title: Sputum PGP is reduced by azithromycin treatment in patients with COPD and correlates with exacerbations.
abstract: BACKGROUND
  Proline-glycine-proline (PGP), a neutrophil chemoattractant derived from the enzymatic breakdown of collagen, is elevated in sputum of patients with chronic obstructive pulmonary disease (COPD) and may contribute to disease progression. Whether sputum levels of PGP respond to therapy for COPD or predict outcomes is unknown.
  
  
  OBJECTIVE
  We conducted a study ancillary to a multicenter trial of the efficacy of azithromycin treatment for 1 year in preventing COPD exacerbations to test whether sputum levels of PGP were altered by treatment or associated with exacerbation frequency.
  
  
  METHODS
  We collected remnant sputa from trial participants and assayed them in a blinded fashion for PGP, myeloperoxidase and matrix metalloproteinase (MMP)-9 and for the ability to generate PGP from collagen ex vivo. Once the parent trial was unblinded, the results were correlated with use of azithromycin or placebo and exacerbations in participants.
  
  
  RESULTS
  Azithromycin treatment significantly reduced sputum levels of PGP and myeloperoxidase in patients with COPD, particularly with increased duration of therapy. We found no difference in sputum MMP-9 or PGP generation between participants taking azithromycin or placebo. Sputum PGP levels were highest around the time of an exacerbation and declined with successful treatment.
  
  
  CONCLUSIONS
  These data support a role for PGP in the airway and parenchymal neutrophilic inflammation that drives COPD progression and exacerbations, and provide new information on the anti-inflammatory properties of macrolides. PGP may have potential as a target for novel anti-inflammatory therapies in COPD and as a biomarker for clinical trials.
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Lung Health Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: O'Reilly
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Jackson
authors.forename: J Michael
authors.initials: JM
authors.lastname: Wells
authors.forename: Mark T
authors.initials: MT
authors.lastname: Dransfield
authors.forename: Paul D
authors.initials: PD
authors.lastname: Scanlon
authors.forename: J Edwin
authors.initials: JE
authors.lastname: Blalock
keywords: PGP