Analysis of correlation between pulmonary function and expression levels of matrix metalloproteinases-9 and tissue inhibitor of metalloproteinase-1 among toluene diisocyanate exposed workers

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To investigate the effect of occupational toluene diisocyanate(TDI) exposure on matrix metalloproteinases-9 (MMP-9) and tissue inhibitor of metalloproteinase-1(TIMP-1), and analysis of the correlation of MMP-9,TIMP-1,MMP-9/TIMP-1 and lung function. In October 2014, based on cluster sampling, we conducted a cross-sectional study in a TDI production factory located in China's western region. 61 exposed workers were recruited from workers engaged in packing, operating and checking. Based on different levels of the external exposure, the packers were classified as high exposed group, while operators and checkers as low exposed group. 58 factory managers, matching age and agent, were selected as controls, having same work intense and not contacting the TDI or other allergens. The questionnaire surveys were used to obtain the agent, age, work age, smoking and drinking, personal and family allergic history, occupational history, and the recent health conditions. The levels of MMP-9 and TIMP-1 in serum of subjects were determind by ELISA. The time weighted average concentrations (8h-TWA) were used to describe the levels of TDI air exposure in working environment. Spearman correlation assay was used to investigate the correlation of MMP-9, TIMP-1, MMP-9/TIMP-1 and lung function, exposure time. 8-hour TWA means of TDI air levels in exposed group, packers, operators and checkers were 0.39, 0.76, 0.25 mg/m(3), respectively . According to the external exposure concentration, the packers were classified as high exposed group, and the operators and checkers were classified as low exposed group. In controls, low exposed group and high exposed group, the levels of MMP-9, respectively, were (807.21±347.70),(586.91±317.50),(388.94±312.01) ng/ml (χ(2)=16.69, P<0.001), respectively, and the P50(P25-P75) of MMP-9/TIMP-1 were 4.67(2.87-6.68), 2.3(1.44-3.48), 1.11(0.59-1.48) (χ(2)=39.42, P<0.001), respectively, and the concentrations of TIMP-1, were (173.44±72.67), (236.12±51.98), (302.81±44.39) ng/ml (F=20.09, P< 0.001), respectively. The levels P50(P25-P75) of FVC, FEV1.0 and FEV1.0/FVC in exposed group were, 92.8% (86.0%-101.8%), 85.5%(76.7%-92.8%), 112.5(108.2-118.5), respectively, which were lower than that in control group (124.3%(107.9%-144.2%), 142.7%(119.1%-155.7%), 129.2(123.5-134))(Z values were 7.70, 8.97, 8.62, and all P<0.001). Spearman rank correlation analysis showed that levels of MMP-9 were positively associated with FEV1.0, and FEV1.0/FVC (r values were 0.27, 0.25, respectively, all P<0.05), and The levels of TIMP-1 were negatively associated with FVC, FEV1.0, and FEV1.0/FVC (r valuse were -0.33, -0.39, -0.39, all P<0.05).The levels of MMP-9 were negatively correlated with exposure time(r=-0.26, P=0.040). The positive correlations of MMP-9/TIMP-1 with FVC, FEV1.0, and FEV1.0/FVC were also found (r valuse were 0.34, 0.44, 0.40, all P<0.05). TDI exposure could induce the downs of MMP-9 and MMP-9/TIMP-1 associated with lung functions. The MMP-9 and MMP-9/TIMP-1,in a way, could reflect the respiratory inflammatory injury caused by TDI exposure.