共查询到20条相似文献，搜索用时 15 毫秒
1.
Christine L. Chan Timothy Vigers Laura Pyle Philip S. Zeitler Scott D. Sagel Kristen J. Nadeau 《Journal of cystic fibrosis》2018,17(6):783-790
Background
To characterize glucose patterns with continuous glucose monitoring (CGM) in cystic fibrosis (CF) and assess relationships between CGM and clinical outcomes.Methods
110 CF youth and healthy controls (HC), 10–18?years, wore CGM up to 7?days. Correlations between CGM and lung function and BMI z-score change over the prior year were determined.Results
Multiple CGM measures were higher in CF Normal Glycemic (CFNG) youth versus HC (peak glucose, excursions >140?mg/dl/day, %time?>?140?mg/dl, standard deviation (SD) and mean amplitude of glycemic excursions (MAGE)). Hypoglycemia was no different among groups. In CF, decline in FEV1% and FVC% correlated with maximum CGM glucose, excursions >200?mg/dl/day, SD, and MAGE.Conclusions
CFNG youth have higher glucoses and glucose variability than HC on CGM. Higher and more variable glucoses correlate with lung function decline. Whether earlier treatment of CGM abnormalities improves lung function in CF requires further study. 相似文献2.
Rossa Brugha Marie Wright Suzie Nolan Nicola Bridges Siobhán B. Carr 《Journal of cystic fibrosis》2018,17(6):791-797
Background
Cystic fibrosis related diabetes (CFRD) is associated with increased morbidity in CF. Variability in physiological systems is associated with dysfunctional homeostasis. We examined whether fluctuation in glucose is a marker of CFRD or “pre-diabetes”.Methods
Using a machine learning approach, we compared glucose IQR to current diagnostic criteria in a review of continuous glucose monitoring data.Results
Analysis was performed on 248 studies from 142 children. Calculated IQR (cIQR) was increased between children with CFRD, normal glucose homeostasis and indeterminate status (p < 0.0001) and impaired glucose tolerance (p < 0.05, Kruskal–Wallis test). In subjects who developed CFRD (n = 20), cIQR increased between baseline and diagnosis (1.4 mmol/L versus 2.4 mmol/L, p < 0.0001, Wilcoxon test). Area under the curve for CFRD on the basis of cIQR was 0.865 (p < 0.0001). Neither episodes of hypoglycaemia nor cIQR at baseline predicted CFRD.Conclusions
Glucose fluctuation on CGMS can be quantified by calculating the IQR. This information may improve early recognition of abnormal glucose homeostasis. 相似文献3.
Natasha Armaghanian Tania P. Markovic Jennie C. Brand-Miller Peter T.P. Bye Carmel P. Moriarty Kate S. Steinbeck 《Journal of cystic fibrosis》2018,17(4):542-547
Background
Hypoglycaemia in cystic fibrosis (CF) is known to occur during oral glucose tolerance tests (OGTT) and continuous glucose monitoring, however demographic, clinical and mechanistic data are limited. The aims of this study were to review patient electronic medical records (EMR) in order to 1) describe patient characteristics of a university teaching hospital CF clinic, 2) determine the prevalence of hypoglycaemia on OGTT and explore associations with demographic and clinical characteristics, and 3) explore patient reported symptoms suggestive of hypoglycaemia documented in the EMR.Methods
Adults who attended the RPA CF clinic between January 2009 to April 2016 were included in the study. The prevalence of hypoglycaemia on OGTT was determined and clinical and demographic data were compared to age, sex and glucose tolerance matched controls. Reported symptoms suggestive of hypoglycaemia documented in EMR were qualitatively explored.Results
Hypoglycaemia on OGTT was prevalent in 25 (3 fasting and 22 reactive) of 169 patients who had an OGTT. They were heavier, less likely to have pancreatic insufficiency and had a lower insulin response at 2-h. Another 14 patients reported symptoms suggestive of hypoglycaemia in their EMR. No patient appropriately suppressed insulin at 2-h on OGTT.Conclusions
This study identified two potentially different presentations of hypoglycaemia occur in different clinic sub-populations. Knowledge gaps in the aetiology and triggers of hypoglycaemia remain. 相似文献4.
