title: Colonization of CF patients' upper airways with S. aureus contributes more decisively to upper airway inflammation than P. aeruginosa.
abstract: In cystic fibrosis (CF) patients' airways, inflammatory processes decisively contribute to remodeling and pulmonary destruction. The aims of this study were to compare upper airway (UAW) inflammation in the context of Staphylococcus aureus and Pseudomonas aeruginosa colonization in a longitudinal setting, and to examine further factors influencing UAW inflammation. Therefore, we analyzed soluble inflammatory mediators in noninvasively obtained nasal lavage (NL) of CF patients together with microbiology, medication, and relevant clinical parameters. NL, applying 10 mL of isotonic saline per nostril, was serially performed in 74 CF patients (326 samples). Concentrations of the inflammatory mediators' interleukin (IL)-1β, IL-6, IL-8, matrix metalloproteinase (MMP)-9, and its anti-protease TIMP-1 were quantified by bead-based multiplexed assay, neutrophil elastase (NE) via ELISA. Culture-based microbiology of the upper and lower airways (LAW), as well as serological and clinical findings, were compiled. Our results indicate that UAW colonization with S. aureus significantly impacts the concentration of all measured inflammatory mediators in NL fluid except TIMP-1, whereas these effects were not significant for P. aeruginosa. Patients with S. aureus colonization of both the UAW and LAW showed significantly increased concentrations of IL-1β, IL-6, IL-8, MMP-9, and slightly elevated concentrations of NE in NL fluid compared to non-colonized patients. This work elaborates a survey on S. aureus' virulence factors that may contribute to this underestimated pathology. Serial assessment of epithelial lining fluid by NL reveals that colonization of the UAW with S. aureus contributes more to CF airway inflammatory processes than hitherto expected.
authors.affiliation: Department of Pediatrics, Cystic Fibrosis Center, Jena University Hospital, Kochstrasse 2, 07745, Jena, Germany.
authors.forename: Wibke Katharina
authors.initials: WK
authors.lastname: Janhsen
authors.affiliation: Department of Pediatrics, Cystic Fibrosis Center, Jena University Hospital, Kochstrasse 2, 07745, Jena, Germany.
authors.forename: Christin
authors.initials: C
authors.lastname: Arnold
authors.affiliation: Department of Pediatrics, Cystic Fibrosis Center, Jena University Hospital, Kochstrasse 2, 07745, Jena, Germany.|Institute of Human Genetics, Leipzig University Hospital, Leipzig, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Hentschel
authors.affiliation: Institute of Medical Statistics, Computer Sciences and Documentation, Jena University Hospital, Jena, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lehmann
authors.affiliation: Institute of Medical Microbiology, Jena University Hospital, Jena, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Pfister
authors.affiliation: Institute of Medical Microbiology, Jena University Hospital, Jena, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Baier
authors.affiliation: Institute for Clinical Chemistry and Laboratory Diagnostics, Jena University Hospital, Jena, Germany.
authors.forename: Klas
authors.initials: K
authors.lastname: Böer
authors.affiliation: Septomics Research Center, Friedrich Schiller University of Jena, Jena, Germany.|Leibniz-Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute, Jena, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Hünniger
authors.affiliation: Septomics Research Center, Friedrich Schiller University of Jena, Jena, Germany.|Leibniz-Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute, Jena, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Kurzai
authors.affiliation: Department of Dermatology, Jena University Hospital, Jena, Germany.
authors.forename: Uta-Christina
authors.initials: UC
authors.lastname: Hipler
authors.affiliation: Department of Pediatrics, Cystic Fibrosis Center, Jena University Hospital, Kochstrasse 2, 07745, Jena, Germany. Jochen.Mainz@med.uni-jena.de.
authors.forename: Jochen Georg
authors.initials: JG
authors.lastname: Mainz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D003550:Cystic Fibrosis / Q000150:complications* / Q000473:pathology; D016207:Cytokines / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D055556:Nasal Lavage; D017817:Nasal Lavage Fluid / Q000737:chemistry; D010447:Peptide Hydrolases / Q000032:analysis; D011552:Pseudomonas Infections / Q000382:microbiology / Q000473:pathology*; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification; D012141:Respiratory Tract Infections / Q000382:microbiology* / Q000473:pathology*; D013203:Staphylococcal Infections / Q000382:microbiology / Q000473:pathology*; D013211:Staphylococcus aureus / Q000302:isolation & purification; D055815:Young Adult
chemical_list: D016207:Cytokines; D010447:Peptide Hydrolases
keywords: Cystic fibrosis; Inflammation; Nasal lavage; Staphylococcus aureus