胡瓊英,艾承錦,張　爽,熊大遷,江澤友,張朝明

(成都中醫(yī)藥大學(xué)附屬醫(yī)院檢驗(yàn)科　610072)

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·論著·

CRP在慢性阻塞性肺疾病診斷中的應(yīng)用

胡瓊英,艾承錦,張爽,熊大遷,江澤友,張朝明△

(成都中醫(yī)藥大學(xué)附屬醫(yī)院檢驗(yàn)科610072)

目的探討C-反應(yīng)蛋白(CRP)對(duì)慢性阻塞性肺疾病(COPD)的診斷價(jià)值，為COPD的診斷發(fā)掘新的標(biāo)志物。方法收集COPD患者199例、肺惡性腫瘤患者159例，以及同期健康體檢者115例，檢測(cè)并比較3組的全血CRP水平，繪制CRP診斷COPD的受試者工作特征曲線(ROC曲線)，計(jì)算靈敏度、特異度和約登指數(shù)，尋找診斷界值Cut-off值。結(jié)果與健康體檢者比較，CRP在COPD患者及肺惡性腫瘤患者中均顯著升高，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)；ROC曲線下面積為0.768，最大約登指數(shù)為0.418，靈敏度和特異度分別為64.7%和77.1%，對(duì)應(yīng)的Cut-off值為49.75 mg/L。結(jié)論CRP對(duì)COPD具有一定的診斷價(jià)值，可作為COPD診斷的新指標(biāo)。

C-反應(yīng)蛋白；慢性阻塞性肺疾??；靈敏度；特異度

C-反應(yīng)蛋白(CRP)是機(jī)體受到感染或組織損傷時(shí)，由肝臟合成、釋放入血的急性時(shí)相蛋白，可激活補(bǔ)體和加強(qiáng)吞噬細(xì)胞功能，從而清除入侵機(jī)體的病原微生物和損傷、壞死、凋亡的組織細(xì)胞，在機(jī)體的天然免疫過程中發(fā)揮著重要的保護(hù)作用[1]。據(jù)報(bào)道，CRP可以作為多種疾病診斷、鑒別診斷及預(yù)后判斷的標(biāo)志物，如胃癌[2]、前列腺癌[3]、高血壓[4]、心力衰竭[5]、腹腔感染[6]、急性呼吸道感染[7]及類風(fēng)濕關(guān)節(jié)炎等[8]。

慢性阻塞性肺疾病(COPD)指終末細(xì)支氣管遠(yuǎn)端部分(包括呼吸性細(xì)支氣管、肺泡管、肺泡囊和肺泡)膨脹，并伴有氣腔壁的損傷的一類疾病[9]。COPD是發(fā)病率和病死率最高的疾病之一，且隨著大氣污染和吸煙人數(shù)的增加，其發(fā)病率呈逐年上升的趨勢(shì)[10]。目前COPD的臨床診斷主要依靠典型癥狀和體征，結(jié)合胸部X線片檢查，但對(duì)于臨床表現(xiàn)不典型者，其診斷和鑒別診斷困難[11-12]。實(shí)驗(yàn)室檢查主要以炎性反應(yīng)的指標(biāo)為主，但缺乏有診斷價(jià)值的評(píng)價(jià)。因此對(duì)CRP的早期診斷和鑒別診斷對(duì)COPD的診治和預(yù)后有重要的臨床指導(dǎo)意義。本研究對(duì)COPD患者、肺惡性腫瘤患者，以及健康體檢者CRP水平進(jìn)行檢測(cè)，以期發(fā)現(xiàn)CRP對(duì)COPD的診斷價(jià)值?，F(xiàn)報(bào)道如下。

1　資料與方法

1.1一般資料選擇2015年11～12月本院收治的COPD患者199例，肺惡性腫瘤患者159例，以及同期健康體檢者115例。COPD患者平均年齡(70.0±11.7)歲，肺惡性腫瘤患者平均年齡(62.8±10.2)歲，健康對(duì)照者平均年齡(52.7±9.8)歲。肺惡性腫瘤患者確診標(biāo)準(zhǔn)為病理活檢，其余疾病確診以最新臨床指南為準(zhǔn)。

1.2方法抽取所有研究對(duì)象空腹靜脈血2 mL，乙二胺四乙酸(EDTA)抗凝，檢測(cè)其全血CRP值。CRP測(cè)定使用深圳國賽公司Omlipo全自動(dòng)特定蛋白儀。該儀器參加原衛(wèi)生部臨檢中心及四川省臨檢中心的室間質(zhì)量評(píng)價(jià)，合格率均為100%，能確保檢測(cè)的可比性、一致性、重復(fù)性及準(zhǔn)確性。