Background
Cystic fibrosis (CF, mucoviscidosis) is caused by mutations in the gene encoding CF transmembrane conductance regulator (CFTR), which is a chloride and bicarbonate channel necessary for fluid secretion and extracellular alkalization. For a long time, research concentrated on abnormal Cl- and Na+ transport, but neglected bicarbonate as a crucial factor in CF.Methods
The present short review reports early findings as well as recent insights into the role of CFTR for bicarbonate transport and its defects in CF.Results
The available data indicate impaired bicarbonate transport not only in pancreas, intestine, airways, and reproductive organs, but also in salivary glands, sweat duct and renal tubular epithelial cells. Defective bicarbonate transport is closely related to the impaired mucus properties and mucus blocking in secretory organs of CF patients, causing the life threatening lung disease.Conclusions
Apart from the devastating lung disease, abrogated bicarbonate transport also leads to many other organ dysfunctions, which are outlined in the present review. 相似文献5.
Jennifer Guimbellot George M. Solomon Arthur Baines Sonya L. Heltshe Jill VanDalfsen Elizabeth Joseloff Scott D. Sagel Steven M. Rowe 《Journal of cystic fibrosis》2019,18(1):102-109
Background
The cystic fibrosis transmembrane conductance regulator (CFTR) potentiator ivacaftor is approved for patients with CF with gating and residual function CFTR mutations. We report the results of an observational study investigating its effects in CF patients with non-G551D gating mutations.Methods
Patients with non-G551D gating mutations were recruited to an open-label study evaluating ivacaftor. Primary outcomes included: lung function, sweat chloride, weight gain, and quality of life scores.Results
Twenty-one subjects were enrolled and completed 6?months follow-up on ivacaftor; mean age was 25.6?years with 52% <18. Baseline ppFEV1 was 68% and mean sweat chloride 89.6?mEq/L. Participants experienced significant improvements in ppFEV1 (mean absolute increase of 10.9% 95% CI?=?[2.6,19.3], p?=?0.0134), sweat chloride (?48.6 95% CI?=?[?67.4,-29.9], p?<?0.0001), and weight (5.1?kg, 95% CI?=?[2.8, 7.3], p?=?0.0002).Conclusions
Patients with non-G551D gating mutations experienced improved lung function, nutritional status, and quality of life. This study supports ongoing use of ivacaftor for patients with these mutations. 相似文献6.
Jan C. Thomassen Matthias I. Mueller Miguel A. Alejandre Alcazar Ernst Rietschel Silke van Koningsbruggen-Rietschel 《Journal of cystic fibrosis》2018,17(2):271-275
Objective
To investigate the effect of Lumacaftor/Ivacaftor on glucose metabolism and insulin secretion in patients with cystic fibrosis (CF) (Phe508del/Phe508del).Methods
A standard oral glucose tolerance test (OGTT) and an intravenous glucose tolerance test (IVGTT) were performed to investigate glucose metabolism and insulin secretion before and after 6–8 weeks of treatment with Lumacaftor/Ivacaftor in 5 Phe508del-homozygous CF patients. The area under the curve (AUC) for glucose and insulin levels was calculated using the trapezoidal approximation.Results
5 participants were investigated. Treatment with Lumacaftor/Ivacaftor was followed by an improvement of the 2 h glucose levels in 3 patients and worsening in 2 patients. Analysis of the time course of blood glucose levels during OGTT revealed an increase of the AUC in 3 of 5 patients. In response to IVGTT, acute insulin secretion improved in 2 patients and worsened in 3.Conclusion
The investigation could not demonstrate that treatment with Lumacaftor/Ivacaftor had a consistent impact on glucose tolerance and insulin secretion. Further adequately-powered studies examining glucose metabolism are needed to properly evaluate drug response in the endocrine pancreas and to test whether this treatment could eventually prevent the development of cystic fibrosis-related diabetes (CFRD). 相似文献7.
