ESPEN-ESPGHAN-ECFS guideline on nutrition care for cystic fibrosis.

BACKGROUND: Nutritional status is paramount in Cystic Fibrosis (CF) and is directly correlated with morbidity and mortality. The first ESPEN-ESPGHAN-ECFS guidelines on nutrition care for infants, children, and adults with CF were published in 2016. An update to these guidelines is presented. METHODS: The study was developed by an international multidisciplinary working group in accordance with officially accepted standards. Literature since 2016 was reviewed, PICO questions were discussed and the GRADE system was utilized. Statements were discussed and submitted for on-line voting by the Working Group and by all ESPEN members. RESULTS: The Working Group updated the nutritional guidelines including assessment and management at all ages. Supplementation of vitamins and pancreatic enzymes remains largely the same. There are expanded chapters on pregnancy, CF-related liver disease, and CF-related diabetes, bone disease, nutritional and mineral supplements, and probiotics. There are new chapters on nutrition with highly effective modulator therapies and nutrition after organ transplantation.

Standards for the care of people with cystic fibrosis; establishing and maintaining health.

This is the second in a series of four papers updating the European Cystic Fibrosis Society (ECFS) standards for the care of people with CF. This paper focuses on establishing and maintaining health. The guidance is produced using an evidence-based framework and with wide stakeholder engagement, including people from the CF community. Authors provided a narrative description of their topic and statements, which were more directive. These statements were reviewed by a Delphi exercise, achieving good levels of agreement from a wide group for all statements. This guidance reinforces the importance of a multi-disciplinary CF team, but also describes developing models of care including virtual consultations. The framework for health is reinforced, including the need for a physically active lifestyle and the strict avoidance of all recreational inhalations, including e-cigarettes. Progress with cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy is reviewed, including emerging adverse events and advice for dose reduction and interruption. This paper contains guidance that is pertinent to all people with CF regardless of age and eligibility for and access to modulator therapy.

Effect of 18 months elexacaftor-tezacaftor-ivacaftor on body mass index and glycemic control in adults with cystic fibrosis.

BACKGROUND & AIMS: Malnutrition and cystic fibrosis related diabetes (CFRD) are common comorbidities in cystic fibrosis (CF). Cystic fibrosis transmembrane regulator (CFTR) modulators have shown beneficial effects on respiratory status. This study aims to determine the effect of elexacaftor-tezacaftor-ivacaftor (ETI) on body mass index (BMI) and glycemic control. METHODS: A retrospective, observational study of a cohort of 17 adult CF patients was conducted at the CF reference center of Ghent University Hospital. BMI evolution was analyzed 18 months before and 0, 3, 6, 12 and 18 months after the start of ETI. The evolution of insulin dependence and the 2 h oral glucose tolerance test (OGTT) results were described until 36 months after start of ETI, in a small subgroup of ten patients with CFRD or impaired glucose tolerance (IGT). RESULTS: A significant increase in mean BMI of 1.2 kg/m2 (±1.3 SD) was observed. Most weight gain was observed in the first 3 months after starting treatment. This effect was sustained during the observed period of 18 months. Six patients had insulin dependent CFRD, of which three were able to stop insulin after starting ETI. Two patients with CFRD treated with dietary measures showed an initial normalization of the 2 h OGTT, but deterioration at 36 month follow-up. CONCLUSIONS: After initiation of ETI an increase in BMI was observed in adults with CF. ETI can have a beneficial impact on glucose metabolism in patients with CFRD, leading to a possible need for reduction or cessation of insulin therapy.

Standards of care for CFTR variant-specific therapy (including modulators) for people with cystic fibrosis.

Cystic fibrosis (CF) has entered the era of variant-specific therapy, tailored to the genetic variants in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. CFTR modulators, the first variant-specific therapy available, have transformed the management of CF. The latest standards of care from the European CF Society (2018) did not include guidance on variant-specific therapy, as CFTR modulators were becoming established as a novel therapy. We have produced interim standards to guide healthcare professionals in the provision of variant-specific therapy for people with CF. Here we provide evidence-based guidance covering the spectrum of care, established using evidence from systematic reviews and expert opinion. Statements were reviewed by key stakeholders using Delphi methodology, with agreement (≥80%) achieved for all statements after one round of consultation. Issues around accessibility are discussed and there is clear consensus that all eligible people with CF should have access to variant-specific therapy.

