Pancreatic Sufficient Patients Research Articles

Diagnosis of Cystic Fibrosis Beyond Childhood in India

Abstract Cystic fibrosis (CF) is a life-limiting genetic condition with multisystemic manifestations. However, there are vast phenotypic as well as genotypic variations. This contributes to delay in diagnosis, especially in pancreatic-sufficient patients who may not manifest typical symptomatology. The last decade has witnessed significant breakthroughs in CF therapeutics. This in combination with early diagnosis through newborn screening, and aggressive supportive care can offer near-normal life expectancy for a majority of patients with CF (pwCF) worldwide. Even while addressing disparities in CF care around the world, it is crucial to train medical professionals to suspect and diagnose CF in children as well as in adults. Here, we share our experience of pwCF diagnosed beyond 16 years of age with an aim to highlight the clinical presentations in young adults, the need for screening family members of a newly diagnosed pwCF, and the negative effects of late diagnosis of CF.

Nutrition support in children and adolescents with cystic fibrosis: Is there a difference between pancreatic sufficient and insufficient patients?

1. Nagy R, Gede N, Ocskay K, et al. Association of Body Mass Index With Clinical Outcomes in Patients With Cystic Fibrosis: A Systematic Review and Meta-analysis. JAMA Netw Open. 2022;5(3):e220740. doi:10.1001/jamanetworkopen.2022.0740 CrossRef Google Scholar

Preclinical atherosclerosis in cystic fibrosis: Two distinct presentations are related to pancreatic status

BackgroundPatients with cystic fibrosis (CF) are exposed to overlapping cardiovascular risk factors. We hypothesized that CF is characterized by increased arterial stiffness and greater intima-media thickness (IMT). MethodsThis cross-sectional study assessed the digital volume pulse arterial stiffness index (SIDVP) using photopletysmography, measured intima-media complex thickness (IMT) at the common carotid artery, and obtained an extended set of clinical and atherosclerosis-related laboratory parameters. ResultsFifty-five patients with moderate-to-severe CF (mean age 26.3±8.6 years, BMI 20.3±3.1 kg/m2, FEV1 62±26%) and 51 healthy controls (25.1±4.4 years, BMI 21.7±3.0 kg/m2) entered the study. SIDVP was greater in pancreatic insufficient (PI), but not pancreatic sufficient (PS) CF patients compared with control (7.3±1.8 m/s vs 6.0±1.2 m/s; p=7.1 × 10−5). IMT was increased in PS (but not PI) participants relative to control (552±69 µm vs 456±95 µm, p=0.0011). SIDVP was also greater in PI than in PS patients (7.3±1.8 m/s vs 6.3±1.7 m/s, p=0.0232) and IMT was higher in PS compared with PI (552±69 µm vs 453±82 µm, p=0.0002). SIDVP independently associated with age, PI, the lack of liver cirrhosis, and with Pseudomonas aeruginosa colonization. PS was the only independent correlate of IMT in CF. ConclusionsPI patients are at risk of developing general arterial stiffness. PS may relate to carotid IMT thickening, which underscores the need for further study that could lead to reconsideration of dietary guidance in PS CF.

Prevalența pancreatitei acute la copiii cu fibroză chistică și utilizarea scorului PIP în predicția acesteia

One of the affected organs in cystic fibrosis (CF) is the pancreas, mainly translated into exocrine pancreatic insufficiency. Although rare, acute pancreatitis (AP) has been described, mostly in pancreatic sufficient patients. Objectives. Estimating AP prevalence in CF pediatric population of the I.N.S.M.C. „AlessandrescuRusescu” CF centre. Material and methods. 5 year retrospective study (2011-2016) including INSMC CF centre pediatric population aged 3-18 years. PA diagnosis was established on the presence of minimum 2 criteria between: characteristic abdominal pain, x3 normal value for age elevation of amylase/lipase, medical imaging evaluation suggestive for AP. Patients were evaluated with different criteria including PIP score of predicting AP risk. Outcomes. 48 patients were included with a slight female predominance (54%). 3 of them presented diagnostic criteria for AP (6,25%), all heaving pancreatic insufficiency and high PIP score (low risk of developing AP); 2 of them have low compliance with pancreatic enzymes substitution therapy; one of them presented recurrent episodes of AP. Conclusions. AP is a rare CF complication. It can be easily missed due to a large number of abdominal pain and emesis causes in CF patients. Although it is usually associated with pancreatic sufficiency, all our patients were pancreatic insufficient.

