title: Fluticasone impact on airway dendritic cells in smokers: a randomized controlled trial.
abstract: BACKGROUND
  Myeloid Dendritic cells are key drivers of inflammation in smoke-related lung diseases, whereas plasmacytoid DCs play a crucial role in the defense against infections. Effects of inhaled corticosteroids (ICS) on airway DCs in smokers are unknown.
  
  
  METHODS
  In this randomized, double-blind, placebo-controlled clinical trial, 45 active cigarette smokers inhaled placebo, fluticasone or fluticasone plus salmeterol twice daily for 4 weeks. Bronchoalveolar lavage fluid DCs were analyzed using four-color flow cytometry before and after the inhalation period. In addition, fluticasone effects were tested on T-cell proliferation in co-cultures with blood myeloid DCs from smokers.
  
  
  RESULTS
  Inhalation of fluticasone plus salmeterol, but not fluticasone alone or placebo, reduced endobronchial concentrations of myeloid DCs (median decrease: 24%), macrophages (median decrease: 26%) and neutrophils (median decrease: 76%). In contrast, fluticasone reduced plasmacytoid DC concentrations independently of salmeterol. There were no changes in the expression of function-associated surface molecules on myeloid DC (such as CD1a, Langerin, BDCA-1, CD83 or CCR5) in all groups after treatment. Fluticasone (either alone or in combination with salmeterol) suppressed T-cell proliferation in co-cultures with blood myeloid DCs from smokers.
  
  
  CONCLUSIONS
  Resistance to ICS monotherapy in smokers might in part be due to lacking effects on airway myeloid DCs, whereas the increased risk for infections during ICS therapy could be attributable to a reduction in plasmacytoid DCs. Combination therapy of fluticasone with salmeterol is associated with a reduction in airway myeloid DCs, but also airway macrophages and neutrophils.
  
  
  BACKGROUND
  Registered at ClinicalTrials.gov (identifier: NCT00908362) and the European Clinical Trial Database, EudraCT (identifier: 2009-009459-40).
authors.affiliation: Department of Pneumology, University of Rostock, Rostock, Germany. marek.lommatzsch@med.uni-rostock.de.
authors.forename: Marek
authors.initials: M
authors.lastname: Lommatzsch
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kraeft
authors.forename: Laura
authors.initials: L
authors.lastname: Troebs
authors.forename: Katharina
authors.initials: K
authors.lastname: Garbe
authors.forename: Andrea
authors.initials: A
authors.lastname: Bier
authors.forename: Paul
authors.initials: P
authors.lastname: Stoll
authors.forename: Sebastian
authors.initials: S
authors.lastname: Klammt
authors.forename: Michael
authors.initials: M
authors.lastname: Kuepper
authors.forename: Kai
authors.initials: K
authors.lastname: Bratke
authors.forename: Johann Christian
authors.initials: JC
authors.lastname: Virchow
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D000730:Androstadienes / Q000008:administration & dosage / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects* / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000187:drug effects* / Q000473:pathology*; D004311:Double-Blind Method; D005434:Flow Cytometry; D000068298:Fluticasone; D006801:Humans; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000473:pathology; D000068299:Salmeterol Xinafoate; D012907:Smoking / Q000473:pathology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000473:pathology
chemical_list: D000730:Androstadienes; D001993:Bronchodilator Agents; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol