混合效应模型在研究接触—效应关系中的应用

Application of Mixed Effect Model to the Study of Exposure-effect Relationship

目的用混合效应模型研究工人接苯水平与白细胞水平的关系及其影响因素,并确定最适接触剂量指标。方法在21个体检年度分别对每个研究对象的每次体检时估算区域浓度、8 h时间加权平均浓度(TWA8)、年度接触水平和累积接触水平。将接触水平定义为协变量,白细胞计数定义为效应变量,用混合效应模型分析剂量—效应关系。结果共观察接苯对象147名26 292人月,白细胞计数样本1 147份、对照组66名14 112人月白细胞计数样本396份。接触组、对照组白细胞计数平均水平分别为5.36×109,6.13×109/L。平均区域浓度、TWA8、年度接触水平和累积接触水平分别为5.10 mg/m3,4.69 mg/m3,72.90 mg/m3.月,783.70 mg/m3.月。4个混合效应模型均能收敛,其中以TWA8信息标准值最低。工人接苯水平增加、接触时间增长,白细胞水平下降。性别、吸烟与否对白细胞水平无明显影响。结论工人接苯水平和时间明显影响工人白细胞水平,TWA8可能是最适接触剂量指标。

Objective To study the relationship of benzene exposure level and leukocyte count and its risk factors by mixed effect model, and to determine the most appropriate index of exposure level. Methods Area concentrations, 8 hours time weighted averages（TWA8 ）, yearly levels and cumulated exposure levels were assessed respectively for every case within 21 physical check years. Defining exposure levels and leukocyte counts as co-variables and leukocyte counts as effect variables, the dose-effect relationship was analyzed by mixed effect model. Results 147 benzene exposed workers were observed for 26 292 personmonths collecting 1 147 leukocyte count samples. 396 leukocyte count .samples collected from 66 workers within 14 112 per.son-months were taken as the controls. The mean values of leukocyte counts for exposed cases and the controls were 5.36×10^9/L and 6.13 × 10^9/L respectively. The mean area exposure levels, TWAs, yearly levels and cumulated levels were 5.10 mg/m^3, 4.69 mg/m^3, 72.90 mg/m^2· month and 783.70 mg/m^3 month. All four mixed effect model.s could converge, among them the critical information value of TWA8 model was the lowest. Leukocyte counts decreased with the increase of exposure level and time. No significant effect was found to be associated with the leukocyte count levels and sex or smoking. Conclusions For benzene exposed workers, the exposure level and time remarkably affect the leukocyte counts. TWA8 might be the most appropriate index of exposure level.