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：立体学工具箱。

吸入空气中的颗粒物可能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/或肺的组织病理学改变。常规的病理学评估通常通过对组织学病变进行评分，以获得“定量”信息和病变严重程度的估计值。这种方法不仅包括潜在的主观偏见（取决于检查者的判断），而且还传达了轻度改变无法引起研究者注意的风险。获取有关组织，细胞的三维（3D）特征的无偏定量信息的最准确方法，二维物理或光学切片中的细胞器是通过立体学（基于图像的形态计量学的黄金标准）进行的。然而，仅通过形态计量学参数（例如体积，表面，长度或数量）来表达组织病理学变化可能是具有挑战性的。因此，在本综述中，我们概述了与颗粒和纤维毒理学有关的呼吸道中不同的组织病理学病变，以及如何应用立体学方法正确量化和解释呼吸道中的组织学病变。本文的目的还在于指出定量组织病理学中的常见陷阱，并就如何通过立体学改善呼吸道毒理学提供一些建议。因此，