Yehya Nadir
Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA, USA.
Transl Pediatr. 2021 Oct;10(10):2689-2699. doi: 10.21037/tp-20-341.
Since first described, acute respiratory distress syndrome (ARDS) has been understood to be an inflammatory disease with a dysregulated hyperinflammatory response. While fewer investigations have studied these phenomena in pediatric ARDS (PARDS), similar pathways are believed to be involved. Significant attention has been paid to the innate immune system, particularly neutrophils and neutrophil-related signaling, more recent studies have provided additional nuance regarding the role of upstream damage-associated molecular patterns (DAMPs) and subsequent neutrophil-mediated inflammation, lung permeability, and alveolar epithelial damage. For example, neutrophil extracellular traps (NETs) and inflammasome signaling have been identified as critical mediators existing at the junction of DAMPs and downstream inflammation. We demonstrate how the conclusions obtained from pre-clinical studies of lung injury are highly dependent upon the model chosen, and how this can lead us astray when developing therapies. More recently the adaptive immune system, specifically select T cell subpopulations, have also been implicated in ARDS. This raises the possibility of antigen-specific immunomodulation as a potential therapeutic avenue in ARDS. Finally, we briefly review randomized controlled trials attempting to manipulate the immune dysregulation in ARDS, including pleiotropic immunomodulators like corticosteroids and interferon-β, and what these studies can teach us about the design of novel therapeutics and the design of future trials.
自首次被描述以来，急性呼吸窘迫综合征（ARDS）就被认为是一种炎症性疾病，其炎症反应失调且过度。虽然针对小儿急性呼吸窘迫综合征（PARDS）中这些现象的研究较少，但据信涉及类似的途径。人们一直高度关注先天免疫系统，尤其是中性粒细胞和与中性粒细胞相关的信号传导，最近的研究对上游损伤相关分子模式（DAMPs）的作用以及随后中性粒细胞介导的炎症、肺通透性和肺泡上皮损伤提供了更多细微差别。例如，中性粒细胞胞外陷阱（NETs）和炎性小体信号传导已被确定为存在于DAMPs与下游炎症交界处的关键介质。我们展示了从肺损伤的临床前研究中得出的结论如何高度依赖于所选择的模型，以及这在开发治疗方法时如何可能使我们误入歧途。最近，适应性免疫系统，特别是特定的T细胞亚群，也被认为与ARDS有关。这增加了抗原特异性免疫调节作为ARDS潜在治疗途径的可能性。最后，我们简要回顾了试图控制ARDS免疫失调的随机对照试验，包括多效免疫调节剂如皮质类固醇和干扰素-β，以及这些研究能让我们了解新型治疗方法的设计和未来试验的设计。
