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

doi:10.1186/1465-9921-15-5

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

Medicine

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

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 75^th 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 language	English (US)
Article number	5
Journal	Respiratory Research
Volume	15
Issue number	1
DOIs	https://doi.org/10.1186/1465-9921-15-5
State	Published - Jan 12 2014

Keywords

Biomarkers
Lung disease
Occupational exposure

ASJC Scopus subject areas

Pulmonary and Respiratory Medicine

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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",

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doi = "10.1186/1465-9921-15-5",

language = "English (US)",

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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

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

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Keywords

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