Surfactant protein D is a biomarker of influenza-related pediatric lung injury.

Surfactant protein D is a biomarker of influenza-related pediatric lung injury.
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DOI:
10.1002/ppul.25776
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发表时间:
2022-03
影响因子:
3.1
通讯作者:
Pediatric Intensive Care Influenza (PICFLU) Investigators
Pediatric Intensive Care Influenza (PICFLU) Investigators
中科院分区:
医学3区
文献类型:
--
作者:
Chakrabarti A;Nguyen A;Newhams MM;Ohlson MB;Yang X;Ulufatu S;Liu S;Park S;Xu M;Jiang J;Halpern WG;Anania VG;McBride JM;Rosenberger CM;Randolph AG;Pediatric Intensive Care Influenza (PICFLU) Investigators

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可以对流感病毒下呼吸道感染儿童进行风险分层的生物标志物可以确定有针对性干预的患者。这些患者血液中肺泡相关蛋白的早期升高可能预示着更严重的肺损伤,预示着更糟糕的结果。我们使用人类流感感染小鼠模型,评估了肺病理生理与表面活性剂蛋白D (SP-D)、SP-A和俱乐部细胞蛋白16 (CC16)之间的关系。然后,我们测量了94名流感相关急性呼吸衰竭儿童(PICFLU队列)血浆样本中的SP-A、SP-D和CC16水平,排除了有潜在疾病解释疾病严重程度的儿童。我们检测了循环蛋白水平与疾病严重程度之间的关系,包括急性呼吸窘迫综合征(ARDS)的诊断、机械呼吸机、重症监护病房和住院天数以及住院死亡率。在流感感染后肺泡血管通透性增加的小鼠中,循环SP-D比SP-A和CC16增加更多。在PICFLU队列中,SP-D与中重度ARDS诊断(p=0.01)相关,与无细菌合并感染的流感感染儿童的机械呼吸机(r= 0.45, p=0.002)、ICU (r=0.44, p=0.002)和住院天数(r= 0.37, p=0.001)相关。继发性细菌性肺炎患儿SP-D水平较低(p=0.01),与预后无关。CC16和SP-A水平与细菌共感染没有差异,也不一致与严重结局相关。SP-D有潜力作为反映儿童流感病毒感染直接引起肺损伤程度的早期循环生物标志物。继发性细菌性肺炎改变SP-D生物标志物的性能。
Biomarkers that can risk-stratify children with influenza virus lower respiratory infection may identify patients for targeted intervention. Early elevation of alveolar-related proteins in the bloodstream in these patients could indicate more severe lung damage portending worse outcomes. We used a mouse model of human influenza infection and evaluated relationships between lung pathophysiology and surfactant protein D (SP-D), SP-A, and Club cell protein 16 (CC16). We then measured SP-A, SP-D and CC16 levels in plasma samples from 94 children with influenza-associated acute respiratory failure (PICFLU cohort), excluding children with underlying conditions explaining disease severity. We tested for associations between levels of circulating proteins and disease severity including the diagnosis of acute respiratory distress syndrome (ARDS), mechanical ventilator, intensive care unit and hospital days, and hospital mortality. Circulating SP-D showed a greater increase than SP-A and CC16 in mice with increased alveolar-vascular permeability following influenza infection. In the PICFLU cohort, SP-D was associated with moderate-severe ARDS diagnosis (p=0.01) and with mechanical ventilator (r =0.45, p=0.002), ICU (r=0.44, p=0.002), and hospital days (r = 0.37, p=0.001) in influenza infected children without bacterial coinfection. Levels of SP-D were lower in children with secondary bacterial pneumonia (p=0.01) and not associated with outcomes. CC16 and SP-A levels did not differ with bacterial coinfection and were not consistently associated with severe outcomes. SP-D has potential as an early circulating biomarker reflecting degree of lung damage caused directly by influenza virus infection in children. Secondary bacterial pneumonia alters SP-D biomarker performance.
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