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.
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.
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 language | English |
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Pages (from-to) | 557-563 |
Number of pages | 7 |
Journal | Journal of Cystic Fibrosis |
Volume | 13 |
Issue number | 5 |
Early online date | 10 Feb 2014 |
DOIs | |
Publication status | Published - Sept 2014 |
Bibliographical note
AcknowledgementsThis work was supported by awards from the University of Aberdeen Development Trust and (TMRC INF_AU_124) from the Translational Medicine Research Collaboration — a consortium made up of the Universities of Aberdeen, Dundee, Edinburgh and Glasgow, the four associated NHS Health Boards (Grampian, Tayside, Lothian and Greater Glasgow & Clyde), Scottish Enterprise and Wyeth Pharmaceuticals. We would like to acknowledge the help of Mrs Irene Pucci who collected the paediatric samples in Aberdeen, Mrs Gillian Moir who processed the sputum and blood samples in Aberdeen, and Nicola Stevens and Dr Anna Tommasi who were involved in the collection and processing of samples in Dundee.
Keywords
- cystic fibrosis
- FEV1
- MMP-9
- TIMP-1
- mortality