静脉注射丙种球蛋白在重症腺病毒肺炎患儿中的应用策略

Application strategy of intravenous immunoglobulin in children with severe adenovirus pneumonia

目的探讨重症腺病毒肺炎患儿静脉注射丙种球蛋白(IVIG)的治疗时机、剂量选择对疾病转归的影响及安全性评估。方法回顾性分析2019年1月至2020年1月广州医科大学附属广州市妇女儿童医疗中心呼吸科使用IVIG治疗的重症腺病毒肺炎患儿临床资料。根据IVIG治疗的时间分层, 分为早期应用(病程5~10 d)和晚期应用(病程11~15 d);再根据不同剂量的丙种球蛋白分组, 方案1组:1 g/(kg·d), 共2 d;方案2组:0.4~0.5 g/(kg·d), 共3~5 d, 收集患儿的临床资料进行分析。连续变量的2组分析采用非参数Mann-Whitney U检验;分类变量采用Fisher′s精确检验。结果共202例患儿入组, 中位年龄为12(12, 36)个月, 其中128例(63.37%)为早期应用者, 74例(36.63%)为晚期应用者。晚期应用患儿发热时长较早期应用患儿更长[18.00(14.00, 23.25) d比11.00(9.00, 14.00) d], 对机械通气的需求增加(33.78%比20.31%), 后遗症支气管扩张的发生率更高(9.46%比1.56%), 差异均有统计学意义(均P<0.05)。对于早期应用患儿, 2种剂量组在高级生命支持的需求、预后和后遗症方面比较差异均无统计学意义(均P<0.05)。而对于晚期应用患儿, 方案1组较方案2组患儿发热时间缩短[18.00(14.00, 21.00) d比21.00(15.50, 30.75) d], 体外膜肺(ECMO)的需求率明显降低(2.13%比18.52%), 差异均有统计学意义(均P<0.05)。肺部后遗症, 如感染后闭塞性细支气管炎和支气管扩张的发生率在2种剂量组间比较差异均无统计学意义(均P>0.05)。IVIG时不良事件发生率为5.77%, 2种剂量组比较差异无统计学意义(P>0.05)。结论早期给予IVIG治疗对改善重症腺病毒肺炎患儿的预后非常重要。对于晚期应用患儿, 高剂量IVIG治疗可缩短发热时间, 减少ECMO的使用。

Objective To observe the therapeutic timing and dosage of intravenous immunoglobulin(IVIG)in children with severe adenovirus pneumonia.Methods Clinical data of children with severe adenovirus pneumonia treated with IVIG at the Department of Respiratory,Guangzhou Women and Children′s Medical Center,Guangzhou Medical University from January 2019 to January 2020 were retrospectively analyzed.Participants were classified as early presenters(5-10 days of illness course)and later presenters(11-15 days of illness course)according to the timing of IVIG treatment.They were further subdivided into plan 1 group[1 g/(kg·d)IVIG for 2 days]and plan 2 group[0.4-0.5 g/(kg·d)IVIG for 3-5 days].Continuous variables and categorical variables between groups were analyzed by the nonparametric Mann-Whitney U test and the Fisher′s exact test,respectively.Results A total of 202 patients with the median age of 12(12,36)months were recruited,involving 128 early presenters(63.37%)and 74 later presen-ters(36.63%).Later presenters had a longer duration of fever[18.00(14.00,23.25)days vs.11.00(9.00,14.00)days],more demands for mechanical ventilation(33.78%vs.20.31%),and higher incidence of bronchiectasis(9.46%vs.1.56%)than those of early presenters(all P<0.05).For early presenters,no significant differences were detected in the demand for advanced life support,outcomes and sequelae between plan 1 group and plan 2 group(all P>0.05).For later presenters,a shorter duration of fever[18.00(14.00,21.00)days vs.21.00(15.50,30.75)days]and lower usage of extracorporeal membrane oxygenation(ECMO,2.13%vs.18.52%)were observed in the plan 1 group than that of plan 2 group(all P<0.05).The incidence of post-infectious bronchiolitis obliterans and bronchiectasis as pulmonary sequelae was comparable between plan 1 group and plan 2 group(P>0.05).The incidence of adverse events was 5.77%during IVIG infusion,showing no significant difference between plan 1 group and plan 2 group(P>0.05).Conclusions Early treatment of IVIG are very important to improve the prognosis of children with severe adenovirus pneumonia.For later presenters,a high dosage of IVIG is effective in reducing the ECMO use and shortening the duration of fever,thus providing clinical benefits.