Published in:
Open Access 01-12-2014 | Research
MMP-2 and TIMP-1 predict healing of WTC-lung injury in New York City firefighters
Published in: Respiratory Research | Issue 1/2014
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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.