title: Effect of treatment of cystic fibrosis pulmonary exacerbations on systemic inflammation.
abstract: BACKGROUND
  In cystic fibrosis (CF), pulmonary exacerbations present an opportunity to define the effect of antibiotic therapy on systemic measures of inflammation.
  
  
  OBJECTIVE
  Investigate whether plasma inflammatory proteins demonstrate and predict a clinical response to antibiotic therapy and determine which proteins are associated with measures of clinical improvement.
  
  
  METHODS
  In this multicenter study, a panel of 15 plasma proteins was measured at the onset and end of treatment for pulmonary exacerbation and at a clinically stable visit in patients with CF who were 10 years of age or older.
  
  
  RESULTS
  Significant reductions in 10 plasma proteins were observed in 103 patients who had paired blood collections during antibiotic treatment for pulmonary exacerbations. Plasma C-reactive protein, serum amyloid A, calprotectin, and neutrophil elastase antiprotease complexes correlated most strongly with clinical measures at exacerbation onset. Reductions in C-reactive protein, serum amyloid A, IL-1ra, and haptoglobin were most associated with improvements in lung function with antibiotic therapy. Having higher IL-6, IL-8, and α1-antitrypsin (α1AT) levels at exacerbation onset were associated with an increased risk of being a nonresponder (i.e., failing to recover to baseline FEV1). Baseline IL-8, neutrophil elastase antiprotease complexes, and α1AT along with changes in several plasma proteins with antibiotic treatment, in combination with FEV1 at exacerbation onset, were predictive of being a treatment responder.
  
  
  CONCLUSIONS
  Circulating inflammatory proteins demonstrate and predict a response to treatment of CF pulmonary exacerbations. A systemic biomarker panel could speed up drug discovery, leading to a quicker, more efficient drug development process for the CF community.
authors.affiliation: 1 Department of Pediatrics, Children's Hospital Colorado and University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Sagel
authors.forename: Valeria
authors.initials: V
authors.lastname: Thompson
authors.forename: James F
authors.initials: JF
authors.lastname: Chmiel
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Montgomery
authors.forename: Samya Z
authors.initials: SZ
authors.lastname: Nasr
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Perkett
authors.forename: Milene T
authors.initials: MT
authors.lastname: Saavedra
authors.forename: Bonnie
authors.initials: B
authors.lastname: Slovis
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Anthony
authors.forename: Peggy
authors.initials: P
authors.lastname: Emmett
authors.forename: Sonya L
authors.initials: SL
authors.lastname: Heltshe
mesh_terms: D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008168:Lung / Q000503:physiopathology*; D008297:Male; D011379:Prognosis
chemical_list: D000900:Anti-Bacterial Agents; D015415:Biomarkers; D016207:Cytokines; D002097:C-Reactive Protein
keywords: biomarker; cystic fibrosis; inflammation; plasma; pulmonary exacerbation