Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials.
Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials.
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DOI：
10.1016/s2213-2600(14)70097-9
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发表时间：
2014-08
影响因子：
76.2
通讯作者：
Matthay, Michael A.
中科院分区：
文献类型：
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作者：
Calfee, Carolyn S.;Delucchi, Kevin;Parsons, Polly E.;Thompson, B. Taylor;Ware, Lorraine B.;Matthay, Michael A.
在异质性综合征如哮喘和乳腺癌中已确定了亚表型，具有重要的治疗意义。急性呼吸窘迫综合征（ARDS）是另一种异质性综合征，其亚表型是否存在尚不清楚。我们应用潜在类建模，以确定从两个NHLBI ARDS随机对照试验的临床和生物学数据的亚表型，建模是在每个队列独立进行。然后，我们测试了两个队列中的亚表型与临床结果的相关性，以及第二个队列中对呼气末正压（PEEP）的反应。独立的潜在类模型表明，两个类（即两个亚表型）模型是最佳的两个队列。在这两个队列中，我们确定了一种高炎症亚表型（表型2），其特征是与表型1相比，炎症生物标志物的血浆水平较高，血管加压药使用的患病率较高，血清碳酸氢盐较低，败血症的患病率较高。在两个队列中，表型2受试者的死亡率较高，无呼吸机和无器官衰竭天数较少。在第二个队列中，通气策略对死亡率、无呼吸机和无器官衰竭天数的影响因表型而显著不同（相互作用p=0.003-0.049）。潜在类别模型识别了ARDS中的两种亚表型，其中一种的特征在于更严重的炎症、休克和代谢性酸中毒以及显著更差的临床结果。在PEEP策略的随机试验中，对治疗的反应基于亚表型而不同。ARDS亚表型的鉴定可能有助于临床试验患者的选择。国立卫生研究院
Subphenotypes have been identified within heterogeneous syndromes such as asthma and breast cancer, with important therapeutic implications. Whether subphenotypes exist within the acute respiratory distress syndrome (ARDS), another heterogeneous syndrome, is unknown. We applied latent class modeling to identify subphenotypes using clinical and biological data from two NHLBI ARDS randomized controlled trials; modeling was conducted independently in each cohort. We then tested the association of subphenotypes with clinical outcomes in both cohorts and with the response to positive end-expiratory pressure (PEEP) in the second cohort. Independent latent class models indicated that a two-class (i.e. two subphenotype) model was optimal for both cohorts. In both cohorts, we identified a hyperinflammatory subphenotype (Phenotype 2) that was characterized by higher plasma levels of inflammatory biomarkers, a higher prevalence of vasopressor use, lower serum bicarbonate, and a higher prevalence of sepsis, compared to Phenotype 1. Subjects in Phenotype 2 had higher mortality and fewer ventilator-free and organ failure-free days in both cohorts. In the second cohort, the effects of ventilation strategy on mortality, ventilator and organ failure-free days differed significantly by phenotype (p=0.003–0.049 for interactions). Latent class models identify two subphenotypes within ARDS, one of which is characterized by more severe inflammation, shock, and metabolic acidosis and by significantly worse clinical outcomes. Response to treatment in a randomized trial of PEEP strategies differed based on subphenotype. Identification of ARDS subphenotypes may be useful in selecting patients for clinical trials. National Institutes of Health