Morphological features of pulmonary fibrosis in workers occupationally exposed to alpha radiation

Purpose: The article reports on a comparative analysis of biological specimens of lung tissues collected from workers with pulmonary fibrosis induced by internal exposure to plutonium alpha-particles (plutonium-induced pulmonary fibrosis [PuPF]) and with etiologically different pulmonary fibrosis (non-PuPF) that developed as an outcome of a chronic obstructive pulmonary disease (COPD). Materials and methods: To perform histological examinations, lung tissues were sampled during autopsy. Six samples of various lung regions (the apical region, the lingula of the left lung and the inferior lobe) were collected from each donor. The resected tissue samples were fixed in 10% neutral-buffered formalin during 24 h and embedded into paraffin blocks (FFPE). FFPE blocks with lung tissue specimens collected from 56 workers with PuPF, 34 workers with non-PuPF and 35 workers without any lung disease were used in the study. To perform microscopic examination, lung tissue specimens were hematoxylin and eosin stained. To examine the connective-tissue scaffold of lung stroma and identify foci of pulmonary fibrosis, the cut sections of paraffin blocks were stained by Van Gizon’s method (to assess the total volume of fibrosis-affected tissues), Gomori’s technique (to define the reticular scaffold of lung stroma) and Weigert’s technique (to examine elastic fibers). Morphological patterns of all biological specimens were studied using immunohistochemistry. To fit the empirical data, the Weibull’s model was used. Results and conclusions: The study found qualitative and quantitative morphological features specific for PuPF compared to non-PuPF. The study demonstrated that hyper-production of collagen type V plays a key role in PuPF. The collagen type V content in fibrotic foci in lung tissue specimens from workers with PuPF was found to be increased.本研究旨在对比分析两类肺组织生物标本：一类取自因内照射钚α粒子诱发肺纤维化（钚诱导肺纤维化，plutonium-induced pulmonary fibrosis, PuPF）的从业者，另一类取自因慢性阻塞性肺疾病（chronic obstructive pulmonary disease, COPD）继发的病因不同的肺纤维化患者（非PuPF肺纤维化）。 材料与方法：本研究通过尸检获取肺组织样本以开展组织学检测。每名供体采集6份不同肺区域的样本，包括肺尖区、左肺舌叶及下叶。将切除的组织样本置于10%中性缓冲福尔马林中固定24小时，随后包埋制成石蜡块（福尔马林固定石蜡包埋，formalin-fixed paraffin-embedded, FFPE）。本研究共使用三类FFPE肺组织样本块：56份来自钚诱导肺纤维化从业者、34份来自非PuPF肺纤维化从业者，以及35份来自无任何肺部疾病的供体。 显微镜检测环节，首先对肺组织切片进行苏木精-伊红（hematoxylin and eosin, HE）染色；为观察肺基质结缔组织支架并定位肺纤维化病灶，分别采用范吉森（Van Gizon）染色法评估纤维化受累组织总体积、戈莫里（Gomori）染色法显示肺基质网状支架，以及韦格特（Weigert）染色法检测弹性纤维。所有生物样本的形态学特征均通过免疫组织化学方法进行分析。为拟合实验数据，本研究采用威布尔（Weibull）模型。 结果与结论：本研究发现，相较于非PuPF肺纤维化，钚诱导肺纤维化具有特异性的定性与定量形态学特征。研究证实，Ⅴ型胶原的过度生成在钚诱导肺纤维化进程中发挥关键作用，且钚诱导肺纤维化患者肺组织纤维化病灶内的Ⅴ型胶原含量显著升高。