2　結(jié)　　果

2.1各組CRP水平比較COPD組、肺惡性腫瘤組、健康對(duì)照組CRP水平分別為(52.7±4.6)、(49.6±3.9)、(2.3±0.5)mg/L。COPD組及肺惡性腫瘤組CRP水平高于健康對(duì)照組，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)；COPD組CRP水平高于肺惡性腫瘤組，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。

2.2CRP對(duì)COPD的診斷價(jià)值進(jìn)一步擬合CRP診斷COPD的ROC曲線，得到曲線下面積(AUC)為0.768，通過ROC曲線原始數(shù)據(jù)結(jié)點(diǎn)分析計(jì)算，得到靈敏度為64.7%，特異度為77.1%，陽性似然比為2.83，陰性似然比為0.30，陽性預(yù)測(cè)值為67.19%，陰性預(yù)測(cè)值為75.09%，準(zhǔn)確度為71.88%，約登指數(shù)為0.418，通過計(jì)算其對(duì)應(yīng)的Cut-off值為49.75 mg/L。見圖1。

圖1　　CRP診斷COPD的ROC曲線

3　討　　論

近年來越來越多的研究顯示，CRP在醫(yī)學(xué)其他領(lǐng)域的作用和新應(yīng)用。Kleniewska等[13]比較了職業(yè)性哮喘和COPD患者的血清和誘導(dǎo)痰中的生物標(biāo)記物，他們發(fā)現(xiàn)痰中的生物標(biāo)志物，如白細(xì)胞介素-1β、基質(zhì)金屬蛋白酶-9和CRP，比其在血清中的水平高，且CRP在COPD患者誘導(dǎo)痰中的水平比IL-1β和基質(zhì)金屬蛋白酶-9更高。Patel等[14]發(fā)現(xiàn)COPD患者唾液中的CRP和降鈣素原水平高于健康對(duì)照組。CRP有望成為COPD評(píng)估和預(yù)后的標(biāo)志物[15]。本研究結(jié)果顯示，CRP水平在COPD組和肺惡性腫瘤組都顯著升高，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)；進(jìn)一步對(duì)這種差異進(jìn)行診斷價(jià)值指標(biāo)的計(jì)算，如靈敏度、特異度、陽性似然比、陰性似然比等。

ROC曲線上各個(gè)點(diǎn)代表相應(yīng)臨界值的靈敏度和特異度，所以ROC曲線綜合反映了診斷性試驗(yàn)的特性，即診斷性試驗(yàn)對(duì)目標(biāo)疾病的診斷價(jià)值，也可以根據(jù)診斷性試驗(yàn)的使用目的，來確定Cut-off值[16-18]。靈敏度和特異度取值范圍在ROC曲線上是連續(xù)分布的，如何取值取決于標(biāo)志物的用途，如果用作篩選的方法，本著多發(fā)現(xiàn)患者的原則，可考慮犧牲特異度來獲取較高的靈敏度；但如果是用作診斷和鑒別診斷疾病的方法，可偏重考慮特異度?？傮w而言，應(yīng)綜合具體疾病的危害和臨床需求等因素考慮平衡靈敏度和特異度的界點(diǎn)[19]。本研究的目的是為了探尋診斷的標(biāo)志物，所以希望盡可能少假陽性，需要考慮更高的特異度，故通過對(duì)ROC曲線原始數(shù)據(jù)進(jìn)行分析，計(jì)算約登指數(shù)，取約登指數(shù)最大的點(diǎn)(0.418)作為最佳診斷界點(diǎn)，此時(shí)靈敏度為64.7%，特異度為77.1%，陽性似然比為2.83，陰性似然比為0.30，對(duì)應(yīng)的Cut-off值為49.75 mg/L。

CRP作為快速、簡單、花費(fèi)小的檢驗(yàn)項(xiàng)目，有可能成為COPD的診斷和預(yù)后評(píng)估的標(biāo)志物。但考慮其AUC為0.768，作為診斷標(biāo)志物，該診斷效能并不十分理想，接下來的研究還需擴(kuò)大樣本量，對(duì)目標(biāo)疾病進(jìn)行分期、分型，以期得出更高的診斷價(jià)值和其對(duì)應(yīng)的Cut-off值；此外，還可以多指標(biāo)聯(lián)合診斷，例如和紅細(xì)胞分布寬度聯(lián)合診斷COPD，其診斷價(jià)值可能比單一標(biāo)志物更為理想。

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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年成都中醫(yī)藥大學(xué)科技發(fā)展基金資助項(xiàng)目[030029045]。

胡瓊英，女，主管技師，主要從事臨床檢驗(yàn)分子診斷研究?！?/p>

，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)