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BMC Pulmonary Medicine
Published in: BMC Pulmonary Medicine 1/2020

01-12-2020 | Idiopathic Pulmonary Fibrosis | Research article

Circulating matrix metalloproteinases and tissue metalloproteinase inhibitors in patients with idiopathic pulmonary fibrosis in the multicenter IPF-PRO Registry cohort

Authors: Jamie L. Todd, Richard Vinisko, Yi Liu, Megan L. Neely, Robert Overton, Kevin R. Flaherty, Imre Noth, L. Kristin Newby, Joseph A. Lasky, Mitchell A. Olman, Christian Hesslinger, Thomas B. Leonard, Scott M. Palmer, John A. Belperio, on behalf of the IPF-PRO Registry investigators

Published in: BMC Pulmonary Medicine | Issue 1/2020

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Abstract

Background

Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) play important roles in the turnover of extracellular matrix and in the pathogenesis of idiopathic pulmonary fibrosis (IPF). This study aimed to determine the utility of circulating MMPs and TIMPs in distinguishing patients with IPF from controls and to explore associations between MMPs/TIMPs and measures of disease severity in patients with IPF.

Methods

The IPF cohort (n = 300) came from the IPF-PRO Registry, an observational multicenter registry of patients with IPF that was diagnosed or confirmed at the enrolling center in the past 6 months. Controls (n = 100) without known lung disease came from a population-based registry. Generalized linear models were used to compare circulating concentrations of MMPs 1, 2, 3, 7, 8, 9, 12, and 13 and TIMPs 1, 2, and 4 between patients with IPF and controls, and to investigate associations between circulating levels of these proteins and measures of IPF severity. Multivariable models were fit to identify the MMP/TIMPs that best distinguished patients with IPF from controls.

Results

All the MMP/TIMPs analyzed were present at significantly higher levels in patients with IPF compared with controls except for TIMP2. Multivariable analyses selected MMP8, MMP9 and TIMP1 as top candidates for distinguishing patients with IPF from controls. Higher concentrations of MMP7, MMP12, MMP13 and TIMP4 were significantly associated with lower diffusion capacity of the lung for carbon monoxide (DLCO) % predicted and higher composite physiologic index (worse disease). MMP9 was associated with the composite physiologic index. No MMP/TIMPs were associated with forced vital capacity % predicted.

Conclusions

Circulating MMPs and TIMPs were broadly elevated among patients with IPF. Select MMP/TIMPs strongly associated with measures of disease severity. Our results identify potential MMP/TIMP targets for further development as disease-related biomarkers.
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Metadata
Title
Circulating matrix metalloproteinases and tissue metalloproteinase inhibitors in patients with idiopathic pulmonary fibrosis in the multicenter IPF-PRO Registry cohort
Authors
Jamie L. Todd
Richard Vinisko
Yi Liu
Megan L. Neely
Robert Overton
Kevin R. Flaherty
Imre Noth
L. Kristin Newby
Joseph A. Lasky
Mitchell A. Olman
Christian Hesslinger
Thomas B. Leonard
Scott M. Palmer
John A. Belperio
on behalf of the IPF-PRO Registry investigators
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Pulmonary Medicine / Issue 1/2020
Electronic ISSN: 1471-2466
DOI
https://doi.org/10.1186/s12890-020-1103-4

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