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Background/objectives: Early life gut microbiota plays a pivotal role in shaping immunity, metabolism, and overall health outcomes. This is relevant in healthy infants but may be even more crucial in infants with chronic devastating diseases, such as cystic fibrosis (CF). While the introduction of solid foods in healthy infants modifies the composition of colonic microbiota, less knowledge is available on those with CF. The aim of this descriptive observational study was to assess the composition of fecal microbiota in six exclusively breast-fed infants with CF, and then explore the changes induced upon the introduction of different foods., Methods: two types of fecal samples were collected from each subject: one during the exclusive-breastfeeding period, and the other after incorporating each new food in the ad libitum diet. The microbiota composition was analyzed by 16S rRNA amplicon sequencing., Results: Wide heterogenicity in the composition at the phylum level (variable proportions of Actinobacteriota, Proteobacteria, and Firmicutes, and the absence of Bacteroidota in all subjects) was found, and different enterotypes were characterized in each subject by the main presence of one genus: Bifidobacterium in Subject 1 (relative abundance of 54.4%), Klebsiella in Subject 3 (49.1%), Veillonella in Subjects 4 and 5 (32.7% and 36.9%, respectively), and Clostridium in Subject 6 (48.9%). The transition to complementary feeding induced variable changes in microbiota composition, suggesting a subject-specific response and highlighting the importance of inter-individual variation., Conclusions: Further studies are required to identify which foods contribute to shaping colonic microbiota in the most favorable way for patients with CF using a personalized approach.

Objective: Intestinal inflammation with contradictory data on faecal calprotectin (fCP) levels is documented in patients with cystic fibrosis (CF). The aim of this study was to longitudinally evaluate fCP in a cohort of children with CF and their relationship with clinical variables., Design: Prospective observational study to assess evolution of fCP levels, primary aimed at improving fat absorption. Along 1.5 years of follow-up (November 2016-May 2018) with four study visits pertaining to a pilot study (two of four) and to a clinical trial (two of four), the study outcomes were measured., Setting: Six European CF centres in the context of MyCyFAPP Project., Subjects: Children with CF and pancreatic insufficiency (2-18 years old)., Main Outcome Measurements: fCP levels, pulmonary function (percentage of forced expiratory volume in 1 s (FEV 1 %)) and coefficient of fat absorption (CFA). Additionally, in the last two visits, gastrointestinal (GI) symptoms were evaluated through the PedsQL-GI Questionnaire. Linear mixed regression models were applied to assess association between fCP and FEV 1 , CFA and GI symptoms., Results: Twenty-nine children with CF and pancreatic insufficiency were included. fCP levels were inversely associated with total modified specific PedsQL-GI score (p=0.04) and positively associated with diarrhoea (p=0.03), but not with CFA. Along the four study visits, fCP significantly increased (from 62 to 256 µg/g) and pulmonary function decreased (from 97% to 87%), with a significant inverse association between the two study outcomes (p<0.001)., Conclusions: In children with CF, fCP levels are inversely associated with pulmonary function and thus the specificity of fCP as a marker of intestinal inflammation in paediatric patients with CF warrants further investigation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Children with cystic fibrosis (CF) present with gut dysbiosis, and current evidence impedes robust recommendations on the use of prebiotics. This study aimed at establishing the prebiotic potential of a commercial beta-glucan on the in vitro colonic microbiota of a child with CF compared to a healthy counterpart (H)., Methods: A dynamic simulator of colonic fermentation (twin-SHIME® model) was set up including the simulation of the proximal (PC) and distal colon (DC) of the CF and the H subjects by colonizing the bioreactors with faecal microbiota. During two weeks the system was supplied with the beta-glucan. At baseline, during treatment and post-treatment, microbiota composition was profiled by 16 S rRNA and short-chain fatty acids (SCFA) production was determined by GS-MS., Results: At baseline, Faecalibacterium, was higher in CF' DC than in the H, along higher Acidaminococcus and less Megasphaera and Sutterella. Beta-glucan supplementation induced increased microbiota richness and diversity in both subjects during the treatment. At genus level, Pseudomonas and Veillonella decreased, while Akkermansia and Faecalibacterium increased significantly in CF., Conclusion: The supplementation with beta-glucan suggests positive results on CF colonic microbiota in the in vitro context, encouraging further research in the in vivo setting., Impact: Current evidence supports assessing the effect of prebiotics on modifying cystic fibrosis microbiota. The effect of beta-glucan supplementation was evaluated in a controlled dynamic in vitro colonic ecosystem. Beta-glucan supplement improved diversity in cystic fibrosis colonic microbiota. The treatment showed increased abundance of Faecalibacterium and Akkermansia in cystic fibrosis. New evidence supports the use of prebiotics in future clinical studies., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

