Delayed release pancrelipase for the treatment of pancreatic exocrine insufficiency associated with cystic fibrosis.
Ontology highlight
ABSTRACT:
SUBMITTER: Baker SS
PROVIDER: S-EPMC2621407 | biostudies-other | 2008 Oct
REPOSITORIES: biostudies-other
Publications
Delayed release pancrelipase for the treatment of pancreatic exocrine insufficiency associated with cystic fibrosis.
Therapeutics and clinical risk management 20081001 5
Pancreatic enzyme replacement therapy (PERT) is the only treatment for malabsorption in cystic fibrosis (CF) caused by pancreatic insufficiency (PI). PI occurs in approximately 85% of patients with CF. PERT overcomes some, but not all the signs and symptoms of malabsorption. Clinical parameters such as growth, abdominal pain, diarrhea and gassiness, commonly used to adjust PERT dosing, are shown not to be good indicators of their effectiveness. The FDA does not provide oversight of preparations ...[more]
Similar Datasets
Project description:To test the hypothesis that multiple constituents of the apical plasma membrane residing alongside the causal cystic fibrosis (CF) transmembrane conductance regulator protein, including known CF modifiers SLC26A9, SLC6A14, and SLC9A3, would be associated with prenatal exocrine pancreatic damage as measured by newborn screened (NBS) immunoreactive trypsinogen (IRT) levels.NBS IRT measures and genome-wide genotype data were available on 111 subjects from Colorado, 37 subjects from Wisconsin, and 80 subjects from France. Multiple linear regression was used to determine whether any of 8 single nucleotide polymorphisms (SNPs) in SLC26A9, SLC6A14, and SLC9A3 were associated with IRT and whether other constituents of the apical plasma membrane contributed to IRT.In the Colorado sample, 3 SLC26A9 SNPs were associated with NBS IRT (min P=1.16×10(-3); rs7512462), but no SLC6A14 or SLC9A3 SNPs were associated (P>.05). The rs7512462 association replicated in the Wisconsin sample (P=.03) but not in the French sample (P=.76). Furthermore, rs7512462 was the top-ranked apical membrane constituent in the combined Colorado and Wisconsin sample.NBS IRT is a biomarker of prenatal exocrine pancreatic disease in patients with CF, and a SNP in SLC26A9 accounts for significant IRT variability. This work suggests SLC26A9 as a potential therapeutic target to ameliorate exocrine pancreatic disease.
| S-EPMC4530786 | biostudies-literature
Project description:Unexpectedly high serum B12 concentrations were noted in most study subjects with cystic fibrosis (CF) and pancreatic insufficiency (PI) participating in a nutrition intervention at the baseline evaluation. The objectives of this study were to determine dietary, supplement-based, and enzyme-based B12 intake, serum B12 concentrations, and predictors of vitamin B12 status in children with CF and PI.Serum B12 status was assessed in subjects (5-18 years) and categorized as elevated (serum B12 above reference range for age and sex [Hi-B12]) or within reference range (serum B12 within reference range for age and sex) for age and sex. Serum homocysteine, plasma B6, red blood cell folate, height, weight, and body mass index z scores, pulmonary function, energy, and dietary and supplement-based vitamin intake were assessed.A total of 106 subjects, mean age 10.4?±?3.0 years, participated in the study. Median serum B12 was 1083?pg/mL, with 56% in the Hi-B12 group. Dietary and supplement-based B12 intakes were both high representing 376% and 667% recommended dietary allowance (RDA), respectively. The Hi-B12 group had significantly greater supplement-based B12 intake than the serum B12 within reference range for age and sex group (1000% vs 583% RDA, P?<?0.001). Multiple logistic regression analysis showed that high supplement-based B12 intake and age >12 years increased the risk of Hi-B12, whereas higher forced expiratory volume at 1 second (FEV1) decreased the risk (pseudo-R?=?0.18, P?<?0.001).Serum B12 was elevated in the majority of children with CF and PI. Supplement-based B12 intake was 6 to 10 times the RDA, and strongly predicted elevated serum B12 status. The health consequences of lifelong high supplement-based B12 intake and high serum B12 are unknown and require further study, as does the inversed correlation between serum B12 and forced expiratory volume at 1 second.
