Introduction: In recent years, guidelines for vitamin D supplementation have been updated and prophylactic recommended doses have been increased in patients with cystic fibrosis (CF). Objective: To evaluate safety and efficacy of these new recommendations. Results: Two cohorts of pancreatic insufficient CF patients were compared before (cohort 1: 179 patients) and after (cohort 2: 71 patients) American CF Foundation and European CF Society recommendations were published. Cohort 2 patients received higher Vitamin D doses: 1509 (1306–1711 95% CI) vs 1084 (983–1184 95% CI) IU/Day (p < 0.001), had higher 25 OH vitamin D levels: 30.6 (27.9–33.26 95% CI) vs. 27.4 (25.9–28.8 95% CI) ng/mL (p = 0.028), and had a lower prevalence of insufficient vitamin D levels (<30 ng/mL): 48% vs 65% (p = 0.011). Adjusted by confounding factors, patients in cohort 1 had a higher risk of vitamin D insufficiency: OR 2.23 (1.09–4.57 95% CI) (p = 0.028). Conclusion: After the implementation of new guidelines, CF patients received higher doses of vitamin D and a risk of vitamin D insufficiency decreased. Despite this, almost a third of CF patients still do not reach sufficient serum calcidiol levels.

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.

This is a prospective, multicenter study of a cohort of 224 cystic fibrosis (CF) patients treated with CF transmembrane conductance regulator (CFTR) modulators (CFTRm). Our aim was to prospectively analyze the effect of CFTRm treatment on fat‐soluble vitamin serum levels. Demographic and clinical data were recorded, and fat‐soluble vitamin levels were analyzed at baseline, and at 6 and 12 months after starting treatment. Two groups were analyzed separately: patients receiving dual therapy lumacaftor/ivacaftor or tezacaftor/ivacaftor (Lum/Tez+Iva), and those on triple therapy with elexacaftor/tezacaftor/ivacaftor (ETI). We found that treatment with ETI produced a significant increase in vitamin D and A levels within the first 6 months, which was maintained at 12 months. However, with dual therapy, we observed an increase only in vitamin A levels within the first 6 months, which was not maintained at 12 months. No differences were found in vitamin E serum levels between the groups.

We aimed to elucidate the cystic fibrosis (CF) microbiota composition (shotgun metagenomics) and functionality (short-chain fatty acids, SCFAs). Fecal and sputum samples were recruited from 39 clinically stable CF subjects. Bacillota and Pseudomonadota were dominant in both gut and lung compartments, whereas Ascomycota were the most abundant fungi in feces, and Basidiomycota, especially Malassezia globosa, in sputum. Viruses accounted for 0.4 % of the relative abundance in the gut and 0.6 % in lungs. Mycobacteroides abscessus was genetically identified in 10 individuals, although only 2 had positive cultures. Patients with higher levels of Pseudomonas filamentous phages had negative cultures for P. aeruginosa. The protozoan Toxoplasma gondii was detected in all sputum samples, accounting for 0.25 % of the metagenomic reads, with further PCR-confirmation in 50 % of subjects, including children. No correlation was found between SCFA and lung function or microbial composition. The resistome of the fecal compartment was higher than that of the lungs, and a greater abundance of SCFAs in the intestine was associated with poorer lung function. Patients with normal-mild lung function had higher alpha diversity in the respiratory microbiota; however, beta diversity in the stool was statistically different compared with the group with poorer lung function. Although there were no differences in SCFA concentrations, butyrate-producing bacteria were more abundant in the sputum of the group with better lung function. In fecal samples, resistome to tetracyclines, glycopeptides, and aminoglycosides predominated, whereas in sputum an enrichment of ARGs related to tetracyclines, beta-lactams, and macrolides was observed.

Introduction: Limited studies have explored the impact of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators on glucose tolerance and insulin secretion in patients with CF, yielding varied results. This study aims to assess alterations in glucose metabolism and insulin secretion over 24 and 52 weeks following CFTR modulator initiation in a cohort of pediatric and adult patients with CF. Materials and Methods: A prospective longitudinal study conducting oral glucose tolerance test (OGTT) with C-peptide and insulin levels. The insulin secretion rate at 60 min (ISR60) and the insulinogenic index (IGI) were calculated during the first 60 and 30 min of the OGTT, respectively. Glucose metabolism status was categorized as normal (NGT), indeterminate (INDET), impaired glucose tolerance (IGT), or cystic fibrosis-related diabetes (CFRD). Additionally, continuous glucose monitoring (CGM) was performed for 14 days at each visit. We employed a repeated-measures general linear model to assess changes in insulin secretion and CGM metrics, with glucose tolerance status as the between-subjects factor and visit (baseline, 24 and 52 weeks) as the within-subjects factor. Results: The study comprised 25 patients (11 adults and 14 pediatrics). At baseline, 2 patients (8%) had NGT, 8 (32%) had INDET, 10 (40%) had IGT, and 5 (20%) had CFRD. Overall, there were no significant changes in insulin and C-peptide area under the curve (AUC), IGI and DI after 52 weeks. However, we observed an increase in ISR60 among NGT patients (mean change: 1.766; 95% CI: 1.414; 2.118, p < 0.001). Consistently, average glucose exhibited a significant decrease in NGT patients between 24 and 52 weeks (mean change: −5.645; 95% CI: −4.233; −10.866, p = 0.028). Conclusions: Treatment with CFTR modulators potentially enhances insulin secretion in patients with CF NGT. Early initiation of treatment, as evaluated through long-term prospective trials, is essential to further investigate whether decreased glucose control is preventable or reversible.