Serum LD1 isoenzyme and blood lymphocyte subsets as prognostic indicators for severe acute respiratory syndrome
Serum LD1 isoenzyme and blood lymphocyte subsets as prognostic indicators for severe acute respiratory syndrome
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DOI：
10.1111/j.1365-2796.2004.01323.x
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发表时间：
2004-04-01
影响因子：
11.1
通讯作者：
Lam, CWK
中科院分区：
文献类型：
--
作者：
Chan, MHM;Wong, VWS;Lam, CWK
背景。目前对严重急性呼吸综合征 (SARS) 的病理生理学知之甚少，但高龄和血清总乳酸脱氢酶 (LD) 活性 >300 U L-1 与不良临床结果相关。据报道，北京 38 名患者的血液白细胞和淋巴细胞亚群分别下降了 47% 和 100%。然而，它们的预后影响尚未得到彻底研究。 目的。旨在研究血清总LD、LD同工酶和其他参数（包括血液淋巴细胞亚群）作为SARS患者入住重症监护病房（ICU）和死亡等不良临床结果的预后指标。设计。回顾性分析。主题和方法。根据世界卫生组织修订后的SARS病例定义，从香港两家主要急症医院共招募了109名临床诊断为SARS的患者。他们要么参与了SARS最初的爆发，要么参与了2003年3月10日至5月5日期间淘大花园社区爆发的病例。随后通过血清学检测和/或分子分析证实了临床诊断。入院时每天测量血清总 LD 和 LD 同工酶活性、全血图像（白细胞总数和分类计数）、CD3+、CD4+、CD8+、自然杀伤细胞和 B 淋巴细胞的绝对计数。接受者操作特征曲线分析用于确定和比较峰值血清总 LD 浓度时各种生化和免疫学参数的不同截止值，以预测不良临床结果。结果。共有 109 名患者，其中 41 人入住 ICU，42 人死亡。 42名死亡患者中，24人死于ICU，18人死于普通内科病房。研究发现年龄是死亡的独立预后指标，曲线下面积 (AUC) 为 0.96 [95% 置信区间 (CI) = 0.90-0.99]，但不是入住 ICU 的独立预后指标 [AUC = 0.61 (CI = 0.51-0.70)]。虽然血清总 LD 只能达到 AUC 0.68 (CI = 0.59-0.77) 来预测死亡，但 LD1 同工酶被发现是最好的生化预后指标，AUC 为 0.84 (CI = 0.75-0.90)，敏感性为 62% (CI = 46-76%)，特异性为 93% (CI = 83-98%) 截止活性大于或等于80 U L-1。 CD3+、CD4+、CD8+ 和自然杀伤细胞计数是预测入住 ICU 的有前途的免疫预后指标，AUC 分别为 0.94 (CI = 0.86-0.98)、0.91 (CI = 0.81-0.96)、0.93 (CI = 0.85-0.98) 和 0.87 (CI = 0.76-0.94), 分别得出结论。除年龄外，与血清LD总活性、血红蛋白浓度、白细胞和淋巴细胞计数相比，血清LD1活性是预测SARS患者死亡的最佳预后指标。它的释放可能来自血红细胞和心肌以外的身体组织。与年龄、白细胞计数和 LD 同工酶相比，血液 CD3+、CD4+、CD8+ 和自然杀伤细胞计数被发现是预测 SARS 患者入住 ICU 的良好预后指标。 CD3+、CD4+、CD8+ 和自然杀伤细胞计数受到抑制也与 SARS 的病理生理学有关。应密切监测血清 LD1 升高的患者，以确保及时治疗，对于淋巴细胞亚群抑制的患者，可以提前计划进入 ICU 的准备。
Background. The pathophysiology of severe acute respiratory syndrome (SARS) is at present poorly understood, but advanced age and serum total lactate dehydrogenase (LD) activity >300 U L-1 have been associated with adverse clinical outcomes. Blood leucocytes and lymphocyte subsets were reported to decrease, respectively, in 47% and up to 100% of 38 patients in Beijing. However, their prognostic implications have not been thoroughly investigated.Objective. To investigate serum total LD, LD isoenzymes, and other parameters including blood lymphocyte subsets as prognostic indicators in SARS patients for adverse clinical outcomes in terms of admission to intensive care unit (ICU) and death.Design. Retrospective analysis.Subjects and methods. A total of 109 patients with a clinical diagnosis of SARS according to the modified World Health Organization case definition of SARS were recruited from two major acute hospitals in Hong Kong. They were either involved in the initial outbreak of SARS, or cases from the community outbreak of Amoy Gardens between 10 March and 5 May 2003. The clinical diagnosis was subsequently confirmed by serological test and/or molecular analysis. Serum total LD and LD isoenzyme activities, complete blood picture with total leucocyte count and differential counts, absolute counts of CD3+, CD4+, CD8+, natural killer cells and B lymphocytes were measured daily upon admission. Receiver operating characteristic curve analysis was used to determine and compare different cut-offs for various biochemical and immunological parameters at peak serum total LD concentration in predicting adverse clinical outcomes.Results. Of a total of 109 patients, 41 were admitted to ICU and 42 died. Of 42 fatal patients, 24 died in ICU and 18 died in general medical wards. Age was found to be an independent prognostic indictor for death with an area under curve (AUC) of 0.96 [95% confidence interval (CI) = 0.90-0.99] but not for admission to ICU [AUC = 0.61 (CI = 0.51-0.70)]. Whilst serum total LD could only achieve AUC of 0.68 (CI = 0.59-0.77) for predicting death, LD1 isoenzyme was found to be the best biochemical prognostic indicator with AUC of 0.84 (CI = 0.75-0.90), sensitivity of 62% (CI = 46-76%), specificity of 93% (CI = 83-98%) at cut-off activity of greater than or equal to80 U L-1. CD3+, CD4+, CD8+ and natural killer cell counts were promising immunological prognostic indicators for predicting admission to ICU with AUC of 0.94 (CI = 0.86-0.98), 0.91 (CI = 0.81-0.96), 0.93 (CI = 0.85-0.98), and 0.87 (CI = 0.76-0.94), respectively.Conclusions. Apart from age, serum LD1 activity was the best prognostic indicator for predicting death in patients with SARS compared with serum total LD activity, haemoglobin concentration, leucocyte and lymphocyte counts. Its release could possibly be from blood erythrocytes and body tissues other than the myocardium. Blood CD3+, CD4+, CD8+ and natural killer cell counts were found to be good prognostic indicators for predicting admission to ICU in patients with SARS compared with age, leucocyte count and LD isoenzymes. The suppressed CD3+, CD4+, CD8+, and natural killer cell counts were also implicated in the pathophysiology of SARS. Patients with increased serum LD1 should be closely monitored to ensure prompt management, and preparation for admission to ICU could be planned ahead for patients with suppressed lymphocyte subsets.