| S-EPMC4214079 | biostudies-literature
Project description:BACKGROUND: The biological function of the Reg protein, a non-enzymic protein produced in fairly large amounts by pancreatic acinar cells, remains elusive. Its susceptibility to proteolysis leading to precipitation of the proteolysis product at neutral pH suggests that it could contribute to the protein plugging observed in cystic fibrosis (CF). AIMS: To study its behaviour in the serum of CF patients with or without pancreatic insufficiency and to compare it with that of other pancreatic secretory proteins. PATIENTS: 170 patients (93 with CF, 55 controls, and 22 with chronic pancreatitis) were studied. METHODS: Reg protein was measured using a specific enzyme immunoassay and its molecular form in CF sera was characterised by gel filtration. Molecular gene expression was investigated by dot-blot hybridisation. RESULTS: Reg protein was present in all CF sera studied from patients with or without pancreatic insufficiency, and in all cases the level was significantly higher than in controls. Its chromatographic behaviour in CF sera was identical with that of the protein present in normal serum. No correlation was found between the levels of Reg protein and trypsin(ogen) (or lipase) in CF, nor in control sera or normal pancreatic juice. Molecular gene expression of the corresponding proteins investigated in pancreatic tissues showed an absence of correlation between the mRNA levels. CONCLUSIONS: Reg protein may not be a secretory exocrine protein like the digestive enzymes but rather a hormone-like secretory substance with an endocrine or paracrine function.
| S-EPMC1727456 | biostudies-other
Project description:OBJECTIVES:The aim of the study was to assess the impact of LYM-X-SORB (LXS), an organized lipid matrix that has been shown to be absorbable without pancreatic enzyme therapy on fat-soluble vitamin status in children with cystic fibrosis (CF) and pancreatic insufficiency (PI). METHODS:Children with CF and PI were randomized to daily LXS or an isocaloric placebo comparison supplement for 12 months. Serum vitamins A (retinol), D (25-hydroxyvitamin D[25D]), E (?-tocopherol, ?-tocopherol:cholesterol ratio), and K (percentage of undercarboxylated osteocalcin [%ucOC] and plasma proteins induced by vitamin K absence factor II [PIVKA II]) were assessed at baseline and 12 months. Dietary intake was determined using 3-day weighed food records and supplemental vitamin intake by a comprehensive questionnaire. RESULTS:A total of 58 subjects (32 boys, age 10.3 ± 2.9 years [mean ± standard deviation]) with complete serum vitamin, dietary and supplemental vitamin data were analyzed. After adjusting for dietary and supplemental vitamin intake, serum retinol increased 3.0 ± 1.4 ?g/dL (coefficient ± standard error) (adjusted R2 = 0.02, P = 0.03) and vitamin K status improved as demonstrated by a decreased percentage of undercarboxylated osteocalcin of -6.0% ± 1.6% by 12 months (adjusted R2 = 0.15, P < 0.001). These changes occurred in both the LXS and placebo comparison groups. No changes in serum 25D or ?-tocopherol were detected. Both nutrition interventions increased caloric intake a mean of 83 ± 666 kcal/day by 12 months. CONCLUSIONS:Vitamins A and K status improved, whereas vitamins D and E status was unchanged during 12 months of LXS and isocaloric placebo comparison supplement in children with CF and PI.
| S-EPMC4212898 | biostudies-literature
Project description:Restitution of normal fat absorption in exocrine pancreatic insufficiency remains an elusive goal. Although many patients achieve satisfactory clinical results with enzyme therapy, few experience normalization of fat absorption, and many, if not most, will require individualized therapy. Increasing the quantity of lipase administered rarely eliminates steatorrhea but increases the cost of therapy. Enteric coated enzyme microbead formulations tend to separate from nutrients in the stomach precluding coordinated emptying of enzymes and nutrients. Unprotected enzymes mix well and empty with nutrients but are inactivated at pH 4 or below. We describe approaches for improving the results of enzyme therapy including changing to, or adding, a different product, adding non-enteric coated enzymes, (e.g., giving unprotected enzymes at the start of the meal and acid-protected formulations later), use of antisecretory drugs and/or antacids, and changing the timing of enzyme administration. Because considerable lipid is emptied in the first postprandial hour, it is prudent to start therapy with enteric coated microbead prior to the meal so that some enzymes are available during that first hour. Patients with hyperacidity may benefit from adjuvant antisecretory therapy to reduce the duodenal acid load and possibly also sodium bicarbonate to prevent duodenal acidity. Comparative studies of clinical effectiveness of different formulations as well as the characteristics of dispersion, emptying, and dissolution of enteric-coated microspheres of different diameter and density are needed; many such studies have been completed but not yet made public. We discuss the history of pancreatic enzyme therapy and describe current use of modern preparations, approaches to overcoming unsatisfactory clinical responses, as well as studies needed to be able to provide reliably effective therapy.
