title: An observational study of matrix metalloproteinase (MMP)-9 in cystic fibrosis.
abstract: BACKGROUND
  In cystic fibrosis (CF), cross-sectional studies have reported sputum matrix metalloproteinase (MMP)-9 to be elevated and negatively correlated with FEV1. This longitudinal study examined the association between MMP-9 and tissue inhibitors of metalloproteinases (TIMPs) to prognostic parameters in CF.
  
  
  METHODS
  A cross-sectional survey of CF and control subjects; CF patients were followed up for a median of 49 months. MMP-9 and TIMP-1 and TIMP-2 were quantified in sputum and plasma.
  
  
  RESULTS
  Seventy-three patients with CF, median age 22 years, and 40 controls were recruited. Fifty-three of these CF patients were followed up. Prospectively, in CF subjects, plasma MMP-9 activity was adversely associated with FEV1 (β -1.15 (95% CI -2.10, -0.20), p = 0.019) and rate of FEV1 decline, and plasma TIMP-1 was adversely associated with mortality: hazard ratio 3.66 (1.91-7.04), p < 0.001.
  
  
  CONCLUSIONS
  These associations further justify investigation of MMP-9 and TIMP-1 as biomarkers for short- to medium-term FEV1 decline and mortality in patients with CF.
authors: Section of Population Health, University of Aberdeen, Aberdeen AB25 2ZG, UK; Respiratory Medicine, Aberdeen Royal Infirmary, Aberdeen AB25 2ZN, UK. Electronic address: g.devereux@abdn.ac.uk.
authors: Graham
authors: G
authors: Devereux
authors: Respiratory Medicine, Aberdeen Royal Infirmary, Aberdeen AB25 2ZN, UK.
authors: Sandra
authors: S
authors: Steele
authors: Respiratory Medicine, Aberdeen Royal Infirmary, Aberdeen AB25 2ZN, UK.
authors: Timothy
authors: T
authors: Jagelman
authors: Section of Population Health, University of Aberdeen, Aberdeen AB25 2ZG, UK.
authors: Shona
authors: S
authors: Fielding
authors: School of Nursing and Midwifery, University of Dundee, Dundee DD1 9SY, UK.
authors: Robert
authors: R
authors: Muirhead
authors: TMRC Laboratory, University of Dundee, Dundee DD1 5EH, UK.
authors: Jeff
authors: J
authors: Brady
authors: TMRC Laboratory, University of Dundee, Dundee DD1 5EH, UK.
authors: Christal
authors: C
authors: Grierson
authors: Department of Paediatrics, Royal Aberdeen Children's Hospital, Aberdeen AB25 2ZG, UK.
authors: Richard
authors: R
authors: Brooker
authors: Department of Respiratory Medicine, Ninewells Hospital, Dundee DD1 9SY, UK.
authors: John
authors: J
authors: Winter
authors: Department of Respiratory Medicine, Ninewells Hospital, Dundee DD1 9SY, UK.
authors: Tom
authors: T
authors: Fardon
authors: Department of Respiratory Medicine, Ninewells Hospital, Dundee DD1 9SY, UK.
authors: Jonathan
authors: J
authors: McCormick
authors: TMRC Laboratory, University of Dundee, Dundee DD1 5EH, UK; Discovery Translational Medicine, Pfizer Research, Collegeville, PA 19426, USA.
authors: Jeffrey T J
authors: JT
authors: Huang
authors: Discovery Translational Medicine, Pfizer Research, Collegeville, PA 19426, USA.
authors: Douglas
authors: D
authors: Miller
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000032:analysis; D002648:Child; D003430:Cross-Sectional Studies; D003550:Cystic Fibrosis / Q000201:enzymology* / Q000401:mortality / Q000503:physiopathology; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000032:analysis* / Q000097:blood; D013183:Sputum / Q000201:enzymology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis; D055815:Young Adult
chemical_list: D015415:Biomarkers; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Cystic fibrosis; FEV(1); MMP-9; Mortality; TIMP-1