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., Competing Interests: Conflict of interest The expert members of the working group were accredited by the ESPEN Guidelines Group, the ESPEN Education and Clinical Practice Committee, and the ESPEN executive. All expert members have declared their individual conflicts of interest according to the rules of the International Committee of Medical Journal Editors (ICMJE). If potential conflicts were indicated, they were reviewed by the ESPEN guideline officers and, in cases of doubts, by the ESPEN executive. None of the expert panel had to be excluded from the working group or from co-authorship because of serious conflicts. The conflict of interest forms are stored at the ESPEN guideline office and can be reviewed with legitimate interest upon request to the ESPEN executive., (Copyright © 2023 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

A "high-fat, high-energy diet" is commonly recommended for children with cystic fibrosis (CF), leading to negative consequences on dietary patterns that could contribute to altered colonic microbiota. The aim of this study was to assess dietary intake and to identify possible associations with the composition of faecal microbiota in a cohort of children with CF. A cross-sectional observational study was conducted, including a 3-day food record simultaneously with the collection of faecal samples. The results showed a high fat intake (43.9% of total energy intake) and a mean dietary fibre intake of 10.6 g/day. The faecal microbiota was characterised at the phylum level as 54.5% Firmicutes and revealed an altered proportion between Proteobacteria (32%) and Bacteroidota (2.2%). Significant associations were found, including a negative association between protein, meat, and fish intake and Bifidobacterium, a positive association between lipids and Escherichia/Shigella and Streptococcus, a negative association between carbohydrates and Veillonella and Klebsiella , and a positive association between total dietary fibre and Bacteroides and Roseburia . The results reveal that a "high-fat, high-energy" diet does not satisfy dietary fibre intake from healthy food sources in children with CF. Further interventional studies are encouraged to explore the potential of shifting to a high-fibre or standard healthy diet to improve colonic microbiota.

Background: low evidence on the dose of enzymatic supplements used in pancreatic enzyme replacement therapy (PERT) is available., Aim: assessing if fat, protein and starch absorption could be related to the dose of the enzymatic supplement, the intra-patient variability in the dose and macronutrient intake., Methods: Four-day food records and 3-day faecal samples were prospectively collected in 69 children with cystic fibrosis. Pearson correlations between enzyme dose and macronutrient absorption, and beta regression models were applied to explain the results., Results: the supply of protease units per protein intake (PU/g protein) in relation to lipase units per fat intake (LU/g fat) was low and the intra-patient variability in the dose of enzymes was ±1331 LU/g fat. Fat and starch absorption was >90% while for protein it was 81.5%. The coefficient of fat absorption was associated with an interaction between the dose of LU/g fat and its variability among different days. Lipid and protein intake were also determinants of the coefficient of fat absorption., Conclusion: the dose of PERT should be re-adjusted to the amount of dietary fat of every meal (constant LU/g fat) to minimize variability and increase fat absorption. Also, the supply of protease should be increased to prevent from protein malabsorption., Competing Interests: Conflict of interest None declared., (Copyright © 2022 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Patients with cystic fibrosis (CF) and pancreatic insufficiency need pancreatic enzyme replacement therapy (PERT) for dietary lipids digestion. There is limited evidence for recommending the adequate PERT dose for every meal, and controlling steatorrhea remains a challenge. This study aimed to evaluate a new PERT dosing method supported by a self-management mobile-app., Methods: Children with CF recruited from 6 European centres were instructed to use the app, including an algorithm for optimal PERT dosing based on in vitro digestion studies for every type of food. At baseline, a 24h self-selected diet was registered in the app, and usual PERT doses were taken by the patient. After 1 month, the same diet was followed, but PERT doses were indicated by the app. Change in faecal fat and coefficient of fat absorption (CFA) were determined., Results: 58 patients (median age 8.1 years) participated. Baseline fat absorption was high: median CFA 96.9%, median 2.4g faecal fat). After intervention CFA did not significantly change, but range of PERT doses was reduced: interquartile ranges narrowing from 1447-3070 at baseline to 1783-2495 LU/g fat when using the app. Patients with a low baseline fat absorption (CFA<90%, n=12) experienced significant improvement in CFA after adhering to the recommended PERT dose (from 86.3 to 94.0%, p=0.031)., Conclusion: the use of a novel evidence-based PERT dosing method, based on in vitro fat digestion studies incorporating food characteristics, was effective in increasing CFA in patients with poor baseline fat absorption and could safely be implemented in clinical practice., (Copyright © 2020. Published by Elsevier B.V.)

