Anania Veronica G, Randolph Adrienne G, Yang Xiaoying, Nguyen Allen, Newhams Margaret M, Mathews W Rodney, Rosenberger Carrie M, McBride Jacqueline M
Department of Biomarker Development, Genentech, Inc., South San Francisco, California, USA.
Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts, USA.
Open Forum Infect Dis. 2020 Apr 9;7(5):ofaa122. doi: 10.1093/ofid/ofaa122. eCollection 2020 May.
Biomarkers are needed for early identification of patients at risk of severe complications from influenza infection, including prolonged respiratory failure and death. Eicosanoids are bioactive lipid mediators with pro- and anti-inflammatory properties produced in response to infection. This study assessed the relationships between the host bioactive lipid response, influenza viral load, and clinical outcomes.
Influenza-positive, intubated children ≤18 years old were enrolled across 26 US pediatric intensive care units (PICUs). Mass spectrometry was used to measure >100 lipid metabolites in endotracheal and nasopharyngeal samples. Influenza viral load was measured by quantitative polymerase chain reaction.
Age and bacterial co-infection were associated with multiple bioactive lipids ( < .05). Influenza viral load was lower in patients with bacterial co-infection compared with those without, and pro-inflammatory bioactive lipids positively correlated with viral load in bacterially co-infected children ( < .05). Lipids associated with disease resolution correlated with viral load in patients without bacterial co-infection ( < .01). After adjusting for age and bacterial co-infection status, elevated pro- and anti-inflammatory lipids measured early in the intensive care unit course were associated with higher mortality, whereas influenza viral load and endotracheal cytokine levels were not associated with clinical outcomes. Prostaglandin E, arachidonic acid, docosahexaenoic acid, and 12-hydroxyeicosatetraenoic acid measured within 72 hours of PICU admission predicted death or prolonged (≥28 days) mechanical ventilator support (area under the curve, 0.72-0.79; < .02) not explained by admission illness severity.
Children with influenza-related complications have early bioactive lipid responses that may reflect lung disease severity. Respiratory bioactive lipids are candidate prognostic biomarkers to identify children with the most severe clinical outcomes.
需要生物标志物来早期识别有流感感染严重并发症风险的患者，这些并发症包括延长的呼吸衰竭和死亡。类花生酸是具有促炎和抗炎特性的生物活性脂质介质，在感染时产生。本研究评估了宿主生物活性脂质反应、流感病毒载量和临床结局之间的关系。
在美国26个儿科重症监护病房（PICU）招募了18岁及以下的流感阳性插管儿童。采用质谱法测量气管内和鼻咽样本中的100多种脂质代谢物。通过定量聚合酶链反应测量流感病毒载量。
年龄和细菌合并感染与多种生物活性脂质相关（P<0.05）。与无细菌合并感染的患者相比，有细菌合并感染的患者流感病毒载量较低，在细菌合并感染的儿童中，促炎生物活性脂质与病毒载量呈正相关（P<0.05）。与疾病缓解相关的脂质与无细菌合并感染患者的病毒载量相关（P<0.01）。在调整年龄和细菌合并感染状态后，在重症监护病房病程早期测量的促炎和抗炎脂质升高与较高的死亡率相关，而流感病毒载量和气管内细胞因子水平与临床结局无关。在PICU入院72小时内测量的前列腺素E、花生四烯酸、二十二碳六烯酸和12-羟基二十碳四烯酸可预测死亡或延长（≥28天）机械通气支持（曲线下面积，0.72-0.79；P<0.02），这不能用入院时疾病严重程度来解释。
患有流感相关并发症的儿童有早期生物活性脂质反应，这可能反映了肺部疾病的严重程度。呼吸生物活性脂质是识别临床结局最严重儿童的候选预后生物标志物。