Lisa A. Mannik Kristy A. Chang Pascalyn Q.K. Annoh Jenna Sykes Julie Gilmour Ronalee Robert Anne L. Stephenson 《Journal of cystic fibrosis》2018,17(4):536-541
Background
Hypoglycemia in cystic fibrosis (CF) patients during the oral glucose tolerance test (OGTT) has been reported; however, these patients have not been well-characterized. Few studies have examined whether hypoglycemia during the OGTT increases the risk of developing CF-related diabetes (CFRD). Objectives of this study were to describe the characteristics of CF patients with hypoglycemia during the OGTT and to determine the incidence and time to development of CFRD in those with hypoglycemia.Methods
This cohort study included 466 adults with CF at the Toronto Adult CF Clinic between 1996 and 2015. Subjects were classified into two groups based on their plasma glucose (PG) level 2?h after a 75?g OGTT: hypoglycemia (PG?≤?3.9?mmol/L) or no hypoglycemia (PG?>?3.9?mmol/L). Clinical and demographic data were collected from the clinic visit closest to the OGTT. Differences between groups were assessed using Fisher's exact test or Mann-Whitney-Wilcoxon test.Results
138 patients (29.6%) experienced hypoglycemia during the OGTT. More males experienced hypoglycemia compared to no hypoglycemia (69.6% vs. 54.6% respectively; p?=?0.003). Those who were heterozygous deltaF508 were more likely to experience hypoglycemia (p?=?0.006). Subjects who experienced hypoglycemia were less likely to develop CFRD at ten years compared to no hypoglycemia (12.0% vs. 42.1%, respectively; p?<?0.001).Conclusions
Hypoglycemia following OGTT is common in CF however the 10?year risk of developing CFRD in these patients was low. Males and those who were heterozygous deltaF508 were at higher risk for hypoglycemia. 相似文献8.
C. Lehoux Dubois V. Boudreau F. Tremblay A. Lavoie Y. Berthiaume R. Rabasa-Lhoret A. Coriati 《Journal of cystic fibrosis》2017,16(3):418-424
Background
Diabetes is common in cystic fibrosis (CF). Glucose can be detected in the airway when the blood glucose is elevated, which favours bacterial growth. We investigated the relationship between dysglycemia and lung pathogens in CF.Methods
Cross-sectional and prospective analysis of CF patients (N = 260) who underwent a 2 h-oral glucose tolerance test. Clinical data was collected.Results
Stenotrophomonas maltophilia (S. maltophilia) was the sole bacteria increased in dysglycemic (AGT: 20.2%, CFRD: 21.6%) patients compared to normotolerants (NGT: 8.7%). S. maltophilia positive patients with dysglycemia had more pulmonary exacerbation events compared to NGTs (1.22 vs 0.63, P = 0.003). The interaction between S. maltophilia colonisation and glucose tolerance status significantly increases the risk of lower lung function (P = 0.003). Its growth was not affected by the evolution of the glucose tolerance after three years follow-up.Conclusion
Prevalence of S. maltophilia was higher in dysglycemic patients, supporting the idea that S. maltophilia is a marker of disease severity in CF. 相似文献9.
