The inhalation of airborne particles can lead to pathological changes in the respiratory tract. For this reason, toxicology studies on effects of inhalable particles and fibers often include an assessment of histopathological alterations in the upper respiratory tract, the trachea and/or the lungs. Conventional pathological evaluations are usually performed by scoring histological lesions in order to obtain “quantitative” information and an estimation of the severity of the lesion. This approach not only comprises a potential subjective bias, depending on the examiner’s judgment, but also conveys the risk that mild alterations escape the investigator’s eye. The most accurate way of obtaining unbiased quantitative information about three-dimensional (3D) features of tissues, cells, or organelles from two-dimensional physical or optical sections is by means of stereology, the gold standard of image-based morphometry. Nevertheless, it can be challenging to express histopathological changes by morphometric parameters such as volume, surface, length or number only. In this review we therefore provide an overview on different histopathological lesions in the respiratory tract associated with particle and fiber toxicology and on how to apply stereological methods in order to correctly quantify and interpret histological lesions in the respiratory tract. The article further aims at pointing out common pitfalls in quantitative histopathology and at providing some suggestions on how respiratory toxicology can be improved by stereology. Thus, we hope that this article will stimulate scientists in particle and fiber toxicology research to implement stereological techniques in their studies, thereby promoting an unbiased 3D assessment of pathological lesions associated with particle exposure.

中文翻译：

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评估呼吸系统中的颗粒和纤维毒理学：体视学工具箱。


吸入空气中的颗粒物可导致呼吸道发生病理变化。因此，关于可吸入颗粒和纤维影响的毒理学研究通常包括评估上呼吸道、气管和/或肺部的组织病理学变化。传统的病理评估通常通过对组织学病变进行评分来进行，以获得“定量”信息并估计病变的严重程度。这种方法不仅包含潜在的主观偏见（取决于检查者的判断），而且还传达了轻微改变逃过研究者眼睛的风险。从二维物理或光学切片获取有关组织、细胞或细胞器的三维 (3D) 特征的无偏见定量信息的最准确方法是通过体视学，这是基于图像的形态测量的黄金标准。然而，仅通过体积、表面、长度或数量等形态参数来表达组织病理学变化可能具有挑战性。因此，在这篇综述中，我们概述了与颗粒和纤维毒理学相关的呼吸道不同组织病理学病变，以及如何应用体视学方法来正确量化和解释呼吸道组织学病变。本文进一步旨在指出定量组织病理学中的常见陷阱，并就如何通过体视学改进呼吸毒理学提供一些建议。 因此，我们希望本文能够刺激颗粒和纤维毒理学研究的科学家在他们的研究中实施体视学技术，从而促进对与颗粒暴露相关的病理损伤进行公正的 3D 评估。