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

doi:10.1016/j.jcf.2014.01.010

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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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.

Original language	English
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	https://doi.org/10.1016/j.jcf.2014.01.010
Publication status	Published - Sep 2014

Keywords

cystic fibrosis
FEV1
MMP-9
TIMP-1
mortality

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10.1016/j.jcf.2014.01.010

An observational study of matrix metalloproteinase (MMP)-9 in cystic fibrosis
NOTICE: this is the author’s version of a work that was accepted for publication in Journal of Cystic Fibrosis. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Cystic Fibrosis VOL 13, ISSUE 5, 2014 DOI: 10.1016/j.jcf.2014.01.010
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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 negativelycorrelated with FEV1. This longitudinal study examined the association between MMP-9 and tissue inhibitors of metalloproteinases (TIMPs) toprognostic 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 andTIMP-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 rateof 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 andmortality in patients with CF.",

keywords = "cystic fibrosis, FEV1, MMP-9, TIMP-1, mortality",

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

note = "Acknowledgements This 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.",

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T1 - An observational study of matrix metalloproteinase (MMP)-9 in cystic fibrosis

AU - Devereux, Graham

AU - Steele, Sandra

AU - Jagelman, Timothy

AU - Fielding, Shona

AU - Muirhead, Robert

AU - Brady, Jeff

AU - Grierson, Christal

AU - Booker, Richard

AU - Winter, John

AU - Fardon, Tom

AU - McCormick, Jonathan

AU - Huang, Jeffrey

AU - Miller, Douglas

N1 - Acknowledgements This 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.

PY - 2014/9

Y1 - 2014/9

N2 - Background: In cystic fibrosis (CF), cross-sectional studies have reported sputum matrix metalloproteinase (MMP)-9 to be elevated and negativelycorrelated with FEV1. This longitudinal study examined the association between MMP-9 and tissue inhibitors of metalloproteinases (TIMPs) toprognostic 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 andTIMP-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 rateof 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 andmortality in patients with CF.

AB - Background: In cystic fibrosis (CF), cross-sectional studies have reported sputum matrix metalloproteinase (MMP)-9 to be elevated and negativelycorrelated with FEV1. This longitudinal study examined the association between MMP-9 and tissue inhibitors of metalloproteinases (TIMPs) toprognostic 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 andTIMP-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 rateof 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 andmortality in patients with CF.

KW - cystic fibrosis

KW - FEV1

KW - MMP-9

KW - TIMP-1

KW - mortality

U2 - 10.1016/j.jcf.2014.01.010

DO - 10.1016/j.jcf.2014.01.010

M3 - Article

VL - 13

SP - 557

EP - 563

JO - Journal of Cystic Fibrosis

JF - Journal of Cystic Fibrosis

SN - 1569-1993

IS - 5

ER -

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

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