Glycemic indices at night measured by CGM are predictive for a lower pulmonary function in adults but not in children with cystic fibrosis.

INTRODUCTION: In patients with cystic fibrosis (CF), it is still unclear to which extent glucose abnormalities - preceding the diagnosis of cystic fibrosis related diabetes (CFRD) - are associated with pulmonary and nutritional outcome parameters. This study related circadian glycemic patterns to clinical outcomes in a group of CF patients not previously diagnosed with diabetes. METHODS: Continuous glucose monitoring (CGM) readings (7 days) of 47 CF patients (26 children, 21 adults) with an impaired oral glucose tolerance test (OGTT) (n = 25) and/or increased Hb1Ac (> 5.5%) were analyzed. Biometric, pulmonary function and clinical parameters were retrospectively collected over a period of 1 year before (T-1) and 1 year after (T + 1) CGM (T0). RESULTS: 96% (45/47) of CGM readings showed glucose values > 140 mg/dL ≥ 4.5% of the time and at least one ≥ 200 mg/dL. In the pediatric cohort, no significant associations were found between CGM parameters and pulmonary and nutritional outcome parameters. In the adult cohort, an area under the curve (AUC) > 140 mg/dL and%-time > 140 mg/dL during the night were associated with a lower forced expiratory volume in 1 s (FEV1)% predicted (pp) at time of evaluation but not with change in FEV1pp. CONCLUSION: This is the first study reporting the circadian glycemic pattern in children and adults at risk for CFRD. In the adult cohort an association between detection of abnormal glucose exposure and a lower FEV1pp was found. Our results support continued screening for glucose intolerance in patients with CF.

Urinary sodium/creatinine ratio is a predictor for fractional sodium excretion and related to age in patients with cystic fibrosis.

Electrolyte disturbances are common in patients with cystic fibrosis (CF). Current guidelines on monitoring sodium status are based on research in a small group of infants and require blood sampling. The aim of this study was to evaluate urinary salt parameters as a surrogate for sodium-status in different age-groups. Blood and urine samples for electrolytes were collected from 222 patients followed at the Ghent University Hospital CF-center. Fractional sodium excretion (FENa) and several urinary parameters were calculated. Clinical characteristics did not differ according to sodium status, defined as FENa <0.5%. ROC analysis demonstrated that sodium/creatinine ratio (UNa/Creat) predicted the sodium status most accurately with high sensitivity and specificity (97 and 91% respectively). The UNa/Creat cut-off predicting a FENa <0.5% differed significantly according to age. The UNa/Creat is an excellent marker for the sodium status defined as a FENa <0.5%. However, different cut-offs according to age category should be applied.

The effect of an intensive residential rehabilitation program on body composition in patients with cystic fibrosis.

The pulmonary function of patients with cystic fibrosis (CF) is associated with nutritional status not only expressed as body mass index (BMI) but also as fat-free mass index (FFMI). This study evaluated the effect of a residential rehabilitation program on nutritional status (BMI, FFMI). The rehabilitation program provided supervised respiratory and nutritional treatment and daily physical activity for 3 weeks (median stay 20 (19-25) days). At the start and the end of the program, weight, height, pulmonary function, and body composition using dual-energy X-ray absorptiometry were prospectively collected. Supervised weighed food records were obtained, and physical activity intensity was measured using a SenseWear Pro3 Armband. CF-related complications were collected from the patient. Thirty-four patients (21 males, median age 18 years old (12-27)) were included. The diet contained a median of 30 EN% fat, 16 EN% protein, and 52 EN% of carbohydrates. A significant median weight gain (+1.45 kg (0.58; 2.6) (p < 0.0001) and a significant increase in BMI (+0.24 kg/m2 (0.11; 0.38)) (p < 0.0001), FFMI (+0.26 kg/m2 (0.01; 0.55)) (p < 0.0001), and FMI (+0.19 kg/m2 (0.04; 0.41)) (p < 0.0001) were obtained.Conclusion: A short rehabilitation program in individuals with CF between 6 and 40 years old is able to improve nutritional status and body composition.Trial registration: NCT04527796 What is Known: • Fat-free mass depletion is frequently present in CF. • In CF pulmonary function is associated with nutritional status measured as body mass index but also fat-free mass index. What is New: • Nutritional status and body composition improve significantly after a short-term rehabilitation program. • The rehabilitation program was able to improve nutritional outcome even with a diet containing less fat than currently advised in the guidelines.

