CRP在慢性阻塞性肺疾病诊断中的应用
2016-10-10胡琼英艾承锦熊大迁江泽友张朝明
胡琼英,艾承锦,张 爽,熊大迁,江泽友,张朝明
(成都中医药大学附属医院检验科 610072)
·论著·
CRP在慢性阻塞性肺疾病诊断中的应用
胡琼英,艾承锦,张爽,熊大迁,江泽友,张朝明△
(成都中医药大学附属医院检验科610072)
目的探讨C-反应蛋白(CRP)对慢性阻塞性肺疾病(COPD)的诊断价值,为COPD的诊断发掘新的标志物。方法收集COPD患者199例、肺恶性肿瘤患者159例,以及同期健康体检者115例,检测并比较3组的全血CRP水平,绘制CRP诊断COPD的受试者工作特征曲线(ROC曲线),计算灵敏度、特异度和约登指数,寻找诊断界值Cut-off值。结果与健康体检者比较,CRP在COPD患者及肺恶性肿瘤患者中均显著升高,差异有统计学意义(P<0.05);ROC曲线下面积为0.768,最大约登指数为0.418,灵敏度和特异度分别为64.7%和77.1%,对应的Cut-off值为49.75 mg/L。结论CRP对COPD具有一定的诊断价值,可作为COPD诊断的新指标。
C-反应蛋白;慢性阻塞性肺疾病;灵敏度;特异度
C-反应蛋白(CRP)是机体受到感染或组织损伤时,由肝脏合成、释放入血的急性时相蛋白,可激活补体和加强吞噬细胞功能,从而清除入侵机体的病原微生物和损伤、坏死、凋亡的组织细胞,在机体的天然免疫过程中发挥着重要的保护作用[1]。据报道,CRP可以作为多种疾病诊断、鉴别诊断及预后判断的标志物,如胃癌[2]、前列腺癌[3]、高血压[4]、心力衰竭[5]、腹腔感染[6]、急性呼吸道感染[7]及类风湿关节炎等[8]。
慢性阻塞性肺疾病(COPD)指终末细支气管远端部分(包括呼吸性细支气管、肺泡管、肺泡囊和肺泡)膨胀,并伴有气腔壁的损伤的一类疾病[9]。COPD是发病率和病死率最高的疾病之一,且随着大气污染和吸烟人数的增加,其发病率呈逐年上升的趋势[10]。目前COPD的临床诊断主要依靠典型症状和体征,结合胸部X线片检查,但对于临床表现不典型者,其诊断和鉴别诊断困难[11-12]。实验室检查主要以炎性反应的指标为主,但缺乏有诊断价值的评价。因此对CRP的早期诊断和鉴别诊断对COPD的诊治和预后有重要的临床指导意义。本研究对COPD患者、肺恶性肿瘤患者,以及健康体检者CRP水平进行检测,以期发现CRP对COPD的诊断价值。现报道如下。
1 资料与方法
1.1一般资料选择2015年11~12月本院收治的COPD患者199例,肺恶性肿瘤患者159例,以及同期健康体检者115例。COPD患者平均年龄(70.0±11.7)岁,肺恶性肿瘤患者平均年龄(62.8±10.2)岁,健康对照者平均年龄(52.7±9.8)岁。肺恶性肿瘤患者确诊标准为病理活检,其余疾病确诊以最新临床指南为准。
1.2方法抽取所有研究对象空腹静脉血2 mL,乙二胺四乙酸(EDTA)抗凝,检测其全血CRP值。CRP测定使用深圳国赛公司Omlipo全自动特定蛋白仪。该仪器参加原卫生部临检中心及四川省临检中心的室间质量评价,合格率均为100%,能确保检测的可比性、一致性、重复性及准确性。
2 结 果
2.1各组CRP水平比较COPD组、肺恶性肿瘤组、健康对照组CRP水平分别为(52.7±4.6)、(49.6±3.9)、(2.3±0.5)mg/L。COPD组及肺恶性肿瘤组CRP水平高于健康对照组,差异有统计学意义(P<0.05);COPD组CRP水平高于肺恶性肿瘤组,差异有统计学意义(P<0.05)。
2.2CRP对COPD的诊断价值进一步拟合CRP诊断COPD的ROC曲线,得到曲线下面积(AUC)为0.768,通过ROC曲线原始数据结点分析计算,得到灵敏度为64.7%,特异度为77.1%,阳性似然比为2.83,阴性似然比为0.30,阳性预测值为67.19%,阴性预测值为75.09%,准确度为71.88%,约登指数为0.418,通过计算其对应的Cut-off值为49.75 mg/L。见图1。
图1 CRP诊断COPD的ROC曲线
3 讨 论
近年来越来越多的研究显示,CRP在医学其他领域的作用和新应用。Kleniewska等[13]比较了职业性哮喘和COPD患者的血清和诱导痰中的生物标记物,他们发现痰中的生物标志物,如白细胞介素-1β、基质金属蛋白酶-9和CRP,比其在血清中的水平高,且CRP在COPD患者诱导痰中的水平比IL-1β和基质金属蛋白酶-9更高。Patel等[14]发现COPD患者唾液中的CRP和降钙素原水平高于健康对照组。CRP有望成为COPD评估和预后的标志物[15]。本研究结果显示,CRP水平在COPD组和肺恶性肿瘤组都显著升高,差异有统计学意义(P<0.05);进一步对这种差异进行诊断价值指标的计算,如灵敏度、特异度、阳性似然比、阴性似然比等。
