CCM:炎症亚型在免疫功能低下脓毒症患者的预后相关性

Abstract

Objectives: Hyperinflammatory and hypoinflammatory molecular subphenotypes in sepsis and acute respiratory distress syndrome have divergent mortality and treatment responses in secondary analyses of randomized controlled trials. However, the prevalence of immunocompromise is low in these populations, and how preexisting immunocompromise contributes to subphenotypes is unknown. We studied two observational sepsis cohorts to test associations between immunocompromise and the hyperinflammatory subphenotype and to assess whether the prognostic relevance of molecular subphenotypes is generalizable to immunocompromised populations.

目的：在脓毒症和急性呼吸窘迫综合征中，高炎症反应和低炎症反应的分子亚型在随机对照试验的二次分析中显示出不同的死亡率和治疗反应。然而，这些人群中免疫功能低下的患病率较低，且先前存在的免疫抑制如何影响这些亚型的分布尚不清楚。我们研究了两个观察性脓毒症队列，以检验免疫抑制与高炎症亚型之间的关联，并评估分子亚型的预后相关性是否可推广至免疫功能低下人群。

Design: Observational cohort study.

设计：观察性队列研究。

Setting: Prospective data from two ICU cohorts in the United States.

场所：来自美国两个重症监护病房（ICU）队列的前瞻性数据。

Patients: We included 1826 patients from two combined sepsis cohorts.

患者：共纳入来自两个合并脓毒症队列的1826名患者

Interventions: None.

Measurements and main results: We defined immunocompromise as a history of solid organ transplant, AIDS, hematologic malignancy, solid malignancy on chemotherapy, or immunosuppressive medication use. Subphenotype was previously assigned using latent class analysis. We used logistic regression to investigate associations between type of immunocompromise and hyperinflammatory subphenotype. Models were repeated with individual covariates known or hypothesized to be associated with the hyperinflammatory subphenotype. Kaplan-Meier survival plots were used to assess mortality differences by subphenotype. Hematologic malignancy was strongly associated with the hyperinflammatory subphenotype (odds ratio [OR], 4.3; p < 0.0001), an association that persisted after adjustment for identified pathogen, presence of bacteremia, or illness severity. History of solid organ transplantation was also associated with the hyperinflammatory subphenotype (OR, 1.6; p = 0.02) but was no longer significant after accounting for bacteremia. Hyperinflammatory classification was associated with a decreased likelihood of survival in hematologic malignancy, but not in organ transplant or solid malignancy populations.

测量指标和主要结果：我们将免疫功能低下定义为曾接受实体器官移植、艾滋病（AIDS）、血液系统恶性肿瘤、正在接受化疗的实体恶性肿瘤，或使用免疫抑制药物。亚型此前已通过潜在类别分析进行划分。我们使用逻辑回归分析不同类型的免疫抑制与高炎症亚型之间的关联。模型还加入了已知或假设与高炎症亚型相关的个体协变量进行重复分析。采用Kaplan-Meier生存曲线评估不同亚型间的死亡率差异。结果显示，血液系统恶性肿瘤与高炎症亚型显著相关（比值比[OR]为4.3；p < 0.0001），该关联在调整了病原体类型、是否存在菌血症或疾病严重程度后依然存在。实体器官移植史也与高炎症亚型相关（OR为1.6；p = 0.02），但在考虑菌血症因素后不再具有统计学意义。在高炎症分类中，血液系统恶性肿瘤患者的生存概率降低，而在器官移植或实体恶性肿瘤患者中未观察到这种关联。