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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. ispartof: PLOS ONE vol:14 issue:12 ispartof: location:United States status: published

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. ispartof: PLOS ONE vol:14 issue:3 ispartof: location:United States status: published

Background Tiotropium is a once-daily, long-acting anticholinergic bronchodilator with the potential to alleviate airway obstruction in cystic fibrosis. Our objective was to evaluate the efficacy and safety of 2.5 and 5 µg once-daily tiotropium delivered via the Respimat Soft Mist Inhaler vs. placebo in people with cystic fibrosis. Methods This phase 2, 12-week, randomized, double-blind, placebo-controlled parallel-group study of tiotropium Respimat as add-on to usual cystic fibrosis maintenance therapy included people with cystic fibrosis with pre-bronchodilator forced expiratory volume in 1 second (FEV1) ≥25% predicted. Co-primary efficacy end points were change from baseline in percent-predicted FEV1 area under the curve from 0 to 4 hours (FEV1 AUC0–4h), and trough FEV1 at the end of week 12. Findings A total of 510 subjects with cystic fibrosis aged 5–69 years were randomized. Both doses of tiotropium resulted in significant improvement compared with placebo in the co-primary efficacy end points at the end of week 12 (change from baseline in percent-predicted FEV1 AUC0–4h: 2.5 µg: 2.94%, 95% confidence interval 1.19–4.70, p = 0.001; 5 µg: 3.39%, 95% confidence interval 1.67–5.12, p = 0.0001; in percent-predicted trough FEV1∶2.5 µg: 2.24%, p = 0.2; 5 µg: 2.22%, p = 0.02). There was a greater benefit with tiotropium 5 vs. 2.5 µg. No treatment-related adverse events or unexpected safety findings were observed in patients taking tiotropium. Conclusions Tiotropium significantly improved lung function in people with cystic fibrosis. The improvement was greater with the higher dose than the lower dose, with no difference in adverse events. Trial Registration ClinicalTrials.gov NCT00737100 EudraCT 2008-001156-43.

Insulin (Ins) and angiotensin II (AII) play pivotal roles in the control of two vital and closely related systems: the metabolic and the circulatory, respectively. A failure in the proper action of each of these hormones results, to a variable degree, in the development of two highly prevalent and commonly overlapping diseases--diabetes mellitus (DM) and hypertension (AH). In recent years, a series of studies has revealed a tight connection between the signal transduction pathways that mediate Ins and AII actions in target tissues. This molecular cross-talk occurs at multiple levels and plays an important role in phenomena that range from the action of anti-hypertensive drugs to cardiac hypertrophy and energy acquisition by the heart. At the extracellular level, the angiotensin-converting enzyme controls AII synthesis but also interferes with Ins signaling through the proper regulation of AII and the accumulation of bradykinin. At an early intracellular level, AII, acting through JAK-2/IRS-1/PI3-kinase, JNK and ERK, may induce the serine phosphorylation and inhibition of key elements of the Ins-signaling pathway. Finally, by inducing the expression of the regulatory protein SOCS-3, AII may impose a late control on the Ins signal. This review will focus on the main advances obtained in this field and will discuss the implications of this molecular cross-talk in the common clinical association between DM and AH.

This work describes the first epidemiological survey of Burkholderia cepacia involved in pulmonary infections among the Portuguese population with cystic fibrosis (CF) who attended the major CF treatment Center in Lisbon at Sta. Maria Hospital from 1995 to the end of 1997. The characterization of the genomic relatedness of the isolates was based on the analysis of their ribopatterns (with Eco RI) followed by construction of a ribotype-based phylogenetic tree. This study was complemented with macrorestriction fragment analysis by pulsed-field gel electrophoresis. After optimization of the solid growth medium, we found that exopolysaccharide (EPS) production by B. cepacia CF isolates is not as rare a phenomenon as was thought before; indeed, 70% of the isolates examined were EPS producers.