MMP-2 and TIMP-1 predict healing of WTC-lung injury in New York City firefighters

Anna Nolan, Sophia Kwon, Soo J. Cho, Bushra Naveed, Ashley L. Comfort, David J. Prezant, William N. Rom, Michael D. Weiden

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Rationale: After 9/11/2001, most FDNY workers had persistent lung function decline but some exposed workers recovered. We hypothesized that the protease/anti-protease balance in serum soon after exposure predicts subsequent recovery.Methods: We performed a nested case-control study measuring biomarkers in serum drawn before 3/2002 and subsequent forced expiratory volume at one second (FEV1) on repeat spirometry before 3/2008. Serum was assayed for matrix metalloproteinases (MMP-1,2,3,7,8,9,12 and 13) and tissue inhibitors of metalloproteinases (TIMP-1,2,3,4). The representative sub-cohort defined analyte distribution and a concentration above 75th percentile defined elevated biomarker expression. An FEV1 one standard deviation above the mean defined resistance to airway injury. Logistic regression was adjusted for pre-9/11 FEV1, BMI, age and exposure intensity modeled the association between elevated biomarker expression and above average FEV1.Results: FEV1 in cases and controls declined 10% of after 9/11/2001. Cases subsequently returned to 99% of their pre-exposure FEV1 while decline persisted in controls. Elevated TIMP-1 and MMP-2 increased the odds of resistance by 5.4 and 4.2 fold while elevated MMP-1 decreased it by 0.27 fold.Conclusions: Resistant cases displayed healing, returning to 99% of pre-exposure values. High TIMP-1 and MMP-2 predict healing. MMP/TIMP balance reflects independent pathways to airway injury and repair after WTC exposure.

Original languageEnglish (US)
Article number5
JournalRespiratory Research
Volume15
Issue number1
DOIs
StatePublished - Jan 12 2014

Fingerprint

Firefighters
Tissue Inhibitor of Metalloproteinase-1
Lung Injury
Matrix Metalloproteinases
Biomarkers
Peptide Hydrolases
Serum
Tissue Inhibitor of Metalloproteinase-2
Matrix Metalloproteinase 1
Airway Resistance
Spirometry
Forced Expiratory Volume
Wounds and Injuries
Case-Control Studies
Logistic Models
Lung

Keywords

  • Biomarkers
  • Lung disease
  • Occupational exposure

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

MMP-2 and TIMP-1 predict healing of WTC-lung injury in New York City firefighters. / Nolan, Anna; Kwon, Sophia; Cho, Soo J.; Naveed, Bushra; Comfort, Ashley L.; Prezant, David J.; Rom, William N.; Weiden, Michael D.

In: Respiratory Research, Vol. 15, No. 1, 5, 12.01.2014.

Research output: Contribution to journalArticle

Nolan, A, Kwon, S, Cho, SJ, Naveed, B, Comfort, AL, Prezant, DJ, Rom, WN & Weiden, MD 2014, 'MMP-2 and TIMP-1 predict healing of WTC-lung injury in New York City firefighters', Respiratory Research, vol. 15, no. 1, 5. https://doi.org/10.1186/1465-9921-15-5
Nolan, Anna ; Kwon, Sophia ; Cho, Soo J. ; Naveed, Bushra ; Comfort, Ashley L. ; Prezant, David J. ; Rom, William N. ; Weiden, Michael D. / MMP-2 and TIMP-1 predict healing of WTC-lung injury in New York City firefighters. In: Respiratory Research. 2014 ; Vol. 15, No. 1.
@article{a46022f900eb49d4857c527d4efc19fd,
title = "MMP-2 and TIMP-1 predict healing of WTC-lung injury in New York City firefighters",
abstract = "Rationale: After 9/11/2001, most FDNY workers had persistent lung function decline but some exposed workers recovered. We hypothesized that the protease/anti-protease balance in serum soon after exposure predicts subsequent recovery.Methods: We performed a nested case-control study measuring biomarkers in serum drawn before 3/2002 and subsequent forced expiratory volume at one second (FEV1) on repeat spirometry before 3/2008. Serum was assayed for matrix metalloproteinases (MMP-1,2,3,7,8,9,12 and 13) and tissue inhibitors of metalloproteinases (TIMP-1,2,3,4). The representative sub-cohort defined analyte distribution and a concentration above 75th percentile defined elevated biomarker expression. An FEV1 one standard deviation above the mean defined resistance to airway injury. Logistic regression was adjusted for pre-9/11 FEV1, BMI, age and exposure intensity modeled the association between elevated biomarker expression and above average FEV1.Results: FEV1 in cases and controls declined 10{\%} of after 9/11/2001. Cases subsequently returned to 99{\%} of their pre-exposure FEV1 while decline persisted in controls. Elevated TIMP-1 and MMP-2 increased the odds of resistance by 5.4 and 4.2 fold while elevated MMP-1 decreased it by 0.27 fold.Conclusions: Resistant cases displayed healing, returning to 99{\%} of pre-exposure values. High TIMP-1 and MMP-2 predict healing. MMP/TIMP balance reflects independent pathways to airway injury and repair after WTC exposure.",
keywords = "Biomarkers, Lung disease, Occupational exposure",
author = "Anna Nolan and Sophia Kwon and Cho, {Soo J.} and Bushra Naveed and Comfort, {Ashley L.} and Prezant, {David J.} and Rom, {William N.} and Weiden, {Michael D.}",
year = "2014",
month = "1",
day = "12",
doi = "10.1186/1465-9921-15-5",
language = "English (US)",
volume = "15",
journal = "Respiratory Research",
issn = "1465-9921",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - MMP-2 and TIMP-1 predict healing of WTC-lung injury in New York City firefighters

