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

"BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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."

Sunlight is an important determinant of vitamin D serum concentrations in cystic fibrosis.

BACKGROUND/OBJECTIVES: The increase of bone disease in adult cystic fibrosis (CF) patients is partly attributed to inadequate serum concentrations of 25-OH cholecalciferol (25 (OH) D) blamed on fat malabsorption. Based on physiological, clinical and biochemical observations this pathogenesis is debatable. The objective was to ascertain the relative importance of different 25 (OH) D sources. SUBJECTS/METHODS: Over 4 consecutive years, 474 annual 25 (OH) D serum concentrations from 141 CF patients of all ages were compared with values of healthy peers and weighed against annual ultraviolet B (UVB) exposure. RESULTS: Ranked per month, 25 (OH) D concentrations depicted a curve strikingly parallel to the amount of UVB exposure in the preceding months. A significant difference exists between 25 (OH) D concentrations in the 'Months with high UVB exposure' (May-October) and the 'Months with low UVB exposure' (November-April) but not with healthy controls in the same period. CONCLUSIONS: 25 (OH) D concentrations clearly respond to the amount of sunshine in preceding months. They are not clearly influenced by daily oral supplements of 800 IU of cholecalciferol. Sun exposure should be encouraged, and the recommended dosage of oral supplements increased.

The effect of zinc supplements in cystic fibrosis patients.

AIM: To study the effect of Zn supplements in cystic fibrosis (CF) on disease evolution. METHODS: A retrospective study of all CF patients treated with Zn supplements (January 2002 to December 2004). Data from patient files for the year before and the first year of supplementation were compared. The controls were CF patients with normal serum Zn and without Zn supplementation. RESULTS: 21 patients (7 females), median age 8.9 (interquartile range 13.1) years, received 5 mg/kg Zn sulfate/day (maximum 150 mg). The number of infections decreased from 3 (1.25) to 2 (2.0) (tied p < 0.02) and the forced expiratory volume in 1 s (FEV(1)) increased from 72.0 (38.4) to 76.5 (52)% (p < 0.02). Energy intake improved (92.3 (14.5) to 117.0 (28.5)%; tied p < 0.02), as did weight for height (W/H; 90 (9.4) to 94 (8.5)%; tied p = 0.043). In the CF control patients the number of infections (2.0 (2.0)), energy intake (116 (43.3)%) and nutritional status remained stable (W/H 99 (17.2)%), but pulmonary function decreased significantly (DeltaFEV(1) loss of 2.0 (8.0)%). There was a significantly different evolution for the change in forced vital capacity (p < 0.004) and DeltaFEV(1) (p < 0.001) between supplemented and control patients. CONCLUSIONS: Analysis of the clinical data on Zn supplementation in CF showed beneficial effects in Zn-deficient CF patients. These results must be confirmed in a prospective double-blind randomized control trial.

Oral DHA supplementation in DeltaF508 homozygous cystic fibrosis patients.

AIM: The aim of this study was to evaluate whether the previously observed changes in the fatty acid profile, as a result of DHA supplementation, could be maintained during longer study trials and to observe its effect on the clinical outcome of cystic fibrosis (CF) patients. METHOD: A year-long double-blind placebo-controlled study was performed in DeltaF508 homozygous CF patients above the age of 6. Clinical data, including pulmonary function and number of infections, were collected. Blood for the determination of the fatty acid (FA) composition of serum phospholipid, vitamin E, liver enzymes, immunoglobulins, erythrocyte sedimentation rate and coagulation was drawn at the beginning and then every 6 months after the start of the study. RESULTS: Seventeen patients were included; one dropped out. The treatment group was supplemented with an algal DHA-rich oil and the control group with sunflower seed oil. There was no difference between the control and treatment groups for W/H%, caloric intake, FEV1% and FVC% at the start of the study and after 1 year of supplements. The phospholipid FA composition did not change in the control group. The treatment group had a significant increase in DHA and eicosapentaenoic acid (EPA) concentration. A concomitant decrease of dihomo-gammalinolenic acid, arachidonic acid, 22:5 n-6 and Mead acid was observed. The laboratory results showed no changes in vitamin E level, liver enzymes, albumin, erythrocyte sedimentation rate and IgG concentration in either the placebo or the intervention group. CONCLUSION: Although DHA-rich oil shifted the serum phospholipid FAs to a less pro-inflammatory profile, no conclusive clinical improvement could be observed so far.

The role of acceptance in psychological functioning in adolescents with cystic fibrosis: a preliminary study.

This study explored the role of acceptance in accounting for the heterogeneity in psychological functioning in adolescents suffering from cystic fibrosis. Thirty-four adolescents completed a battery of questionnaires assessing acceptance, anxiety, depression, and disability. Regression analyses revealed that acceptance had a significant and unique contribution in explaining adolescents' anxiety, depression, and disability beyond the effects of demographic variables and parameters of disease severity. Forced expiratory volume, a parameter of disease severity, had a unique contribution in explaining disability, but not in explaining anxiety and depression. Our results support the idea that accepting the limitations imposed by a chronic disease and readjusting life goals has a positive effect upon psychological functioning in adolescents with cystic fibrosis. Acceptance-based therapies might prove useful in promoting well-being in adolescents with cystic fibrosis.

