PMID- 32171287
OWN - NLM
STAT- MEDLINE
DCOM- 20210120
LR  - 20221216
IS  - 1471-2466 (Electronic)
IS  - 1471-2466 (Linking)
VI  - 20
IP  - 1
DP  - 2020 Mar 14
TI  - Circulating matrix metalloproteinases and tissue metalloproteinase inhibitors in 
      patients with idiopathic pulmonary fibrosis in the multicenter IPF-PRO Registry 
      cohort.
PG  - 64
LID - 10.1186/s12890-020-1103-4 [doi]
LID - 64
AB  - 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 (DL(CO)) % 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.
FAU - Todd, Jamie L
AU  - Todd JL
AUID- ORCID: 0000-0003-4247-3693
AD  - Duke Clinical Research Institute, Durham, NC, USA. jamie.todd@duke.edu.
AD  - Division of Pulmonary, Allergy, and Critical Care Medicine, Department of 
      Internal Medicine, Duke University Medical Center, DUMC Box 103002, Durham, NC, 
      27710, USA. jamie.todd@duke.edu.
FAU - Vinisko, Richard
AU  - Vinisko R
AD  - Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA.
FAU - Liu, Yi
AU  - Liu Y
AD  - Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA.
FAU - Neely, Megan L
AU  - Neely ML
AD  - Duke Clinical Research Institute, Durham, NC, USA.
AD  - Division of Pulmonary, Allergy, and Critical Care Medicine, Department of 
      Internal Medicine, Duke University Medical Center, DUMC Box 103002, Durham, NC, 
      27710, USA.
FAU - Overton, Robert
AU  - Overton R
AD  - Duke Clinical Research Institute, Durham, NC, USA.
FAU - Flaherty, Kevin R
AU  - Flaherty KR
AD  - Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann 
      Arbor, MI, USA.
FAU - Noth, Imre
AU  - Noth I
AD  - University of Virginia, Charlottesville, VA, USA.
FAU - Newby, L Kristin
AU  - Newby LK
AD  - Duke Clinical Research Institute, Durham, NC, USA.
AD  - Division of Pulmonary, Allergy, and Critical Care Medicine, Department of 
      Internal Medicine, Duke University Medical Center, DUMC Box 103002, Durham, NC, 
      27710, USA.
AD  - Duke Clinical & Translational Science Institute, Durham, NC, USA.
FAU - Lasky, Joseph A
AU  - Lasky JA
AD  - School of Medicine, Tulane University, New Orleans, LA, USA.
FAU - Olman, Mitchell A
AU  - Olman MA
AD  - Department of Inflammation and Immunity and Respiratory Institute, Cleveland 
      Clinic, Cleveland, OH, USA.
FAU - Hesslinger, Christian
AU  - Hesslinger C
AD  - Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
FAU - Leonard, Thomas B
AU  - Leonard TB
AD  - Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA.
FAU - Palmer, Scott M
AU  - Palmer SM
AD  - Duke Clinical Research Institute, Durham, NC, USA.
AD  - Division of Pulmonary, Allergy, and Critical Care Medicine, Department of 
      Internal Medicine, Duke University Medical Center, DUMC Box 103002, Durham, NC, 
      27710, USA.
