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[儿童重症腺病毒肺炎临床特征及危险因素分析]

[Analysis of the clinical features and the risk factors of severe adenovirus pneumonia in children].

作者信息

Huang H, Chen Y, Ma L Y, Yan M M, Deng Y, Zhang W D, Yuan Y, Xiong P, Fang F, Liu T L

机构信息

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.

出版信息

Zhonghua Er Ke Za Zhi. 2021 Jan 2;59(1):14-19. doi: 10.3760/cma.j.cn112140-20200704-00687.

Abstract

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. 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 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. 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) 8% (2/26), χ=12.949, <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>1 000 μg/L, lactate dehydrogenase (LDH)>1 500 U/L, 5 lung lobes involvement, pleural effusion and (or) air leakage (all 0.05). Among them, 5 lung lobes involvement was the independent risk factor for critical illness (adjusted =49.641, 95% 4.186-588.618, =0.002). Risk factors for death included longer duration of fever after being admitted to PICU, oxygenation index<100 mmHg, ferritin>2 000 μg/L, interleukin (IL)-6>100 ng/L, LDH>1 500 U/L, pleural effusion and (or) air leakage (all <0.05). Among them, IL-6>100 ng/L was the independent risk factor for the mortalities of critically ill children (adjusted =16.094, 95% 2.059-25.787, =0.008). 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.

摘要

分析儿童重症腺病毒肺炎的临床特征、危重症及死亡的危险因素,为早期诊断及可靠治疗提供临床依据。研究2019年1月至10月在华中科技大学同济医学院附属同济医院收治的75例儿童重症腺病毒肺炎病例。回顾性调查其临床特征、实验室及影像学资料、治疗方法、治疗效果及预后。将患者分为重症组和危重组。采用卡方检验和曼-惠特尼秩和检验分析两组数据。通过单因素和多因素Logistic回归分析危重症及死亡的危险因素。75例患儿中,男52例,女23例,年龄3个月至8岁,其中重症30例,危重症45例。鼻咽拭子腺病毒抗原阳性率为21%(15/72),血清腺病毒IgM抗体阳性率仅为13%(10/75)。然而,鼻咽拭子腺病毒核酸阳性率为75%(21/28)。此外,血浆和支气管肺泡灌洗液宏基因组下一代测序(mNGS)阳性率分别为92%(33/36)和96%(54/56),其中95%(63/66)确诊为7型腺病毒。采用了相对高剂量的利巴韦林及综合治疗方法(呼吸支持、糖皮质激素、免疫球蛋白及器官支持治疗)。恢复率为77%(58/75),好转率为8%(6/75),死亡率为15%(11/75)。危重组利巴韦林治疗后发热持续时间>3天的患儿比例显著高于重症组(51%(18/35)比8%(2/26),χ=12.949,P<0.05)。危重症的危险因素为年龄<4岁、入住PICU前后发热持续时间长、氧合指数<300 mmHg(1 mmHg = 0.133 kPa)、铁蛋白>1 000 μg/L、乳酸脱氢酶(LDH)>1 500 U/L、5个肺叶受累、胸腔积液和(或)气胸(均P<0.05)。其中,5个肺叶受累是危重症的独立危险因素(校正β = 49.641,95%CI 4.186 - 588.618,P = 0.002)。死亡的危险因素包括入住PICU后发热持续时间长、氧合指数<100 mmHg、铁蛋白>2 000 μg/L、白细胞介素(IL)-6>100 ng/L、LDH>1 500 U/L、胸腔积液和(或)气胸(均P<0.05)。其中,IL-6>100 ng/L是危重症患儿死亡的独立危险因素(校正β = 16.094,95%CI 2.059 - 25.787,P = 0.008)。7型腺病毒所致儿童重症腺病毒肺炎死亡率高。鼻咽拭子腺病毒核酸及血浆或支气管肺泡灌洗液mNGS阳性率高有助于早期诊断,mNGS还可用于血清分型。4岁以下幼儿、持续发热、肺部病变广泛及IL-6等炎性细胞因子显著升高是危重症及预后不良的预警指标。相对高剂量的利巴韦林联合综合治疗方法有利于预后。

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