Rationale: Cystic fibrosis (CF), caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, leads to impaired pancreatic function and therefore reduced intestinal absorption of lipids and fat-soluble vitamins especially in patients with CF developing pancreatic insufficiency (PI). Previous studies showed that CFTR modulator therapy with lumacaftor-ivacaftor (LUM/IVA) in Phe508del-homozygous patients with CF results in improvement of pulmonary disease and thriving. However, the effects of LUM/IVA on plasma concentration of the lipid soluble vitamins A and E remain unknown. Objectives: To investigate the course of plasma vitamin A and E in patients with CF under LUM/IVA therapy. Methods: Data from annual follow-up examinations of patients with CF were obtained to assess clinical outcomes including pulmonary function status, body mass index (BMI), and clinical chemistry as well as fat-soluble vitamins in Phe508del-homozygous CF patients before initiation and during LUM/IVA therapy. Results: Patients with CF receiving LUM/IVA improved substantially, including improvement in pulmonary inflammation, associated with a decrease in blood immunoglobulin G (IgG) from 9.4 to 8.2 g/L after two years (p < 0.001). During the same time, plasma vitamin A increased significantly from 1.2 to 1.6 µmol/L (p < 0.05), however, levels above the upper limit of normal were not detected in any of the patients. In contrast, plasma vitamin E as vitamin E/cholesterol ratio decreased moderately over the same time from 6.2 to 5.5 µmol/L (p < 0.01). Conclusions: CFTR modulator therapy with LUM/IVA alters concentrations of vitamins A and vitamin E in plasma. The increase of vitamin A must be monitored critically to avoid hypervitaminosis A in patients with CF.

ObjectivesTo evaluate the influence of exposure parameters and raw-data-based iterative reconstruction (IR) on computer-aided segmentation and quantitative analysis of the tracheobronchial tree on multidetector computed tomography (MDCT).Material and methods10 porcine heart-lung-explants were mounted inside a dedicated chest phantom. MDCT was performed at 120kV and 80kV with 120, 60, 30 and 12 mAs each. All scans were reconstructed with filtered back projection (FBP) or IR, resulting in a total of 160 datasets. The maximum number of detected airway segments, most peripheral airway generation detected, generation-specific airway wall thickness (WT), total diameter (TD) and normalized wall thickness (pi10) were compared.ResultsThe number of detected airway segments decreased slightly with dose (324.8±118 at 120kV/120mAs vs. 288.9±130 at 80kV/30mAs with FBP, p<0.05) and was not changed by IR. The 20th generation was constantly detected as most peripheral. WT did not change significantly with exposure parameters and reconstruction algorithm across all generations: range 1st generation 2.4–2.7mm, 5th 1.0–1.1mm, and 10th 0.7mm with FBP; 1st 2.3–2.4mm, 5th 1.0–1.1mm, and 10th 0.7–0.8mm with IR. pi10 was not affected as well (range 0.32–0.34mm).ConclusionsExposure parameters and IR had no relevant influence on measured airway parameters even for WT <1mm. Thus, no systematic errors would be expected using automatic airway analysis with low-dose MDCT and IR.