Binyu Lu Li Li Molly Schneider Craig A. Hodges Calvin U. Cotton James D. Burgess Thomas J. Kelley 《Journal of cystic fibrosis》2019,18(2):175-181
Background
Previous studies have demonstrated that CF epithelial cells exhibit increased cholesterol content at the plasma membrane compared to wild type controls as measured by electrochemical methods. Microtubule dysregulation that impacts intracellular transport has also been identified in CF cells and is reversible with histone deacetylase 6 (HDAC6) inhibition, a regulator of tubulin acetylation. The hypothesis of this study is that increased membrane cholesterol content in CF cells is dependent on HDAC6 regulation.Methods
Electrochemical measurement of membrane cholesterol in mouse trachea and in primary human CF bronchial epithelial cells is used to monitor CFTR correction and manipulation of cholesterol processing by HDAC6 inhibition.Results
Data demonstrate that induction of Cftr expression in an inducible CF mouse model restores tubulin acetylation levels and normalizes membrane cholesterol content. To test the relationship between tubulin acetylation, membrane cholesterol levels were measured in a CF mouse model depleted of Hdac6 expression (CF/HDA). CF/HDA mouse trachea have WT membrane cholesterol levels while CF mice have approximately two-fold increase in membrane cholesterol compared to WT consistent with previous studies. Pharmacological inhibition of HDAC6 in primary human CF bronchial epithelial cells also reduces membrane cholesterol levels.Conclusions
This study demonstrates that elevated membrane cholesterol in CF epithelium is regulated by HDAC6 function and that the electrochemical measure of membrane cholesterol correlates with both genetic and pharmacological CFTR correction. 相似文献10.
11.
Samuel Jessula Michiel Van Den Hof Dimas Mateos-Corral Jessica Mills Dafydd Davies Rodrigo LP Romao 《Journal of pediatric surgery》2018,53(11):2150-2154
Background/Purpose
To identify prenatal and perinatal predictors of surgery and describe surgical findings/outcomes of neonates with Meconium Ileus (MI) secondary to Cystic Fibrosis (CF).Methods
Potential risk factors (prenatal bowel echogenicity, CF genotype, birthweight, prematurity and sex) for MI and surgery were examined in a retrospective cohort of neonates with CF presenting to a tertiary center between 1997 and 2015. Following univariable analysis, predictors of MI and surgery were determined using multivariable logistic regression. For surgical patients, detailed operative findings and outcomes were examined.Results
MI was diagnosed in 26/120 (21.7%) neonates with CF and 19/26 (73.0%) required surgery. Prematurity was significantly associated with increased risk of MI and operative intervention (p-value 0.022 and p-value 0.016 respectively); lower birthweight was associated with operative intervention (p-value 0.039); genotype and echogenic bowel were associated with neither. Surgical data were available for 17/19 patients; median age at surgery was 2?days (IQR1–3), 4/17 had an atresia and 6/17 received an ostomy. Median NICU and hospital stays were 34.5 and 70?days while median time on TPN and time to ostomy reversal were 28.5 and 97?days, respectively.Conclusions
In patients with CF, prematurity and lower birthweight were identified as risk factors for meconium ileus and need for surgery. Specific genotypes and echogenic bowel were not predictors of either.Level of evidence
Level III. 相似文献12.
Tobias G.P. Engel Lydie Slabbers Carmen de Jong Willem J.G. Melchers Ferry Hagen Paul E. Verweij Peter Merkus Jacques F. Meis 《Journal of cystic fibrosis》2019,18(2):221-226
Background
Progressive lung injury in Cystic Fibrosis (CF) patients can lead to chronic colonization with bacteria and fungi. Fungal colonization is obtained from the environment which necessitates locally performed epidemiology studies. We prospectively analyzed respiratory samples of CF patients during a 3-year period, using a uniform fungal culture protocol, focusing on filamentous fungi and azole resistance in Aspergillus fumigatus.Methods
Over a 3-year period, all respiratory specimens collected from CF patients in 5 Dutch CF centers, were analyzed. Samples were inoculated onto the fungal culture media Sabouraud dextrose agar (SDA) and Medium B+. All fungal isolates were collected and identified in one centre, using Amplified Fragment Length Polymorphism (AFLP) fingerprinting, rDNA PCR and ITS, calmodulin and β-tubulin sequencing. Azole resistance was assessed for all A. fumigatus using a qPCR assay followed by phenotypic confirmation.Results
Filamentous fungi were recovered from 699 patients from at least one respiratory sample, corresponding with 3787 cultured fungal species. A. fumigatus was cultured most often with a mean prevalence of 31.7%, followed by Penicillium species (12.6%), non-fumigatus Aspergillus species (5.6%), Scedosporium species (4.5%) and Exophiala dermatitidis and Cladosporium species (1.1% each). In total 107 different fungal species were identified, with 39 Penicillium species and 15 Aspergillus species. Azole resistance frequency in A. fumigatus was 7.1%, with TR34/L98H being the dominant resistance mechanism.Conclusion
A vast diversity of filamentous fungi was demonstrated, dominated by Aspergillus and Penicillium species. We observed a mean azole resistance prevalence of 7.1% of A. fumigatus culture positive patients. 相似文献13.
