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 language | English (US) |
|---|---|
| Article number | 5 |
| Journal | Respiratory Research |
| Volume | 15 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 12 2014 |
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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 journal › Article
}
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 -