Silica Exposure & Silicosis: Effect of Mixed Exposures

描述(申请人提供)：数量关系 接触结晶性二氧化硅与矽肺的发展尚不确定 尽管进行了大量研究。不明朗的原因有以下几点： (A)曝光重建通常基于稀疏数据 重大不确定性；(B)获得累积 工人的肺部负担，不占同期接触的较少 有毒粉尘，归类为未作其他分类的颗粒(PNOC)。这个 本研究的目的是获得定量的剂量-反应关系。 结晶二氧化硅和矽肺之间的关系，以解决上述问题 三个问题。北卡罗来纳州达斯蒂贸易计划提供了大量数据 1935-1980年人类接触二氧化硅、PNOC和矽肺病例 为了这个目的。一种新的综合专家的贝叶斯方法 判断、曝光模型和历史测量将用于 曝光重建。药物动力学模型将被用来估计 肺内二氧化硅、PNOC和PNOC的累积剂量以及巨噬细胞形成的时间 在这种混合暴露的情况下超载。一项病例对照研究将是 对矽肺患者和无疾病参照者进行比较，并测试 以下假设：(1)累积暴露指标，包括 二氧化硅和PNOC与矽肺的发生发展的关系比 单独接触二氧化硅，(2)巨噬细胞超载的时间是 在尘埃行业中受雇的案例比非案例短，(3)时间 由于暴露在二氧化硅和PNOC混合物中，导致巨噬细胞超载 与矽肺患者首次接触疾病的时间有关。

DESCRIPTION (provided by applicant): The quantitative relationship between exposure to crystalline silica and development of silicosis is uncertain despite a number of studies. The uncertainty is due to the following reasons: (a) exposure reconstructions are typically based on sparse data with significant uncertainty; (b) dose reconstructions that obtain the cumulative lung burden of the worker, do not account for simultaneous exposures to less toxic dusts, categorized as particles not otherwise classified (PNOC). The purpose of this study is to obtain the quantitative dose-response relationship between crystalline silica and silicosis in a manner that addresses the above three issues. The North Carolina Dusty Trades program, provides a large data set of human exposures to silica and PNOC and silicosis cases from 1935-1980 for this purpose. A novel Bayesian methodology that synthesizes expert judgment, exposure models, and historical measurements will be used for exposure reconstruction. Pharmacokinetic modeling will be used to estimate the cumulative lung does of silica and PNOC, and PNOC, and the time to macrophage overload in this mixed exposure scenario. A case-control study will be conducted to compare silicotics and disease free referents and test the following hypotheses: (1) A cumulative exposure metric, which includes both silica and PNOC, is more related to the development of silicosis than cumulative silica exposure alone, (2) The time to macrophage overload is shorter among cases than non-cases employed in the dusty trades, (3) The time to macrophage overload, due to exposures to mixtures of silica and PNOC, is related to the time from first exposure to disease among silicosis cases.