摘要
目的分析儿童重症腺病毒肺炎的临床特征、危重症及其死亡高危因素,为早期诊断及合理治疗提供临床依据。方法回顾性分析华中科技大学同济医学院附属同济医院儿童重症医学科(PICU)2019年1至10月收治的75例重症腺病毒肺炎患儿的临床资料和实验室检查资料,按照病情分析分为重症组和危重症组,采用χ^(²)检验或Mann-Whitney秩和检验对比分析进行组间比较,危重症及其死亡的高危因素分析采用单因素和多因素Logistic回归分析。结果75例重症腺病毒肺炎患儿中男52例、女23例,年龄为3月龄至8岁,重症组30例、危重症组45例。鼻咽拭子腺病毒抗原阳性率为21%(15/72),血清腺病毒IgM抗体阳性率为13%(10/75),鼻咽拭子腺病毒核酸阳性率为75%(21/28)。血浆和肺泡灌洗液的病原微生物宏基因组二代测序(mNGS)阳性率分别为92%(33/36)和96%(54/56),95%(63/66)确定为腺病毒7型。采用较大剂量利巴韦林和综合治疗措施(呼吸支持、糖皮质激素、免疫球蛋白及器官功能维护等),治愈率为77%(58/75),好转率8%(6/75),病死率为15%(11/75)。危重症组的利巴韦林治疗后发热>3 d比率明显高于重症组[51%(18/35)比8%(2/26),χ^(²)=12.949,P<0.05]。重症病例发生危重症的高危因素包括年龄<4岁、入PICU前发热时间、入PICU后发热时间、氧合指数(P/F)<300 mmHg(1 mmHg=0.133 kPa)、铁蛋白>1000μg/L、乳酸脱氢酶(LDH)>1500 U/L、5个肺叶受累、并发胸腔积液和(或)气漏(均P<0.05)。其中,5个肺叶受累为独立高危因素(校正OR=49.641,95%CI 4.186~588.618,P=0.002)。危重症病例的死亡高危因素包括入PICU后发热时间、P/F<100 mmHg、铁蛋白>2000μg/L、白细胞介素(IL)-6>100 ng/L、LDH>1500 U/L、并发胸腔积液和(或)气漏(均P<0.05)。其中,IL-6>100 ng/L为独立高危因素(校正OR=16.094,95%CI 2.059~25.787,P=0.008)。结论腺病毒7型所致儿童重症腺病毒肺炎的病死率较高;鼻咽拭子腺病毒核酸和血浆或肺泡灌洗液mNGS检出率高,有助于早期诊断,后者可用于分型;对于4岁以下儿童,持续发热、肺部广泛病变和IL-6水平明显增高者应高度警惕危重症和不良预后;早期较大剂量利巴韦林联合综合疗法有助于改善其预后。
Objective To analyze the clinical characteristics,risk factors for critical illness and death of severe adenovirus pneumonia in children,so as to provide clinical evidences for early diagnosis and reliable treatment.Methods A total of 75 pediatric cases with severe adenovirus pneumonia admitted to Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology from January to October 2019 were studied.The clinical features,laboratory and imaging data,therapeutic approaches,efficacy of the treatments and prognosis were investigated retrospectively.Patients were divided into severe group and critical group.Chi square test and Mann-Whitney U rank sum test were used to analyze the data of the two groups.The risk factors for critical illness and death were analyzed by univariate and multivariate Logistic regression.Results Among the 75 children,there were 52 males and 23 females,aged from 3 months to 8 years,including 30 of severe cases and 45 of critical case.The positive rate of adenovirus antigen in nasopharyngeal swab was 21%(15/72),and the positive rate of serum adenovirus IgM antibody was only 13%(10/75).However,the positive rate of adenovirus nucleic acid in nasopharyngeal swab was 75%(21/28).What is more,the positive rates of metagenomics next generation sequencing(mNGS)in plasma and bronchoalveolar lavage fluid were 92%(33/36)and 96%(54/56),respectively,of which 95%(63/66)were confirmed as adenovirus type 7.Relatively high dose of ribavirin and integrated therapeutic approaches(respiratory support,glucocorticoids,immunoglobulin and organ supportive therapies)were used.The recovery rate was 77%(58/75),the improvement rate was 8%(6/75)and the mortality rate was 15%(11/75).The proportion of children with the duration of fever longer than 3 days after ribavirin treatment in the critical group was significantly higher than that in the severe group(51%(18/35)vs.8%(2/26),χ^(2)=12.949,P<0.05).The risk factors for critical illness were younger than 4 years,longer duration of fever before and after admission to PICU,oxygenation index<300 mmHg(1 mm Hg=0.133 kPa),ferritin>1000μg/L,lactate dehydrogenase(LDH)>1500 U/L,5 lung lobes involvement,pleural effusion and(or)air leakage(all P<0.05).Among them,5 lung lobes involvement was the independent risk factor for critical illness(adjusted OR=49.641,95%CI 4.186-588.618,P=0.002).Risk factors for death included longer duration of fever after being admitted to PICU,oxygenation index<100 mmHg,ferritin>2000μg/L,interleukin(IL)-6>100 ng/L,LDH>1500 U/L,pleural effusion and(or)air leakage(all P<0.05).Among them,IL-6>100 ng/L was the independent risk factor for the mortalities of critically ill children(adjusted OR=16.094,95%CI 2.059-25.787,P=0.008).Conclusions The mortality rate of severe pediatric adenovirus pneumonia caused by adenovirus type 7 is high.High positive rates of adenovirus nucleic acid in nasopharyngeal swabs and mNGS in plasma or bronchoalveolar lavage fluid contribute to early diagnosis,and mNGS can also be used for serotyping.Younger children under 4 years of age,persistent fever,extensive pulmonary lesions and significantly increased inflammatory cytokines such as IL-6 are warning indicators for critical illness and poor prognosis.Relatively high dose of ribavirin combined with integrated therapeutic approaches are beneficial for prognosis.
作者
黄浩
陈瑜
马丽娅
闫苗苗
邓钰
张文迪
袁义
熊鹏
方峰
刘铜林
Huang Hao;Chen Yu;Ma Liya;Yan Miaomiao;Deng Yu;Zhang Wendi;Yuan Yi;Xiong Peng;Fang Feng;Liu Tonglin(Department of Pediatrics,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China;Department of Radiology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China)
出处
《中华儿科杂志》
CAS
CSCD
北大核心
2021年第1期14-19,共6页
Chinese Journal of Pediatrics
基金
湖北省自然科学基金(2018CFB746)。
关键词
腺病毒
人
重症肺炎
儿童
利巴韦林
Adenoviruses,human
Severe pneumonia
Child
Ribavirin