Sodium Status and Replacement in Children and Adults Living with Cystic Fibrosis: A Narrative Review.

Patients with cystic fibrosis (CF) have a two- to four-fold higher sodium chloride sweat content compared with healthy controls. This high sweat salt loss increases the risk for electrolyte disturbances, associated with subacute or chronic complications. Sodium status therefore needs to be adequately monitored and salt intake adjusted to individual needs. The lack of current evidence to formulate specific recommendations and assess sodium status is reflected in a variability of recommendations in international guidelines. This narrative review presents an overview of the current evidence. Infants with CF in particular are at risk for severe sodium deficiency, potentially leading to metabolic alkalosis due to low intake and high sweat losses. More research on the assessment of sodium status and efficacy of sodium chloride supplements in the population of patients with CF, especially given the changing era of CF transmembrane conductance regulator modulatory treatment, is warranted.

The nutritional status in CF: Being certain about the uncertainties.

BACKGROUND: Nutritional therapy is one of the cornerstones in cystic fibrosis (CF) therapy. There is a strong association between nutritional status and pulmonary function and thus longevity. Therefore nutritional therapy should be continuously adapted to preserve or improve the nutritional status. This narrative review was written to reconsider nutritional therapy in CF based on the latest evidence available since the publication of the ESPEN - ESPGHAN - ECFS guidelines on nutrition care for infants, children and adults with CF. METHODS: A literature search in Pubmed, Scopus and Web of Science was conducted to identify new research focusing on the use of growth charts, body composition, protein intake and pancreatic enzyme therapy (PERT) in CF between June 2014 and June 2017. RESULTS: The search strategy resulted in a total of 1810 hits across the databases. After reviewing title and abstract only 17 studies were included of which 2 animal studies. The use of growth charts was discussed in 3 studies, body composition in 6, protein intake and digestion in 4 and PERT in 4. CONCLUSION: According to the current guidelines and the available evidence of the discussed topics, it is important that the nutritional therapy in CF is redefined according to age, pancreatic function and disease stage. Macronutrients balances are of importance and change over lifetime. As a consequence an accurate PERT intake is required and thus further research on timing and dosage is necessary. To improve the nutritional assessment a proper use of the growth charts and a consensus on body composition measurements, references and thresholds is advised.

The effect of enteral tube feeding in cystic fibrosis: A registry based study.

BACKGROUND: Long-term effect of enteral tube feeding (ETF) in cystic fibrosis (CF) remains equivocal. METHODS: A Belgian CF registry based, retrospective, longitudinal study, evaluated the pre- and post- ETF (n = 113) clinical evolution and compared each patient with 2 age, gender, pancreatic status and genotype class-matched controls. RESULTS: At baseline ETF had a worse BMI z-score (p < 0.0001) and FEV1% (p < 0.0001) compared to controls. Patients eventually receiving ETF, had already a significant worse nutritional status and pulmonary function at first entry in the registry. Both parameters displayed a significant decline before ETF-introduction. ETF had more hospitalization and intravenous antibiotic (IVAB) treatment days (p < 0.0001). After ETF introduction hospitalizations and IVAB decreased significantly. After ETF-introduction BMI z-score recuperated towards the original curve before the decline, but remained below the controls. Starting ETF had no effect on rate of height gain in children. The pre-index FEV1 decline (-1.52%/year (p = 0.002)) stabilized to +0.39%/year afterwards. Controls displayed decline of -0.48%/year (p < 0.0001). CONCLUSION: ETF introduction improved BMI z-score and stabilized FEV1, associated with less hospitalizations and IVAB treatments. Higher mortality and transplantation in the ETF cases, leading to drop-outs, made determination of the effect size difficult.

Clinical effects of probiotics in cystic fibrosis patients: A systematic review.

