摘要
目的 分析重症甲型H1N1流感（甲流）患者的早期免疫学特征,为预测该病的预后提供理论依据.方法 采用回顾性分析方法,收集2015年10月至2016年12月在南京医科大学附属上海一院临床医学院就诊并确诊为重症甲流的15例患者临床资料,根据28 d预后分为存活组和死亡组;比较两组间早期临床特征、治疗方案、器官功能、炎症反应和免疫功能状态,通过Cox多因素回归法分析免疫功能是否为重症甲流患者28 d死亡的独立危险因素.结果 15例重症甲流患者均纳入最终分析.患者早期主要表现为咳嗽（93.3%）、发热（86.7%）、咳痰（80.0%）、气短（73.3%）、肌肉酸痛（40.0%）及乏力（40.0%）等;均给予抗病毒、抗感染、机械通气及抗凝治疗,部分患者使用俯卧位通气、肌松剂或体外膜肺氧合（ECMO）等;患者心、肾功能明显损害;急性生理学与慢性健康状况评分系统Ⅱ（APACHEⅡ）和序贯器官衰竭评分（SOFA）分别为（14.1±6.1）分和（9.6±4.1）分,提示患者病情危重.15例患者28 d死亡4例,11例痊愈出院.与存活组比较,死亡组患者APACHEⅡ评分明显升高（分：22.7±3.8比11.8±3.8）,肌钙蛋白〔cTn（μg/L）：0.52（0.07,2.02）比0.15（0.10,0.45）〕和尿素氮〔BUN（mmol/L）：11.9（6.7,29.1）比3.9（2.7,6.8）〕亦明显升高,而血小板计数（PLT）明显降低（×109/L：76±33比146±49,均P〈0.05）.与存活组相比,死亡组患者入院24 h内C-反应蛋白（CRP）和白细胞介素-6（IL-6）水平显著升高〔CRP（mg/L）：172.2±88.5比74.8±33.1,IL-6（ng/L）：283.3（140.1,711.0）比18.5（12.7,71.4）,均P〈0.01〕;CD3＋、CD4＋、CD8＋T细胞及自然杀伤细胞（NK细胞）比例均显著降低（CD3＋T细胞：0.348±0.119比0.573±0.106,CD4＋T细胞：0.135±0.046比0.344±0.098,CD8＋T细胞：0.089±0.057比0.208±0.054,NK细胞：0.124±0.057比0.252±0.182,均P〈0.05）,但CD4＋/CD8＋比值、人白细胞DR抗原阳性（HLA-DR＋）T细胞与存活组比较差异无统计学意义（CD4＋/CD8＋比值：1.57±0.26比1.83±0.54,HLA-DR＋T细胞：0.035±0.022比0.062±0.036,均P〉0.05）;死亡组B淋巴细胞比例较存活组显著升高（0.477±0.136比0.229±0.121,P〈0.01）.Cox多因素回归分析显示,APACHEⅡ评分〔相对危险度（RR）=20.4,95%可信区间（95%CI）=5.3~31.2,P=0.017〕、CD4＋T细胞（RR=11.1,95%CI=5.1~20.0,P=0.048）和CD8＋T细胞（RR=9.1,95%CI=4.3~16.7,P=0.049）是重症甲流患者28 d死亡的独立危险因素.结论 重症甲流早期即合并免疫功能抑制及剧烈的炎症反应,与疾病预后具有紧密的联系.
