Severe asthma exists despite suppressed tissue inflammation: findings of the U-BIOPRED study.

The U-BIOPRED study is a multicentre European study aimed at a better understanding of severe asthma. It included three steroid-treated adult asthma groups (severe nonsmokers (SAn group), severe current/ex-smokers (SAs/ex group) and those with mild-moderate disease (MMA group)) and healthy controls (HC group). The aim of this cross-sectional, bronchoscopy substudy was to compare bronchial immunopathology between these groups.In 158 participants, bronchial biopsies and bronchial epithelial brushings were collected for immunopathologic and transcriptomic analysis. Immunohistochemical analysis of glycol methacrylate resin-embedded biopsies showed there were more mast cells in submucosa of the HC group (33.6 mm-2) compared with both severe asthma groups (SAn: 17.4 mm-2, p<0.001; SAs/ex: 22.2 mm-2, p=0.01) and with the MMA group (21.2 mm-2, p=0.01). The number of CD4+ lymphocytes was decreased in the SAs/ex group (4.7 mm-2) compared with the SAn (11.6 mm-2, p=0.002), MMA (10.1 mm-2, p=0.008) and HC (10.6 mm-2, p<0.001) groups. No other differences were observed.Affymetrix microarray analysis identified seven probe sets in the bronchial brushing samples that had a positive relationship with submucosal eosinophils. These mapped to COX-2 (cyclo-oxygenase-2), ADAM-7 (disintegrin and metalloproteinase domain-containing protein 7), SLCO1A2 (solute carrier organic anion transporter family member 1A2), TMEFF2 (transmembrane protein with epidermal growth factor like and two follistatin like domains 2) and TRPM-1 (transient receptor potential cation channel subfamily M member 1); the remaining two are unnamed.We conclude that in nonsmoking and smoking patients on currently recommended therapy, severe asthma exists despite suppressed tissue inflammation within the proximal airway wall.

Occupational exposure to veterinary antibiotics: Pharmacokinetics of enrofloxacin in humans after dermal, inhalation and oral uptake - A clinical study.

Occupational exposure to veterinary antibiotics in hen houses at poultry feeding farms was demonstrated by biomonitoring campaigns in the past. The objective of this study was to investigate pharmacokinetics of three uptake routes: dermal, oral and inhaled. In an open-label cross-over study, six healthy volunteers were exposed to single occupational relevant doses of enrofloxacin. Plasma and urine samples were analysed for enrofloxacin and ciprofloxacin. Physiologically based pharmacokinetic (PBPK) modelling based on bioanalysis data showed underestimation for the elimination rate in comparison to experimental data pointing towards a lack of sufficient ADME information and limitations of available physico-chemical properties of the parent drug. The data obtained in this study indicate that oral uptake with its various sources, e.g. airborne enrofloxacin, direct hand-mouth contact, is the major source for occupational exposure to enrofloxacin in hen houses. Dermal exposure was considered negligible.