MMP-2 and TIMP-1 predict healing of WTC-lung injury in New York City firefighters.
BACKGROUND
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.
Anna
A
Nolan
Sophia
S
Kwon
Soo Jung
SJ
Cho
Bushra
B
Naveed
Ashley L
AL
Comfort
David J
DJ
Prezant
William N
WN
Rom
Division of Pulmonary, Critical Care and Sleep, New York University, School of Medicine, 462 First Avenue, NB7N24, New York NY, USA. michael.weiden@med.nyu.edu.
Michael D
MD
Weiden
D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D061388:Firefighters; D006801:Humans; D055370:Lung Injury / Q000097:blood* / Q000175:diagnosis* / Q000453:epidemiology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D008875:Middle Aged; D009519:New York City / Q000453:epidemiology; D016273:Occupational Exposure / Q000032:analysis*; D011237:Predictive Value of Tests; D047851:September 11 Terrorist Attacks; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*
D015415:Biomarkers; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2