Objective To analysis the immunological characteristics of patients with severe H1N1 influenza A, and to provide theoretical basis for predicting the prognosis of the disease. Methods A retrospective analysis was conducted. The clinical data of 15 patients diagnosed with severe H1N1 influenza A and admitted to Shanghai General Hospital of Nanjing Medical University from October 2015 to December 2016 were collected. All the patients were divided into survival and death groups according to 28-day survival. Clinical characteristics, treatment algorithm, organ function, inflammatory reaction and immune cell status were compared, and Cox regression was used to decide the risk factors of 28-day death in patients with severe H1N1 infection A. Results All 15 patients with severe H1N1 infection A were enrolled, most of who presented with cough （93.3%）, fever （86.7%）, sputum production （80.0%）, shortness of breath （73.3%）, myalgia （40.0%） and fatigue （40.0%）. All had been received anti-virus, antibiotics, mechanical ventilation and anti-coagulation therapy; some were treated with prone position, neuromuscular blocker and extracorporeal membrane oxygenation （ECMO）. The incidences of acute myocardial and kidney injury were high, and the acute physiology and chronic health evaluation Ⅱ （APACHE Ⅱ） score （14.1±6.1） and sequential organ failure assessment （SOFA） score （9.6±4.1） implicated the critical condition. Of 15 patients, 4 patients died in 28 days, while 11 were cured and discharged. Compared with survival group, the patients in death group had higher levels of APACHE Ⅱscore （22.7±3.8 vs. 11.8±3.8）, troponin [cTn （μg/L）： 0.52 （0.07, 2.02） vs. 0.15 （0.10, 0.45）] and blood urea nitrogen [BUN （mmol/L）： 11.9 （6.7, 29.1） vs. 3.9 （2.7, 6.8）] and a lower level of blood platelets count [PLT （×109/L）： 76±33 vs. 146±49, all P 〈 0.05]. The levels of C-reactive protein （CRP） and interleukin-6 （IL-6） within 24 hours of admission in death group were significantly higher than those of survival group [CRP （mg/L）： 172.2±88.5 vs. 74.8±33.1, IL-6 （ng/L）：283.3 （140.1, 711.0） vs. 18.5 （12.7, 71.4）, both P 〈 0.01]. Compared with survival group, the expressions of CD3＋, CD4＋, CD8＋ T cells and natural killer cell （NK cell） in death group were significantly decreased （CD3＋ T cell： 0.348±0.119 vs. 0.573±0.106, CD4＋ T cell： 0.135±0.046 vs. 0.344±0.098, CD8＋ T cell： 0.089±0.057 vs. 0.208±0.054, NK cell： 0.124±0.057 vs. 0.252±0.182, all P 〈 0.05）, but there were no significant differences in CD4＋/CD8＋ ratio and human leucocyte antigen-DR positive （HLA-DR＋） T cell between death group and survival group （CD4＋/CD8＋ ratio：1.57±0.26 vs. 1.83±0.54, HLA-DR＋ T cell： 0.035±0.022 vs. 0.062±0.036, both P 〉 0.05）. B lymphocyte in death group was significantly higher than that of survival group （0.477±0.136 vs. 0.229±0.121, P 〈 0.01）. Cox regression analysis revealed that APACHE Ⅱ score [risk ratio （RR） = 20.4, 95% confidence interval （95%CI） = 5.3-31.2, P = 0.017], CD4＋ T cell （RR = 11.1, 95%CI = 5.1-20.0, P = 0.048） and CD8＋ T cell （RR = 9.1, 95%CI = 4.3-16.7, P = 0.049） were independently risk factors of 28-day survival of patients with severe H1N1 influenza A. Conclusion Immunological paralysis and severe inflammatory response were early complicated with severe H1N1 influenza A, and these were significantly associated with prognosis.
作者
钱永兵
谢晖
田锐
陆健
金卫
王瑞兰
Qian Yongbing Xie Hui Tian Rui Lu Jian Jin Wei Wang Ruilan(Department of Critical Care Medicine, Shanghai General Hospital of Nanjing Medical University, Shanghai 201620, China)
出处
《中华危重病急救医学》
CAS
CSCD
北大核心
2017年第7期581-585,共5页
Chinese Critical Care Medicine
基金
国家自然科学基金（81471891）
上海市医药卫生科技发展基金（14411971100）
关键词
甲型H1N1
免疫功能
炎症反应
重症
H1N1 influenza A
Immune function
Inflammatory response
Critically illness
