An observational study of matrix metalloproteinase (MMP)-9 in cystic fibrosis

Graham Devereux, Sandra Steele, Timothy Jagelman, Shona Fielding, Robert Muirhead, Jeff Brady, Christal Grierson, Richard Booker, John Winter, Tom Fardon, Jonathan McCormick, Jeffrey Huang, Douglas Miller

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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.
Method: 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 b 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.
Original languageEnglish
Pages (from-to)557-563
Number of pages7
JournalJournal of Cystic Fibrosis
Issue number5
Early online date10 Feb 2014
Publication statusPublished - Sep 2014


  • cystic fibrosis
  • FEV1
  • MMP-9
  • TIMP-1
  • mortality


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