title: Factors associated with response to treatment of pulmonary exacerbations in cystic fibrosis patients.
abstract: BACKGROUND
  Pulmonary exacerbations are associated with significant lung function decline from baseline in cystic fibrosis (CF) and it is not well understood why some patients do not respond to antibiotic therapy. The objective of this study was to identify factors associated with lung function response to antibiotic treatment of pulmonary exacerbations.
  
  
  METHODS
  As a secondary analysis of a randomized, controlled trial of intravenous antibiotic treatment for pulmonary exacerbations in CF patients, we investigated whether baseline factors and changes in sputum bacterial density, serum or sputum inflammatory markers were associated with recovery of lung function and risk of subsequent exacerbation.
  
  
  RESULTS
  In 36 of the 70 exacerbations (51%), patients' lung function returned to >100% of their baseline at day 14 of antibiotic treatment; 34 exacerbations were classified as non-responders. Baseline characteristics were not significantly different between responders and non-responders. Less of a drop in FEV1 from baseline to exacerbation (OR 1.09, 95% CI 1.0, 1.18, p=0.04) as well as a greater decrease in sputum neutrophil elastase (OR 2.94, 95% CI 1.07, 8.06, p=0.04) were associated with response to antibiotic treatment at day 14. In addition, higher CRP (HR 1.35 (95% CI: 1.01, 1.78), p=0.04) and sputum neutrophil elastase (HR 1.71 (95% CI: 1.02, 2.88), p=0.04) at day 14 of antibiotic therapy were associated with an increased risk of subsequent exacerbation.
  
  
  CONCLUSIONS
  Inadequate reduction of inflammation during an exacerbation is associated with failure to recover lung function and increased risk of subsequent re-exacerbation in CF patients.
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto. Electronic address: Valerie.Waters@sickkids.ca.
authors.forename: Valerie J
authors.initials: VJ
authors.lastname: Waters
authors.affiliation: Division of Respiratory Medicine, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto. Electronic address: Sanja.Stanojevic@sickkids.ca.
authors.forename: Sanja
authors.initials: S
authors.lastname: Stanojevic
authors.affiliation: Division of Respiratory Medicine, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto. Electronic address: n.sonneveld@erasmusmc.nl.
authors.forename: Nicole
authors.initials: N
authors.lastname: Sonneveld
authors.affiliation: Division of Respiratory Medicine, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto. Electronic address: michelle.klingel@sickkids.ca.
authors.forename: Michelle
authors.initials: M
authors.lastname: Klingel
authors.affiliation: Division of Respiratory Medicine, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto. Electronic address: Hartmut.Grasemann@sickkids.ca.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Grasemann
authors.affiliation: Division of Microbiology, Department of Pediatric Laboratory Medicine, Hospital for Sick Children, University of Toronto, Toronto. Electronic address: Yvonne.Yau@sickkids.ca.
authors.forename: Yvonne C W
authors.initials: YC
authors.lastname: Yau
authors.affiliation: Division of Respirology and Keenan Research Centre of Li Ka Shing Knowledge Institute, Department of Medicine, St. Michael's Hospital, University of Toronto, Toronto. Electronic address: Tullise@smh.ca.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Tullis
authors.affiliation: Division of Respiratory Medicine, Department of Medicine, St Paul's Hospital, University of British Columbia, Vancouver. Electronic address: PWilcox@providencehealth.bc.ca.
authors.forename: Pearce
authors.initials: P
authors.lastname: Wilcox
authors.affiliation: Division of Respiratory Medicine, Department of Medicine, Hamilton Health Sciences Center, McMaster University, Hamilton. Electronic address: freitaga@mcmaster.ca.
authors.forename: Andreas
authors.initials: A
authors.lastname: Freitag
authors.affiliation: Division of Respiratory Medicine, Department of Pediatrics, British Columbia Children's Hospital, Vancouver. Electronic address: mchilvers@cw.bc.ca.
authors.forename: Mark
authors.initials: M
authors.lastname: Chilvers
authors.affiliation: Division of Respiratory Medicine, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto. Electronic address: Felix.Ratjen@sickkids.ca.
authors.forename: Felix A
authors.initials: FA
authors.lastname: Ratjen
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003550:Cystic Fibrosis / Q000150:complications*; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008171:Lung Diseases / Q000188:drug therapy* / Q000209:etiology*; D008297:Male; D055815:Young Adult
keywords: antibiotics; cystic fibrosis; inflammation; pulmonary exacerbations