Katherine Keenan Annie Dupuis Katherine Griffin Carlo Castellani Elizabeth Tullis Tanja Gonska 《Journal of cystic fibrosis》2019,18(2):265-270
Background
The “mild” gene variant, p.Arg117His in cystic fibrosis (CF) results in highly variable phenotypes ranging from male infertility to severe lung disease. Due to current interest to include this group in CFTR-targeted therapies, this study aims to describe the disease spectrum.Methods
Retrospective study of Toronto CF and CFTR-related p.Arg117His patients. Longitudinally captured clinical data were compared between patients with 5T/7T-variants and those with a CF or CFTR-related diagnosis. Comparison was made between p.Arg117His adults and infants identified through CF newborn screening (NBS).Results
Twenty of fifty patients carried the 5T variant, all with a diagnosis of CF (p.Arg117His-5TCF), and 30/50 carried 7T, 7 diagnosed with CF (p.Arg117His-7TCF) and 23 with a CFTR-related disorder (p.Arg117His-7TCFTR). For those with chest HRCT results available, 75% p.Arg117His-5TCF, 33% p.Arg117His-7TCF and 27% p.Arg117His-7TCFTR patients had bronchiectasis. Further, 79% p.Arg117His-5T, 29% p.Arg117His-7TCF and 13% p.Arg117His-7TCFTR had abnormal lung function. Of those, 80% grew CF-related pathogens on respiratory culture. Interestingly, the mean maximum sweat chloride and the percentage of patients growing CF-related bacterial pathogens were identical in p.Arg117His-7?TCFTR adults and p.Arg117His infants.Conclusions
Generally, p.Arg117His-5T patients had more severe CF disease. However, a subset of p.Arg117His-7?T patients demonstrated equally severe disease, thus warranting clinical monitoring of all p.Arg117His patients including p.Arg117His infants identified via NBS. 相似文献14.
Freddy Frost Paula Dyce Dilip Nazareth Victoria Malone Martin J. Walshaw 《Journal of cystic fibrosis》2018,17(6):798-803
Introduction
Continuous glucose monitoring (CGM) allows assessment of day to day glycaemic excursions and detects early glucose handling abnormalities that may not be apparent on oral glucose tolerance testing (OGTT). However, there is little published evidence as to whether these early dysglycaemic changes are amenable to treatment. We present outcomes following CGM guided insulin initiation at our centre.Methods
Adults without a prior diagnosis of cystic fibrosis related diabetes (CFRD) whom underwent >72?h CGM at our adult CF centre were included in the study. Clinical outcomes including weight and pulmonary function changes over the next 12?months were compared between groups based on CGM results and subsequent management.Results
CGM profiles for 59 patients were analysed. Insulin was commenced in 37 patients who had evidence of hyperglycaemia on CGM. Significant improvements in mean [95% confidence intervals] forced expiratory volume in 1?s (FEV1) (+4.3% predicted [1.06–7.48], p?=?0.01) and weight (+1.2?kg [0.32–2.15], p?=?0.01) were observed at 3?months in the insulin group. Annual rate of pulmonary function decline was also improved following insulin initiation.Conclusion
Insulin treatment targeted towards glycaemic excursions seen on CGM is associated with improvements in lung function and weight with subsequent reduced pulmonary function decline. 相似文献15.