Cystic fibrosis (CF) is characterised by a build-up of thick, intransient mucus linings of the digestive and respiratory mucosa, which disrupts digestive system functioning and microbiota composition. In view of the potential for probiotics to enhance microbiota composition in other contexts, this study investigated the current evidence for probiotics as an adjunct to usual therapy for CF. Electronic clinical databases were interrogated for human randomised, controlled, intervention trials (1985-2015) testing the effects of probiotics on clinical endpoints in CF were reviewed. From 191 articles identified in initial searches, six studies met the critical inclusion criteria, and were reviewed in detail. These studies varied in size (n = 22 to 61) but were generally small and showed substantial diversity in protocol, specific probiotic species used and range of clinical outcomes measured. Probiotic administration showed beneficial effects on fecal calprotectin levels, pulmonary exacerbation risk, and quality of life indicators. In one study, such changes were associated with variations in gut microbiota composition. Despite encouraging preliminary results, the limited number of small and highly varied studies to date do not justify the addition of probiotics as an adjunct to current CF treatment protocols. Importantly, very minimal adverse effects of probiotics have been reported.

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.

Nutrition and pancreatic enzyme intake in patients with cystic fibrosis with distal intestinal obstruction syndrome.

BACKGROUND: The etiology of distal intestinal obstruction syndrome (DIOS) remains unclear. Food intake and pancreatic enzyme replacement therapy (PERT) are often blamed for its occurrence. This study evaluates the nutrition intake and PERT of patients with cystic fibrosis (CF) at a first episode of DIOS. METHODS: All patients with CF perform annually a 3-day intake diary to evaluate their caloric, protein, fat, dietary fiber, liquid, and PERT intake. Patients diagnosed with a first episode of DIOS (n = 12) retrospectively completed an intake diary of the 3 days preceding the DIOS episode supervised by an expert dietitian. RESULTS were compared with those of 1 year before and also with 36 CF controls matched for age, sex, genotype, and disease severity. All were pancreatic insufficient. RESULTS: A first DIOS episode was diagnosed in 12 patients with CF. Only the absolute median fat intake (P = .015) and pancreatic enzyme intake (P = .035) were higher at the time of the DIOS attack in comparison to the preceding year. This could result from the difference in data collection or from the recommendations to increase fat intake and concomitant enzyme intake, since this trend was also found in the control group. The significant difference disappears when enzyme intake is expressed as units of lipase/g of fat. No other significant dietary differences were found. CONCLUSIONS: This study provides no indications for a potential role of nutrition factors or pancreatic enzymes in the first occurrence of DIOS.

Relation between fatty acid composition and clinical status or genotype in cystic fibrosis patients.

OBJECTIVE: To evaluate the relation of clinical parameters and genotype with the serum phospholipid fatty acid (FA) composition in cystic fibrosis (CF) patients. METHODS: A blood sample was taken from CF patients with stable pulmonary disease for the determination of phospholipid FA composition and vitamin E concentration who had been followed for at least 6 months at our Cystic Fibrosis Centre. Genotype, age, pancreatic function, nutritional status, caloric intake, pulmonary function and presence of Pseudomonas colonization, liver disease or diabetes mellitus were recorded. Patients were divided into two groups according to their genotype (group A: mutation class I, II, or III, group B: mutation class IV, V). RESULTS: CF patients (group A and B together) have significantly lower docosahexaenoic acid (DHA) (p < 0.007) and linoleic acid (LA) (p < 0.0001) and higher dihomogammalinolenic acid (DHGLA) (p < 0.0001), oleic acid (OA) (p < 0.0001) and Mead acid (MA) (p < 0.0001), resulting in an increased ratio of arachidonic acid (AA)/DHA (p < 0.004), MA/AA (p < 0.0001) and OA/LA (p < 0.0001). Compared to group B, group A had a lower LA (p < 0.002) and a higher DHGLA (p < 0.002), 22:4omega-6 (p < 0.03), 22:5omega-6 (p < 0.03) and 20:3omega-9 (p < 0.04). There was however no significant difference between the groups for age, pulmonary function, nutritional status and vitamin E concentration. There was no relation of serum FA composition with nutritional status, caloric intake, pancreatic function, gender, pulmonary function, Pseudomonas colonization or diabetes mellitus. In CF with liver disease the DHA was lower than in the patients of the same genotype. CONCLUSION: FA disturbances are more pronounced in the severe CF genotypes and the presence of CF-related liver disease. Future studies on supplementation should take these parameters into account.