Research Article Changes of Proteases, Antiproteases, and Pathogens in Cystic Fibrosis Patients’ Upper and Lower Airways after IV-Antibiotic Therapy Ulrike Müller, 1 Julia Hentschel, 1 Wibke K. Janhsen, 1 Kerstin Hünniger, 2,3 Uta-Christina Hipler, 4 Jürgen Sonnemann, 5 Wolfgang Pfister, 6 Klas Böer, 7 Thomas Lehmann, 8 and Jochen G. Mainz 1 1 Department of Pediatrics, Cystic Fibrosis Center, Jena University Hospital, 07740 Jena, Germany 2 Septomics Research Center, Friedrich Schiller University, 07745 Jena, Germany 3 Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Jena, Germany 4 Department of Dermatology, Jena University Hospital, 07740 Jena, Germany 5 Department of Pediatric Hematology and Oncology, Jena University Hospital, 07740 Jena, Germany 6 Institute of Medical Microbiology, University of Jena, 07740 Jena, Germany 7 Institute for Clinical Chemistry and Laboratory Diagnostics, Jena University Hospital, 07740 Jena, Germany 8 Institute of Medical Statistics, Computer Sciences and Documentation, Jena University Hospital, 07740 Jena, Germany Correspondence should be addressed to Jochen G. Mainz; jochen.mainz@med.uni-jena.de Received 19 December 2014; Accepted 18 March 2015 Academic Editor: Christian Taube Copyright © 2015 Ulrike M¨ uller et al. his is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. In cystic ibrosis (CF) the upper (UAW) and lower airways (LAW) are reservoirs for pathogens like Pseudomonas aeruginosa. he consecutive hosts’ release of proteolytic enzymes contributes to inlammation and progressive pulmonary destruction. Objectives were to assess dynamics of protease : antiprotease ratios and pathogens in CF-UAW and LAW sampled by nasal lavage (NL) and sputum before and ater intravenous- (IV-) antibiotic therapy. Methods. From 19 IV-antibiotic courses of 17 CF patients NL (10mL/nostril) and sputum were collected before and ater treatment. Microbiological colonization and concentrations of NE/SLPI/CTSS (ELISA) and MMP-9/TIMP-1 (multiplex bead array) were determined. Additionally, changes of sinonasal symptoms were assessed (SNOT-20). Results. IV-antibiotic treatment had more pronounced efects on inlammatory markers in LAW, whereas trends to decrease were also found in UAW. Ratios of MMP-9/TIMP-1 were higher in sputum, and ratios of NE/SLPI were higher in NL. Remarkably, NE/SLPI ratio was 10-fold higher in NL compared to healthy controls. SNOT-20 scores decreased signiicantly during therapy ( = 0.001). Conclusion. For the irst time, changes in microbiological patterns in UAW and LAW ater IV-antibiotic treatments were assessed, together with changes of protease/antiprotease imbalances. Delayed responses of proteases and antiproteases to IV-antibiotic therapy were found in UAW compared to LAW. 1. Introduction Cystic ibrosis (CF) is the most common lethal autosomal recessive inherited chronic disease in the Caucasian popula- tion and is caused by mutations in the cystic ibrosis trans- membrane conductance regulator (CFTR, 7q31). Defective ion channels lead to production of viscous secretions from exocrine glands. In CF, the innate immunity is inefective because of impaired mucociliary clearance and immune cellular causes [1]. his allows chronic pathogen colonization and in airway, inlammation which results in progressive pulmonary destruction as main reason for increased mor- bidity and mortality in CF [2–5]. Pathogen colonization with Staphylococcus (S.) aureus and Haemophilus inluenzae commonly begins in the irst few months of life [6]. Later on, gram-negative organisms dominate, as Pseudomonas (P.) aeruginosa which chronically colonizes the lungs of 70–80% of adult CF patients [7]. P. aeruginosa enhances inlammation Hindawi Publishing Corporation Mediators of Inflammation Article ID 626530