Department of Fisheries and Wildlife, Michigan State University, 303 Manly Miles Building, East Lansing, Michigan 48824, United States.
Environ Sci Technol. 2011 Jul 1;45(13):5828-33. doi: 10.1021/es200901e. Epub 2011 Jun 13.
The quantitative yardstick for quantitative microbial risk assessment (QMRA) is the dose response assessment phase. In this phase of the QMRA paradigm a mathematical model is used to describe the relationship between host response (infection, disease, etc.) and pathogen dose. There are, however, key uncertainties which if addressed can expand our understanding of the dose response relationship and improve its accuracy. The dose response models most frequently used in this phase of QMRA are based on the average exposed dose (i.e., inhaled, ingested, etc.). However once inhaled, spores are considered infectious after being transported to a specific region of the lungs (alveoli), therefore, average exposed dose does not account for this required spore transport through the respiratory system. It is the aim of this manuscript to develop a model for the in vivo delivered dose to the alveolated region of the lungs that accounts for losses of spores through the respiratory system. A stochastic system is used to account for the physics in the respiratory system that account for the various sinks during respiration. This stochastic system is then integrated into the exponential and beta Poisson dose response models. The stochastic model is also then expanded to the respiratory systems of guinea pigs and rhesus macaques as these are common animal models. This work develops a framework for a new class of dose response models accounting for host physiology, making progress to understanding dose response heterogeneity among hosts.
定量微生物风险评估（QMRA）的定量尺度是剂量反应评估阶段。在 QMRA 范式的这一阶段，使用数学模型来描述宿主反应（感染、疾病等）与病原体剂量之间的关系。然而，存在一些关键的不确定性因素，如果加以解决，可以扩展我们对剂量反应关系的理解，并提高其准确性。在 QMRA 的这一阶段最常使用的剂量反应模型基于平均暴露剂量（即吸入、摄入等）。然而，一旦吸入，孢子在被运送到肺部的特定区域（肺泡）后就被认为具有传染性，因此，平均暴露剂量并未考虑到通过呼吸系统进行的这种必需的孢子运输。本文的目的是开发一种模型，用于计算肺部肺泡区域的体内输送剂量，该模型考虑了通过呼吸系统损失的孢子。使用随机系统来解释呼吸系统中的物理学，这些物理学解释了呼吸过程中的各种汇。然后，将该随机系统集成到指数和贝塔泊松剂量反应模型中。然后，该随机模型还扩展到豚鼠和恒河猴的呼吸系统，因为这些是常见的动物模型。这项工作为一类新的剂量反应模型开发了一个框架，该模型考虑了宿主生理学，为理解宿主之间的剂量反应异质性迈出了一步。
