title: Changes of Proteases, Antiproteases, and Pathogens in Cystic Fibrosis Patients' Upper and Lower Airways after IV-Antibiotic Therapy.
abstract: BACKGROUND
  In cystic fibrosis (CF) the upper (UAW) and lower airways (LAW) are reservoirs for pathogens like Pseudomonas aeruginosa. The consecutive hosts' release of proteolytic enzymes contributes to inflammation 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 after intravenous- (IV-) antibiotic therapy.
  
  
  METHODS
  From 19 IV-antibiotic courses of 17 CF patients NL (10 mL/nostril) and sputum were collected before and after 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 effects on inflammatory 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 significantly during therapy (P = 0.001).
  
  
  CONCLUSIONS
  For the first time, changes in microbiological patterns in UAW and LAW after 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.
authors.affiliation: Department of Pediatrics, Cystic Fibrosis Center, Jena University Hospital, 07740 Jena, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Müller
authors.affiliation: Department of Pediatrics, Cystic Fibrosis Center, Jena University Hospital, 07740 Jena, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Hentschel
authors.affiliation: Department of Pediatrics, Cystic Fibrosis Center, Jena University Hospital, 07740 Jena, Germany.
authors.forename: Wibke K
authors.initials: WK
authors.lastname: Janhsen
authors.affiliation: Septomics Research Center, Friedrich Schiller University, 07745 Jena, Germany ; Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Jena, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Hünniger
authors.affiliation: Department of Dermatology, Jena University Hospital, 07740 Jena, Germany.
authors.forename: Uta-Christina
authors.initials: UC
authors.lastname: Hipler
authors.affiliation: Department of Pediatric Hematology and Oncology, Jena University Hospital, 07740 Jena, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Sonnemann
authors.affiliation: Institute of Medical Microbiology, University of Jena, 07740 Jena, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Pfister
authors.affiliation: Institute for Clinical Chemistry and Laboratory Diagnostics, Jena University Hospital, 07740 Jena, Germany.
authors.forename: Klas
authors.initials: K
authors.lastname: Böer
authors.affiliation: Institute of Medical Statistics, Computer Sciences and Documentation, Jena University Hospital, 07740 Jena, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lehmann
authors.affiliation: Department of Pediatrics, Cystic Fibrosis Center, Jena University Hospital, 07740 Jena, Germany.
authors.forename: Jochen G
authors.initials: JG
authors.lastname: Mainz
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D016022:Case-Control Studies; D002403:Cathepsins / Q000032:analysis; D002648:Child; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000201:enzymology / Q000382:microbiology; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D019272:Leukocyte Elastase / Q000032:analysis; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D008875:Middle Aged; D011446:Prospective Studies; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification*; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000032:analysis; D013183:Sputum / Q000382:microbiology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis*
chemical_list: D000900:Anti-Bacterial Agents; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; D019715:Tissue Inhibitor of Metalloproteinase-1; D002403:Cathepsins; D019272:Leukocyte Elastase; C028217:cathepsin S; D020780:Matrix Metalloproteinase 9