Biomarkers for Adverse Lung Injury Following Pediatric Cardiopulmonary Bypass.
Biomarkers for Adverse Lung Injury Following Pediatric Cardiopulmonary Bypass.
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DOI：
10.1097/cce.0000000000000528
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发表时间：
2021-09
影响因子：
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通讯作者：
Ambalavanan N
中科院分区：
文献类型：
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作者：
Asfari A;Hock KM;Byrnes JW;Borasino S;Halloran BA;Mobley JA;Ambalavanan N
补充数字内容可在文本中找到。心脏搭桥术引发全身炎症，导致肺损伤，并经常导致长时间的机械通气。需要全身炎症的生物标志物来预测此类并发症的风险。我们假设特定的血清蛋白可以作为生物标志物来预测心脏手术后肺损伤的严重程度。回顾性病历审查研究。收集临床变量并与使用质谱法的无偏蛋白质组学分析结合使用，所述无偏蛋白质组学分析对来自研究组（术后机械通气> 48小时的患者）和对照组（术后机械通气< 48小时的患者）的冷冻血浆样品进行。纳入的受试者为接受类似复杂性心脏手术（胸外科医师协会-欧洲心胸外科协会3级或4级）的婴儿，采用心肺转流术。两组患者的体重、年龄和体外循环持续时间相匹配。没有。在心前分流术、0和心肺分流术后48小时样本中，对4名对照和4名研究患者进行蛋白质组学分析，鉴定出483种蛋白质（99%最小置信度和2种肽最小值，蛋白质错误发现率0.1%）。178种蛋白质中有36种差异显著（≥ 1.5倍; p < 0.05）在心前旁路时（顶部增加：腱生蛋白;顶部减少：四连接素），140种蛋白质中的18种在0小时（最高增加：血红蛋白β;最低降低：C8 β），以及术后48小时166种蛋白质中的25种（顶部增加：蛋白聚糖4;顶部减少：半乳糖凝集素-3-结合蛋白）。顶部途径涉及细胞骨架重塑。其他途径涉及免疫反应和血液凝固。通过酶联免疫吸附测定法在不同组样品中验证蛋白聚糖4（n = 20/组;平均值± sd：128 ± 67 vs 195 ± 160 ng/mL）（p = 0.037）。多种蛋白质组学生物标志物与呼吸结局恶化相关。心前旁路生物标志物可能指示风险因素（例如，凝血异常），而在0小时和心肺转流后鉴定的那些可能反映了正在进行的病理生物学机制。
Supplemental Digital Content is available in the text. Cardiopulmonary bypass triggers systemic inflammation, resulting in lung injury, and frequently leads to prolonged mechanical ventilation. Biomarkers of systemic inflammation are required to predict the risk of such complications. We hypothesize that specific serum proteins can be used as biomarkers to predict the severity of lung injury following cardiac surgery. Retrospective chart review study. Clinical variables were collected and used in conjuncture with unbiased proteomic analysis using mass spectrometry that was performed on frozen plasma samples from a study group (patients with mechanical ventilation > 48 hr post surgery) and a control group (patients with mechanical ventilation < 48 hr post surgery). Subjects included were infants who underwent cardiac surgery with similar complexity (Society of Thoracic Surgeons-European Association for Cardiothoracic Surgery 3 or 4) using cardiopulmonary bypass. Patients in both groups were matched for their weight, age, and duration of cardiopulmonary bypass. None. Four-hundred eighty-three proteins were identified (99% minimum confidence and two peptides minimum, protein false discovery rate 0.1%) on proteomic analysis of four control and four study patients at precardiopulmonary bypass, 0, and 48 hours postcardiopulmonary bypass samples. Thirty-six of 178 proteins were significantly different (≥ 1.5-fold; p < 0.05) at precardiopulmonary bypass (top increased: tenascin; top decreased: tetranectin), 18 of 140 proteins at 0 hour (top increased: hemoglobin beta; top decreased: C8 beta), and 25 of 166 proteins at 48 hours post surgery (top increased: proteoglycan 4; top decreased: galectin-3–binding protein). The top pathway involved cytoskeleton remodeling. Other pathways involved immune response and blood coagulation. Proteoglycan 4 was validated by enzyme-linked immunosorbent assay in a different set of samples (n = 20/group; mean ± sd: 128 ± 67 vs 195 ± 160 ng/mL) (p = 0.037). Multiple proteomic biomarkers were associated with worse respiratory outcomes. Precardiopulmonary bypass biomarkers might indicate risk factors (e.g., abnormalities of coagulation), whereas those identified at 0 hour and post cardiopulmonary bypass may reflect mechanisms of ongoing pathobiology.