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Title: [Analysis of the relationship between the changes of lung function and serum proinflammatory cytokines in workers occupationally exposed to toluene diisocyanate].
Author: Niu Y, Miao PP, Wang JC, Meng T, Jia Q, Shen ML, Bin P, Duan HW, Shao H, Dai YF.
Journal: Zhonghua Yu Fang Yi Xue Za Zhi; 2020 Jun 06; 54(6):673-678. PubMed ID: 32842285.
Abstract:
Objective: To analyze the correlation between the changes of lung function and serum proinflammatory cytokines in workers occupationally exposed to toluene diisocyanate (TDI), and to explore the evaluation index of respiratory toxicity of TDI. Methods: In October 2014, 61 male workers engaged in TDI synthesis process, purification process, packaging process and the above production process in a TDI factory in western China were selected as TDI exposure group; 62 male enterprise managers who were not exposed to TDI and other known allergenic chemicals were selected as control group, which were matched at the age of workers in exposure group. The questionnaire survey obtained information such as gender, length of service, age, occupational history, exposed length of service and so on. The lung function indexes [forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC] and serum levels of interleukin (IL)-1 β, IL-6, IL-8, tumor necrosis factor (TNF)-α, macrophage inflammatory factor-1 β, monocyte chemoattractant factor-1 and vascular endothelial growth factor were measured. The urine was collected after the weekend shift, and the concentration of (TDA), the metabolite of TDI, was determined as the index of internal exposure. Spearman rank correlation was used to analyze the correlation between cytokines and lung function indexes, and multivariate linear regression was used to analyze the changes of lung function indexes and cytokines with TDI exposure concentration and time. Results: The median age (P₅-P₉₅) of the exposed group and the control group was 36.5 (24.0-51.0) and 38.0 (24.0-50.0) years, respectively. In the exposed group, the median length of service (P₅-P₉₅) was 6.94 (0.97-26.33) years, and the median concentration of TDA in urine was 15.56 (2.28-112.16) ng/ml. The three indexes of lung function, FVC, FEV1, FEV1/FVC and the levels of serum IL-8 and TNF-α were significantly lower than those in the control group (P<0.01). With the increase of exposure concentration and exposure time, the level of serum TNF-α, FVC and FEV1 decreased, and showed a good dose-effect and time-effect relationship (all P_trend values< 0.05). Serum IL-8 and TNF-α were positively correlated with FVC, FEV1 and FEV1/FVC (all P values<0.01). Conclusion: The levels of serum inflammatory factors IL-8 and TNF-α in worker exposed to TDI are related to lung function indexes, which can be used as early evaluation indexes of respiratory toxicity induced by TDI. 目的： 分析甲苯二异氰酸酯（TDI）职业暴露工人肺功能的改变与血清促炎细胞因子的相关性，探索TDI呼吸系统毒作用的效应评价指标。 方法： 于2014年10月，以中国西部地区某TDI生产厂中从事TDI合成工序、提纯工序、包装工序及上述生产过程的巡检工序的61名男性作业工人为TDI暴露组，主要经吸入蒸汽和气溶胶暴露；以该工厂中不接触TDI及其他已知致敏性化学物的62名男性企业管理人员作为对照组，与暴露组工人年龄匹配。问卷调查获得性别、工龄、年龄、职业史、暴露工龄等信息，检测工人肺功能指标[第一秒用力呼吸容积（FEV₁）、用力肺活量（FVC）、FEV₁/FVC]及血清中细胞因子[白细胞介素（IL）-8、肿瘤坏死因子（TNF）-α等]水平；收集周末班后尿，测定尿液中TDI的代谢物甲苯二胺（TDA）浓度作为内暴露指标。采用Spearman秩相关分析细胞因子与肺功能指标的相关性；采用多重线性回归分析肺功能指标、细胞因子随TDI暴露浓度和时间变化的趋势。 结果： 暴露组和对照组工人年龄M（P₅~P₉₅）分别为36.5（24.0~51.0）和38.0（24.0~50.0）岁，暴露组工龄M（P₅~P₉₅）为6.94（0.97~26.33）年，尿液TDA浓度M（P₅ ~ P₉₅）为15.56（2.28~112.16）ng/ml。与对照组比较，暴露组肺功能3项指标FVC、FEV₁、FEV₁/FVC以及血清中IL-8和TNF-α水平均明显降低（P值均<0.05）。随着暴露浓度的增加和暴露时间的延长，血清TNF-α水平及FVC、FEV₁均呈降低的趋势，且呈剂量-效应和时间-效应关系（P_趋势值均< 0.05）。血清IL-8、TNF-α均与FVC、FEV₁、FEV₁/FVC呈正相关（P值均<0.05）。 结论： TDI暴露工人血清炎性因子IL-8和 TNF-α水平与肺功能指标有关联，可作为TDI致呼吸系统毒作用的早期效应评价指标。.

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