摘要
创伤性肠破裂（TE）患者术后常可能伴发急性肺损伤（ALI）/急性呼吸窘迫综合征（ARDS），危及生命，因此，选择合适的早期预测及病情严重程度评估指标具有重要意义。本研究探讨外周血肺表面活性蛋白D（SP-D）、肺表面活性蛋白A（SP-A）、白细胞介素1β（IL-1β）动态监测对TE术后伴发ALI/ARDS的早期预测及病情评估价值。
回顾性分析2019年8月—2020年12月收治的78例TE患者的临床资料，其中52例术后未发生肺损伤组（对照组），15例术后发生ALI（ALI组），11例术后发生ARDS（ARDS组），分析三组患者的临床指标与外周血SP-D、SP-A、IL-1β水平的动态变化。通过受试者工作曲线（ROC）及相关性分析评判各观察指标对TE术后伴发ALI/ARDS的早期预测价值及病情严重程度评估效能。
各组患者年龄、性别、BMI、致伤因素、损伤部位、手术方式、手术时长及术中出血量差异无统计学意义（均P>0.05），而机械通气时长、降钙素原（PCT）水平、肺损伤预测评分（LIPS）及肺损伤评分（LIS）在对照组、ALI组、ARDS组依次增加，而氧合指数在对照组、ALI组、ARDS组依次降低，差异均有统计学意义（均P<0.05）。术前及术后1、4、7 d的SP-D、SP-A、IL-1β水平在ALI组、ARDS组依次且持续增高，除ALI组与ARDS组术后7 d的SP-A水平差异无统计学意义外（P>0.05），其余差异均有统计学意义（均P<0.05）。ROC曲线分析显示，SP-D、SP-A、IL-1β水平早期预测ALI/ARDS的曲线下面积（0.800、0.919、0.755/0.902、0.931、0.957）均高于PCT（0.739/0.721）及LIPS评分（0.851/0.788），三者联合进行平行试验可提高预测ALI/ARDS的灵敏度至0.997/0.988，三者联合进行系列试验可提高预测ALI/ARDS的特异度至0.999/0.997。相关性分析提示，SP-D、SP-A、IL-1β三项指标与氧合指数均呈明显负相关（r=-0.504、-0.657、-0.717，均P<0.01）、与LIS评分呈明显正相关（r=0.471、0.654、0.634，均P<0.01）。
Chinese Journal of General Surgery, 2021, 30(10):1203-1211.
急性肺损伤（acute lung injury，ALI）/急性呼吸窘迫综合征（acute respiratory distress syndrome，ARDS）是以急性低氧血症为主要临床表现的严重呼吸系统疾
本研究经安徽医科大学第二附属医院伦理委员会批准。收集我院急诊外科2019年8月—2020年12月诊治的78例TE患者相关临床资料，男51例，女27例；年龄32~71岁。ALI/ARDS的共识定义及分类原则由Europe-America ARDS联席委员会制定通
纳入标准：⑴ 所有纳入对象均诊断为TE且无其他脏器损伤，并在我院检查和手术，ALI和ARDS组患者符合相应的诊断及分类标准；⑵ 均在发病后6 h以内入院，且之前未接受任何治疗措施；⑶ 临床资料完整。排除标准：⑴ 3个月内有外伤及输血史的患者；⑵ 恶性肿瘤个人史且接受过放化疗的患者；⑶ 既往或长期服用免疫抑制剂及激素的患者；⑷ 既往伴有急慢性肺部疾病的患者；⑸ 术后7 d内死亡的入组患者。符合任何一条排除标准的患者，都将被排除出研究队列。
所有患者入院后均行急诊开放性腹部手术治疗。并在宋磊
对照组、ALI组及ARDS组患者间年龄、性别、BMI、致伤因素、损伤部位、手术方式、手术时长及术中失血量的差异无统计学意义（均P>0.05）；ALI组和ARDS组患者的机械通气时长、PCT水平、肺损伤预测评分（LIPS）以及肺损伤评分（LIS）在ALI组和ARDS组患者中均明显高于对照组，且ARDS组明显高于ALI组，差异均有统计学意义（均P<0.05）；ALI组和ARDS组患者的氧合指数明显低于对照组，且ARDS组明显低于ALI组，差异均有统计学意义（均P<0.05）（
注： 1）与ALI组比较，P<0.05
Note: 1) P<0.05 vs. ALI group
术前外周血SP-D、SP-A、IL-1β水平在ALI组和ARDS组患者中均明显高于对照组，且ARDS组明显高于ALI组（均P<0.05）。动态分析发现，ALI组和ARDS组患者SP-D、SP-A、IL-1β水平在不同时间点均明显高于对照组（P<0.01）；ALI和ARDS组间比较发现，除SP-A水平在术后第7天两组无明显差异外（P>0.05），其余各时间点ARDS组的SP-D、SP-A、IL-1β水平均明显高于ALI组（P<0.01）（
图1 外周血SP-D、SP-A、IL-1β水平在三组患者不同时间点的动态变化比较
