S1P、LXA4对评估急性呼吸窘迫综合征患者治疗反应性的价值.pdf

:1836:nary disease risk:A meta-analysis J.Int J Clin Exp Med,2017,10(7):1037510381.17 Chi AF,Ctan A,Soriu O,et al.Interleukin-6 serum level and-597Journal of Clinical and Experimental Medicine Vol.22,No.17 Sep.2023A/G gene polymorphism in moderate and severe chronic obstructive pul-monary diseaseJ.Eur J Inflamm,2020,18(5):654-662.（收稿日期：2 0 2 3-0 3-2 0)D0I:10.3969/j.issn.1671-4695.2023.17.012S1P、LXA 4对评估急性呼吸窘迫综合征患者治疗反应性的价值田鹏陈春兰钟江姗黄成亮范贤明*（西南医科大学附属医院呼吸与危重症医学科四川泸州6 46 0 0 0)【摘要】目的分析1-磷酸鞘氨醇（S1P）、脂氧素A4(LXA4)对评估急性呼吸窘迫综合征（ARDS）患者治疗反应性的价值。方法回顾性选取2 0 2 1年1月至12 月西南医科大学附属医院收治的ARDS患者153例为研究对象,设为ARDS 组,另选取同期健康体检者153 名为对照组。比较 ARDS 组患者与对照组 S1P,LXA4 水平。统计 ARDS 患者治疗反应性情况,并比较不同治疗反应性患者相关资料。采用Logistic 回归分析ARDS患者治疗反应性的影响因素,构建ARDS患者治疗反应性的列线图预测模型并以校准曲线验证,绘制ARDS患者治疗反应性的决策曲线并进行分析。结果ARDS组患者S1P水平为（192 1.7 2 17 8.54)nmol/L，高于对照组（956.6 917 1.33）nmol/L,LXA4水平为（7 2.138.0 5)n g/L,低于对照组（94.6 6 9.7 1)ng/L，差异均有统计学意义（P0.05）。支气管哮喘、降钙素原、C反应蛋白、APACHEI评分、S1P水平升高是ARDS患者治疗反应性差的独立危险因素（P0.05）,氧合指数、LXA4水平升高是治疗反应性差的独立保护因素（P0.05)。根据Logistic 回归分析结果构建ARDS 患者治疗反应性的列线图预测模型，一致性指数为0.9 55(9 5%CI：0.9 0 9 0.9 8 2）；采用校准曲线验证模型的精准度发现，校准曲线接近理想参考线，具有较高一致性，表明精准度、区分度较好。决策曲线分析显示，当风险阈值为0.18 0.8 9时，S1P、LXA 4联合检测的净受益率大于单独检测。结论SIP、LXA 4 水平可用于评估ARDS患者治疗反应性,且 S1P高表达、LXA4 低表达表明患者治疗反应性较差,应根据患者情况及时改进治疗方案，具有临床指导价值。【关键词】急性呼吸窘迫综合征1磷酸鞘氨醇脂氧素A4治疗反应性决策曲线Value of SiP and LXA4 in evaluating the treatment responsiveness of patients with acute respiratory distress syndrome.TIAN Peng,CHEN Chun-lan,ZHONG Jiang-shan,et al.Department of Respiratory and Critical Care Medicine,Affiliated Hospital of Southwest Medical U-niversity,Luzhou Sichuan 646000,China.Abstract)Objective To analyze the value of sphingosine 1-phosphate(SIP)and lipoxin A4(LXA4)in evaluating the treatment re-sponsiveness of patients with acute respiratory distress syndrome(ARDS).Methods A total of 153 ARDS patients in Affiliated Hospital ofSouthwest Medical University from January to December 2021 were selected as the research objects,as the ARDS group,and 153 healthy subjectsduring the same period were selected as the control group.The levels of SIP and LXA4 in ARDS patients and healthy subjects were compared.Thetreatment responsiveness of ARDS patients was counted,and the related data of patients with different treatment responsiveness were compared.Lo-gistic regression was used to analyze the influencing factors of treatment responsiveness in ARDS patients:A nomogram prediction model of ARDSpatientstreatment responsiveness was constructed and validated with a calibration curve,and a decision curve of ARDS patientstreatment respon-siveness was drawn and