@article{BaruchaMauchDucksteinetal.2022, author = {Barucha, Anton and Mauch, Renan Marrichi and Duckstein, Franziska and Zagoya, Carlos and Mainz, Jochen G.}, title = {The potential of volatile organic compound analysis for pathogen detection and disease monitoring in patients with cystic fibrosis}, series = {Expert review of respiratory medicine}, volume = {16}, journal = {Expert review of respiratory medicine}, number = {7}, publisher = {Routledge, Taylor \& Francis Group}, address = {Abingdon}, issn = {1747-6348}, doi = {10.1080/17476348.2022.2104249}, pages = {723 -- 735}, year = {2022}, abstract = {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.}, language = {en} } @article{HalilbasicFuerstHeidenetal.2020, author = {Halilbasic, Emina and Fuerst, Elisabeth and Heiden, Denise and Japtok, Lukasz and Diesner, Susanne C. and Trauner, Michael and Kulu, Askin and Jaksch, Peter and Hoetzenecker, Konrad and Kleuser, Burkhard and Kazemi-Shirazi, Lili and Untersmayr, Eva}, title = {Plasma levels of the bioactive sphingolipid metabolite S1P in adult cystic fibrosis patients}, series = {Nutrients}, volume = {12}, journal = {Nutrients}, number = {3}, publisher = {MDPI}, address = {Basel}, issn = {2072-6643}, doi = {10.3390/nu12030765}, pages = {11}, year = {2020}, abstract = {Recent research has linked sphingolipid (SL) metabolism with cystic fibrosis transmembrane conductance regulator (CFTR) activity, affecting bioactive lipid mediator sphingosine-1-phosphate (S1P). We hypothesize that loss of CFTR function in cystic fibrosis (CF) patients influenced plasma S1P levels. Total and unbound plasma S1P levels were measured in 20 lung-transplanted adult CF patients and 20 healthy controls by mass spectrometry and enzyme-linked immunosorbent assay (ELISA). S1P levels were correlated with CFTR genotype, routine laboratory parameters, lung function and pathogen colonization, and clinical symptoms. Compared to controls, CF patients showed lower unbound plasma S1P, whereas total S1P levels did not differ. A positive correlation of total and unbound S1P levels was found in healthy controls, but not in CF patients. Higher unbound S1P levels were measured in Delta F508-homozygous compared to Delta F508-heterozygous CF patients (p = 0.038), accompanied by higher levels of HDL in Delta F508-heterozygous patients. Gastrointestinal symptoms were more common in Delta F508 heterozygotes compared to Delta F508 homozygotes. This is the first clinical study linking plasma S1P levels with CFTR function and clinical presentation in adult CF patients. Given the emerging role of immunonutrition in CF, our study might pave the way for using S1P as a novel biomarker and nutritional target in CF.}, language = {en} } @article{PewznerJungTabazavarehGrassmeetal.2014, author = {Pewzner-Jung, Yael and Tabazavareh, Shaghayegh Tavakoli and Grassme, Heike and Becker, Katrin Anne and Japtok, Lukasz and Steinmann, Joerg and Joseph, Tammar and Lang, Stephan and Tuemmler, Burkhard and Schuchman, Edward H. and Lentsch, Alex B. and Kleuser, Burkhard and Edwards, Michael J. and Futerman, Anthony H. and Gulbins, Erich}, title = {Sphingoid long chain bases prevent lung infection by Pseudomonas aeruginosa}, series = {EMBO molecular medicine}, volume = {6}, journal = {EMBO molecular medicine}, number = {9}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {1757-4676}, doi = {10.15252/emmm.201404075}, pages = {1205 -- 1214}, year = {2014}, abstract = {Cystic fibrosis patients and patients with chronic obstructive pulmonary disease, trauma, burn wound, or patients requiring ventilation are susceptible to severe pulmonary infection by Pseudomonas aeruginosa. Physiological innate defense mechanisms against this pathogen, and their alterations in lung diseases, are for the most part unknown. We now demonstrate a role for the sphingoid long chain base, sphingosine, in determining susceptibility to lung infection by P.aeruginosa. Tracheal and bronchial sphingosine levels were significantly reduced in tissues from cystic fibrosis patients and from cystic fibrosis mouse models due to reduced activity of acid ceramidase, which generates sphingosine from ceramide. Inhalation of mice with sphingosine, with a sphingosine analog, FTY720, or with acid ceramidase rescued susceptible mice from infection. Our data suggest that luminal sphingosine in tracheal and bronchial epithelial cells prevents pulmonary P.aeruginosa infection in normal individuals, paving the way for novel therapeutic paradigms based on inhalation of acid ceramidase or of sphingoid long chain bases in lung infection.}, language = {en} }