Cystic Fibrosis (CF) is a life-long genetic disease, causing increased energy needs and a healthy diet with a specific nutrient distribution. Nutritional status is an indicator of disease prognosis and survival. This study aimed at assessing the effectiveness of a self-management mobile app in supporting patients with CF to achieve the dietary goals set by the CF nutrition guidelines. A clinical trial was conducted in pancreatic insufficient children with CF, followed in six European CF centres, where the self-management app developed within the MyCyFAPP project was used for six months. To assess secondary outcomes, three-day food records were compiled in the app at baseline and after 3 and 6 months of use. Eighty-four subjects (mean 7.8 years old) were enrolled. Compared to baseline, macronutrient distribution better approximated the guidelines, with protein and lipid increasing by 1.0 and 2.1% of the total energy intake, respectively, by the end of the study. Consequently, carbohydrate intake of the total energy intake decreased significantly (-2.9%), along with simple carbohydrate intake (-2.4%). Regarding food groups, a decrease in ultra-processed foods was documented, with a concomitant increase in meat and dairy. The use of a self-management mobile app to self-monitor dietary intake could become a useful tool to achieve adherence to guideline recommendations, if validated during a longer period of time or against a control group.

Background: Despite treatment with pancreatic enzyme replacement therapy (PERT), patients with cystic fibrosis (CF) can still suffer from fat malabsorption. A cause could be low intestinal pH disabling PERT. The aim of this study was to assess the association between faecal pH (as intestinal pH surrogate) and coefficient of fat absorption (CFA). Additionally, faecal free fatty acids (FFAs) were quantified to determine the amount of digested, but unabsorbed fat., Methods: In a 24-h pilot study, CF patients followed a standardised diet with fixed PERT doses, corresponding to theoretical optimal doses determined by an in vitro digestion model. Study variables were faecal pH, fat and FFA excretion, CFA and transit time. Linear mixed regression models were applied to explore associations., Results: In 43 patients, median (1st, 3rd quartile) faecal pH and CFA were 6.1% (5.8, 6.4) and 90% (84, 94), and they were positively associated (p < 0.001). An inverse relationship was found between faecal pH and total fat excretion (p < 0.01), as well as total FFA (p = 0.048). Higher faecal pH was associated with longer intestinal transit time (p = 0.049) and the use of proton pump inhibitors (p = 0.009)., Conclusions: Although the clinical significance of faecal pH is not fully defined, its usefulness as a surrogate biomarker for intestinal pH should be further explored., Impact: Faecal pH is a physiological parameter that may be related to intestinal pH and may provide important physiopathological information on CF-related pancreatic insufficiency. Faecal pH is correlated with fat absorption, and this may explain why pancreatic enzyme replacement therapy is not effective in all patients with malabsorption related to CF. Use of proton pump inhibitors is associated to higher values of faecal pH. Faecal pH could be used as a surrogate biomarker to routinely monitor the efficacy of pancreatic enzyme replacement therapy in clinical practice. Strategies to increase intestinal pH in children with cystic fibrosis should be targeted.

