Graham Devereux1, Sandra Steele2, Timothy Jagelman2, Shona Fielding3, Robert Muirhead4, Jeff Brady5, Christal Grierson5, Richard Brooker6, John Winter7, Tom Fardon7, Jonathan McCormick7, Jeffrey T J Huang8, Douglas Miller9. 1. 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. 2. Respiratory Medicine, Aberdeen Royal Infirmary, Aberdeen AB25 2ZN, UK. 3. Section of Population Health, University of Aberdeen, Aberdeen AB25 2ZG, UK. 4. School of Nursing and Midwifery, University of Dundee, Dundee DD1 9SY, UK. 5. TMRC Laboratory, University of Dundee, Dundee DD1 5EH, UK. 6. Department of Paediatrics, Royal Aberdeen Children's Hospital, Aberdeen AB25 2ZG, UK. 7. Department of Respiratory Medicine, Ninewells Hospital, Dundee DD1 9SY, UK. 8. TMRC Laboratory, University of Dundee, Dundee DD1 5EH, UK; Discovery Translational Medicine, Pfizer Research, Collegeville, PA 19426, USA. 9. Discovery Translational Medicine, Pfizer Research, Collegeville, PA 19426, USA.
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 < 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.
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.
Authors: Benjamin T Kopp; James Fitch; Lisa Jaramillo; Chandra L Shrestha; Frank Robledo-Avila; Shuzhong Zhang; Sabrina Palacios; Fred Woodley; Don Hayes; Santiago Partida-Sanchez; Octavio Ramilo; Peter White; Asuncion Mejias Journal: J Cyst Fibros Date: 2019-08-29 Impact factor: 5.482
Authors: Michele Y F Kong; Richard J Whitley; Ning Peng; Robert Oster; Trenton R Schoeb; Wayne Sullender; Namasivayam Ambalavanan; John Paul Clancy; Amit Gaggar; J Edwin Blalock Journal: Viruses Date: 2015-07-30 Impact factor: 5.048