AU - Nolan, Anna

AU - Kwon, Sophia

AU - Cho, Soo J.

AU - Naveed, Bushra

AU - Comfort, Ashley L.

AU - Prezant, David J.

AU - Rom, William N.

AU - Weiden, Michael D.

PY - 2014/1/12

Y1 - 2014/1/12

N2 - Rationale: After 9/11/2001, most FDNY workers had persistent lung function decline but some exposed workers recovered. We hypothesized that the protease/anti-protease balance in serum soon after exposure predicts subsequent recovery.Methods: We performed a nested case-control study measuring biomarkers in serum drawn before 3/2002 and subsequent forced expiratory volume at one second (FEV1) on repeat spirometry before 3/2008. Serum was assayed for matrix metalloproteinases (MMP-1,2,3,7,8,9,12 and 13) and tissue inhibitors of metalloproteinases (TIMP-1,2,3,4). The representative sub-cohort defined analyte distribution and a concentration above 75th percentile defined elevated biomarker expression. An FEV1 one standard deviation above the mean defined resistance to airway injury. Logistic regression was adjusted for pre-9/11 FEV1, BMI, age and exposure intensity modeled the association between elevated biomarker expression and above average FEV1.Results: FEV1 in cases and controls declined 10% of after 9/11/2001. Cases subsequently returned to 99% of their pre-exposure FEV1 while decline persisted in controls. Elevated TIMP-1 and MMP-2 increased the odds of resistance by 5.4 and 4.2 fold while elevated MMP-1 decreased it by 0.27 fold.Conclusions: Resistant cases displayed healing, returning to 99% of pre-exposure values. High TIMP-1 and MMP-2 predict healing. MMP/TIMP balance reflects independent pathways to airway injury and repair after WTC exposure.

AB - Rationale: After 9/11/2001, most FDNY workers had persistent lung function decline but some exposed workers recovered. We hypothesized that the protease/anti-protease balance in serum soon after exposure predicts subsequent recovery.Methods: We performed a nested case-control study measuring biomarkers in serum drawn before 3/2002 and subsequent forced expiratory volume at one second (FEV1) on repeat spirometry before 3/2008. Serum was assayed for matrix metalloproteinases (MMP-1,2,3,7,8,9,12 and 13) and tissue inhibitors of metalloproteinases (TIMP-1,2,3,4). The representative sub-cohort defined analyte distribution and a concentration above 75th percentile defined elevated biomarker expression. An FEV1 one standard deviation above the mean defined resistance to airway injury. Logistic regression was adjusted for pre-9/11 FEV1, BMI, age and exposure intensity modeled the association between elevated biomarker expression and above average FEV1.Results: FEV1 in cases and controls declined 10% of after 9/11/2001. Cases subsequently returned to 99% of their pre-exposure FEV1 while decline persisted in controls. Elevated TIMP-1 and MMP-2 increased the odds of resistance by 5.4 and 4.2 fold while elevated MMP-1 decreased it by 0.27 fold.Conclusions: Resistant cases displayed healing, returning to 99% of pre-exposure values. High TIMP-1 and MMP-2 predict healing. MMP/TIMP balance reflects independent pathways to airway injury and repair after WTC exposure.

KW - Biomarkers

KW - Lung disease

KW - Occupational exposure

UR - http://www.scopus.com/inward/record.url?scp=84892607238&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84892607238&partnerID=8YFLogxK

U2 - 10.1186/1465-9921-15-5

DO - 10.1186/1465-9921-15-5

M3 - Article

C2 - 24447332

AN - SCOPUS:84892607238

VL - 15

JO - Respiratory Research

JF - Respiratory Research

SN - 1465-9921

IS - 1

M1 - 5

ER -