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

Publication ,  Journal Article
Todd, JL; Vinisko, R; Liu, Y; Neely, ML; Overton, R; Flaherty, KR; Noth, I; Newby, LK; Lasky, JA; Olman, MA; Hesslinger, C; Leonard, TB ...
Published in: BMC Pulm Med
March 14, 2020

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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Published In

BMC Pulm Med

DOI

EISSN

1471-2466

Publication Date

March 14, 2020

Volume

20

Issue

1

Start / End Page

64

Location

England

Related Subject Headings

  • Vital Capacity
  • Tissue Inhibitor of Metalloproteinases
  • Respiratory System
  • Predictive Value of Tests
  • Multivariate Analysis
  • Middle Aged
  • Matrix Metalloproteinases, Secreted
  • Male
  • Lung
  • Linear Models
 

Citation

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Todd, J. L., Vinisko, R., Liu, Y., Neely, M. L., Overton, R., Flaherty, K. R., … IPF-PRO Registry investigators, . (2020). Circulating matrix metalloproteinases and tissue metalloproteinase inhibitors in patients with idiopathic pulmonary fibrosis in the multicenter IPF-PRO Registry cohort. BMC Pulm Med, 20(1), 64. https://doi.org/10.1186/s12890-020-1103-4
Todd, Jamie L., Richard Vinisko, Yi Liu, Megan L. Neely, Robert Overton, Kevin R. Flaherty, Imre Noth, et al. “Circulating matrix metalloproteinases and tissue metalloproteinase inhibitors in patients with idiopathic pulmonary fibrosis in the multicenter IPF-PRO Registry cohort.BMC Pulm Med 20, no. 1 (March 14, 2020): 64. https://doi.org/10.1186/s12890-020-1103-4.
Todd, Jamie L., et al. “Circulating matrix metalloproteinases and tissue metalloproteinase inhibitors in patients with idiopathic pulmonary fibrosis in the multicenter IPF-PRO Registry cohort.BMC Pulm Med, vol. 20, no. 1, Mar. 2020, p. 64. Pubmed, doi:10.1186/s12890-020-1103-4.
Todd JL, Vinisko R, Liu Y, Neely ML, Overton R, Flaherty KR, Noth I, Newby LK, Lasky JA, Olman MA, Hesslinger C, Leonard TB, Palmer SM, Belperio JA, IPF-PRO Registry investigators. Circulating matrix metalloproteinases and tissue metalloproteinase inhibitors in patients with idiopathic pulmonary fibrosis in the multicenter IPF-PRO Registry cohort. BMC Pulm Med. 2020 Mar 14;20(1):64.
Journal cover image

Published In

BMC Pulm Med

DOI

EISSN

1471-2466

Publication Date

March 14, 2020

Volume

20

Issue

1

Start / End Page

64

Location

England

Related Subject Headings

  • Vital Capacity
  • Tissue Inhibitor of Metalloproteinases
  • Respiratory System
  • Predictive Value of Tests
  • Multivariate Analysis
  • Middle Aged
  • Matrix Metalloproteinases, Secreted
  • Male
  • Lung
  • Linear Models