Alveolar Biomarker Profiles in Subphenotypes of the Acute Respiratory Distress Syndrome.
Alveolar Biomarker Profiles in Subphenotypes of the Acute Respiratory Distress Syndrome.
复制标题
急性呼吸窘迫综合征亚表型的肺泡生物标志物概况。
DOI：
10.1097/ccm.0000000000005704
复制
发表时间：
2023
影响因子：
8.8
通讯作者：
Mikacenic,Carmen
中科院分区：
文献类型：
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作者：
Sathe,NehaA;Morrell,EricD;Bhatraju,PavanK;Fessler,MichaelB;Stapleton,ReneeD;Wurfel,MarkM;Mikacenic,Carmen
目的：我们试图确定与血浆生物标志物差异和死亡风险相关的高炎症性急性呼吸窘迫综合征（ARDS）和低炎症性ARDS是否也显示出支气管肺泡灌洗（BALF）生物标志物谱的差异。然后，我们描述了高炎症性 ARDS 和低炎症性 ARDS 与使用 BALF 生物标志物衍生的新亚表型之间的关系。设计：对测试 omega-3 脂肪酸治疗 ARDS 的随机对照试验进行二次分析。设置：五个北美重症监护病房。患者：ARDS 发病 48 小时内接受有创机械通气的成人 (n= 88)。干预措施：无。测量和主要结果：我们使用先前验证的逻辑回归模型将 57 名患者分类为低炎症，31 名患者分类为高炎症。在分析的 14 种 BALF 生物标志物中，与低炎症性 ARDS 患者相比，高炎症性 ARDS 患者的白细胞介素 6 和粒细胞集落刺激因子较高，但这种差异经多重假设检验并不稳健。然后，我们对 14 个 BALF 生物标志物进行了从头潜在类别分析，以识别由肺泡轮廓很好分隔的两个类别。与 1 类 (n = 25) 相比，2 类 (n = 63) 显示出显着更高的白细胞介素 6、血管性血友病因子、可溶性程序性细胞死亡受体 1、中性粒细胞百分比和其他炎症生物标志物。这些 BALF 衍生类别与血浆衍生的高炎症和低炎症类别的重叠极小，并且这两种血浆衍生类别的大多数属于 BALF 衍生类别 2，并以高 BALF 生物标志物为特征。此外，BALF 衍生的类别与肺部疾病的临床严重程度相关，其中 2 类表现出较低的 Pa o 2 至 F io 2 和不同的通气参数，这与血浆衍生的类别不同，后者仅与非肺器官功能障碍相关。 结论：高炎症和低炎症 ARDS 亚表型在肺泡生物学特征上没有表现出显着差异。使用 BALF 测量识别 ARDS 亚组是一种独特的方法，它补充了从血浆中获得的信息，有可能为肺部靶向治疗试验中的富集策略提供信息。
OBJECTIVES:We sought to determine whether hyperinflammatory acute respiratory distress syndrome (ARDS) and hypoinflammatory ARDS, which have been associated with differences in plasma biomarkers and mortality risk, also display differences in bronchoalveolar lavage (BALF) biomarker profiles. We then described the relationship between hyperinflammatory ARDS and hypoinflammatory ARDS to novel subphenotypes derived using BALF biomarkers.DESIGN:Secondary analysis of a randomized control trial testing omega-3 fatty acids for the treatment of ARDS.SETTING:Five North American intensive care units.PATIENTS:Adults (n= 88) on invasive mechanical ventilation within 48 hours of ARDS onset.INTERVENTIONS:None.MEASUREMENTS AND MAIN RESULTS:We classified 57 patients as hypoinflammatory and 31 patients as hyperinflammatory using a previously validated logistic regression model. Of 14 BALF biomarkers analyzed, interleukin-6 and granulocyte colony stimulating factor were higher among patients with hyperinflammatory ARDS compared with hypoinflammatory ARDS, though the differences were not robust to multiple hypothesis testing. We then performed a de novo latent class analysis of the 14 BALF biomarkers to identify two classes well separated by alveolar profiles. Class 2 (n= 63) displayed significantly higher interleukin-6, von Willebrand factor, soluble programmed cell death receptor-1,% neutrophils, and other biomarkers of inflammation compared with class 1 (n= 25). These BALF-derived classes had minimal overlap with the plasma-derived hyperinflammatory and hypoinflammatory classes, and the majority of both plasma-derived classes were in BALF-derived class 2 and characterized by high BALF biomarkers. Additionally, the BALF-derived classes were associated with clinical severity of pulmonary disease, with class 2 exhibiting lower Pa o 2 to F io 2 and distinct ventilatory parameters, unlike the plasma-derived classes, which were only related to nonpulmonary organ dysfunction.CONCLUSIONS:Hyperinflammatory and hypoinflammatory ARDS subphenotypes did not display significant differences in alveolar biologic profiles. Identifying ARDS subgroups using BALF measurements is a unique approach that complements information obtained from plasma, with potential to inform enrichment strategies in trials of lung-targeted therapies.