Treatment of Infants and Toddlers With Cystic Fibrosis–related Pancreatic Insufficiency and Fat Malabsorption With Pancrelipase MT

2011 ◽  
Vol 53 (1) ◽  
pp. 61-64 ◽  
Author(s):  
Els Van de Vijver ◽  
Kristine Desager ◽  
Andrew E Mulberg ◽  
Sofie Staelens ◽  
Henkjan J Verkade ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pancreatic Insufficiency ◽  
Infants And Toddlers ◽  
Fat Malabsorption

CFTR knockdown stimulates lipid synthesis and transport in intestinal Caco-2/15 cells

2009 ◽  
Vol 297 (6) ◽  
pp. G1239-G1249 ◽  
Author(s):  
Geneviève Mailhot ◽  
Zaava Ravid ◽  
Soraya Barchi ◽  
Alain Moreau ◽  
Rémi Rabasa-Lhoret ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pancreatic Insufficiency ◽  
Scavenger Receptor ◽  
Lipid Synthesis ◽  
Cftr Gene ◽  
Nutritional Deficiencies ◽  
Type I ◽  
Protein Activity ◽  
Fat Malabsorption ◽  
The Impact

Cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel highly expressed in epithelial cells of the gastrointestinal tract. Mutations in the CFTR gene cause cystic fibrosis (CF), a disease characterized by pancreatic insufficiency, fat malabsorption, and steatorrhea. Despite the administration of pancreatic enzymes to normalize malabsorption, CF patients still experienced lipid fecal loss, nutritional deficiencies, and abnormalities in serum lipid profile, suggesting the presence of intrinsic defects in the intestinal handling of nutrients. The objective of the present study was to assess the impact of CFTR gene knockdown on intracellular lipid metabolism of the intestinal Caco-2/15 cell line. Partial CFTR gene inactivation led to cellular lipid accretion of phospholipids, triglycerides, and cholesteryl esters. Likewise, secretion of these lipid fractions was significantly increased following CFTR gene manipulation. As expected from these findings, the output of triglyceride-rich lipoproteins showed the same increasing pattern. Investigation of the mechanisms underlying these changes revealed that CFTR knockdown resulted in raised levels of apolipoproteins in cells and media and microsomal transfer protein activity, two important factors for the efficient assembly and secretion of lipoproteins. Similarly, scrutiny of the enzymatic monoacylglycerol acyltransferase and diacylglycerol acyltransferase, which exhibit dynamic function in triacylglycerol resynthesis and chylomicron formation in enterocytes, revealed a significant augmentation in their activity. Conversely, cholesterol uptake mediated by Niemann-Pick C1 like 1, Scavenger Receptor Class B Type I, and ATP-binding cassette G8 remains unaffected by genetic modification of CFTR. Collectively, these results highlight the role played by CFTR in intestinal handling of lipids and may suggest that factors other than defective CFTR are responsible for the abnormal intracellular events leading to fat malabsorption in CF patients.

scholarly journals Benefits of LYM-X-SORB, a Highly Absorbed Structured Lipid Compound, in Children with Cystic Fibrosis and Pancreatic Insufficiency with Varying Degrees of Malabsorption (P08-125-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Virginia Stallings ◽  
Asim Maqbool ◽  
Maria Mascarenhas ◽  
Joan Schall
Keyword(s):  
Cystic Fibrosis ◽  
Nutritional Status ◽  
Linolenic Acid ◽  
Pancreatic Insufficiency ◽  
Structured Lipid ◽  
Dramatic Improvement ◽  
Double Blind ◽  
Growth Status ◽  
Z Scores ◽  
Fat Malabsorption

Abstract Objectives The treatment of fat malabsorption and optimizing growth and nutritional status in patients with cystic fibrosis (CF) and pancreatic insufficiency (PI) is a challenge. A readily absorbable structured lipid (LYM-X-SORB™ [LXS]) improved fat absorption, growth, choline and essential fatty acid (EFA) status in children with CF and PI. Our objective in this secondary analysis is to determine if subjects with varying degrees of fat malabsorption show greater improvements with 3-month LXS treatment. Methods Subjects with CF and PI (5–17yrs) participated in a 12-month double-blind randomized placebo-controlled LXS trial with a 3-month interim visit. LXS and placebo had similar calorie (303 or 456 kcal/d) and fat content (11 or 18 g/d), and LXS had 7-fold greater choline; dose depended on age. CFA was assessed with 72-hour stool and 3-day weighed food records. Height, weight and BMI Z-scores were calculated. Plasma linoleic and α-linolenic acid were assessed. Secondary analyses were restricted to children with baseline CFA who completed 3-month treatment (n = 66, 10.5 ± 3.0 yrs, 40% female). Subjects were divided into two groups at baseline: those with lower CFA (≤87.8%, median) and higher CFA (above median). Results In those with lower baseline CFA, 3-month LXS treatment improved CFA significantly (8.7%, from 77.4 to 86.0%, P < 0.01), with a significant drop in stool fat loss (−6.6 g/24 hours) and no change in dietary fat intake. This was accompanied by significantly increased (P < 0.01) linoleic acid (434 nmol/L, 19% increase) and α-linolenic acid (25 nmol/L, 53% increase). Both weight and BMI Z scores increased ≥0.16 (P < 0.01). With placebo treatment, CFA did not change (72.5 to 71.1%), nor did EFA status, and growth status improved less (≤0.14, P < 0.05). For subjects with higher CFA at baseline, CFA did not change (92.1 to 90.1%) with either treatment, although EFA and growth status improved somewhat, with greater improvement evident in the LXS group. Conclusions Subjects with CF and PI at higher risk for fat malabsorption had a dramatic improvement in CFA with LXS treatment, accompanied by improved EFA and growth status. This suggests that LXS may help those with CF and other pancreatic diagnoses in need of optimizing nutritional status and avoiding unintentional weight loss. Funding Sources Supported by NIH.

