Acute Respiratory Distress Syndrome Subphenotypes Respond Differently to Randomized Fluid Management Strategy
Acute Respiratory Distress Syndrome Subphenotypes Respond Differently to Randomized Fluid Management Strategy
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DOI：
10.1164/rccm.201603-0645oc
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发表时间：
2017-02-01
影响因子：
24.7
通讯作者：
Calfee, Carolyn S.
中科院分区：
文献类型：
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作者：
Famous, Katie R.;Delucchi, Kevin;Calfee, Carolyn S.
基本原理：我们先前在两个独立的随机对照试验中发现了两种急性呼吸窘迫综合征（ARDS）亚表型，对呼气末正压有不同的反应。目的：在第三个ARDS队列中确定这些亚表型，以测试亚表型是否对液体管理策略有不同的反应，并建立一个实用的亚表型识别模型。方法：我们使用基线临床和血浆生物标志物数据的潜在类别分析来识别FACTT（液体和导管治疗试验; n = 1，000）中的亚表型。逻辑回归用于检验亚表型和治疗对死亡率的影响。我们使用逐步建模生成一个模型，在FACTT亚表型识别和验证其准确性在两个队列中，我们以前确定的ARDS subphenotypes. Measures和主要结果：我们证实，两个类（两个亚表型）模型最好地描述了研究人群。亚表型2再次以较高的炎症生物标志物和低血压为特征。液体管理策略对两种亚表型的90天死亡率有显著不同的影响（相互作用P = 0.0039）;亚表型1液体保守策略的死亡率为26%，而液体自由策略的死亡率为18%，而亚表型2液体保守策略的死亡率为40%，而液体自由策略的死亡率为50%。一个三变量模型的IL-8，碳酸氢盐，和肿瘤坏死因子受体-1准确分类的subphenotypes.Conclusions：该分析证实了存在两个ARDS亚表型，可以准确地确定与有限数量的变量和不同的随机分配的液体管理。这些发现支持了可能需要不同治疗方法的ARDS亚型的存在。
Rationale: We previously identified two acute respiratory distress syndrome (ARDS) subphenotypes in two separate randomized controlled trials with differential response to positive end-expiratory pressure.Objectives: To identify these subphenotypes in a third ARDS cohort, to test whether subphenotypes respond differently to fluid management strategy, and to develop a practical model for subphenotype identification.Methods: We used latent class analysis of baseline clinical and plasma biomarker data to identify subphenotypes in FACTT (Fluid and Catheter Treatment Trial; n = 1,000). Logistic regression was used to test for an interaction between subphenotype and treatment for mortality. We used stepwise modeling to generate a model for subphenotype identification in FACTT and validated its accuracy in the two cohorts in which we previously identified ARDS subphenotypes.Measurements and Main Results: We confirmed that a two-class (two-subphenotype) model best described the study population. Subphenotype 2 was again characterized by higher inflammatory biomarkers and hypotension. Fluid management strategy had significantly different effects on 90-day mortality in the two subphenotypes (P = 0.0039 for interaction); mortality in subphenotype 1 was 26% with fluid-conservative strategy versus 18% with fluid-liberal, whereas mortality in subphenotype 2 was 40% with fluid-conservative strategy versus 50% in fluid-liberal. A three variable model of IL-8, bicarbonate, and tumor necrosis factor receptor-1 accurately classified the subphenotypes.Conclusions: This analysis confirms the presence of two ARDS subphenotypes that can be accurately identified with a limited number of variables and that responded differently to randomly assigned fluid management. These findings support the presence of ARDS subtypes that may require different treatment approaches.