Background: Cystic fibrosis (CF) patients have an alteration in fatty acid (FA) metabolism, associated with increased omega-6 and low omega-3 FA. Previous studies on supplementation with omega-3 FA in CF had contradictory results, and to date there is no evidence to recommend routine use of omega-3 supplements in CF patients. We hypothesized that long-term supplementation with docosahexaenoic acid (DHA) will have beneficial effects in these patients, by reducing pulmonary, systemic and intestinal inflammation., Methods: This was a randomized, double-blind, parallel, placebo-controlled trial. CF patients (age >2 months) were randomized to receive a seaweed DHA oil solution (50 mg/Kg/day) or matching placebo for 48 weeks. Primary outcomes were pulmonary (interleukin [IL]-8), systemic (IL-8) and intestinal (calprotectin) inflammatory biomarkers. Secondary outcomes included other pulmonary (IL-1β, IL-6, neutrophil elastase, lactate and calprotectin) and systemic (serum-IL-1β, IL-6) inflammatory biomarkers, as well as clinical outcomes (FEV 1 , pulmonary exacerbations, antibiotic use, nutritional status and quality of life)., Results: Ninety six CF patients, 44 female, age 14.6±11.9 years (48 DHA and 48 placebo) were included. At trial completion, there were no differences in all primary outcomes [serum-IL-8 (p=0.909), respiratory-IL-8 (p=0.384) or fecal calprotectin (p=0.948)], all secondary inflammatory biomarkers, or in any of the clinical outcomes evaluated. There were few adverse events, with similar incidence in both study groups., Conclusion: In this study, long-term DHA supplementation in CF patients was safe, but did not offer any benefit on inflammatory biomarkers, or in clinical outcomes compared with placebo. (NCT01783613)., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Most patients with cystic fibrosis (CF) suffer from pancreatic insufficiency (PI), leading to fat malabsorption, malnutrition, abdominal discomfort and impaired growth. Pancreatic enzyme replacement therapy (PERT) is effective, but evidence based guidelines for dose adjustment are lacking. A mobile app for self-management of PERT was developed in the context of the HORIZON 2020 project MyCyFAPP. It contains an algorithm to calculate individual PERT-doses for optimal fat digestion, based on in vitro and in vivo studies carried out in the same project. In addition, the app includes a symptoms diary, educational material, and it is linked to a web tool allowing health care professionals to evaluate patient's data and provide feedback., Methods: A 6-month open label prospective multicenter interventional clinical trial was performed to assess effects of using the app on gastro-intestinal related quality of life (GI QOL), measured by the CF-PedsQL-GI (shortened, CF specific version of the Pediatric Quality of Life Inventory, Gastrointestinal Symptoms Module)., Results: One hundred and seventy-one patients with CF and PI between 2 and 18 years were recruited at 6 European CF centers. Self-reported CF-PedsQL-GI improved significantly from month 0 (M0) (84.3, 76.4-90.3) to month 6 (M6) (89.4, 80.35-93.5) (p< 0.0001). Similar improvements were reported by parents. Lower baseline CF-PedsQL-GI was associated with a greater improvement at M6 (p < 0.001)., Conclusions: The results suggest that the MyCyFAPP may improve GI QOL for children with CF. This tool may help patients to improve self-management of PERT, especially those with considerable GI symptoms., Competing Interests: Declaration of competing interest All authors report grants from the European Commission Horizon 2020 during the conduct of the study. Dr. Mainz reports grants and personal fees from Vertex Corp.,  during the conduct of the study; Dr. Janssens reports grants from Vectura, personal fees from Vertex, outside the submitted work; Dr. Boon reports grants from University Hospital Leuven, outside the submitted work; Dr. De Boeck reports other financial support from Boehringer, Protalix, Raptor, Teva, Novabiotics, Eloxx, Vertex, Galapagos, Chiesi, outside the submitted work. Several authors of this publication are member of the European Reference Network for Rare Respiratory Diseases (ERN-LUNG) - Project ID No 739546., (Copyright © 2020 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Background: Most patients with cystic fibrosis (CF) suffer from pancreatic insufficiency, leading to fat malabsorption, malnutrition and abdominal discomfort. Until recently, no specific tool was available for assessing gastro-intestinal related quality of life (GI QOL) in patients with CF. As the Horizon2020 project MyCyFAPP aims to improve GI QOL by using a newly designed mobile application, a sensitive and reliable outcome measure was needed. We aimed to study the applicability of the existing child-specific Pediatric Quality of Life Inventory, Gastrointestinal Symptoms Scales and Module (PedsQL GI) in children with CF., Methods: A multicenter, prospective observational study was performed in 6 European centers to validate the PedsQL GI in children with CF during 3 months., Results: In total, 248 children and their parents were included. Within-patient variability of PedsQL GI was low (24.11), and there was reasonable agreement between children and parents (ICC 0.681). Nine of 14 subscales were informative (no ceiling effect). The PedsQL GI and the median scores for 4 subscales were significantly lower in patients compared to healthy controls. Positive associations were found between PedsQL GI and age (OR = 1.044, p = 0.004) and between PedsQL GI and BMI z-score (OR = 1.127, p = 0.036). PedsQL GI correlated with most CFQ-R subscales (r 0.268 to 0.623) and with a Visual Analogue Scale (r = 0.20)., Conclusions: PedsQL GI is a valid and applicable instrument to assess GI QOL in children with CF. Future research efforts should examine the responsiveness of the CF PedsQL GI to change in the context of clinical interventions and trials., Competing Interests: The authors have declared that no competing interests exist.

