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

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 (FEV(1)) 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 FEV(1) one standard deviation above the mean defined resistance to airway injury. Logistic regression was adjusted for pre-9/11 FEV(1), BMI, age and exposure intensity modeled the association between elevated biomarker expression and above average FEV(1). RESULTS: FEV(1) in cases and controls declined 10% of after 9/11/2001. Cases subsequently returned to 99% of their pre-exposure FEV(1) 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.