Late diagnosis and poor nutrition in cystic fibrosis diagnosed before implementation of newborn screening.

Denmark has a high standard cystic fibrosis care. However, newborn screening was not implemented until 2016. This article describes the clinical status of cystic fibrosis patients at time of diagnosis prior to newborn screening. Patients diagnosed with cystic fibrosis in Denmark in 2010-2014 were reviewed using the Danish Cystic Fibrosis Registry as well as patient files. Parameters collected were age at diagnosis, gender, weight, height, forced expiratory volume at 1second, cystic fibrosis transmembrane regulator-genotype, lung bacteriology at diagnosis and previous diagnoses. A total of 63 patients were diagnosed in the study period. The most typical pre-cystic fibrosis diagnoses were asthma and pneumonia. The median age at diagnosis was 1.4years for the pancreatic insufficient and 27.3years for the pancreatic sufficient patients. Of the pancreatic insufficient patients, 21% had moderate to severe malnutrition with BMI below minus 2 SD and 40% had moderate to severe stunting with height below minus 2 SD. Diagnosis was delayed considerably compared to diagnosis by newborn screening in other countries. Many cystic fibrosis patients diagnosed due to clinical symptoms were moderately to severely underweight or stunted at diagnosis.

Hyponatremic dehydration and metabolic alkalosis as dominant manifestation in cystic fibrosis infants with mild phenotype - a case series

Introduction. Due to increased losses of chloride and sodium in the sweat, children with cystic fibrosis (CF) are predisposed to develop episodes of hyponatremic/hypochloremic dehydration with hypokalemia and metabolic alkalosis when they sweat excessively. Even the patients with mild phenotype may have such episodes of dehydration and salt depletion. Outline of cases. Six cases of pancreatic sufficient (PS) CF patients complicated with episodes of severe hyponatremic dehydration with metabolic alkalosis in infancy are presented. The mean age was 6.3 ? 2.16 months at admission. All the cases had no symptoms suggestive of CF before admission. The most common clinical symptoms at the time of hospitalization were vomiting, anorexia, weight loss, dehydration, irritation, or lethargy. Mean values of blood pH, serum bicarbonate, sodium, chloride, and potassium (mmol/l) were as follows: 7.59 ? 0.06, 41.73 ? 5.78, 117.52 ? 2.88, 66.0 ? 11.58 and 2.62 ? 0.37, respectively. Sweat chloride test was pathological and ranged 69?120 mmol/L. The determination of fecal elastase-1 proved that they were PS (values > 200 ?g/g stool). CF transmembrane conductance regulator gene analyses in six cases confirmed the diagnosis of CF; namely, patients were compound heterozygotes for F508del and other rare mutation or compound heterozygotes for two rare mutations. Conclusion. Distinctive about these cases is that they were PS and had very mild presentation of CF. Without these episodes of dehydration, these patients would have remained undiagnosed until later age. CF should be considered in infants and children presenting with hypoelectrolytemia and metabolic alkalosis even in the absence of respiratory or gastrointestinal symptoms.