Background: Optimal nutrition for children with cystic fibrosis (CF) improves prognosis and survival, but an increased caloric intake recommendation for this population raises concerns about the nutrient profile of their diets., Objective: Our aim was to assess the relative contribution of food groups to the total macronutrient intake of European pediatric patients with CF., Design: We conducted a cross-sectional study in which the participants recorded dietary intake from 2016 to 2017. Specifically developed nutritional composition databases were used to obtain nutritional data, including macronutrients and food groups, according to previously standardized criteria., Participants/setting: Two hundred and seven pediatric patients with CF from six European centers were involved in the My App for Cystic Fibrosis self-management project., Main Outcome Measures: Participants reported dietary intake with a detailed 4-day food record., Statistical Analysis Performed: Descriptive analyses of nutrient intake, food group consumption, and dietary origin of macronutrients were conducted with R software., Results: Similar patterns were found in nutrient and food group intake; both sugar and saturated fatty acids contributed >10% each to the total daily energy intake in all the centers. Large mean and median percent differences were observed in the intake of other nutrient and food groups, because sweets and snacks were consumed once or twice a day, and fruit and vegetables were consumed two or three times a day. Milk, meat, sweets and snacks, and oils were the main sources of fat in all centers., Conclusions: Study findings indicated less than optimal nutrient profiles, especially for sugars and saturated fatty acids, resulting from the high consumption of meat, dairy, and processed products and low consumption of fish, nuts, and legumes. These results can serve as a basis for future tailored interventions that target improved adherence to nutritional recommendations for patients with CF., (Copyright © 2019 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Background: Remote care services and patient empowerment have boosted mobile health (mHealth). A study of user needs related to mHealth for pediatric cystic fibrosis (PCF) identified the set of preferred features mobile apps should support; however, the potential use of PCF apps and their suitability to fit into PCF clinical management remains unexplored., Objective: We examine whether PCF holds potential for the implementation of mHealth care., Methods: The study is based on a literature review and qualitative analysis of content and was conducted in two parts: (1) we reviewed scientific and gray literature to explore how European countries manage PCF and conducted a qualitative study of 6 PCF units and (2) we performed a systematic review of apps available in the myhealthapps.net repository searching for cystic fibrosis (CF) management and nutrition apps, which we analyzed for characteristics, business models, number of downloads, and usability., Results: European CF routine care guidelines are acknowledged in most European countries, and treatments are fully covered in almost all countries. The majority of teams in CF units are interdisciplinary. With respect to the systematic review of apps, we reviewed 12 apps for CF management and 9 for general nutrition management in the myhealthapps.net directory. All analyzed apps provided functionalities for recording aspects related to the disease and nutrition such as medication, meals, measurements, reminders, and educational material. None of the apps reviewed in this study supported pancreatic enzyme replacement therapy. CF apps proved to be less appealing and usable than nutrition apps (2.66 [SD 1.15] vs 4.01 [SD 0.90]; P<.001, z-value: -2.6). User needs detected in previous research are partially matched by current apps for CF management., Conclusions: The health care context for PCF is a unique opportunity for the adoption of mHealth. Well-established clinical guidelines, heterogeneous clinical teams, and coverage by national health care systems provide a suitable scenario for the use of mHealth solutions. However, available apps for CF self-management do not cover essential aspects such as nutrition and education. To increase the adoption of mHealth for CF self-management, new apps should include these features., International Registered Report Identifier (irrid): RR2-10.1136/bmjopen-2016-014931., (©Antonio Martinez-Millana, Annabel Zettl, Jacqueline Floch, Joaquim Calvo-Lerma, Jose Luis Sevillano, Carmen Ribes-Koninckx, Vicente Traver. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 18.04.2019.)

