Vaping is an increasing health threat in the US and worldwide. The damaging impact of vaping on the human distal lung has been highlighted by the recent epidemic of electronic cigarette or vaping use-associated lung injury (EVALI). The pathogenesis of EVALI remains incompletely understood, due to a paucity of models that recapitulate the structural and functional complexity of the human distal lung and the still poorly defined culprit exposures to vaping products and respiratory viral infections. Our aim was to establish the feasibility of using single cell RNA-sequencing (scRNA-seq) technology in human precision-cut lung slices (PCLS) as a more physiologically relevant model to better understand how vaping regulates the antiviral and pro-inflammatory response to influenza A virus infection. Normal healthy donor PCLS were treated with vaping extract and influenza A viruses for scRNA-seq analysis. Vaping extract augmented host antiviral and pro-inflammatory responses in structural cells such as lung epithelial cells and fibroblasts, as well as in immune cells such as macrophages and monocytes. Our findings suggest that human distal lung slice model is useful to study the heterogeneous responses of immune and structural cells under EVALI conditions, such as vaping and respiratory viral infection.

中文翻译：

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人体精密切割肺切片的单细胞 RNA 测序：一种研究电子烟和病毒感染对肺部健康影响的新方法。

在美国和世界范围内，电子烟对健康的威胁日益严重。最近流行的电子烟或电子烟使用相关肺损伤（EVALI）凸显了电子烟对人类远端肺部的破坏性影响。由于缺乏能够概括人类远端肺的结构和功能复杂性的模型，并且对电子烟产品暴露和呼吸道病毒感染的罪魁祸首仍不清楚，因此 EVALI 的发病机制仍不完全清楚。我们的目标是确定在人体精密切割肺切片 (PCLS) 中使用单细胞 RNA 测序 (scRNA-seq) 技术作为更具生理相关性的模型的可行性，以更好地了解电子烟如何调节抗病毒和促炎反应甲型流感病毒感染。使用电子烟提取物和甲型流感病毒处理正常健康供体 PCLS 进行 scRNA-seq 分析。电子烟提取物增强了宿主结构细胞（如肺上皮细胞和成纤维细胞）以及免疫细胞（如巨噬细胞和单核细胞）的抗病毒和促炎反应。我们的研究结果表明，人类远端肺切片模型可用于研究 EVALI 条件下（例如电子烟和呼吸道病毒感染）下免疫和结构细胞的异质反应。