What can the CF registry tell us about rare CFTR-mutations? A Belgian study

BackgroundCFTR2 provides clinical and functional information of the most common CFTR-mutations. Rare mutations (RMs) occur in only a few patients with limited reported clinical data. Their role in CF-disease liability is hardly documented.MethodsBelgian CF-Registry 2013 data were analyzed to identify CF with at least 1 RM (CF+RM). Clinical data and sweat chloride of CF+RM were compared to CF-controls, carrying 2 class 1 to 3 mutations (CFclassic). Disease severity was compared between both groups. To avoid bias in the comparison, transplanted patients were excluded from each group.ResultsSeventy-seven CF+RM were identified (77/1183 = 6.5%). Sixty-four different RM were detected, of which 21 had not been previously reported. All RMs, corresponding to HGVS (Human Genome Variation Society) nomenclature, were listed in supplementary data.Seven transplanted CF+RM were excluded for further analysis. CF+RM had higher age at diagnosis [median (IQR)] [3.7 y (0.3–18.3) vs. 0.3y (0.1–2,0) (p < 0.0001)], lower sweat chloride [96 mmol/L (64–107) vs. 104 mmol/L (97–115) (p < 0.0001)], higher FEV1%pred [77%pred (58–96) vs. 68%pred (48–86) (p = 0.017)], were less frequently pancreatic insufficient [56% vs. 98% (p < 0.0001)], Pseudomonas aeruginosa colonized [24% vs. 44% (p = 0.0093)] and needed fewer IV antibiotics [36% vs. 51% (p = 0.041)] than CFclassic. However, a wide spectrum of disease severity was seen amongst CF+RM.ConclusionsCF-patients with a RM cover 6.5% of the Belgian CF-population. Rare mutations can be found in severely ill patients, but more often in late diagnosed, pancreatic sufficient patients.

308 Vitamin D supplementation in pancreatic sufficient and insufficient cystic fibrosis patients

308 Vitamin D supplementation in pancreatic sufficient and insufficient cystic fibrosis patients

ESPEN-ESPGHAN-ECFS guidelines on nutrition care for infants, children, and adults with cystic fibrosis

Malnutrition is both a frequent feature and a comorbidity of cystic fibrosis (CF), with nutritional status strongly associated with pulmonary function and survival. Nutritional management is therefore standard of care in CF patients. ESPEN, ESPGHAN and ECFS recommended guidelines to cover nutritional management of patients with CF. The guidelines were developed by an international multidisciplinary working group in accordance with officially accepted standards. The GRADE system was used for determining grades of evidence and strength of recommendation. Statements were discussed, submitted to Delphi rounds, reviewed by ESPGHAN and ECFS and accepted in an online survey among ESPEN members. The Working Group recommends that initiation of nutritional management should begin as early as possible after diagnosis, with subsequent regular follow up and patient/family education. Exclusive breast feeding is recommended but if not possible a regular formula is to be used. Energy intake should be adapted to achieve normal weight and height for age. When indicated, pancreatic enzyme and fat soluble vitamin treatment should be introduced early and monitored regularly. Pancreatic sufficient patients should have an annual assessment including fecal pancreatic elastase measurement. Sodium supplementation is recommended and a urinary sodium:creatinine ratio should be measured, corresponding to the fractional excretion of sodium. If iron deficiency is suspected, the underlying inflammation should be addressed. Glucose tolerance testing should be introduced at 10 years of age. Bone mineral density examination should be performed from age 8-10 years. Oral nutritional supplements followed by polymeric enteral tube feeding are recommended when growth or nutritional status is impaired. Zinc supplementation may be considered according to the clinical situation. Further studies are required before essential fatty acids, anti-osteoporotic agents, growth hormone, appetite stimulants and probiotics can be recommended. Nutritional care and support should be an integral part of management of CF. Obtaining a normal growth pattern in children and maintaining an adequate nutritional status in adults are major goals of multidisciplinary cystic fibrosis centers.

37 The microbial metagenome of cystic fibrosis lower airways

The use of culture-independent microbiome analysis is expanding our view of respiratory tract infection in Cystic fibrosis (CF). The lower airways of people with CF are colonized with polymicrobial communities of bacteria, viruses, fungi and molds. We investigated the microbial metagenome in 20 exocrine pancreatic insufficient and 10 exocrine pancreatic sufficient CF patients. One to five sputum samples were collected from each patient over a 2-year period. The isolated DNA was sequenced by random whole genome sequencing. The reads were aligned to the human, bacterial, virus, fungi and molds reference genomes. Sequences were normalized by GC content and length reference genome. Analysis of temporal series of specimens indicate that each patient carries a specific signature of microbes in his airways unless drastic interventions were undertaken to eradicate unpleasant pathogens such as Burkholderia spp. The spectrum of bacterial species ranged from metagenomes indistinguishable from a healthy non-CF control to metagenomes dominated by the typical CF pathogens Staphylococcus aureus or Pseudomonas aeruginosa . During exacerbations the relative and absolute abundance of species changed, but not the overall signature. On the average several hundred bacterial and viral species, but just a few fungal species were detected by our pipeline. Five to forty species made up 95% of the bacterial metagenome. Our paradigmatic pilot study demonstrates that whole genome sequencing provides deep insight into the microbial CF lung metagenome. Supported by Mukoviszidose e.V. and the German Center for Lung Research (DZL).