Background: A method to adjust Pancreatic Enzyme Replacement Therapy in Cystic Fibrosis is not currently available., Objectives: To assess the in vivo efficacy of a method to adjust the dose of enzymatic supplement in CF extrapolated from previous in vitro digestion studies (theoretical optimal dose, TOD). Secondly, to assess how individual patient characteristics influence the expected coefficient of fat absorption (CFA) and thus to identify an individual correction factor to improve TOD., Methods: A prospective interventional study in 43 paediatric patients with CF from 5 European centres. They followed a 24h fixed diet with the theoretical optimal dose for each meal. Faecal collection was carried out between colorimetric markers in order to include all the faeces corresponding to the fixed diet. Beta regression models were applied to assess the associations of individual patient characteristics with the CFA., Results: Median CFA was 90% (84, 94% 1st, 3rd Q.) with no significant differences among centres. Intestinal transit time was positively associated with CFA (p = 0.007), but no statistical associations were found with and age, gender, phenotype or BMI. Regression model showed no improvement of the in vitro predicted theoretical optimal dose when taking individual patient characteristics into account., Conclusion: Strict adherence to the theoretical optimal dose of enzymatic supplement for a prescribed meal, led to median CFA levels at the clinical target of 90% with a low variability between patients. The proposed method can be considered as a first approach for an evidence-based method in PERT dosing based on food characteristics. Results have to be confirmed in free dietary settings., Competing Interests: The authors have declared that no competing interests exist.

Background: Patients with cystic fibrosis have to take enzymatic supplements to allow for food digestion. However, an evidence-based method to adjust Pancreatic Enzyme Replacement Therapy (PERT) is inexistent, and lipid content of meals is used as a rough criterion., Objective: In this study, an in vitro digestion model was set up to determine the theoretical optimal dose (TOD) of enzymatic supplement for a selection of foods, which is the dose that allows for maximum lipolysis extent., Methods: A static in vitro digestion model was applied to simulate digestion of eight foods covering a wide range of lipid contents. First, the dose of the enzymatic supplement was fixed at 2000 lipase units per gram of fat (LU/g fat) using intestinal pH and bile salt concentration as variables. Second, intestinal pH and bile salt concentrations were fixed and the variable was the dose of the enzymatic supplement. Lipolysis extent was determined by measuring the free fatty acids released from initial triglycerides content of foods after digestion. Results in terms of percentage of lipolysis extent were fitted into a linear-mixed segmented model and the deducted equations were used to predict the TOD to reach 90% of lipolysis in every food. In addition, the effect of intestinal pH and bile salt concentration were investigated., Results: The predictive equations obtained for the assessed foods showed that lipolysis was not only dependent on the dose of the enzyme supplement or the lipid content. Moreover, intestinal pH and bile salt concentration had significant effects on lipolysis. Therefore an evidence-based model can be developed taking into account these variables., Conclusions: Depending on food characteristics, a specific TOD should be assigned to achieve an optimal digestion extent. This work represents a first step towards an evidence-based method for PERT dosing, which will be applied in an in vivo setting to validate its efficacy., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Pancreatic enzyme replacement therapy (PERT) remains a backbone in the nutritional treatment of cystic fibrosis. Currently, there is a lack of an evidence-based tool that allows dose adjustment. To date, no studies have found an association between PERT dose and fat absorption. Therefore, the aim of the study was to assess the influence of both the PERT dose and the variability in this dose on the coefficient of fat absorption (CFA)., Methods: This is a retrospective longitudinal study of 16 pediatric patients (192 food records) with three consecutive visits to the hospital over a twelve-month period. Dietary fat intake and PERT were assessed via a four-day food record and fat content in stools was determined by means of a three-day stool sample collection. A beta regression model was built to explain the association between the CFA and the interaction between the PERT dose (lipase units [LU]/g dietary fat) and the variability in the PERT dose (standard deviation [SD])., Results: The coefficient of fat absorption increased with the PERT dose when the variability in the dose was low. In contrast, even at the highest PERT dose values, the CFA decreased when the variability was high. The confidence interval suggested an association, although the analysis was not statistically significant., Conclusion: The variability in the PERT dose adjustment should be taken into consideration when performing studies on PERT efficiency. A clinical goal should be the maintenance of a constant PERT dose rather than trying to obtain an optimal value.

