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首页> 外文学位 >Development of a biomathematical lung model to describe respirable particle retention and to investigate exposure, dose, and disease in United States coal miners.
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Development of a biomathematical lung model to describe respirable particle retention and to investigate exposure, dose, and disease in United States coal miners.

机译：开发生物数学肺模型以描述可吸入颗粒物的保留情况，并研究美国煤矿工人的暴露，剂量和疾病。

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摘要

Biomathematical and statistical models were used in this study to describe exposure, dose, and disease relationships in coal miners. A three-compartment lung model was developed to investigate the long-term retention of insoluble, respirable particles in human lungs. The purposes of this model were to (1) predict the lung and lymph node dust burdens in U.S. coal miners from their working lifetime exposure histories, and (2) evaluate in humans the relevance of certain findings in rat studies, including the overloading of alveolar clearance. The 131 miners in this study had worked in the Beckley, West Virginia, area and were included in an autopsy study during the 1960's. Initial parameter estimates for this model were based on information on the biological and physical factors influencing particle deposition and clearance in the lungs of humans and animals. The model fit to the data was evaluated using both qualitative and quantitative (least squares) approaches. The lung dust burdens in these coal miners exceed those expected from first-order clearance kinetics. Yet, in the biomathematical exposure-dose models, the assumption of overloading of alveolar macrophage-mediated clearance was neither sufficient nor necessary to explain the lung dust burdens in these miners. The models that provided the best fit to the data were those that included first-order interstitialization/sequestration and either no dose-dependent decline in alveolar clearance or much less decline than expected from the rat studies. These finding are consistent with the particle retention patterns observed in the lungs of larger, nonrodent mammals. In logistic regression models, both the measured and the model-predicted lung dust burdens indicate similar probabilities of developing fibrotic lung disease in these miners. This biomathematical exposure-dose model may be useful in the development of risk assessment methods for particle-induced lung diseases.
机译：在这项研究中，使用了生物数学和统计模型来描述煤矿工人的暴露，剂量和疾病之间的关系。建立了一个三室肺模型，以研究人肺中不溶性，可呼吸颗粒的长期保留。该模型的目的是（1）根据其工作寿命暴露历史预测美国煤矿工人的肺部和淋巴结尘埃负担，以及（2）在人类中评估大鼠研究中某些发现的相关性，包括肺泡超负荷清除。这项研究中的131名矿工曾在西弗吉尼亚州贝克利工作，并于1960年代被纳入尸检研究。该模型的初始参数估计是基于有关影响人和动物肺部颗粒沉积和清除的生物学和物理因素的信息。使用定性和定量（最小二乘）方法评估适合数据的模型。这些煤矿工人的肺尘负担超过了一阶清除动力学所预期的负担。然而，在生物数学暴露剂量模型中，肺泡巨噬细胞介导的清除能力超负荷的假设既不足以也没有必要解释这些矿工的肺尘负担。提供最适合数据的模型是那些包括一阶间质化/隔离和既没有剂量依赖性的肺泡清除率下降，也没有比大鼠研究预期的少得多的模型。这些发现与在较大的非啮齿类哺乳动物的肺中观察到的颗粒保留模式一致。在逻辑回归模型中，无论是实测的还是模型预测的肺尘埃负荷，都表明在这些矿工中发生纤维化性肺病的可能性相似。这种生物数学的暴露-剂量模型可能有助于开发颗粒物诱发的肺部疾病的风险评估方法。

著录项

  • 作者

    Kuempel, Eileen Devine.;

  • 作者单位

    University of Cincinnati.;

  • 授予单位 University of Cincinnati.;
  • 学科 Health Sciences Occupational Health and Safety.;Health Sciences Toxicology.
  • 学位 Ph.D.
  • 年度 1997
  • 页码 364 p.
  • 总页数 364
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 职业性疾病预防;毒物学（毒理学）;
  • 关键词

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