analyzed.Results The level of S1P in ARDS patients was(1 921.72+178.54)nmol/L,which was higher than thecontrol group (956.69 171.33)nmol/LJ,and the level of LXA4 was(72.13 8.05)ng/L,which was lower than the control group(94.66+9.71)ng/L,the differences were statistically significant(P 0.05).Bronchial asthma,elevated levels of procalcitonin,C-reactive pro-tein,APACHE II score,and S1P were independent risk factors for poor treatment response in ARDS patients(P 0.05),and elevated oxygen-ation index and LXA4 levels were independent protective factors for poor treatment response(P 0.05），具有可比性。所有对象均知情本研究、签署同意书，本研究获西南医科大学附属医院伦理委员会批准。1.2纳入与排除标准纳入标准：（1)均符合ARDS 诊断标准 6 ；(2)均为肺部感染所致且1周内存在呼吸症状加重,胸部X线片或CT扫描可见双侧阴影且难以用胸腔积液、结节、肺叶/肺萎陷解释；（3)存在不同程度缺氧症状；排除标准：存在重症肺炎、肺动脉栓塞、心功能不全、特发性肺纤维化急性加重、心源性休克、心律失常、上消化道梗阻或穿孔患者。1.3方法1.3.1治疗方法（1)常规干预：完善相关检查，常规抗感染，遏制全身炎症反应；禁食，持续性胃肠减压，给予营养支持并维持电解质、酸碱平衡，加强脏器功能监测,预防器官功能障碍综合征；在确保组织灌注前提下实施限制性液体管理，若患者出现低蛋白血症，则补充白蛋白胶体溶液及利尿剂。（2）呼吸支持：给予吸氧治疗改善低氧血症,使动脉血氧分压为6 0 8 0 mmHg;积极进行机械通气，若患者神志清楚、血流动力学稳定且经严密监测可随时进行气管插管时,或预计病情可在短期快速缓解时，首选无创机械通气，无创机械通气12h后若低氧血症及全身状况改善明显，则继续无创机械通气；若低氧血症改善不明显或全身症状恶化，则及时改为有创通气；机械通气时采用肺保护性通气策略，维持气道平台压不超过30 35cmH,0,采用肺复张手法促使患者塌陷肺泡复张，体位选择30 45半卧位，同时积极预防呼吸机相关性肺炎。:18371.3.2检测方法健康体检者于体检当日、ARDS患者于收人病房2 4 h内采集空腹静脉血4 mL,离心15min（转速150 0 r/min）,取上层清液低温保存，以酶联免疫吸附试验(FX-6MG酶联免疫光谱分析仪)检测血清S1P、LXA4水平,试剂盒购自珠海丽珠试剂股份有限公司。1.3.3治疗反应性。治疗反应性良好定义为治疗7 d后临床症状基本消失或显著缓解,转出重症监护室 3d仍无病情加重倾向。治疗反应性差定义为治疗7 d后仍需继续有创机械通气,或人院2 8 d内死亡 7 。1.4观察指标（1）比较2 组研究对象 S1P、LXA 4水平。（2)统计ARDS患者治疗反应性情况,并比较不同治疗反应性患者相关资料,包括性别、ARDS 既往史、致病原因、基础疾病、年龄、血肌酐、脑钠肽、总胆红素、降钙素原、C反应蛋白、收缩压、动脉氧分压、二氧化碳分压、急性生理学和慢性健康状况评价（acute physiologyand chronic health score，A PA CH E I）评分、氧合指数、体温、脉搏等,除治疗反应性以外的其他数据均在患者收住或转入病房2 4 h内取得。（3）分析ARDS患者治疗反应性的影响因素。（4)构建ARDS 患者治疗反应性的列线图预测模型并进行验证。（5）绘制ARDS患者治疗反应性的决策曲线并进行分析。1.5统计学处理、采用SPSS22.0对本研究的数据进行处理,计量资料以均数标准差（x s）表示,组间比较采用t检验；计数资料以例或百分率（%）表示，组间比较采用检验；采用Logistic回归分析ARDS患者治疗反应性的影响因素;利用R语言4.2.1软件Deci-sion Curve包构建 ARDS患者治疗反应性的列线图预测模型,并绘制校准曲线进行一致性验证，以风险阈值为横坐标、净受益率为纵坐标,采用dcurvues包绘制决策曲线,分析 S1P、LXA 4评估 ARDS 患者治疗反应性的净受益率；P0.05为差异有统计学意义。2结果2.1ARDS患者与健康体检者S1P、LXA 4水平比较ARDS 组患者的 S1P水平高于对照组,LXA4 水平低于对照组,差异均有统计学意义（P0.05）。见表1。表 1ARDS 患者与健康体检者 S1P、LXA 4 水平比较（x s）组别例数ARDS组153对照组1531值P值2.2不同治疗反应性ARDS患者相关资料比较153例ARDS 患者治疗反应性良好 10 9 例,治疗反应性差44 例。与治疗反应性良好的患者相比,治疗反应性差的 ARDS患者支气管哮喘例数更多,年龄较大,降钙素原、C反应蛋白、APACHE评分、S1P水平更高，氧合指数、LXA4水平更低,差异均有统计学意义（P0.05）。见表2。