人免疫球蛋白及阿司匹林治疗时间对儿童川崎病冠状动脉损害的预后研究

Prognosis of Coronary Artery Lesions in Children with Kawasaki Disease by Human Immunoglobulin and Aspirin Treatment Time

目的探讨人免疫球蛋白及阿司匹林治疗时间对儿童川崎病(KD)冠状动脉损害的预后影响。方法选择2015年10月至2019年10月就诊于宁夏医科大学总医院的75例KD并发冠状动脉损害的患儿,记录患儿急性期血清白细胞计数(WBC)、血红蛋白(HB)、血小板计数(PLT)、人血白蛋白、C-反应蛋白(CRP)和超声心动图检查中冠状动脉内径,主要终点是超声心动图检查提示冠状动脉恢复正常,运用Kaplan-Meier和Log-rank检验估计治疗时间对冠状动脉恢复时间的影响。采用Cox回归模型估计冠状动脉损害恢复时间与相关因素的风险比(HR)。结果经Cox回归模型单因素分析,早期治疗组中位冠状动脉损害期为1.0个月,晚期治疗组中位冠状动脉损害期为10.0个月,早期治疗组与晚期治疗组比较,差异有统计学意义(HR=2.404,95%CI:1.469~3.934,Log-rank检验χ^(2)=18.73,P<0.001)。急性期冠状动脉损害程度(Ⅰ度病变组与Ⅱ度病变组比较)差异有统计学意义(HR=3.400,95%CI:1.892~6.110,Log-rank检验χ^(2)=13.12,P<0.001),进一步分层分析结果显示,在Ⅰ度病变组中,早期治疗组与晚期治疗组比较,差异有统计学意义(HR=2.118,95%CI:1.254~3.577,Log-rank检验χ^(2)=14.17,P<0.001);在Ⅱ度病变组中,早期治疗组与晚期治疗组比较,差异无统计学意义(HR=2.681,95%CI:0.431~16.670,Log-rank检验χ^(2)=1.321,P=0.271)。静脉注射人免疫球蛋白(IVIG)、阿司匹林治疗及急性期冠状动脉损害程度是影响冠状动脉恢复时间的因素与KD并发冠状动脉损害时间密切相关(P<0.05)。经Cox回归模型多因素分析,急性期冠状动脉损害程度(HR=0.35,95%CI:0.12~0.98)、IVIG及阿司匹林治疗时间(HR=0.35,95%CI:0.17~0.69)均与KD并发冠状动脉损害时间密切相关(P均<0.05)。结论早期(发热<10 d)使用IVIG及阿司匹林期治疗KD患儿,可减少冠状动脉损害时间,改善预后。

Objective To investigate the influerce of prognosis of coronary arter lesions in Children with Kawasaki disease by human immunoglobulin and aspirin treatment time.Methods A total of 75 children with Kawasaki disease(KD)and coronary artery damage who were treated at the General Hospital of Ningxia Medical University from October 2015 to October 2019 were selected to record their acute serum white blood cell count(WBC),hemoglobin(HB),platelet count(PLT),human serum albumin,C-reactive protein(CRP),and coronary artery diameter in echocardiography.The primary end point was echocardiographic examination indicated that the coronary arteries had returned to normal.Kaplan-Meier and Log-rank tests were used to estimate the effect of treatment time on coronary recovery time.The Cox regression model was used to estimate the hazard ratio(HR)between the recovery time of coronary artery damage and related factors.Results The Cox model univariate analysis showed that the median duration of coronary artery damage in the early treatment group was 1.0 month,and the median duration of coronary artery damage in the late treatment group was 10.0 months(HR=2.404,95%CI:1.469-3.934,Log-rank χ^(2)=18.73,P<0.001).There was a statistically significant difference in the degree of coronary artery damage in the acute stage(grade Ⅰ group vs.grade Ⅱ group)(HR=3.400,95%CI:1.892-6.110,Log-rank χ^(2)=13.12,P<0.001).Further stratified analysis showed that there was a statistically significant difference between the early treatment group and the late treatment group in grade Ⅰ coronary artery injury(HR=2.118,95%CI:1.254-3.577,Log-rank χ^(2)=14.17,P<0.001).In the grade Ⅱ coronary artery injury,there was no statistically significant difference between the early treatment group and the late treatment group(HR=2.681,95%CI:0.431-16.670,Log-rank χ^(2)=1.321,P=0.271).IVIG and aspirin treatment,the degree of coronary artery damage in the acute phase were the factors affecting the recovery time of coronary artery and were closely related to the time of KD and coronary artery damage(P<0.05).The Cox model multivariate analysis showed the degree of coronary artery damage in the acute stage(HR=0.35,95%CI:0.12-0.98),IVIG and aspirin treatment(HR=0.35,95%CI:0.17-0.69)were closely related to the time of KD with coronary artery damage(P all<0.05).Conclusion Early treatment(fever<10 d)of IVIG and aspirin tretment in children with KD can reduce the time of coronary artery damage and improve the prognosis.