WS11.8 Early diagnosis through newborn screening (NBS) improved long-term growth and adult height at age 18 years in CF patients with pancreatic insufficiency

Objectives To determine if early growth benefit of NBS sustains to adulthood, we compared adolescent peak height velocity (PHV) between screened (diagnosed early via NBS) and control (identified by symptoms) groups in the Wisconsin RCT. Methods Data from 106 patients born in 1985–94 and followed through 2012 with the same care protocol were analyzed. Results Pancreatic sufficient patients (n = 18) achieved normal pubertal PHV and adult height at age 18 y ( th %tile). Meconium ileus patients (MI, n=25) had reduced PHV and shorter adult height at age 18 y (males: 34 th %tile; females: 17 th %tile). In non-MI patients who had pancreatic insufficiency (n = 64), boys in the screened group (n = 22) had normal and slightly higher PHV (9.5 cm/y at 13.5 y) than the control group (n = 29, 8.9 cm/y at 13.6 y), girls in the screened group (n = 13) had later and slightly lower PHV (7.3 cm/y at 12.5 y) compared to control group (n = 11, 7.9 cm/y at 11.7 y), but the lower PHV in screened girls coincided with later menarche (13.6 y vs. 12.2 y) and was compensated by longer duration of pre-pubertal growth. Thus, adult heights at age 18 y in both sexes were taller in screened compared to control (50 th vs. 29 th %tile, p=0.025), which remained significant after adjusting for parental height (32 nd vs 15 th %tile, p=0.003). Multiple regression analysis revealed that the taller adult height in the screened group was primarily due to achievement of better pre-pubertal height (e.g., 47 th vs. 27 th percentile at age 7 y) rather than greater adolescent PHV. Conclusion This longest duration cohort study shows that early diagnosis/care can promote better long term growth and is a sustained benefit of NBS.

Elevated fecal M2-pyruvate kinase in children with cystic fibrosis: a clue to the increased risk of intestinal malignancy in adulthood?

Adult patients with cystic fibrosis (CF) have an increased risk of gastrointestinal malignancies. We hypothesized that increased intestinal cell turnover beginning in childhood may explain the increased risk of malignancy in early adulthood. Therefore, we aimed to measure fecal M2-pyruvate kinase (M2-PK), a biomarker of intestinal cell turnover, in children with CF. To assess whether the increased cell turnover is secondary to intestinal inflammation, the secondary aims were to measure fecal calprotectin and evaluate its association with fecal M2-PK. Fecal samples, for M2-PK and calprotectin measurements, were prospectively collected from children with CF and healthy controls (HC). Thirty-three children with CF (mean [standard deviation] 7.3 [3.8] years old; 29 pancreatic insufficient [PI]) were enrolled and compared with 33 age-matched HC. Fecal M2-PK in CF patients (median [interquartile range, IQR]: 4.7 [1.5-9.7]) was greater than HC (1.0 [1.0-1.0] U/mL; P < 0.0001), and higher in PI (median [IQR]: 5.1 [1.8-13.7]) than pancreatic sufficient patients (1.0 [1.0-1.0] U/mL; P = 0.002). Fecal calprotectin was significantly elevated in CF than HC (median [IQR] 61.3 [43.8-143.8] vs 19.5 [19.5-35.1] mg/kg; P < 0.0001). However, there was no correlation between fecal M2-PK and fecal calprotectin levels among subjects with CF (r = 0.29; P = 0.1). Increased intestinal cell turnover is present in children with PI CF. The lack of relationship between fecal M2-PK and calprotectin suggests that contributing factor(s) other than inflammation may be present.

