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

TY - JOUR

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 - Brooker, Richard

AU - Winter, John

AU - Fardon, Tom

AU - McCormick, Jonathan

AU - Huang, Jeffrey T.J.

AU - Miller, Douglas

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 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<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.

AB - 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<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.

KW - Cystic fibrosis

KW - FEV

KW - MMP-9

KW - Mortality

KW - TIMP-1

U2 - 10.1016/j.jcf.2014.01.010

DO - 10.1016/j.jcf.2014.01.010

M3 - Article

C2 - 24525080

AN - SCOPUS:84926134611

SN - 1569-1993

VL - 13

SP - 557

EP - 563

JO - Journal of Cystic Fibrosis

JF - Journal of Cystic Fibrosis

IS - 5

ER -