急性呼吸窘迫综合症（ARDS）由于其异质性，在经过50年的高水平研究后，尚未有任何可改善死亡率的药物干预。（1）为了推进这一领域，需要更好的ARDS亚组的定义，这些亚组对治疗的反应更加一致。（2-6）大量优质的临床研究已经发现了下一代可溶性生物标志物，这些生物标志物提供了试验招募所需的预测富集，然而血浆可溶性标志物并不指定起源的受损器官，也不提供关于疾病机制的见解。在本文中，我们阐述了查询循环内皮细胞（CECs）的转录组的理由。当这些细胞在炎症侵袭后从血管中脱落时，它们成为特定部位的炎症损伤的先驱。我们回顾了CEC数量对多种疾病表型（包括心肌梗死、血管炎、癌症和ARDS）的应用，每种情况都支持CEC数量与疾病严重程度的关联。我们还提出了单细胞RNA转录组学在了解细胞特异性对疾病病理生理学的贡献以及揭示贡献于ARDS中CEC脱落的信号的潜力。

Acute Respiratory Distress Syndrome (ARDS) has had no mortality-improving pharmacological intervention despite 50 years of high-caliber research due to its heterogeneity.(1) For the field to advance, better definitions for ARDS subgroups that more uniformly respond to therapies are needed.(2-6) A plethora of high quality clinical research has uncovered the next generation of soluble biomarkers that provide the predictive enrichment necessary for trial recruitment, however plasma-soluble markers do not specify the damaged organ of origin nor do they provide insight into disease mechanisms. In this Perspective, we make the case for querying the transcriptome of circulating endothelial cells (CECs), which when shed from vessels after inflammatory insult, become heralds of site-specific inflammatory damage. We review the application of CEC quantification to multiple disease phenotypes (including myocardial infarction, vasculitides, cancer and ARDS), in each case supporting the association of CEC number with disease severity. We also argue for the utility of single-cell RNA transcriptomics to the understanding of cell-specific contributions to disease pathophysiology, and its potential to uncover novel insight on signals contributing to CEC shedding in ARDS.