Search

In cystic fibrosis (CF), 85% to 90% of patients develop exocrine pancreatic insufficiency. Despite enzyme substitution, low pancreatic phospholipase A2 (sPLaseA2-IB) activity causes fecal loss of bile phosphatidylcholine and choline deficiency. We report on a female patient who has CF and progressive hepatosteatosis from 4.5 y onward. At 22.3 y, the liver comprised 27% fat (2385 mL volume) and transaminases were strongly increased. Plasma choline was 1.9 µmol/L (normal: 8-12 mol/L). Supplementation with 3×1g/d choline chloride decreased liver fat and volume (3 mo: 8.2%; 1912 mL) and normalized transaminases. Plasma choline increased to only 5.6 µmol/L upon supplementation, with high trimethylamine oxide levels (12-35 µmol/L; normal: 3 ± 1 mol/L) proving intestinal microbial choline degradation. The patient was homozygous for rs12325817, a frequent single-nucleotide polymorphism in the PEMT gene, associated with severe hepatosteatosis in response to choline deficiency. Resolution of steatosis required 2 y (4.5% fat). Discontinuation/resumption of choline supplementation resulted in rapid relapse/resolution of steatosis, increased transaminases, and abdominal pain.

Background and Objectives: Fungi, particularly Aspergillus and Candida species, are increasingly found in cystic fibrosis (CF) airway fluids. However, their association with other CF pathogens, medications and lung function, especially in CF children, remains elusive. We analyzed the relationship of fungal colonization to microbiological and clinical parameters of pediatric CF patients. Methods and Results: Fungal colonization and long-term clinical parameters like BMI and lung function were retrospectively studied in over 500 CF patients. Colonization was defined based on Chotirmall et al. (Chest 2010). Candida albicans (CA) was the most prevalent fungus detected in CF airway fluids, followed by C. non-albicans > Aspergillus fumigatus (AF) > A. non-fumigatus species. We found an association between fungal colonization and (among other parameters) bacterial co-colonization, lung function, BMI and antibiotic therapy. Conclusion: This study suggests that colonization with CA or AF is affected by bacterial co-colonization and may modulate the disease severity already in pediatric CF patients.

Background Chitinases have recently gained attention in the field of pulmonary diseases, particularly in asthma and chronic obstructive pulmonary disease, but their potential role in patients with cystic fibrosis (CF)–associated lung disease remains unclear. Objective The aim of this study was to assess chitinase activity systemically and in the airways of patients with CF and asthma compared with healthy subjects. Additionally, we assessed factors that regulate chitinase activity within the lungs of patients with CF. Methods Chitinase activities were quantified in serum and bronchoalveolar lavage fluid from patients with CF, asthmatic patients, and healthy control subjects. Mechanistically, the role of CF airway proteases and genetic chitinase deficiency was assessed. Results Chitinase activity was systemically increased in patients with CF compared with that in healthy control subjects and asthmatic patients. Further stratification showed that chitinase activity was enhanced in patients with CF colonized with Candida albicans compared with that in noncolonized patients. CF proteases degraded chitinases in the airway microenvironment of patients with CF. Genetic chitinase deficiency was associated with C albicans colonization in patients with CF. Conclusion Patients with CF have enhanced chitinase activation associated with C albicans colonization. Therefore chitinases might represent a novel biomarker and therapeutic target for CF-associated fungal disease.

Objectives Pseudomonas aeruginosa in the airways of CF-patients restricts the efficacy of antibiotics leading to chronic infections which have a large impact on morbidity and mortality. Antibiotic combination therapy might be more efficient than single antibiotics to combat lung infections in CF. Methods In an observational pilot study CF patients, suffering from chronic P. aeruginosa lung infection, pre-treated either with tobramycin or colistin, were inhalatively treated for 28 days with 300 mg tobramycin in combination with colistin (1 Mio IU) and meropenem 250 mg twice daily. Lung function expressed as expiratory volume in 1 second (FEV 1 ), bacterial cfu and adverse events were determined before and after treatment. Results 15 adult CF patients (mean age 27.9±9.4 years) inhaled b-sympathomimetics prior to the triple antibiotic solution which was well tolerated by all patients. FEV1 increased significantly by 7.8±5.7% absolute and 11.6±10% relative to baseline (p = 0.001) since only one patient showed no benefit after 28 days of inhalation. P. aeruginosa decreased significantly by 1.46±1.4 log cfu/ml (p = 0.042). No adverse reactions were found. Conclusion For the first time administered, the efficacy of an inhalative triple antibiotic solution with meropenem, tobramycin and colistin suggest, that this combination therapy seems to be safe and efficient to increase lung function and decrease chronic Pseudomonas infection in CF patients. This alternative combination of inhalative antibiotics has to be investigated in further trials.

WS6.2 Anti-inflammatory pulmonal therapy of CF patients with amitriptyline and placebo − a randomised, double-blind, placebo-controlled Phase IIb multicenter cohort study C. Adams1, J.G. Mainz2, L. Naehrlich3, C. Engel4, G. Herrmann4, V. Icheva4, U. Graepler-Mainka4, S. Heyder5, M. Stern4, G. Doring6, E. Gulbins1, J. Riethmueller4. 1University of Duisburg-Essen, Dept. of Molecular Biology, Essen, Germany; 2University of Jena, Childrens Hospital, Jena, Germany; 3University of Giessen, Childrens Hospital, Giessen, Germany; 4University of Tubingen, Childrens Hospital, Tubingen, Germany; 5Klinik Schillerhohe, Gerlingen, Germany; 6University of Tubingen, Tubingen, Germany