title: Effect of azithromycin on systemic markers of inflammation in patients with cystic fibrosis uninfected with Pseudomonas aeruginosa.
abstract: BACKGROUND
  While the mechanism of action by which azithromycin exerts positive effects inpatients with cystic fibrosis remains unclear, evidence suggests that azithromycin may act as an immunomodulatory agent. We examined changes in systemic inflammatory markers in a doubleblind, randomized, controlled trial of oral azithromycin in patients 6-18 years of age with cystic fibrosis who were uninfected with Pseudomonas aeruginosa.
  
  
  METHODS
  WBC counts and differential, serum myeloperoxidase (MPO), high-sensitivity C reactive protein (hsCRP), intracellular adhesion molecule 1, IL-6, calprotectin, serum amyloid A (SAA),and granulocyte colony-stimulating factor (G-CSF) were measured at baseline and after 28 and 168 days of treatment in patients receiving either oral azithromycin or placebo.
  
  
  RESULTS
  Inflammatory markers were similar in both groups at baseline. HsCRP, MPO, SAA, calprotectin,and the absolute neutrophil count (ANC) significantly decreased from baseline today 28 in the azithromycin group compared with the placebo group ( P < .05). This treatment effect was sustained at day 168 for ANC, calprotectin, and SAA ( P < .05). Changes in hsCRP, calprotectin,and SAA at day 28 were negatively correlated with changes in FEV 1 (L) and FEV 1(% predicted), as well as both absolute and relative changes in weight ( P < .05). Except for weight (%),the associations remained significant for calprotectin; FEV 1 (L) and weight (%) remained significantly correlated with the 168-day change in hsCRP. The 168-day change in ANC was significantly correlated with changes in lung function, but not in weight; the change in G-CSF was significantly correlated with the change in weight (%) only.
  
  
  CONCLUSIONS
  In patients not infected with P aeruginosa , oral azithromycin significantly reduced neutrophil counts and serum inflammatory markers within 28 days of initiating treatment.
  
  
  BACKGROUND
  ClinicalTrials.gov; No.: NCT00431964; URL: www.clinicaltrials.gov
authors.affiliation: Division of Respiratory Medicine, Department of Pediatrics, and Program in Physiology and Experimental Medicine, SickKids Research Institute, The Hospital for Sick Children, and University of Toronto, Toronto, ON, Canada. Electronic address: felix.ratjen@sickkids.ca.
authors.forename: Felix
authors.initials: F
authors.lastname: Ratjen
authors.affiliation: Department of Pediatrics, Columbia University, New York, NY.
authors.forename: Lisa
authors.initials: L
authors.lastname: Saiman
authors.affiliation: University of Washington, Seattle, WA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Mayer-Hamblett
authors.affiliation: Department of Pediatrics, McGill University, Montreal, QC, Canada.
authors.forename: Larry C
authors.initials: LC
authors.lastname: Lands
authors.affiliation: University of Washington, Seattle, WA.
authors.forename: Margaret
authors.initials: M
authors.lastname: Kloster
authors.affiliation: University of Washington, Seattle, WA.
authors.forename: Valeria
authors.initials: V
authors.lastname: Thompson
authors.affiliation: University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, CO.
authors.forename: Peggy
authors.initials: P
authors.lastname: Emmett
authors.affiliation: Cystic Fibrosis Foundation, Bethesda, MD.
authors.forename: Bruce
authors.initials: B
authors.lastname: Marshall
authors.affiliation: University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, CO.
authors.forename: Frank
authors.initials: F
authors.lastname: Accurso
authors.affiliation: University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, CO.
authors.forename: Scott
authors.initials: S
authors.lastname: Sagel
authors.affiliation: Children's Hospital, Lexington, KY.
authors.forename: Michael
authors.initials: M
authors.lastname: Anstead
mesh_terms: D000293:Adolescent; D017963:Azithromycin / Q000008:administration & dosage / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007958:Leukocyte Count; D039841:Leukocyte L1 Antigen Complex / Q000097:blood; D008297:Male; D009195:Peroxidase / Q000097:blood; D010919:Placebos; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification; D012129:Respiratory Function Tests; D000685:Serum Amyloid A Protein / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D039841:Leukocyte L1 Antigen Complex; D010919:Placebos; D000685:Serum Amyloid A Protein; D018799:Intercellular Adhesion Molecule-1; D016179:Granulocyte Colony-Stimulating Factor; D017963:Azithromycin; D002097:C-Reactive Protein; D009195:Peroxidase