Background: The New European guidelines have established the most updated recommendations on nutrition and pancreatic enzyme replacement therapy (PERT) in CF. In the context of MyCyFAPP project - a European study in children with CF aimed at developing specific tools for improvement of self-management - the objective of the current study was to assess nutritional status, daily energy and macronutrient intake, and PERT dosing with reference to these new guidelines., Methods: Cross sectional study in paediatric patients with CF from 6 European centres. SD-scores for weight-for-age (WFA), height-for-age (HFA) and body mass index-for-age (BMI) were obtained. Through a specific 4-day food and enzyme-dose record, energy and macronutrients intake and PERT-use (LU/g lipids) were automatically calculated by the MyCyFAPP system. Comparisons were made using linear regression models., Results: The lowest quartiles for BMI and HFA were between 0 and -1SD in all the centres with no significant differences, and 33.5% of the patients had a SD-score <0 for all three parameters. The minimum energy intake recommendation was not reached by 40% of the children and mean nutrients intake values were 14%, 51% and 34% of the total energy for protein, carbohydrates and lipids respectively. When assessed per centre, reported PERT doses were in the recommended range in only 13.8% to 46.6% of the patients; from 5.6% up to 82.7% of children were above the recommended doses and 3.3% to 75% were below., Conclusion: Among the 6 centres, a large variability and inconsistency with new guidelines on nutrition and PERT-use was found. Our findings document the lack of a general criterion to adjust PERT and suggest the potential benefit of educational and self-managerial tools to ensure adherence to therapies, both for clinical staff and families. They will be taken into account when developing these new tools during the next stages of MyCyFAPP Project., (Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Introduction: For the optimal management of children with cystic fibrosis, there are currently no efficient tools for the precise adjustment of pancreatic enzyme replacement therapy, either for advice on appropriate dietary intake or for achieving an optimal nutrition status. Therefore, we aim to develop a mobile application that ensures a successful nutritional therapy in children with cystic fibrosis., Methods and Analysis: A multidisciplinary team of 12 partners coordinate their efforts in 9 work packages that cover the entire so-called 'from laboratory to market' approach by means of an original and innovative co-design process. A cohort of 200 patients with cystic fibrosis aged 1-17 years are enrolled. We will develop an innovative, clinically tested mobile health application for patients and health professionals involved in cystic fibrosis management. The mobile application integrates the research knowledge and innovative tools for maximising self-management with the aim of leading to a better nutritional status, quality of life and disease prognosis. Bringing together different and complementary areas of knowledge is fundamental for tackling complex challenges in disease treatment, such as optimal nutrition and pancreatic enzyme replacement therapy in cystic fibrosis. Patients are expected to benefit the most from the outcomes of this innovative project., Ethics and Dissemination: The project is approved by the Ethics Committee of the coordinating organisation, Hospital Universitari La Fe (Ref: 2014/0484). Scientific findings will be disseminated via journals and conferences addressed to clinicians, food scientists, information and communications technology experts and patients. The specific dissemination working group within the project will address the wide audience communication through the website (http://www.mycyfapp.eu), the social networks and the newsletter., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Alpha-1-antitrypsin (a-1AT) is a natural inhibitor of the elastase that is released physiologically by neutrophils in the lung. As a result of the increased neutrophil degranulation secondary to chronic epithelial inflammation in cystic fibrosis patients with chronic infections by Pseudomonas aeruginosa, there are larger amounts of elastase in airway secretions. This results in the a-1AT concentration being insufficient to inhibit the destructive proteolytic degradation, culminating in a chronic epithelial burden and a worsening of the cystic fibrosis pulmonary disease. In this preliminary study, we have evaluated the results obtained from the sputum of 4 cystic fibrosis patients treated with a-1AT (Prolastina, Bayer) in aerosol. The levels of a-1AT, neutrophil elastase, antineutrophil elastase activity, IgG, albumin and clinical parameters were measured. The concentration of sputum a-1AT was increased when compared to the same patient after 8 days with treatment (we compared means with Student's t-test and p < 0.05 was considered significant). We did the same with the impairment of neutrophil elastase, although we found no significant results. Nevertheless, antineutrophil elastase activity increased (p < 0.05). These results encourage us to continue the same treatment for a longer period of time to prevent pulmonary disease in CF subjects.

The present study is based on the typical dendritic forms of the sweat crystallization from patients with cystic fibrosis (CF). The phenomenon was analyzed in sweat collected by pilocarpine iontophoresis in 26 affected subjects (Homozygotes), 42 heterozygotes and 100 healthy-control subjects. The positive crystallization pattern (dendritic form), became useful in identifying the affected patients in 100% of cases and in differentiating them from the healthy-control subjects (100%, negative crystallization). The positive crystallization pattern was not altered by decreasing the electrolytes concentration in the sweat. This test could be a help to evaluate the diagnosis of cystic fibrosis.