S1P(nmol/L)1 921.72 178.54956.69 171.3348.2400.001LXA4(ng/L)72.13 8.0594.66 9.7122.1170.001:1838:表2不同治疗反应性患者相关资料比较指标良好(n=109)差(n=44)x/t值 P值性别 例(%)0.405男性65(61.47)女性44(38.53)ARDS 既往史 例(%)有无致病原因 例(%)直接肺损伤因素间接肺损伤因素基础疾病 例(%)糖尿病高血压支气管哮喘年龄(岁,xs)血肌酐(mol/L,x s)脑钠肽(ng/L,x s)总胆红素(mol/L,xs)降钙素原(ug/L,xs)C反应蛋白(mg/L,xs)收缩压(mmHg,x s)动脉氧分压(mmHg,x s)二氧化碳分压(mmHg,x s)APACHEI评分(分,xs)氧合指数(mmHg,xs)体温(,x s)脉搏(次/min,xs)S1P(nmol/L,x s)LXA4(ng/L,x s)2.3ARDS 患者治疗反应性的影响因素分析ARDS 患者治疗反应性为因变量,以支气管哮喘、年龄、降钙素原、C反应蛋白、APACHEII评分、氧合指数、S1P、LXA 4水平为自变量，采用Logistic回归分析,结果显示,支气管哮喘、降钙素原、C反应蛋白、APACHE评分、S1P水平升高是ARDS患者治疗反应性差的独立危Journal of Clinical and Experimental Medicine Vol.22,No.17 Sep.202323(54.55)21(45.45)4(3.67)3(6.82)105(96.33)41(93.18)58(53.21)26(59.09)51(46.79)18(40.91)10(9.17)5(11.36)14(12.84)9(20.45)5(4.59)10(22.73)52.27 8.0856.83 8.45115.83 10.22118.91 12.06128.37 18.65132.07 20.9217.26 1.6716.89 1.7916.22 2.9619.07 2.8479.26 7.9385.15 7.31138.67 11.52141.26 12.4955.18 5.8153.29 5.1857.02 6.3155.94 5.4716.74 2.6118.13 2.94100.24 9.5393.78 9.0637.52 1.0637.74 1.18105.84 13.21109.04 13.661924.11 158.47 2092.48 164.6574.16 5.430.028,校准曲线接近理想参考线,具有较高一致性,表明精准度、区分度较好，预测效果令人满意。见图2。0.69510分数合井支气管哮哦0.1730.6770.4380.5080.0130.9111.4210.2339.704 0.0023.118 0.0021.6000.1121.0720.2851.2150.2265.4530.0014.2500.0011.228 0.2211.8770.0630.9940.3222.8740.0053.8480.0011.1240.2631.3430.1815.8820.00167.09 5.127.408 0,表30合井20228580501000.4列线图预测值40506075701502000.50.80.95实际结果偏差校正理想线o.60.8706525080603001.0S1PLXA联合NC9010055350以风险险因素（P0.05），氧合指数、LXA4水平升高是治疗反应性差的独立保护因素（P0.05）；青年组患者合并高血压、脑血管疾病、心悸发生率均低于老年组,差异均有统计学意义（P0.05)；青年组及中年组患者心血管疾病均低于老年组,且青年组低于中年组,差异均有统计学意义（P0.05）；青年组患者胸痛发生率高于中年组、老年组,青年组患者静脉溶栓治疗率高于老年组,差异均有统计学意义（P0.05）；青年组、中年组、老年组患者总胆固醇、甘油三酯、LDL-C水平逐渐下降,青年组、中年组、老年组患者Hcy、h s-CR P水平逐渐上升,差异均有统计学意义（P0.05).The incidence rates of hypertension,cerebrovascular disease and palpitation in young group were lower than those in elderly groupthe differences were statistically significant(P 0.05).The incidence rate of cardiovascular disease in young and middle-aged groups was lowerthan that in elderly group,and the incidence rate in young group was lower than that in middle-aged group,the differences were statistically sig-nificant(P 0.05).The incidence rate of chest pain in young group was higher than that in middle-aged group and elderly group,the rate ofintravenous thrombolytic therapy in young group was higher than that in elderly group,the dfferences were statistically significant(P0.05).The levels of total cholester-ol,triglyceride,and LDL-C in young,middle-aged and elderly groups were gradually decreased while the levels of Hcy and hs-CRP weregradually increased,the differences were statistically significant(P0.05).Conclusion In elderly patients with low-risk pulmonary embol-基金项目：秦皇岛市科学技术研究与发展计划（编号：2 0 18 0 5A067）；河北省自然科学基金（编号：H2017209143）*通讯作者：卢文宣,E-mail:文章编号：16 7 1-46 9 5(2 0 2 3)17-18 40-0 4