Patrick A. Flume Claire E. Wainwright D. Elizabeth Tullis Sally Rodriguez Minoo Niknian Mark Higgins Jane C. Davies Jeffrey S. Wagener 《Journal of cystic fibrosis》2018,17(1):83-88
Background
Pulmonary exacerbations (PEx) are associated with acute loss of lung function that is often not recovered after treatment. We investigated lung function recovery following PEx for ivacaftor- and placebo-treated subjects.Methods
Short- and long-term pulmonary function recovery data after PEx were summarized from a placebo-controlled trial in 161 cystic fibrosis patients ≥ 12 years old with the G551D-CFTR mutation (NCT00909532). Short-term recovery was measured 2 to 8 weeks after treatment, and long-term recovery was determined at the end-of-study, both compared with baseline measured just prior to the PEx.Results
Fewer patients receiving ivacaftor experienced a PEx than patients receiving placebo (33.7% vs. 56.4%; P = 0.004) and had a lower adjusted incidence rate of PEx (0.589 vs. 1.382; P < 0.001). The proportion of PEx followed by full short-term recovery of percent predicted forced expiratory volume in 1 s was similar (ivacaftor vs. placebo, 57.1% vs. 53.7), as was the proportion of patients having long-term recovery (46.4% vs. 47.7%).Conclusions
Ivacaftor treatment reduces the frequency of PEx but does not improve on the rate of complete lung function recovery after PEx when compared with placebo. 相似文献16.
Nina N. Sainath Joan Schall Chiara Bertolaso Carolyn McAnlis Virginia A. Stallings 《Journal of cystic fibrosis》2019,18(1):135-143
Background
In patients with cystic fibrosis (CF), ivacaftor treatment results in significant weight gain and the impact on diet has not been explored.Methods
A study in 22 subjects (6.1–61.6?years) compared diet, energy balance, weight gain, and body composition, before and after three months of treatment in Italians and North Americans with CFTR gating mutations.Results
With no differences between groups in energy or macronutrient intake at baseline, fat intake increased in all subjects, and both fat and energy intake increased in Italians. Height, weight, BMI, lean and fat mass, and % body fat increased and resting energy expenditure decreased after treatment. Weight gain was associated with energy and fat intake.Conclusions
Fat intake increased with treatment, possibly due to the recommendation to take ivacaftor with high fat meals. Increased energy and fat intake correlated with weight gain. Regional dietary patterns differed. 相似文献17.
Samuel T. Montgomery A. Susanne Dittrich Luke W. Garratt Lidija Turkovic Dario L. Frey Stephen M. Stick Marcus A. Mall Anthony Kicic 《Journal of cystic fibrosis》2018,17(6):715-722
Background
Little is known about the role of interleukin (IL)-1 in the pathogenesis of cystic fibrosis (CF) lung disease. This study investigated the relationship between IL-1 signalling, neutrophilic inflammation and structural lung changes in children with CF.Methods
Bronchoalveolar lavage fluid (BALf) from 102 children with CF were used to determine IL-1α, IL-1β, IL-8 levels and neutrophil elastase (NE) activity, which were then correlated to structural lung changes observed on chest computed tomography (CT) scans.Results
IL-1α and IL-1β were detectable in BAL in absence of infection, increased in the presence of bacterial infection and correlated with IL-8 (p?<?0.0001), neutrophils (p?<?0.0001) and NE activity (p?<?0.01 and p?<?0.001). IL-1α had the strongest association with structural lung disease (p <?0.01) in the absence of infection (uninfected: p?<?0.01 vs. infected: p?=?0.122).Conclusion
Our data associates IL-1α with early structural lung damage in CF and suggests this pathway as a novel anti-inflammatory target. 相似文献18.