Cystic fibrosis presenting as diabetes insipidus unresponsive to desmopressin.

The diagnosis of cystic fibrosis (CF) can be confusing when only a part of the typical symptoms is present. In children, CF is usually suspected when dealing with chronic pulmonary symptoms (chronic productive cough, recurrent pneumonia or bronchiolitis). The pediatric gastroenterologist will exclude CF in all children with a meconium ileus, rectal prolaps or a poor weight gain. Atypical CF symptoms are hypochloremic alkalosis, recurrent pancreatitis and increased appetite to compensate for the pancreatic insufficiency. This case report shows how a diagnosis can be delayed when you are mislead by atypical symptoms. It shows the importance of looking in napkins and argues for the inclusion of CF in the differential diagnosis of polyuria in infants.

Serum zinc concentrations in cystic fibrosis patients aged above 4 years: a cross-sectional evaluation.

AIM: Assess the risk of zinc (Zn) deficiency in the older cystic fibrosis (CF) population. METHOD: Cross-sectional investigation of all CF patients above the age of 4 followed at the Ghent University center between 2002 and 2003. Data on age, weight, height z-score, pancreatic and pulmonary functions, chronic Pseudomonas infection, and CF transmembrane conductance regulator (CFTR) mutations were collected. Serum Zn, vitamins (vit) A and E, retinol-binding protein (RBP), albumin, sedimentation rate, total IgG, and cholesterol were determined. Serum Zn was compared with a local healthy control group (Van Biervliet et al., Biol Trace Elem Res 94:33-40, 2003) and with literature data (Hotz C, et al. Am J Clin Nutr 78:756-764, 2003). RESULTS: 101 patients (median age 16 years) were included. There was no difference in serum Zn concentration between CF patients and controls. In CF patients no difference in serum Zn concentration between pancreatic-sufficient or pancreatic-insufficient patients was seen. Serum Zn was not associated to nutritional status or height z-score. A significant association serum Zn to serum albumin (p < 0.0005) and to vit A (p < 0.01) was seen. No associations of serum Zn to serum vit E, RBP, cholesterol, or CFTR were present, but there is a significant association serum Zn to forced vital capacity (p < 0.01). Serum Zn was not associated to inflammatory parameters or chronic Pseudomonas infection. CONCLUSION: Comparison of CF patients with local controls revealed no significant differences. However, because persisting steatorrhea increases Zn loss (Easley et al., J Pediatr Gastroenterol Nutr 26:136-139, 1998) and 12.6% of our population has a serum Zn below the p value of 2.5 of the NHANES II study (Hotz C, et al. Am J Clin Nutr 78:756-764, 2003), there could remain an increased risk of Zn deficiency in some CF patients. Furthermore, the association with pulmonary function needs more investigation.

Hypocalcaemic seizures: sign of intestinal disease?

We describe a baby admitted with convulsions, fever, low protein level and coagulation abnormalities where congenital intestinal lymphangiectasia was confirmed by endoscopy and histology. Treatment with a low fat diet, supplemented with medium chain triglycerides (MCT), resulted in a disappearance of the symptoms and normal growth. When confronted with seizure-like attacks, electrolyte disturbances and hypo-albuminemia one should consider the possibility of protein losing enteropathy.

Mesalazine interstitial nephritis presenting as colitis ulcerosa exacerbation.

Mesalazine is the first line treatment in paediatric inflammatory bowel disease (IBD). There are several reports in the literature about nephrotoxicity (1/150 treated patients), from renal insufficiency to reversible nephritis. It is currently advised to follow creatinine in patients treated with mesalazine during the first 5 years of treatment; however this may reveal the problem too late. As demonstrated in this paediatric case, a high degree of clinical suspicion is needed to diagnose the side effects before irreversible kidney damage occurs. Since the treatment of IBD exacerbation and mesalazine induced interstitial nephritis is based upon steroids, delayed diagnosis of the latter is at risk.

Serum zinc in patients with cystic fibrosis at diagnosis and after one year of therapy.

There is no consensus whether zinc (Zn) supplementation is necessary in cystic fibrosis (CF). For assessment of the Zn status, serum Zn concentration is the only easy available method. It is, however age dependent. We compare the serum Zn levels of CF patients with earlier reported normal values. Serum Zn was determined in all new diagnosed CF patients and a second time 1 yr later. Data concerning fat-soluble vitamin status, cholesterol, albumin, pancreatic insufficiency, and genotype were collected. Thirty-two patients, median age of 1.21 yr, were included. Four were pancreatic sufficient. The median Zn concentration at diagnosis was 10.7 micromol/L (5-21.4), with a significant increase 1 yr later (median: 12.1 micromol/L [7,803-16,1]). An association of serum Zn with vitamin A (p < 0.03) and with vitamin E (p < 0.02) was observed. Compared to age-matched healthy controls, there is no significant difference in serum Zn concentration either at diagnosis or 1 yr later. Although it was demonstrated that steatorrhoea causes Zn loss, the serum Zn concentration in CF is not significantly different from healthy controls. The relation with vitamin Aand E points to the increased losses by steatorrhoea. Therefore, Zn supplementation is advised in persisting steatorrhoea.