Vitamin D Status in Children with Cystic Fibrosis. Associations with Inflammation and Bacterial Colonization

Patients with cystic fibrosis (CF) have high rates of vitamin D insufficiency. The relation between vitamin D status and inflammation in patients with CF is poorly understood. To determine the prevalence of vitamin D deficiency and insufficiency in a young CF population and to examine correlations between vitamin D status, disease severity, and inflammatory markers. This was a retrospective chart review of patients with CF under the age of 12 years. Serum laboratory parameters, growth indices, pancreatic status, CFTR genetics, medications, microbiology, and presence of CF-related comorbidities were collected for patients who had fat-soluble vitamin levels measured between January 1, 2009 and December 31, 2011. Vitamin D deficiency was defined as a serum 25(OH)D less than 20 ng/ml and insufficiency as serum 25(OH)D 20 to 29.9 ng/ml. Associations between serum vitamin D concentration and clinical/inflammatory markers were assessed using Chi-square and t tests. Data were collected for 148 children. The mean serum 25(OH)D concentration was 32.4 ng/ml (SD, 8.9). Seven percent (10 of 148) were vitamin D deficient, and 36% (53 of 148) were vitamin D insufficient. Among the pancreatic-sufficient patients, 50% (14 of 28) were vitamin D insufficient/deficient, whereas among pancreatic-insufficient patients, 41% (49 of 120) were vitamin D insufficient/deficient. Pseudomonas aeruginosa was a more common pathogen in the patients who were vitamin D insufficient/deficient (18 of 63 vs. 11 of 85, P = 0.018). There was no difference between vitamin D-sufficient versus -insufficient groups in terms of other bacterial colonization or inflammatory markers. Overall, vitamin D insufficiency is common among young children with CF. Vitamin D insufficiency is prevalent even in children who are pancreatic sufficient. In this population, vitamin D insufficiency is associated with a history of Pseudomonas colonization but not with classic markers of systemic inflammation.

Early acute pancreatitis in a child with compound heterozygosis ∆F508/R1438W/Y1032C cystic fibrosis: a case report

IntroductionRecent studies suggest an important role of the cystic fibrosis transmembrane conductance regulator gene in the development of pancreatitis. It occurs approximately in 20% of patients with cystic fibrosis and almost exclusively in pancreatic sufficient people. Newborn screening and improved panels of deoxyribonucleic acid mutation analysis techniques are revealing more rare and nonclassical pictures of the disease, generally associated with pancreatic sufficiency and with an increased risk of developing pancreatitis. Mutations R1438 and Y1032 are considered rare mutations, and, when singularly associated with ∆F508, lead to a mild phenotype with pancreatic sufficiency and no detectable respiratory involvement.Case presentationWe present the case of a Caucasian girl, aged six years, whose genotype was characterized by three different mutations ∆F508, R1438W and Y1032C, never reported, together, in the same patient. She presented with a positive immunoreactive trypsinogen screening, a borderline sweat test, and, in the first years, a favorable pulmonary course, and pancreatic sufficiency. At the age of six years, she presented with a sudden episode of acute abdominal pain, anorexia and fever. A diagnosis of pancreatitis was made after clinical and laboratory examinations. Venous rehydration, bowel rest and therapy with ursodeoxycholic acid resulted in complete remission.The treatment was successful, with normalization of her symptoms and laboratory parameters within four weeks.ConclusionThere has been a vast expansion in the understanding of the wide range of phenotypes associated with cystic fibrosis transmembrane conductance regulator dysfunction since the discovery of the cystic fibrosis transmembrane conductance regulator gene. The genotype-phenotype correlation in pancreatitis is rare compared to other organ manifestations, since this is seen almost exclusively among pancreatic sufficient patients with cystic fibrosis. Our study supports that compound heterozygosis ∆F508-R1438W/Y1032C is a 'cystic fibrosis-causing genotype' characterized by an immunoreactive trypsinogen positive screening, abnormal sweat chloride testing, and pancreatic sufficiency, with an increased risk of acute pancreatitis at an early age.