FAU - Belperio, John A
AU  - Belperio JA
AD  - David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
CN  - IPF-PRO Registry investigators
LA  - eng
GR  - R01 HL130796/HL/NHLBI NIH HHS/United States
GR  - R01 HL133721/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Multicenter Study
PT  - Observational Study
DEP - 20200314
PL  - England
TA  - BMC Pulm Med
JT  - BMC pulmonary medicine
JID - 100968563
RN  - 0 (Biomarkers)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - EC 3.4.24.- (Matrix Metalloproteinases, Secreted)
SB  - IM
MH  - Aged
MH  - Biomarkers/blood
MH  - Case-Control Studies
MH  - Female
MH  - Humans
MH  - Idiopathic Pulmonary Fibrosis/*blood/pathology
MH  - Linear Models
MH  - Lung/physiopathology
MH  - Male
MH  - Matrix Metalloproteinases, Secreted/*blood
MH  - Middle Aged
MH  - Multivariate Analysis
MH  - Predictive Value of Tests
MH  - Tissue Inhibitor of Metalloproteinases/*blood
MH  - Vital Capacity
PMC - PMC7071646
OTO - NOTNLM
OT  - Biomarkers
OT  - Extracellular matrix
OT  - Fibrosis
OT  - Interstitial lung diseases
OT  - Observational study
COIS- JLT, MLN, RO, LKN and SMP are employees of the Duke Clinical Research Institute, 
      which receives funding support from Boehringer Ingelheim Pharmaceuticals, Inc. to 
      coordinate the IPF-PRO Registry. KRF reports grants and personal fees from 
      Boehringer Ingelheim and Roche/Genentech and personal fees from FibroGen, Sanofi 
      Genzyme, and Veracyte. IN reports personal fees from Boehringer Ingelheim, 
      Genentech and ImmuneWorks. JAL reports personal fees from Boehringer Ingelheim, 
      Roche/Genentech, Galecto, Biogen and Veracyte. MAO reports research grant and 
      grant review fees from Boehringer Ingelheim. RV, KD, YL, CH and TBL are employees 
      of Boehringer Ingelheim. JAB has no competing interests.
FIR - Asi, Wael
IR  - Asi W
FIR - Baker, Albert
IR  - Baker A
FIR - Beegle, Scott
IR  - Beegle S
FIR - Condos, Rany
IR  - Condos R
FIR - Cordova, Francis
IR  - Cordova F
FIR - Culver, Daniel A
IR  - Culver DA
FIR - Luckhardt, Tracey
IR  - Luckhardt T
FIR - Dilling, Daniel
IR  - Dilling D
FIR - Glassberg, Marilyn
IR  - Glassberg M
FIR - Gulati, Mridu
IR  - Gulati M
FIR - Guntupalli, Kalpalatha
IR  - Guntupalli K
FIR - Gupta, Nishant
IR  - Gupta N
FIR - Hotchkin, David
IR  - Hotchkin D
FIR - Huie, Tristan
IR  - Huie T
FIR - Kaner, Robert
IR  - Kaner R
FIR - Kim, Hyun
IR  - Kim H
FIR - Kreider, Maryl
IR  - Kreider M
FIR - Lancaster, Lisa
IR  - Lancaster L
FIR - Lederer, David
IR  - Lederer D
FIR - Lee, Doug
IR  - Lee D
FIR - Liesching, Timothy
IR  - Liesching T
FIR - Lipchik, Randolph
IR  - Lipchik R
FIR - Lobo, Jason
IR  - Lobo J
FIR - Mageto, Yolanda
IR  - Mageto Y
FIR - Menon, Prema
IR  - Menon P
FIR - Morrison, Lake
IR  - Morrison L
FIR - Namen, Andrew
IR  - Namen A
FIR - Oldham, Justin
IR  - Oldham J
FIR - Raj, Rishi
IR  - Raj R
FIR - Ramaswamy, Murali
IR  - Ramaswamy M
FIR - Russell, Tonya
IR  - Russell T
FIR - Sachs, Paul
IR  - Sachs P
FIR - Safdar, Zeenat
IR  - Safdar Z
FIR - Sigal, Barry
IR  - Sigal B
FIR - Silhan, Leann
IR  - Silhan L
FIR - Strek, Mary
IR  - Strek M
FIR - Suliman, Sally
IR  - Suliman S
FIR - Tabak, Jeremy
IR  - Tabak J
FIR - Walia, Rajat
IR  - Walia R
FIR - Whelan, Timothy P
IR  - Whelan TP
EDAT- 2020/03/17 06:00
MHDA- 2021/01/21 06:00
PMCR- 2020/03/14
CRDT- 2020/03/16 06:00
PHST- 2019/07/29 00:00 [received]
PHST- 2020/02/28 00:00 [accepted]
PHST- 2020/03/16 06:00 [entrez]
PHST- 2020/03/17 06:00 [pubmed]
PHST- 2021/01/21 06:00 [medline]
PHST- 2020/03/14 00:00 [pmc-release]
AID - 10.1186/s12890-020-1103-4 [pii]
AID - 1103 [pii]
AID - 10.1186/s12890-020-1103-4 [doi]
PST - epublish
SO  - BMC Pulm Med. 2020 Mar 14;20(1):64. doi: 10.1186/s12890-020-1103-4.