Early elevation of serum MMP-3 and MMP-12 predicts protection from World Trade Center-lung injury in New York City Firefighters: a nested case-control study

PLoS One. 2013 Oct 16;8(10):e76099. doi: 10.1371/journal.pone.0076099. eCollection 2013.

Abstract

Objective: After 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.

Methods: This 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.

Results: Each 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.

Conclusions: Elevated 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Firefighters*
  • Forced Expiratory Volume
  • Gene Expression
  • Humans
  • Logistic Models
  • Lung / metabolism
  • Lung / pathology
  • Lung Injury / blood*
  • Lung Injury / diagnosis
  • Lung Injury / enzymology
  • Lung Injury / pathology
  • Male
  • Matrix Metalloproteinase 12 / blood*
  • Matrix Metalloproteinase 12 / genetics
  • Matrix Metalloproteinase 3 / blood*
  • Matrix Metalloproteinase 3 / genetics
  • Middle Aged
  • New York City
  • Occupational Exposure*
  • Prognosis
  • September 11 Terrorist Attacks*
  • Time Factors

Substances

  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 12