| S-EPMC4155341 | biostudies-literature
Project description:The black-pigmented fungus Exophiala dermatitidis is considered to be a harmless colonizer of the airways of cystic fibrosis (CF) patients. The aim of this study was to establish the recovery rate of E. dermatitidis in respiratory specimens from CF patients, transplant recipients, and subjects with other respiratory disorders in Sweden. Second, we wished to determine if particular clinical traits were associated with E. dermatitidis colonization of the airways and the antifungal susceptibility profiles of Exophiala strains. Sputum and bronchoalveolar lavage samples (n = 492) derived from 275 patients were investigated. E. dermatitidis was isolated in respiratory specimens from 19% (18/97) of the CF patients but in none of the other patient categories. All isolates were recovered after 6 to 25 days of incubation on erythritol-chloramphenicol agar (ECA) medium. Morphological and genetic analyses confirmed species identity. Pancreatic insufficiency was positively associated with the presence of E. dermatitidis in sputum samples (P = 0.0198). Antifungal susceptibility tests demonstrated that voriconazole and posaconazole had the lowest MICs against E. dermatitidis. In conclusion, E. dermatitidis is a frequent colonizer of the respiratory tract in CF patients in Sweden and appears to be associated with more advanced disease. Whether E. dermatitidis is pathogenic remains to be elucidated.
| S-EPMC3067733 | biostudies-literature
Project description:European evidence-based guidelines for the treatment and management of chronic pancreatitis (CP) have been made available following the harmonizing diagnosis and treatment of CP across Europe (HaPanEU) initiative by the United European Gastroenterology (UEG). The aim of this study was to evaluate adherence to the guideline recommendations in the management of patients with pancreatic exocrine insufficiency (PEI) at Karolinska University Hospital in Stockholm. UEG guideline recommendations were evaluated and categorized into 55 different quality indicators (QIs). Data from a retrospective cohort of CP patients being treated at Karolinska University Hospital were evaluated with regard to overall adherence as well as adherence to specific QIs. A total number of 118 patients out of 956 patients diagnosed with CP were eligible for inclusion with mean overall adherence of 61.9% to the defined QIs. A significant difference in mean overall adherence was shown between patients diagnosed with CP prior to 1 January 2016 and following 1 January 2016 (59.3% and 67.7% respectively, p = 0.004), with linear regression analysis also demonstrating improvement correlating to date of diagnosis (p = 0.002). In conclusion, diagnosis and treatment of PEI improved after the HaPanEU guidelines became available and is continuously improving; however, there is room for further improvement.
| S-EPMC8233716 | biostudies-literature
Project description:E2F transcription factors are thought to be key regulators of cell growth control. Here we use mutant mouse strains to investigate the function of E2F1 and E2F2 in vivo. E2F1/E2F2 compound-mutant mice develop nonautoimmune insulin-deficient diabetes and exocrine pancreatic dysfunction characterized by endocrine and exocrine cell dysplasia, a reduction in the number and size of acini and islets, and their replacement by ductal structures and adipose tissue. Mutant pancreatic cells exhibit increased rates of DNA replication but also of apoptosis, resulting in severe pancreatic atrophy. The expression of genes involved in DNA replication and cell cycle control was upregulated in the E2F1/E2F2 compound-mutant pancreas, suggesting that their expression is repressed by E2F1/E2F2 activities and that the inappropriate cell cycle found in the mutant pancreas is likely the result of the deregulated expression of these genes. Interestingly, the expression of ductal cell and adipocyte differentiation marker genes was also upregulated, whereas expression of pancreatic cell marker genes were downregulated. These results suggest that E2F1/E2F2 activity negatively controls growth of mature pancreatic cells and is necessary for the maintenance of differentiated pancreatic phenotypes in the adult.