Successful liver transplantation for argininosuccinate lyase deficiency (ASLD).

Liver transplantation was performed in a girl with early-onset ASLD, leading to unrestricted protein intake and no further neurological deterioration.

Percutaneous endoscopic gastrostomy in cystic fibrosis: patient acceptance and effect of overnight tube feeding on nutritional status.

BACKGROUND: Malnutrition remains a common problem in cystic fibrosis (CF) patients, despite pancreatic enzymes and hypercaloric diet advice. When oral supplementation fails, additional overnight gastrostomy tube-feeding is a therapeutic option. METHODS: In our centre gastrostomy tube feeding is proposed when weight for height drops below 85% despite intensive dietetic counselling. All the CF patients at our centre (n = 11) receiving gastrostomy tube feeding were evaluated for changes in nutritional status and pulmonary function. Complications of percutaneous endoscopic gastrostomy were inventarised and patients older than 7 years and all the parents were asked to fill in a questionnaire concerning subjective well-being with gastrostomy supplemental feeding. RESULTS: The patients received 40% of the recommended daily allowances (RDA) for energy by tube feeding. Total daily energy intake increased by 30%. Within 3 months this resulted in a significant improvement in nutritional status expressed as percentage of ideal weight for height or body mass index z-score. After 6 months a significant catch-up growth was detectable. Pulmonary function remained stable. The complications were local irritation (n = 4), night sweating (n = 1) and bed-wetting (n = 1). The gastrostomy was well accepted. CONCLUSION: Gastrostomy appears to be a good and safe way to improve nutritional status, growth and mood of the CF child. As decreased pulmonary function plays a crucial role in the growth of the CF child, full normalisation of growth pattern is not achieved despite catch-up. Gastrostomy tube feeding should perhaps be used earlier to optimalise growth.

Cystic fibrosis: an unusual cause of chronic pancreatitis.

Chronic pancreatitis is most frequently associated with alcohol abuse. This should however not always automatically be accepted as the presumed cause. When the history is doubtful, uncommon etiologies must be considered as is illustrated by the present case. A 38 years old man was in the past 20 years treated for chronic pancreatitis ascribed to ethylisme although he always denied this. When the diagnosis was eventually questioned, new investigations showed slightly elevated sweat electrolyte concentrations and a delta F508/R117H genotype compatible with cystic fibrosis (CF). Demonstration of mild respiratory abnormalities, obstructive azoospermia and CF in his brother supported this diagnosis. Although rarely, pancreatitis typically develops in the kind of CF patients with milder genotypes and less severe symptoms. Systematic analysis for genetic mutations in patients with idiopathic chronic pancreatitis (ICP) revealed however that this mild form of CF is a less exceptional cause than thought. As CF patients increasingly survive into adulthood this disease should be considered as a possible etiology in the differential diagnosis of pancreatitis at all ages.

Nutrition in patients with cystic fibrosis: a European Consensus.

This document is the result of an European Consensus conference which took place in Artimino, Tuscany, Italy, in March 2001 involving 33 experts on nutrition in patients with cystic fibrosis, organised by the European Cystic Fibrosis Society, and sponsored by Axcan-Scandipharm, Baxter, Dr Falk Pharma, Fresenius, Nutricia, SHS International, Solvay Pharmaceuticals (major sponsor). The purpose of the conference was to develop a consensus document on nutrition in patients with cystic fibrosis based on current evidence.

High-dose omeprazole in esophagitis with stenosis after surgical treatment of esophageal atresia.

The authors describe 4 children with recurrent stenosis and persistent esophagitis after secondary repair of a long gap esophageal atresia. They underwent an esophageal reconstruction by elongation of the lesser gastric curvature according to Schärli at the age of 11 to 14 months. All had esophagitis grade III to IV (Savary-Miller classification), esophageal stenosis, and failure to thrive. Effective treatment of the esophagitis and prevention of stenosis consisted in high doses of omeprazole (1.9 to 2.5 mg/kg/d). After this treatment, the need for esophageal dilatation disappeared, and nutritional status normalized.

Directed modification instead of normalization of fatty acid patterns in cystic fibrosis: an emerging concept.

Fatty acid patterns divergent from controls have been described in patients with cystic fibrosis. The range of this divergence is very broad. In some patients the plasma fatty acid pattern is normal, others only have abnormalities of a few essential fatty acids, some have fatty acid deviations tending to a reduced essential fatty acid status or have overt essential fatty acid deficiency. In the past, several nutritional interventions were aimed at normalizing deviating fatty acid patterns. Over the years, biochemical findings have been reported that suggest that it may be more beneficial to change fatty acid status in a directed way rather than normalizing it.