scholarly journals CFTR Modulator Therapy with Lumacaftor/Ivacaftor Alters Plasma Concentrations of Lipid-Soluble Vitamins A and E in Patients with Cystic Fibrosis

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 483
Author(s):  
Olaf Sommerburg ◽  
Susanne Hämmerling ◽  
S. Philipp Schneider ◽  
Jürgen Okun ◽  
Claus-Dieter Langhans ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Vitamin E ◽  
Vitamin A ◽  
Clinical Chemistry ◽  
Pancreatic Insufficiency ◽  
Plasma Concentrations ◽  
Plasma Vitamin ◽  
Hypervitaminosis A ◽  
Cholesterol Ratio ◽  
Fat Soluble Vitamins

Rationale: Cystic fibrosis (CF), caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, leads to impaired pancreatic function and therefore reduced intestinal absorption of lipids and fat-soluble vitamins especially in patients with CF developing pancreatic insufficiency (PI). Previous studies showed that CFTR modulator therapy with lumacaftor-ivacaftor (LUM/IVA) in Phe508del-homozygous patients with CF results in improvement of pulmonary disease and thriving. However, the effects of LUM/IVA on plasma concentration of the lipid soluble vitamins A and E remain unknown. Objectives: To investigate the course of plasma vitamin A and E in patients with CF under LUM/IVA therapy. Methods: Data from annual follow-up examinations of patients with CF were obtained to assess clinical outcomes including pulmonary function status, body mass index (BMI), and clinical chemistry as well as fat-soluble vitamins in Phe508del-homozygous CF patients before initiation and during LUM/IVA therapy. Results: Patients with CF receiving LUM/IVA improved substantially, including improvement in pulmonary inflammation, associated with a decrease in blood immunoglobulin G (IgG) from 9.4 to 8.2 g/L after two years (p < 0.001). During the same time, plasma vitamin A increased significantly from 1.2 to 1.6 µmol/L (p < 0.05), however, levels above the upper limit of normal were not detected in any of the patients. In contrast, plasma vitamin E as vitamin E/cholesterol ratio decreased moderately over the same time from 6.2 to 5.5 µmol/L (p < 0.01). Conclusions: CFTR modulator therapy with LUM/IVA alters concentrations of vitamins A and vitamin E in plasma. The increase of vitamin A must be monitored critically to avoid hypervitaminosis A in patients with CF.

scholarly journals 2 The syndrome of exocrine pancreatic insufficiency – cystic fibrosis or other disease?

2012 ◽  
Vol 11 ◽  
pp. S55
Author(s):  
A. Sobczynska-Tomaszewska ◽  
K. Czerska ◽  
A. Szpecht-Potocka ◽  
D. Popielarz ◽  
K. Wertheim-Tysarowska ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pancreatic Insufficiency ◽  
Exocrine Pancreatic Insufficiency

scholarly journals Inhaled hypertonic saline in infants and toddlers with cystic fibrosis: short-term tolerability, adherence, and safety

2011 ◽  
Vol 46 (7) ◽  
pp. 666-671 ◽  
Author(s):  
Margaret Rosenfeld ◽  
Stephanie Davis ◽  
Lyndia Brumback ◽  
Stephen Daniel ◽  
Ron Rowbotham ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Hypertonic Saline ◽  
Infants And Toddlers ◽  
Short Term ◽  
Term Tolerability

scholarly journals The Multifaceted Roles of MicroRNAs in Cystic Fibrosis

Diagnostics ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1102
Author(s):  
Fatima Domenica Elisa De Palma ◽  
Valeria Raia ◽  
Guido Kroemer ◽  
Maria Chiara Maiuri
Keyword(s):  
Cystic Fibrosis ◽  
Respiratory Infections ◽  
Current Knowledge ◽  
Pancreatic Insufficiency ◽  
Clinical Manifestations ◽  
Predictive Biomarkers ◽  
Loss Of Function ◽  
Gene Encoding ◽  
Multisystemic Disease

Cystic fibrosis (CF) is a lifelong disorder affecting 1 in 3500 live births worldwide. It is a monogenetic autosomal recessive disease caused by loss-of-function mutations in the gene encoding the chloride channel cystic fibrosis transmembrane conductance regulator (CFTR), the impairment of which leads to ionic disequilibria in exocrine organs. This translates into a chronic multisystemic disease characterized by airway obstruction, respiratory infections, and pancreatic insufficiency as well as hepatobiliary and gastrointestinal dysfunction. Molecular characterization of the mutational heterogeneity of CFTR (affected by more than 2000 variants) improved the understanding and management of CF. However, these CFTR variants are linked to different clinical manifestations and phenotypes, and they affect response to treatments. Expanding evidence suggests that multisystemic disease affects CF pathology via impairing either CFTR or proteins regulated by CFTR. Thus, altering the expression of miRNAs in vivo could constitute an appealing strategy for developing new CF therapies. In this review, we will first describe the pathophysiology and clinical management of CF. Then, we will summarize the current knowledge on altered miRNAs in CF patients, with a focus on the miRNAs involved in the deregulation of CFTR and in the modulation of inflammation. We will highlight recent findings on the potential utility of measuring circulating miRNAs in CF as diagnostic, prognostic, and predictive biomarkers. Finally, we will provide an overview on potential miRNA-based therapeutic approaches.

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