EB病毒感染对结缔组织病相关性间质性肺炎的影响研究

Effect of Epstein-Barr Virus Infection on Connective Tissue Disease-associated Interstitial Pneumonia

背景临床上结缔组织病相关性间质性肺炎患者常合并EB病毒感染,然而EB病毒感染后是否增加结缔组织病相关性间质性肺炎患者细菌感染的风险、加重患者的炎性反应程度、增加并发症及延长治疗时间等相关文献鲜少报道。目的研究EB病毒感染对结缔组织病相关性间质性肺炎的影响。方法前瞻性选择贵州省人民医院呼吸与危重症医学科2016年12月—2018年12月收住院的结缔组织病相关性间质性肺炎患者113例为研究对象。依据患者是否感染EB病毒,将其分为结缔组织病相关性间质性肺炎合并EB病毒感染组(EB病毒感染组,39例)和结缔组织病相关性间质性肺炎未合并EB病毒感染组(无EB病毒感染组,74例)。对比分析两组一般资料、合并疾病、血气分析〔二氧化碳分压(PaCO2)、氧分压(PaO2)〕、吸入氧浓度(FiO2)、EB病毒DNA含量、G-菌感染比例、中性粒细胞分数、耐药菌感染比例、治疗有效时间、转重症病房比例,以及炎性指标〔血清C反应蛋白(CRP)、降钙素原(PCT)、诱生型一氧化氮合酶(iNOS)、白细胞计数及白介素(IL)-6、IL-17、IL-33〕。分析EB病毒感染组患者EB病毒DNA含量与其血清中CRP、PCT、iNOS、IL-6、IL-17、IL-33的相关性。结果两组患者一般资料、合并疾病、PaCO2、FiO2、中性粒细胞分数、耐药菌感染比例比较,差异均无统计学意义(P>0.05)。两组PaO2、EB病毒DNA含量>5×102 copies/ml比例、G-菌感染比例、治疗有效时间、转重症病房比例比较,差异有统计学意义(P<0.05)。EB病毒感染组CRP、PCT、iNOS、白细胞计数、IL-6、IL-17、IL-33高于无EB病毒感染组(P<0.05)。EB病毒感染组患者血清CRP、PCT、iNOS、IL-17、IL-33与EB病毒DNA含量呈正相关(r=0.6745、0.5843、0.6204、0.6989、0.5851,P<0.05),IL-6与EB病毒DNA含量无直线相关关系(r=0.1052,P>0.05)。结论与无EB病毒感染患者比较,EB病毒感染患者炎性反应程度加重、耐药菌感染比例增加、预后变差及住院时间延长,EB病毒感染患者EB病毒DNA含量与其血清中炎性指标CRP、PCT、iNOS、IL-17、IL-33呈正相关。提示EB病毒感染可能促进细菌性感染的发生发展或增加细菌性感染的风险,表明EB病毒可促进结缔组织病相关性间质性肺炎患者病情进展与恶化。本研究结果为EB病毒感染的临床研究提供一定的理论依据。

Background We have clinically found that patients with connective tissue disease-associated interstitial pneumonia often combine with Epstein-Barr(EB)virus infection.However,it is rarely reported that whether EB virus infection is associated with higher risk of bacterial infection,aggravation of inflammatory response,complications and prolongation of treatment time in such patients.Objective To provide evidence for further study of the impact of EB virus infection on connective tissue-related interstitial lung disease.Methods 113 patients with connective tissue-related interstitial pneumonia admitted to Department of Respiratory and Critical Care Medicine,Guizhou Provincial People's Hospital were prospectively selected from December 2016 to December 2018,and 39 of them with EB virus infection and other 74 without were assigned to infected group and uninfected group,respectively.The general personal data,combined disease,arterial blood gas markers(PaCO2 and PaO2),fraction of inspired oxygen(FiO2),EB virus DNA content,proportion of G-bacteria infection,neutrophil fraction,proportion of drug-resistant bacteria infection,effective treatment time,proportion of transferred cases to the ICU,and inflammatory markers〔serum C-reactive protein(CRP),procalcitonin(PCT),inducible nitric oxide synthase(iNOS),leukocyte count and interleukin(IL)-6,IL-17 and IL-33〕were compared between the two groups.Relationships of EB virus DNA content with CRP,PCT,iNOS,IL-6,IL-17 and IL-33 in EB virus infected group were analyzed.Results The mean level of PaO2,prevalence of EB virus DNA content greater than 5×102 copies/ml,proportion of G-bacteria infectiong,mean time of effective treatment and proportion of transferred cases to the ICU differed significantly between the two groups(P<0.05),but general personal data,distribution of combined diseases,mean levels of PaCO2,FiO2,neutrophil fraction,and proportion of drug-resistant bacteria infection did not(P>0.05).The mean levels of serum CRP,PCT,iNOS,leukocyte count,IL-6,IL-17 and IL-33 in patients with EB virus infection were significantly higher than those without(P<0.05).In the EB virus infected group,EB virus DNA content was positively correlated with serum CRP,PCT,iNOS,IL-17 and IL-33(r=0.6745,0.5843,0.6204,0.6989,0.5851,P<0.05).There was no linear correlation between IL-6 and EB virus DNA content(r=0.1052,P>0.05).Conclusion Compared with those without EB virus infection,the EB virus-infected patients had aggravated inflammatory response,increased proportion of being infected with drug-resistant bacteria,poorer prognosis,and prolonged hospital stay.The EB virus DNA content in those infected was positively correlated with levels of CRP,PCT,iNOS,IL-17,and IL-33 in the serum.EB virus infection may increase the risk of developing bacterial infection or aggravating the infection.This study shows that EB virus infection may promote the progression and deterioration of patients with connective tissue disease-associated interstitial pneumonia,which provides a certain theoretical basis for clinical research of EB virus infection.