Figure 1 Comparison of dynamic levels of SP-D, SP-A and IL-1β among three groups
考虑到患者术中术后治疗的个体差异性，故选取影响因素较少的术前SP-D、SP-A、IL-1β、PCT检测值以及LIPS评分作为早期预测资料并做ROC曲线分析。
三项指标对TE术后伴发ALI的早期预测分析结果显示：SP-D最佳阈值为0.66 ng/mL，此时灵敏度为90.4%，特异度为62.9%，AUC为0.800；SP-A最佳阈值为20.02 ng/mL，此时灵敏度为90.4%，特异度为82.3%，AUC为0.919；IL-1β最佳阈值为9.81 ng/mL，此时灵敏度为65.4%，特异度为82.3%，AUC为0.755；以SP-D≥0.66 ng/mL、SP-A≥20.02 ng/mL、IL-1β≥9.81 pg/mL为阈值，三者联合进行平行试验时的灵敏度及特异度分别为99.7%、42.6%；三者联合进行系列试验时的灵敏度及特异度分别为53.4%、98.8%（
图2 SP-D、SP-A、IL-1β早期预测ALI的ROC曲线
Figure 2 ROC curves of SP-D, SP-A and IL-1β for early prediction of ALI
三项指标对TE术后伴发ARDS的早期预测分析结果显示：SP-D最佳阈值为0.96 ng/mL，此时灵敏度为87.5%，特异度为84.7%，AUC为0.902；SP-A最佳阈值为21.26 ng/mL，此时灵敏度为93.8%，特异度为80.6%，AUC为0.931；IL-1β最佳阈值为14.64 ng/mL，此时灵敏度为87.5%，特异度为91.8%，AUC为0.957；以SP-D≥0.96 ng/mL、SP-A≥21.26 ng/mL、IL-1β≥14.64 pg/mL为阈值，三者联合进行平行试验时的灵敏度及特异度分别为99.9%、62.7%；三者联合进行系列试验时的灵敏度及特异度分别为71.8%、99.7%（
图3 SP-D、SP-A、IL-1β早期预测ARDS的ROC曲线
Figure 3 ROC curves of SP-D, SP-A and IL-1β for early prediction of ARDS
将三组患者术前各指标水平与氧合指数做Pearson检验并制作散点图，结果显示：SP-D、SP-A、IL-1β检测值与氧合指数值均呈明显负相关（r=-0.504、-0.657、-0.717，均P<0.01）（
图4 SP-D、SP-A、IL-1β与氧合指数的相关性
Figure 4 Correlation of SP-D, SP-A, and IL-1β with oxygenation index
将三组患者术前各指标水平与诊断ALI/ARDS时的LIS评分做Spearman检验并制作散点图，结果显示：SP-D、SP-A、IL-1β检测值与LIS评分均呈显著正相关（r=0.471、0.654、0.634，均P<0.01）（
图5 SP-D、SP-A、IL-1β与LIS评分的相关性
Figure 5 Correlation of SP-D, SP-A, and IL-1β with LIS score
TE在腹部创伤中较为常见，是急诊行剖腹探查术的适应证之
SP-D作为钙依赖性凝集素家族中的糖蛋白，是肺表面活性物质系统的组成部分。其不仅发挥宿主防御和免疫调节功
SP-A属于亲水性糖蛋白，在所有肺表面活性蛋白中占比最大，其水平高低可反映肺泡上皮屏障损伤状
IL-1β是一种热源性的细胞因子，其促炎作用强
在本研究中，ROC曲线分析示SP-D、SP-A、IL-1β各指标单独预测ALI/ARDS的AUC均高于PCT、LIPS评分，表明三者有望替代上述传统指标而对ALI/ARDS的发生具备更有效的预测价值。ROC曲线分析还发现，SP-A在早期预测TE术后伴发ALI/ARDS方面均表现出较高的灵敏度，且ALI和ARDS组患者SP-A水平在术前即开始明显高于对照组，表明SP-A可以作为早期预测TE术后伴发ALI/ARDS的敏感指标之一；IL-1β预测ARDS的AUC最高，表明其在早期预测TE术后伴发ARDS方面具有更高价值。此外，三者联合平行试验可提高预测TE术后伴发ALI/ARDS的灵敏度，系列试验则有助于提高特异度。但基于本研究中TE术后伴发ALI和ARDS患者样本数较少，尚待后续扩大样本以进一步佐证。
综上所述，血清SP-D、SP-A、IL-1β在TE术后患者伴发ALI/ARDS的早期预测和病情严重程度评估中均有一定的临床价值，其中三者联合动态监测的临床价值更高，且各指标检测方便快捷，值得临床上进一步推广应用。
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