Innate immune function and mortality in critically ill children with influenza: a multicenter study.
Innate immune function and mortality in critically ill children with influenza: a multicenter study.
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DOI：
10.1097/ccm.0b013e318267633c
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发表时间：
2013-01
影响因子：
8.8
通讯作者：
Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network PICFlu Study Investigators
中科院分区：
文献类型：
--
作者：
Hall MW;Geyer SM;Guo CY;Panoskaltsis-Mortari A;Jouvet P;Ferdinands J;Shay DK;Nateri J;Greathouse K;Sullivan R;Tran T;Keisling S;Randolph AG;Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network PICFlu Study Investigators
前瞻性评价流感感染危重儿童多中心队列中血清细胞因子水平、先天免疫反应性和死亡率之间的关系。前瞻性、多中心、观察性研究。儿童急性肺损伤和败血症调查员网络成员中的15个儿科icu。≤18岁的社区获得性流感感染患者入住PICU。门诊儿童的对照组也进行了评估。ICU患者在入院72小时内取样，采用标准化刺激方案测量31组血清细胞因子水平和全血体外脂多糖刺激肿瘤坏死因子-α生产能力。门诊对照患者也进行肿瘤坏死因子-α生产能力测定。抽取了52例患者（44例幸存者，8例死亡）。高水平的血清细胞因子（粒细胞巨噬细胞集落刺激因子、白细胞介素-6、白细胞介素-8、干扰素诱导蛋白-10、单核细胞趋化蛋白-1和巨噬细胞炎症蛋白-1α）与死亡率相关（每次比较p < 0.0016），与金黄色葡萄球菌继发感染的存在相关（p = 0.007），特别是耐甲氧西林金黄色葡萄球菌（p < 0.0001）。与门诊对照组（n = 21, p < 0.0001）和ICU幸存者（p < 0.0001）相比，非幸存者免疫抑制伴白细胞减少，肿瘤坏死因子-α生产能力明显降低。在控制多个协变量后，这种关联仍然存在。肿瘤坏死因子-α反应<250 pg/mL高度预测死亡和ICU住院时间延长（p < 0.0001）。金黄色葡萄球菌合并感染的患者表现出最大程度的免疫抑制（p < 0.0001）。在重症流感患儿中，血清中高水平的细胞因子可与明显的先天免疫抑制共存。在这一人群中，严重的早期先天免疫抑制与金黄色葡萄球菌合并感染和死亡率高度相关。多中心先天免疫功能检测是可行的，可以识别这些高危儿童。
To prospectively evaluate relationships among serum cytokine levels, innate immune responsiveness, and mortality in a multicenter cohort of critically ill children with influenza infection. Prospective, multicenter, observational study. Fifteen pediatric ICUs among members of the Pediatric Acute Lung Injury and Sepsis Investigators network. Patients ≤18 yrs old admitted to a PICU with community-acquired influenza infection. A control group of outpatient children was also evaluated. ICU patients underwent sampling within 72 hrs of ICU admission for measurement of a panel of 31 serum cytokine levels and quantification of whole blood ex vivo lipopolysaccharide-stimulated tumor necrosis factor-α production capacity using a standardized stimulation protocol. Outpatient control subjects also underwent measurement of tumor necrosis factor-α production capacity. Fifty-two patients (44 survivors, eight deaths) were sampled. High levels of serum cytokines (granulocyte macrophage colony-stimulating factor, interleukin-6, interleukin-8, interferon-inducible protein-10, monocyte chemotactic protein-1, and macrophage inflammatory protein-1α) were associated with mortality (p < 0.0016 for each comparison) as was the presence of secondary infection with Staphylococcus aureus (p = 0.007), particularly methicillin-resistant S. aureus (p < 0.0001). Nonsurvivors were immunosuppressed with leukopenia and markedly reduced tumor necrosis factor-α production capacity compared with outpatient control subjects (n = 21, p < 0.0001) and to ICU survivors (p < 0.0001). This association remained after controlling for multiple covariables. A tumor necrosis factor-α response <250 pg/mL was highly predictive of death and longer duration of ICU stay (p < 0.0001). Patients with S. aureus coinfection demonstrated the greatest degree of immunosuppression (p < 0.0001). High serum levels of cytokines can coexist with marked innate immune suppression in children with critical influenza. Severe, early innate immune suppression is highly associated with both S. aureus coinfection and mortality in this population. Multicenter innate immune function testing is feasible and can identify these high-risk children.