Host-Response Subphenotypes Offer Prognostic Enrichment in Patients With or at Risk for Acute Respiratory Distress Syndrome*
Host-Response Subphenotypes Offer Prognostic Enrichment in Patients With or at Risk for Acute Respiratory Distress Syndrome*
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DOI：
10.1097/ccm.0000000000004018
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发表时间：
2019-12-01
影响因子：
8.8
通讯作者：
McVerry, Bryan J.
中科院分区：
文献类型：
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作者：
Kitsios, Georgios D.;Yang, Libing;McVerry, Bryan J.
目的：利用血浆生物标志物将急性呼吸窘迫综合征患者分为高炎性和低炎性亚表型，可能有助于更有效的靶向治疗。我们研究了已建立的亚表型是否不仅存在于急性呼吸窘迫综合征患者中，也存在于急性呼吸窘迫综合征（ARFA）风险患者中，然后评估了基线亚表型对宿主反应生物标志物进化和临床结果的预后信息。设计：前瞻性、观察性队列研究。环境：三级学术医疗中心的重症监护室。患者：急性呼吸窘迫综合征（ARFA）机械通气患者。干预措施:没有。测量和主要结果：我们对宿主损伤和炎症的10种血浆生物标志物进行了纵向测量。我们应用无监督潜类分析方法，利用基线临床和生物标志物变量，并证明在急性呼吸窘迫综合征和ARFA患者中，与一类模型相比，两类模型（高与低炎症亚表型）提供了更好的拟合。高炎症亚表型（39/104[38%]急性呼吸窘迫综合征和30/108 [28%]ARFA患者）的基线分配与序贯器官衰竭评估评分和急性呼吸窘迫综合征患者急性肾损伤发生率较高的疾病严重程度以及ARFA患者较高的30天死亡率和较长的机械通气持续时间相关（p < 0.0001）。高炎症患者在插管后2周内表现出先天免疫生物标志物的持续升高。结论：我们的研究结果表明，两种不同的亚表型不仅存在于已确诊的急性呼吸窘迫综合征患者中，也存在于有发展风险的患者中。与低炎症患者相比，基线时的高炎症分类与更高的疾病严重程度、更差的临床结果以及急性危重疾病期间宿主损伤和炎症生物标志物持续升高的轨迹相关。我们的研究结果为在随机临床试验中检查亚表型治疗效果的改变提供了强有力的理论依据，从而为危重病护理的精确治疗方法提供信息。
Objectives: Classification of patients with acute respiratory distress syndrome into hyper- and hypoinflammatory subphenotypes using plasma biomarkers may facilitate more effective targeted therapy. We examined whether established subphenotypes are present not only in patients with acute respiratory distress syndrome but also in patients at risk for acute respiratory distress syndrome (ARFA) and then assessed the prognostic information of baseline subphenotyping on the evolution of host-response biomarkers and clinical outcomes. Design: Prospective, observational cohort study. Setting: Medical ICU at a tertiary academic medical center. Patients: Mechanically ventilated patients with acute respiratory distress syndrome or ARFA. Interventions: None. Measurements and Main Results: We performed longitudinal measurements of 10 plasma biomarkers of host injury and inflammation. We applied unsupervised latent class analysis methods utilizing baseline clinical and biomarker variables and demonstrated that two-class models (hyper- vs hypoinflammatory subphenotypes) offered improved fit compared with one-class models in both patients with acute respiratory distress syndrome and ARFA. Baseline assignment to the hyperinflammatory subphenotype (39/104 [38%] acute respiratory distress syndrome and 30/108 [28%] ARFA patients) was associated with higher severity of illness by Sequential Organ Failure Assessment scores and incidence of acute kidney injury in patients with acute respiratory distress syndrome, as well as higher 30-day mortality and longer duration of mechanical ventilation in ARFA patients (p < 0.0001). Hyperinflammatory patients exhibited persistent elevation of biomarkers of innate immunity for up to 2 weeks postintubation. Conclusions: Our results suggest that two distinct subphenotypes are present not only in patients with established acute respiratory distress syndrome but also in patients at risk for its development. Hyperinflammatory classification at baseline is associated with higher severity of illness, worse clinical outcomes, and trajectories of persistently elevated biomarkers of host injury and inflammation during acute critical illness compared with hypoinflammatory patients. Our findings provide strong rationale for examining treatment effect modifications by subphenotypes in randomized clinical trials to inform precision therapeutic approaches in critical care.