Abstract
ObjectiveAfter 9/11/2001, some Fire Department of New York (FDNY) workers had excessive lung function decline. We hypothesized that early serum matrix metalloproteinases (MMP) expression predicts World Trade Center-Lung Injury (WTC-LI) years later.MethodsThis is a nested case-control analysis of never-smoking male firefighters with normal pre-exposure Forced Expiratory Volume in one second (FEV1) who had serum drawn up to 155 days post 9/11/2001. Serum MMP-1, 2,3,7,8, 9, 12 and 13 were measured. Cases of WTC-LI (N = 70) were defined as having an FEV1 one standard deviation below the mean (FEV1≤77%) at subspecialty pulmonary evaluation (SPE) which was performed 32 months (IQR 21–53) post-9/11. Controls (N = 123) were randomly selected. We modeled MMP's ability as a predictor of cases status with logistic regression adjusted for time to blood draw, exposure intensity, weight gain and pre-9/11 FEV1.ResultsEach log-increase in MMP-3 and MMP-12 showed reduced odds of developing WTC-LI by 73% and 54% respectively. MMP-3 and MMP-12 consistently clustered together in cases, controls, and the cohort. Increasing time to blood draw significantly and independently increased the risk of WTC-LI.ConclusionsElevated serum levels of MMP-3 and MMP-12 reduce the risk of developing WTC-LI. At any level of MMP-3 or 12, increased time to blood draw is associated with a diminished protective effect.
Highlights
During the events of September 11th, 2001, the collapse of the World Trade Center (WTC) pulverized much of the building’s glass and metal structure and released an estimated 10 million tons of particulate matter (WTC-PM).[1,2,3,4] The bulk particulates were composed of cement, carbon, cellulose, and several fiber types including mineral wool, fiberglass and asbestos.[3,4] WTC-PM was collected, sieved, aerosolized, and was found to range in size from PM2.5 to PM53.[4]
This study investigates the levels of matrix metalloproteinases (MMP) present in serum after exposure to WTC dust in rescue workers as potential systemic biomarkers predicting susceptibility to World Trade Center Lung Injury (WTC-LI)
De-identified data devoid of sensitive information acquired through WTC National Institute of Occupational Safety and Health (NIOSH) funding is available to health researchers and others in accordance with the Zadroga Act and in full compliance with the Centers for Disease Control and Prevention (CDC) and the Agency for Toxic Substances and Disease Registry (ATSDR) Policy on Releasing and Sharing Data by request to the WTC Health Program directors
Summary
Study participants This study was approved by both Montefiore Medical Center and New York University IRB. Median time between 9/11/2001 and SPE for the baseline cohort was 34 months (IQR range for all groups 25–57).There was no significant difference in time to MME or SPE for controls and cases [Table 1]. Longitudinal lung function in cases and controls Three sequential pulmonary functions tests (PFT) were performed on this cohort; prior to exposure (Pre-9/11), at MME, and at SPE [Figure 2] [Table 2]. Predictive risk models We tested if the MMPs that were different between cases and controls predicted future lung function with logistic regression. All MMP levels remained as continuous variables and were logtransformed to approximate a normal distribution [Table 4].[38] Covariates in the adjusted models are days to blood draw (9/11 to MME), change in BMI between blood draw and case definition (MME to SPE), WTC exposure intensity, and pre-9/11 FEV1% predicted. As time to blood draw increased, the probability of developing WTCLI ranged from 70–90% in the MMP-3 model and from 40–70% for the MMP-12 model
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