TY - JOUR A1 - Tabori, Harold A1 - Schneider, Jochen A1 - Lüth, Stefan A1 - Zagoya, Carlos A1 - Barucha, Anton A1 - Lehmann, Thomas A1 - Kauf, Eberhard A1 - Barth, Astrid A1 - Mainz, Jochen G. T1 - Elevated levels of toxic bile acids in serum of cystic fibrosis patients with CFTR mutations causing pancreatic insufficiency JF - International journal of molecular sciences N2 - Hepatobiliary involvement is a hallmark in cystic fibrosis (CF), as the causative CF Transmembrane Conductance Regulator (CFTR) defect is expressed in the biliary tree. However, bile acid (BA) compositions in regard to pancreatic insufficiency, which is present at an early stage in about 85% of CF patients, have not been satisfactorily understood. We assess the pattern of serum BAs in people with CF (pwCF) without CFTR modulator therapy in regard to pancreatic insufficiency and the CFTR genotype. In 47 pwCF, 10 free and 12 taurine- and glycine-conjugated BAs in serum were prospectively assessed. Findings were related to genotype, pancreatic insufficiency prevalence (PIP)-score, and hepatic involvement indicated by serum liver enzymes, as well as clinical and ultrasound criteria for CF-related liver disease. Serum concentrations of total primary BAs and free cholic acid (CA) were significantly higher in pwCF with higher PIP-scores (p = 0.025, p = 0.009, respectively). Higher total BAs were seen in pwCF with PIP-scores >= 0.88 (p = 0.033) and with pancreatic insufficiency (p = 0.034). Free CA was higher in patients with CF-related liver involvement without cirrhosis, compared to pwCF without liver disease (2.3-fold, p = 0.036). pwCF with severe CFTR genotypes, as assessed by the PIP-score, reveals more toxic BA compositions in serum. Subsequent studies assessing changes in BA homeostasis during new highly effective CFTR-modulating therapies are of high interest. KW - cystic fibrosis KW - CF liver disease KW - hepatic KW - biliary KW - bile acid KW - high performance liquid chromatography Y1 - 2022 U6 - https://doi.org/10.3390/ijms232012436 SN - 1422-0067 VL - 23 IS - 20 PB - MDPI CY - Basel ER - TY - JOUR A1 - Barucha, Anton A1 - Mauch, Renan Marrichi A1 - Duckstein, Franziska A1 - Zagoya, Carlos A1 - Mainz, Jochen G. T1 - The potential of volatile organic compound analysis for pathogen detection and disease monitoring in patients with cystic fibrosis JF - Expert review of respiratory medicine N2 - Introduction Airway infection with pathogens and its associated pulmonary exacerbations (PEX) are the major causes of morbidity and premature death in cystic fibrosis (CF). Preventing or postponing chronic infections requires early diagnosis. However, limitations of conventional microbiology-based methods can hamper identification of exacerbations and specific pathogen detection. Analyzing volatile organic compounds (VOCs) in breath samples may be an interesting tool in this regard, as VOC-biomarkers can characterize specific airway infections in CF. Areas covered We address the current achievements in VOC-analysis and discuss studies assessing VOC-biomarkers and fingerprints, i.e. a combination of multiple VOCs, in breath samples aiming at pathogen and PEX detection in people with CF (pwCF). We aim to provide bases for further research in this interesting field. Expert opinion Overall, VOC-based analysis is a promising tool for diagnosis of infection and inflammation with potential to monitor disease progression in pwCF. Advantages over conventional diagnostic methods, including easy and non-invasive sampling procedures, may help to drive prompt, suitable therapeutic approaches in the future. Our review shall encourage further research, including validation of VOC-based methods. Specifically, longitudinal validation under standardized conditions is of interest in order to ensure repeatability and enable inclusion in CF diagnostic routine. KW - Breath analysis KW - cystic fibrosis KW - pathogens KW - Pseudomonas aeruginosa KW - volatile organic compounds Y1 - 2022 U6 - https://doi.org/10.1080/17476348.2022.2104249 SN - 1747-6348 SN - 1747-6356 VL - 16 IS - 7 SP - 723 EP - 735 PB - Routledge, Taylor & Francis Group CY - Abingdon ER -