ROC曲线上各个点代表相应临界值的灵敏度和特异度,所以ROC曲线综合反映了诊断性试验的特性,即诊断性试验对目标疾病的诊断价值,也可以根据诊断性试验的使用目的,来确定Cut-off值[16-18]。灵敏度和特异度取值范围在ROC曲线上是连续分布的,如何取值取决于标志物的用途,如果用作筛选的方法,本着多发现患者的原则,可考虑牺牲特异度来获取较高的灵敏度;但如果是用作诊断和鉴别诊断疾病的方法,可偏重考虑特异度。总体而言,应综合具体疾病的危害和临床需求等因素考虑平衡灵敏度和特异度的界点[19]。本研究的目的是为了探寻诊断的标志物,所以希望尽可能少假阳性,需要考虑更高的特异度,故通过对ROC曲线原始数据进行分析,计算约登指数,取约登指数最大的点(0.418)作为最佳诊断界点,此时灵敏度为64.7%,特异度为77.1%,阳性似然比为2.83,阴性似然比为0.30,对应的Cut-off值为49.75 mg/L。
CRP作为快速、简单、花费小的检验项目,有可能成为COPD的诊断和预后评估的标志物。但考虑其AUC为0.768,作为诊断标志物,该诊断效能并不十分理想,接下来的研究还需扩大样本量,对目标疾病进行分期、分型,以期得出更高的诊断价值和其对应的Cut-off值;此外,还可以多指标联合诊断,例如和红细胞分布宽度联合诊断COPD,其诊断价值可能比单一标志物更为理想。
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Application of C-reactive protein in diagnosis of chronic obstructive pulmonary disease*
HUQiongying,AIChengjin,ZHANGShuang,XIONGDaqian,JIANGZeyou,ZHANGChaoming△
(DepartmentofClinicalLaboratory,AffiliatedHospital,ChengduUniversityofChineseMedicine,Chengdu,Sichuan610072,China)
ObjectiveTo explore the diagnostic value of C-reactive protein(CRP) for diagnosing chronic obstructive pulmonary disease(COPD) to dig a new marker for COPD diagnosis.MethodsA total of 199 cases of COPD,159 cases of pulmonary malignant tumor and 115 individuals undergoing the physical examination were collected.The whole blood CRP level was detected in 3 groups and the detection results were compared among 3 groups.The receiver operating characteristic(ROC) curve was drawn.Then the sensitivity,specificity and Youden′s index(YI) were calculated to find the cut-off value of diagnosis.ResultsCompared with the individuals undergoing healthy physical examination,the CRP level in the COPD patients and the patients with pulmonary malignant tumor was significantly increased,the difference was statistically significant(P<0.05);the area under ROC curve(AUC) was 0.768,the maximal YI was 0.418,the sensitivity and specificity were 64.7% and 77.1% respectively,the corresponding cut-off value was 49.75 mg/L.ConclusionCRP has a certain diagnostic value and can serve as a new index of COPD diagnosis.
C-reactive protein;chronic obstructive pulmonary disease;sensitivity;specificity
2015年成都中医药大学科技发展基金资助项目[030029045]。
胡琼英,女,主管技师,主要从事临床检验分子诊断研究。△
,E-mail:18981885705@163.com。
10.3969/j.issn.1673-4130.2016.17.006
A
1673-4130(2016)17-2374-03
2016-05-24
2016-07-01)