Increased mortality in elderly patients with acute respiratory distress syndrome is not explained by host response
Increased mortality in elderly patients with acute respiratory distress syndrome is not explained by host response
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DOI：
10.1186/s40635-019-0270-1
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发表时间：
2019-10-29
影响因子：
3.5
通讯作者：
Wosten-van Asperen, Roelie M.
中科院分区：
文献类型：
--
作者：
Schouten, Laura R. A.;Bos, Lieuwe D. J.;Wosten-van Asperen, Roelie M.
背景：高龄与急性呼吸窘迫综合征（ARDS）患者死亡率增高相关。临床前研究表明，宿主对伤害性攻击的反应是年龄依赖性的。在ARDS患者中，我们研究了年龄和死亡率之间的关联是否通过宿主反应的年龄相关差异来介导。方法：这是一项前瞻性纵向观察队列研究，在两所大学附属医院的icu中进行。根据研究人群的年龄分类，系统宿主反应分为三个预定义的年龄组：年轻人（18至54岁，N = 209），中年人（55至67岁，N = 213）和老年人（67岁及以上，N = 196）。在ARDS发病时获得的血浆中检测炎症、内皮细胞激活和凝血的生物标志物。主要终点为90天死亡率。进行了中介分析，以检查与年龄相关的生物标志物水平差异是否作为介导年龄和死亡率之间关联的潜在因果途径。结果：青年患者90天死亡率为30%(63/209)，中年人为37%(78/213)，老年患者为43%（84/196）。中老年患者的死亡风险高于年轻患者（校正优势比分别为1.5[95%可信区间1.0 ~ 2.3]和2.1[95%可信区间1.4 ~ 3.4]）。与年轻患者相比，老年人的炎症和内皮细胞激活的生物标志物水平明显较低。组织纤溶酶原激活物是凝血标志物，是唯一显示部分介导的生物标志物（介导比例为10%[1 ~ 28]%）。结论：很少有证据表明，年龄与ARDS患者死亡率之间的关系是通过宿主反应途径的年龄依赖性差异介导的。只有组织纤溶酶原激活剂被确定为可能的介质。
Background: Advanced age is associated with increased mortality in acute respiratory distress syndrome (ARDS) patients. Preclinical studies suggest that the host response to an injurious challenge is age-dependent. In ARDS patients, we investigated whether the association between age and mortality is mediated through age-related differences in the host response.Methods: This was a prospective longitudinal observational cohort study, performed in the ICUs of two university-affiliated hospitals. The systemic host response was characterized in three predefined age-groups, based on the age-tertiles of the studied population: young (18 to 54 years, N = 209), middle-aged (55 to 67 years, N = 213), and elderly (67 years and older, N = 196). Biomarkers of inflammation, endothelial activation, and coagulation were determined in plasma obtained at the onset of ARDS. The primary outcome was 90-day mortality. A mediation analysis was performed to examine whether age-related differences in biomarker levels serve as potential causal pathways mediating the association between age and mortality.Results: Ninety-day mortality rates were 30% (63/209) in young, 37% (78/213) in middle-aged, and 43% (84/196) in elderly patients. Middle-aged and elderly patients had a higher risk of death compared to young patients (adjusted odds ratio, 1.5 [95% confidence interval 1.0 to 2.3] and 2.1 [1.4 to 3.4], respectively). Relative to young patients, the elderly had significantly lower systemic levels of biomarkers of inflammation and endothelial activation. Tissue plasminogen activator, a marker of coagulation, was the only biomarker that showed partial mediation (proportion of mediation, 10 [1 to 28] %).Conclusion: Little evidence was found that the association between age and mortality in ARDS patients is mediated through age-dependent differences in host response pathways. Only tissue plasminogen activator was identified as a possible mediator of interest.