Grace Y. Lam Michelle Doll-Shankaruk Jan Dayton Karina Rodriguez-Capote Trefor N. Higgins Dylan Thomas Kimberley Mulchey Maeve P. Smith Neil E. Brown Winnie M. Leung Mathew P. Estey 《Journal of cystic fibrosis》2018,17(1):121-124
Objective
To determine whether serum fructosamine correlates with glycemic control and clinical outcomes in patients being screened for cystic fibrosis-related diabetes (CFRD).Methods
Fructosamine and percent predicted forced expiratory volume in 1 s (FEV1) were measured in patients undergoing a 2 h oral glucose tolerance test (OGTT) for CFRD screening. Fractional serum fructosamine (FSF) was calculated as fructosamine/total protein.Results
FSF exhibited a positive correlation with 2 h OGTT results (r2 = 0.3201, p = 0.009), and ROC curve analysis suggested that FSF can identify patients with an abnormal OGTT (AUC = 0.840, p = 0.0002). FSF also exhibited a negative correlation with FEV1 (r2 = 0.3732, p = 0.035). Patients with FSF ≥ 3.70 μmol/g had significantly lower FEV1 (median 47%) compared to those with FSF < 3.70 μmol/g (median 90%; p = 0.015).Conclusions
FSF correlated with both OGTT results and FEV1, and reliably identified patients with abnormal OGTT results. This simple blood test shows potential as an effective tool in CFRD screening. 相似文献19.
Ivo P. van de Peppel Marcela Doktorova Gitte Berkers Hugo R. de Jonge Roderick H.J. Houwen Henkjan J. Verkade Johan W. Jonker Frank A.J.A. Bodewes 《Journal of cystic fibrosis》2019,18(2):286-293
Objective
Disruption of the enterohepatic circulation of bile acids (BAs) is part of the gastrointestinal phenotype of cystic fibrosis (CF). Ivacaftor (VX-770), a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, improves pulmonary function in CF patients with class III gating mutations. We studied the effect of ivacaftor on the enterohepatic circulation by assessing markers of BA homeostasis and their changes in CF patients.Methods
In CF patients with an S1251N mutation (N?=?16; age 9–35?years S125N study/NTR4873) or a G551D mutation (N?=?101; age 10–24?years; GOAL study/ NCT01521338) we analyzed plasma fibroblast growth factor 19 (FGF19) and 7α-hydroxy-4-cholesten-3-one (C4) levels, surrogate markers for intestinal BA absorption and hepatic synthesis, respectively, before and after treatment with ivacaftor.Results
At baseline, median FGF19 was lower (52% and 53%, P?<?.001) and median C4 higher (350% and 364%, P?<?.001), respectively, for the S1251?N and G551D mutation patient groups compared to healthy controls. Treatment with ivacaftor significantly increased FGF19 and reduced C4 levels towards normalization in both cohorts but this did not correlate with CFTR function in other organs, as measured by sweat chloride levels or pulmonary function.Conclusions
We demonstrate that patients with CFTR gating mutations display interruption of the enterohepatic circulation of BAs reflected by lower FGF19 and elevated C4 levels. Treatment with ivacaftor partially restored this disruption of BA homeostasis. The improvement did not correlate with established outcome measures of CF, suggesting involvement of modulating factors of CFTR correction in different organs. 相似文献20.
Jeannette E. Dankert-Roelse Marelle J. Bouva Bernadette S. Jakobs Hettie M. Janssens Karin M. de Winter-de Groot Yvonne Schönbeck Johan J.P. Gille Vincent A.M. Gulmans Rendelien K. Verschoof-Puite Peter C.J.I. Schielen Paul H. Verkerk 《Journal of cystic fibrosis》2019,18(1):54-63