High Serum Retinol and Lung Function in Young Patients With Cystic Fibrosis

The aim of the present study was to explore the relation between lung function and serum retinol (SR) in cystic fibrosis (CF) patients. This was a cross-sectional study conducted in a group of 98 young patients with CF (6.8-22.3 years), after the exclusion of those with pulmonary exacerbation, vitamin A deficiency, or other risks, from an initial group of 124 cases. Data of forced expiratory volume in 1 second (FEV₁) were widely scattered (87.7% ± 16.9%). These were similar in the 78 pancreatic insufficient and 11 pancreatic sufficient patients. SR (56.6 ± 18.4 μg/dL) was >2.5th percentile of healthy people in the whole group, although 31 patients were situated above the 97.5th percentile (higher value: 110 μg/dL). The FEV₁ was noticeably higher in these than in those within the normal range (93.6 ± 14.0 vs 85.0 ± 17.6 μg/dL; P < 0.05). The z score of SR correlated positively with FEV₁ (r = 0.364; P = 0.000), after adjusting data for sex, age, body mass index, and pancreatic function. The odds ratio for a FEV₁ >80% is 3.78 in patients with SR above the 97.5th percentile, versus only 0.26 in those within the normal range. There were no cases with retinol toxicity. FEV₁ of young patients with CF correlates positively with SR, regardless of age, pancreatic function, or nutritional condition. Those with a moderately high retinol (up to 110 μg/dL) maintain the best respiratory function (FEV₁ ≥80% in >90% of them) without any signs of toxicity.

Factors associated with FEV1 decline in cystic fibrosis: analysis of the ECFS Patient Registry

Pulmonary insufficiency is the main cause of death in cystic fibrosis (CF). We analysed forced expiratory volume in 1 s (FEV1) data of 14,732 patients registered in the European Cystic Fibrosis Society Patient Registry (ECFSPR) database in 2007. We used linear and logistic regressions to investigate associations between FEV1 % predicted and clinical outcomes. Body mass index (BMI), chronic infection by Pseudomonas aeruginosa, pancreatic status and CF-related diabetes (CFRD) showed a statistically significant (all p<0.0001) and clinically relevant effect on FEV1 % pred after adjusting for age. Patients with a lower BMI experience a six-fold increased odds ratio (95% CI 5.0-7.3) of having severe lung disease (FEV1 <40% pred) compared to patients with normal BMI. Being chronically infected with P. aeruginosa increases the odds ratio of severe lung disease by 2.4 (95% CI 2.0-2.7), and patients with pancreatic insufficiency experience a 2.0-fold increased odds ratio (95% CI 1.6-2.5) of severe lung disease compared to pancreatic sufficient patients. Patients with CFRD have a 1.8-fold increased odds ratio (95% CI 1.6-2.2) compared to patients not affected. These potential risk factors for pulmonary disease in patients with CF are to some degree preventable or treatable. We emphasise the importance of their early identification through frequent routine tests, the implementation of infection control measures, and a timely initiation of relevant therapies.

Pubertal Height Velocity and Associations with Prepubertal and Adult Heights in Cystic Fibrosis

To test the hypothesis that pubertal peak height velocity (PHV) in cystic fibrosis (CF) has improved and is influenced by prepubertal growth and genetic potential. PHV from 1862 children born in 1984-87 and documented in the 1986-2008 US CF Foundation Registry was determined by statistical modeling and classified into normal, delayed (2-SD > average age), attenuated (magnitude <5th percentile), or both delayed and attenuated (D&A). Genetic potential for height was estimated by parental stature. PHV averaged 8.4 cm/year at age 14.0 years in boys and 7.0 cm/year at age 12.1 years in girls, ∼6-month delay and ∼15% reduction compared with healthy children. PHV was normal in 60%, delayed in 9%, attenuated in 21%, and D&A in 5%. Patients with delayed PHV reached similar adult height percentile (boys: 34th, girls: 46th) to those with normal PHV (boys: 33rd, girls: 34th); both were significantly taller than the attenuated (boys: 11th, girls: 19th) and D&A PHV subgroups (boys: 8th, girls: 14th). Pancreatic-sufficient patients had taller prepubertal and adult heights but similar PHV compared with pancreatic-insufficient or meconium ileus patients. Adjusting for genetic potential reduced adult height percentiles more in boys (from 25th to 16th) than girls (from 28th to 24th). Height at age 7 years, PHV age and magnitude, and parental stature significantly predicted adult height. Pubertal PHV has improved in children with CF born after mid-1980s compared with older cohorts but remains below normal. Suboptimal prepubertal and pubertal growth led to adult height below genetic potential in CF.

