < 40%, 8.6% ( p = 0.006) for subjects with baseline CFA ≥ 40%, and 10.6% ( p < 0.001) for the overall intent-to-treat population. Similar results were seen for change in CNA. Stool weight was significantly decreased although not stool frequency. Liprotamase was well tolerated with no safety concerns identified. Conclusions In a CF patient population reflective of that encountered in clinical practice, this trial demonstrated that liprotamase at a fixed dose of one capsule per meal or snack (5 capsules per day) was well tolerated and significantly increased fat absorption as measured by improvement in CFA, significantly increased protein absorption as measured by improvement in CNA, and significantly decreased stool weight.

Oral antibiotic therapy improves fat absorption in cystic fibrosis patients with small intestine bacterial overgrowth

Background The aim of the present study was to assess the influence of antibiotic therapy on fat assimilation in cystic fibrosis (CF) patients with small intestine bacterial overgrowth (SIBO). Materials and methods Twenty six pancreatic insufficient CF patients with bronchopulmonary exacerbation and diagnosed SIBO (positive hydrogen–methane breath test) entered the study. 13C mixed triglyceride breath test was performed before and after antibiotic therapy. Sixteen subjects were treated intravenously (ceftazidime and amikacin), ten patients orally (ciprofloxacin). Results Cumulative percentage dose recovery changed significantly in the subgroup receiving antibiotics orally [median (mean ± SEM): 3.6% (4.5 ± 1.3%) vs. 7.2 (6.9 ± 1.6%); p = 0.019]. In the subgroup with intravenous drug administration, the tendency towards improvement was noted [2.7 (4.3 ± 1.5%) vs. 5.2 (5.7 ± 0.8%); p = 0.109]. Conclusions Antibiotic therapy applied in CF patients with SIBO in the course of pulmonary exacerbation results in a significant improvement of fat digestion and absorption.