摘要
目的探讨儿童重症EB病毒感染患儿肺损害的临床特征及预后，分析其发生肺损害与肺纤维化的危险因素。方法选取2011年1月至2014年12月上海市儿童医院重症医学科（PICU）收治的45例重症EB病毒感染患儿为研究对象，根据临床表现及影像学检查，分为重症EB病毒感染无肺损害组（It=27）、肺损害无纤维化组（n=12）及肺纤维化组（n=6）。回顾性观察其中并发肺损害患儿的临床、实验室及影像学检查特点及其转归，采用Logistic回归分析重症EB病毒感染患儿发生肺纤维化的临床危险因素。结果45例患儿中合并肺损害18例（40％），发热及咳嗽18例（100％），气促15例（83％），喘息12例（67％），急性呼吸窘迫综合征（ARDS）6例（33％），肺纤维化6例（33％），机械通气8例（44％）。肺纤维化患儿均有难治性低氧伴高碳酸血症、肺气漏。45例平均EB病毒DNA载量4．42×10^6拷贝／ml（3．25×10^-3～6．59×10^7拷贝／m1）；抗体检测病毒衣壳抗原（VCA）-IgM（＋）18例，VCA—IgG及早期抗原（EA）-IgG（＋）15例，VCA—IgM及VCA—IgG（＋）8例。肺损害患儿x线或高分辨率CT（HRCT）检查呈现肺部广泛间质性炎性浸润，合并部分肺实变4例，胸腔积液2例；肺纤维化患儿病程4周HRCT开始出现网格状阴影和蜂窝影。EB病毒感染无肺损害、肺损害无纤维化、肺纤维化三组间患儿呼吸衰竭发生率、住PICU时间、第三代小儿死亡危险评分（PRISMⅢ）及小儿危重症评分（PCIS）、EB病毒DNA载量、血清TNF—α、CD16＋56＋／CD45＋（NK细胞）百分比、CD4＋／CD8＋T淋巴细胞比率差异有统计学意义（χ2=27．12，F=85．23、78．23、88．68、323．80、7．35，χ2=6．71、12．15；P均〈0．05）。10例EB病毒相关性噬血细胞淋巴组织细胞增多症（EBV—HLH）患儿发生肺纤维化7例（70％），8例非EB—HLH患儿发生肺纤维化1例（13％），差异有统计学意义（χ2=4．82，P=0．03）。多因素分析肺纤维化独立危险因素为EB病毒载量（OR=3．92，P=0．04）及血清TNF—α（OR=5．95，P=0．01）。18例肺损害患儿死亡8例；6例肺纤维化患儿死亡3例，3例存活患儿6个月后随访肺HRCT肺纤维化改善，出院后18个月后离氧。结论重症EB病毒感染肺损害发生率高，易发生呼吸衰竭，部分发展为肺纤维化；肺纤维化高危因素为高EB病毒DNA载量及高TNF—α血症；肺纤维化患儿需长期吸氧，儿童肺纤维化有可逆性。
Objective Severe Epstein-Barr （EB） virus infection is potentially a devastating process that often leads to death encountered in pediatrics recently. Inappropriate control of EB virus replication may cause severe infection resulting in multiple organ dysfunction. However, little information is available on pulmonary complications associated with EB virus infection. The aim of the present study was to investigate severe EB virus （EBV） infection complicated with lung injury in pediatric intensive care unit （PICU） , including clinical characteristics, laboratory or imaging feature and outcomes. Method A total of 45 children with severe EBV infection seen in PICU of Shanghai Children＇s Hospital between January 2011 and December 2014 were retrospectively reviewed. According to clinical characteristics and imaging feature, 45 children were divided into non-lung injury group （n = 27 ）, lung injury without pulmonary fibrosis group（ n = 12） and pulmonary fibrosis group （n = 6 ）. Result In totally 45 cases of severe EBV infection, 21 （46. 7% ） were male and 24 （53.3%） were female,mean age was 2. 4 years; 18 cases were complicatedwith lung injury, including 8 male and 10 female, median age was 31.2 months. All of 18 cases presented with fever and cough, 15 of them exhibited dyspnea, 12 cases were complicated with gasping, and 6 cases with ARDS. Eight cases accepted mechanical ventilation for acute respiratory distress; 6 cases who developed pulmonary fibrosis had taehypnea, refractory hypoxemia and hypercapnia, severe pulmonary air leak. The average EBV-DNA level in peripheral blood was 4.42 × 10^6 copies/m1 （range： 3.25× 10^3 - 6. 59 × 10^7 copies/ml）. Anti-EBV antibodies were positive in 41 cases, 18 cases were positive （ ＋ ） for VCA-IgM,15 cases were VCA-IgG and EA-IgG （ ＋ ）, 8 cases VCA-IgM and VCA-IgG （ ＋ ）. The radiographic findings revealed pulmonary interstitial infiltrates in all 18 cases with lung injury, 4 cases with segmental consolidation and 2 cases showed pleura1 effusions. HRCT scanning found EBV associated fibrosis including muhifoeal patches and diffuse ground-glass attenuation in both lungs, reticular opacities and honeycombing changes were observed 4 weeks after illness onset. There were significant differences in respiratory failure, PICU stay （ days ） , Pediatric risk of mortality Ⅲ（ PRISM Ⅲ ） and pediatric clinical illness score（ PCIS）, serum TNF-α, EBV-DNA levels, percentage of NK cells and CD4 ＋/CD8 ＋T cell ratio among non-lung injury group, lung injury without pulmonary fibrosis group and pulmonary fibrosis group （ χ2 =27.12, F = 85.23, 78.23, 88. 68, 323.80, 7.35, χ2 = 6.71, 12. 15 ; all P 〈 0. 05 ）. COX regression analysis revealed that EBV-DNA and serum TNF-α levels were correlated with pulmonary fibrosis significantly （ OR = 3. 92, P = 0.04; OR = 5.95, P = 0.01 ） . The patients with EBV-associated hemophagocytic lymphohistiocytosis （EBV-HLH） had higher incidence of pulmonary fibrosis compared with non-EB-HLH （70% vs. 13%, χ2 = 4. 82,P = 0. 03）. Of 18 cases, 8 cases died, including 3 cases with pulmonary fibrosis. The surviving cases with pulmonary fibrosis needed longer additional oxygen. Chest HRCT imaging of 3 cases with pulmonary fibrosis was improved at 6 months and oxygen therapy was discontinued at 18 months after discharge. Conclusion EB virus infection complicated with lung injury had higher incidence of respiratory failure, pulmonary fibrosis with a fatal outcome. EBV-DNA and serum TNF-α level were found to be statistically significant indicators of pulmonary fibrosis. Pulmonary fibrosis associated with severe EB virus infection may be reversible.
出处
《中华儿科杂志》
CAS
CSCD
北大核心
2015年第8期586-591,共6页
Chinese Journal of Pediatrics
基金
上海市卫生局科技发展基金面上项目（2013083）