| S-EPMC406522 | biostudies-literature
Project description:Background/objectivesThe epidemiology of exocrine pancreatic insufficiency (EPI) after acute pancreatitis (AP) is uncertain. We sought to determine the prevalence, progression, etiology and pancreatic enzyme replacement therapy (PERT) requirements for EPI during follow-up of AP by systematic review and meta-analysis.MethodsScopus, Medline and Embase were searched for prospective observational studies or randomized clinical trials (RCTs) of PERT reporting EPI during the first admission (between the start of oral refeeding and before discharge) or follow-up (≥ 1 month of discharge) for AP in adults. EPI was diagnosed by direct and/or indirect laboratory exocrine pancreatic function tests.ResultsQuantitative data were analyzed from 370 patients studied during admission (10 studies) and 1795 patients during follow-up (39 studies). The pooled prevalence of EPI during admission was 62% (95% confidence interval: 39-82%), decreasing significantly during follow-up to 35% (27-43%; risk difference: - 0.34, - 0.53 to - 0.14). There was a two-fold increase in the prevalence of EPI with severe compared with mild AP, and it was higher in patients with pancreatic necrosis and those with an alcohol etiology. The prevalence decreased during recovery, but persisted in a third of patients. There was no statistically significant difference between EPI and new-onset pre-diabetes/diabetes (risk difference: 0.8, 0.7-1.1, P = 0.33) in studies reporting both. Sensitivity analysis showed fecal elastase-1 assay detected significantly fewer patients with EPI than other tests.ConclusionsThe prevalence of EPI during admission and follow-up is substantial in patients with a first attack of AP. Unanswered questions remain about the way this is managed, and further RCTs are indicated.
| S-EPMC6584228 | biostudies-literature
Project description:Background: Malnutrition and cachexia are common in patients with advanced pancreatic ductal adenocarcinoma (PDAC) and have a significant influence on the tolerance and response to treatments. If timely identified, malnourished PDAC patients could be treated to increase their capacity to complete the planned treatments and, therefore, possibly, improve their efficacy. Aims: The aim of this study is to assess the impact of nutritional status, pancreatic exocrine insufficiency (PEI), and other clinical factors on patient outcomes in patients with advanced PDAC. Methods: PAncreatic Cancer MAlnutrition and Pancreatic Exocrine INsufficiency in the Course of Chemotherapy in Unresectable Pancreatic Cancer (PAC-MAIN) is an international multicenter prospective observational cohort study. The nutritional status will be determined by means of Mini-Nutritional Assessment score and laboratory blood tests. PEI will be defined by reduced fecal elastase levels.Main outcomeadherence to planned chemotherapy in the first 12 weeks following the diagnosis, according to patients' baseline nutritional status and quantified and reported as "percent of standard chemotherapy dose delivered."Secondary outcomesrate of chemotherapy-related toxicity, progression-free survival, survival at 6 months, overall survival, quality of life, and the number of hospitalizations.Analysischemotherapy dosing over the first 12 weeks of therapy (i.e., percent of chemotherapy received in the first 12 weeks, as defined above) will be compared between well-nourished and malnourished patients.Sample sizebased on an expected percentage of chemotherapy delivered of 70% in well-nourished patients, with a type I error of 0.05 and a type II error of 0.20, a sample size of 93 patients per group will be required in case of a percentage difference of chemotherapy delivered of 20% between well-nourished and malnourished patients, 163 patients per group in case of a difference of 15% between the groups, and 356 patients per group in case of a 10% difference. Centers from Russia, Romania, Turkey, Spain, Serbia, and Italy will participate in the study upon Local Ethics Committee approval. Discussion: PAC-MAIN will provide insights into the role of malnutrition and PEI in the outcomes of PDAC. The study protocol was registered at clinicaltrials.gov as NCT04112836.
| S-EPMC7509408 | biostudies-literature