β-Adrenergic Sweat Secretion as a Diagnostic Test for Cystic Fibrosis

β-Adrenergically induced sweat secretion offers an expedient method to assess native cystic fibrosis transmembrane conductance regulator (CFTR) secretory function in vivo. To evaluate the sensitivity, specificity, and reliability of a test based on the activity and secretory function of CFTR in the sweat gland. Primary and validation trials with prospectively ascertained healthy control subjects, obligate heterozygotes, and patients with a CFTR-related disorder and CF (pancreatic sufficient and insufficient). Diagnostic accuracy and reliability of β-adrenergic sweat secretory rates using an evaporimeter was assessed and compared with sweat chloride concentrations. The cholinergically stimulated mean sweat rate did not differ among groups. The mean maximal β-adrenergically stimulated sweat rate in heterozygotes was about half the rate of healthy control subjects, and completely absent in pancreatic-insufficient patients with CF and pancreatic-sufficient patients with CF (P < 0.0001). Subjects with a CFTR-related disorder showed reduced or absent β-adrenergic sweat secretion. The β-adrenergic secretory response demonstrated high diagnostic accuracy (area under a characteristic receiver-operator curve = 0.99; 95% confidence interval, 0.97-1.00) and reliability (intraclass correlation, 0.90; 95% confidence interval, 0.81-0.95). The diagnostic cutoff level for CF, derived from the primary trial, correctly identified all control subjects, heterozygotes, and patients with CF in the validation cohort, whereas concurrent sweat chloride measurements misclassified one heterozygote and five subjects with CF. The cholinergic and β-adrenergic sweat secretion rates were lower in women compared with men (P < 0.001). β-Adrenergic sweat secretion rate determined by evaporimetry is an accurate and reliable technique to assess different levels of CFTR function and to identify patients with CF.

Self-reported use of vitamins and other nutritional supplements in adult patients with cystic fibrosis. Is daily practice in concordance with recommendations?

In cystic fibrosis (CF), prophylactic supplementation of the fat-soluble vitamins A, D, E, and K is recommended. Limited data is available describing vitamin prescription adherence by adult patients. The aim of this study was to assess the use of prescribed vitamins and other nutritional supplements by adult CF patients. All adult CF patients (n=111) registered at the Utrecht CF Center were invited to participate in a telephone survey on supplement use. Supplemental vitamin intakes were compared with recommendations. In a subsample, associations between supplemental intake and serum vitamin D and E values were assessed. In this study 80% of the patients reported the use of vitamin and/or mineral supplements. Fat-soluble vitamins were used by 43% of pancreatic-sufficient (PS) and 81% of pancreatic-insufficient (PI) patients. Of PI patients reporting supplemental vitamin use, only 9% met the recommendations for vitamin A, 32% for vitamin D, 59% for vitamin E, and 81% for vitamin K. Multivitamin supplements were used by 42% of PI and by 29% of PS patients. Other nutritional supplements were rarely used. A high percentage of PI patients use fat-soluble vitamins below recommendations. Therefore adequate monitoring of vitamin supplementation and status is warranted.

CFTR transcription defects in pancreatic sufficient cystic fibrosis patients with only one mutation in the coding region of CFTR

BackgroundPatients with cystic fibrosis (CF) manifest a multisystem disease due to deleterious mutations in each gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). However, the role of dysfunctional CFTR...