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对重症监护病房感染老年患者免疫特征的深入洞察:来自一项多中心前瞻性观察性研究的证据

Enhanced insights into immunity traits of elderly patients in the intensive care unit with infections: evidence from a multicenter, prospective observational study.

作者信息

Zou Ju, Xiao Yuanyuan, Zhang Lina, Zuo Zhihong, Wang Xianwen, Liao Xuelian, Cui Na, Jin Jialin, Qian Zhaoxin, Wu Anhua, Li Chunhui

机构信息

Department of Infection Control Center, Super drug-resistant Organism Infection Prevention and Control Research Center, Xiangya Hospital, Central South University, Changsha, Hunan Province, China.

National Clinical Research Center for Geriatric Disorders (Xiangya Hospital), Changsha, 410008, Hunan Province, China.

出版信息

Crit Care. 2025 Aug 28;29(1):386. doi: 10.1186/s13054-025-05616-z.

DOI:10.1186/s13054-025-05616-z
PMID:40866971
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12392643/
Abstract

BACKGROUND

Infections, particularly sepsis, are a global health threat and a leading cause of mortality among elderly patients (≥ 60 years) in intensive care units (ICUs). The variable immune responses in this vulnerable population warrant deeper investigation.

METHODS

This multicenter prospective study included elderly patients with infections admitted to the ICUs of four hospitals between May 2023 and October 2024. Patients were classified into sepsis and non-sepsis infection groups based on a ≥2-point increase in Sequential Organ Failure Assessment (SOFA) score. Baseline immune and inflammatory markers were compared between groups. Logistic regression analyses were used to assess associations with mortality. Subgroup analyses were conducted by sex, age, infection site, and pathogen type.

RESULTS

Among 1,152 elderly patients with infections in the ICUs, 640 with sepsis were older (70.0 vs.72.0 years), were predominantly male (55.3% vs. 68.1%), and had more comorbidities, all P < 0.001. Compared with the non-sepsis infection group, the septic group had higher rates of mechanical ventilation (3.12% vs. 40.80%), longer hospitalization (7.00 [4.00;10.0] vs. 11.8 [6.00;18.0] days), and increased mortality (0.98% vs. 9.51%), all P < 0.001. Distinct immune-mortality signatures were observed. In the fully adjusted model, non-septic infection was associated with reduced monocytes, lymphocytes, and TNFα (odds ratio [OR] < 1), elevated interleukin-12 (IL12) and INFγ (OR > 1, all P < 0.05), whereas sepsis was characterized by increased neutrophil and B-cell activation (OR > 1), decreased T cells (OR < 1, all P < 0.05), and no specific cytokine signature (all P > 0.05). Sex differences included higher levels of innate immune markers in males and elevated adaptive immune indicators in females. With age, patients showed reduced T cell counts and increased inflammatory markers (procalcitonin and C-reactive protein). Patients aged > 80 years exhibited marked lymphopenia, lower CD4 T cell counts (β < 1, P < 0.05), and elevated IL6 and platelet levels (β > 1, P < 0.05). Immune profiles also varied by pathogen type: fungal infections were associated with increased lymphocyte and cytotoxic T lymphocyte counts (β > 1, P < 0.05) compared with bacterial infections, whereas viral infections showed reduced T cell subsets and cytokine levels (IL6, IL8, IL17; β < 1, P < 0.05).

CONCLUSIONS

Elderly patients in the ICU, especially those with sepsis, exhibit immune imbalances of hyperinflammation and immunosuppression, varying with age, sex, pathogen type, and infection site. These findings highlight the potential role of immune phenotyping in guiding treatment decisions in this patient population.

摘要

背景

感染,尤其是脓毒症,是一种全球健康威胁,也是重症监护病房(ICU)中老年患者(≥60岁)死亡的主要原因。这一脆弱人群中多变的免疫反应值得深入研究。

方法

这项多中心前瞻性研究纳入了2023年5月至2024年10月期间入住四家医院ICU的老年感染患者。根据序贯器官衰竭评估(SOFA)评分增加≥2分,将患者分为脓毒症组和非脓毒症感染组。比较两组的基线免疫和炎症标志物。采用逻辑回归分析评估与死亡率的关联。按性别、年龄、感染部位和病原体类型进行亚组分析。

结果

在1152例ICU老年感染患者中,640例脓毒症患者年龄更大(70.0岁对72.0岁),男性占比更高(55.3%对68.1%),合并症更多,所有P<0.001。与非脓毒症感染组相比,脓毒症组机械通气率更高(3.12%对40.80%),住院时间更长(7.00[4.00;10.0]天对11.8[6.00;18.0]天),死亡率更高(0.98%对9.51%),所有P<0.001。观察到不同的免疫-死亡率特征。在完全调整模型中,非脓毒症感染与单核细胞、淋巴细胞和肿瘤坏死因子α减少(比值比[OR]<1)、白细胞介素-12(IL12)和干扰素γ升高(OR>1,所有P<0.05)相关,而脓毒症的特征是中性粒细胞和B细胞活化增加(OR>1)、T细胞减少(OR<1,所有P<0.05),且无特定细胞因子特征(所有P>0.05)。性别差异包括男性先天免疫标志物水平较高,女性适应性免疫指标升高。随着年龄增长,患者T细胞计数减少,炎症标志物(降钙素原和C反应蛋白)增加。年龄>80岁的患者表现出明显的淋巴细胞减少、CD4 T细胞计数降低(β<1,P<0.05)以及IL6和血小板水平升高(β>1,P<0.05)。免疫谱也因病原体类型而异:与细菌感染相比,真菌感染与淋巴细胞和细胞毒性T淋巴细胞计数增加(β>1,P<0.05)相关,而病毒感染则表现为T细胞亚群和细胞因子水平降低(IL6、IL8、IL17;β<1,P<0.05)。

结论

ICU中的老年患者,尤其是脓毒症患者,表现出炎症反应过度和免疫抑制的免疫失衡,且随年龄、性别、病原体类型和感染部位而变化。这些发现凸显了免疫表型分析在指导该患者群体治疗决策中的潜在作用。

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