Single dose escalation studies with inhaled POL6014, a potent novel selective reversible inhibitor of human neutrophil elastase, in healthy volunteers and subjects with cystic fibrosis.

BACKGROUND: POL6014 is a novel, orally inhaled neutrophil elastase (NE) inhibitor in development for cystic fibrosis (CF). METHODS: Two studies, one in healthy volunteers (HVs, doses 20 to 960 mg) and one in subjects with CF (doses 80 to 320 mg) were conducted to evaluate the safety, tolerability and pharmacokinetics (PK) of single ascending doses of inhaled POL6014 with a Pari eFlow® nebuliser. PK was evaluated over a period of 24 h. In addition, NE activity in CF sputum was measured. RESULTS: After single doses, POL6014 was safe and well tolerated up to 480 mg in HVs and at all doses in subjects with CF. POL6014 showed a dose-linear PK profile in both populations with Cmax between 0.2 and 2.5 µM in HVs and between 0.2 and 0.5 µM in subjects with CF. Tmax was reached at approximately 2-3 h. Mean POL6014 levels in CF sputum rapidly reached 1000 µM and were still above 10 µM at 24 h. >1-log reduction of active NE was observed at 3 h after dosing. CONCLUSION: Inhalation of POL6014 can safely lead to high concentrations within the lung and simultaneously low plasma concentrations, allowing for a clear inhibition of NE in the sputum of subjects with CF after single dosing. TRIAL REGISTRATION: European Medicines Agency EudraCT-Nr. 2015-001618-83 and 2016-000493-38.

Low vitamin D serum level is inversely associated with eczema in children and adolescents in Germany.

BACKGROUND: Recent studies have yielded heterogeneous results regarding the relationship between vitamin D and atopic conditions. The aim of this study was to investigate the association between serum vitamin D level and the prevalence of eczema in German children and adolescents. METHODS: Data were drawn for children aged 1-17 from the German Health Interview and Examination Survey for Children and Adolescents (KiGGS), a nationwide cross-sectional representative survey. 25-hydroxyvitamin D (25(OH)D) serum concentration was measured in 9838 individuals with eczema and categorized into quartiles. We investigated the association of vitamin D level and eczema by means of logistic regression models. RESULTS: Weighted prevalence of eczema was 13.5% (95% confidence interval (CI) 12.6-14.4%). Mean vitamin D level was significantly higher in those with eczema compared with those without (P < 0.0001). Logistic regression revealed an inverse association between low levels of vitamin D and eczema (multivariate OR for quartile 1 vs quartile 2: 0.76 (95% CI 0.61-0.94)). CONCLUSIONS: This study suggests that low serum vitamin D level is inversely associated with eczema in German children and adolescents. Prospective studies are required to confirm this result, to discuss a potential opportunity for prevention of eczema.