孟凡萍,郝 坡(.重慶三峽中心醫(yī)院檢驗(yàn)科 404000;2.重慶三峽醫(yī)藥高等??茖W(xué)校醫(yī)學(xué)技術(shù)系 404020)
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·論 著·
ROC曲線評(píng)價(jià)多參數(shù)對(duì)新生兒感染的診斷價(jià)值*
孟凡萍1,郝 坡2△(1.重慶三峽中心醫(yī)院檢驗(yàn)科 404000;2.重慶三峽醫(yī)藥高等??茖W(xué)校醫(yī)學(xué)技術(shù)系 404020)
目的 探討多個(gè)實(shí)驗(yàn)室指標(biāo)對(duì)于新生兒感染的早期診斷價(jià)值。方法 選取確診感染入院的新生兒30例,檢測(cè)其血降鈣素原(PCT)、超敏C反應(yīng)蛋白(hs-CRP)、白細(xì)胞介素-6(IL-6)、白細(xì)胞介素-8(IL-8)、腫瘤壞死因子-α(TNF-α)和白細(xì)胞計(jì)數(shù)(WBC),并以未感染的新生兒作為對(duì)照組,比較兩組受試者上述指標(biāo)的水平,用ROC曲線評(píng)價(jià)這些指標(biāo)對(duì)于新生兒感染診斷的臨床應(yīng)用價(jià)值。 結(jié)果 新生兒感染組各參數(shù)均高于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(P<0.05);由ROC曲線可知,PCT和hs-CRP敏感度和特異性達(dá)100.0%,TNF-α敏感度為96.7%,特異性為99.3%;IL-6和IL-8敏感度均為93.3%,但特異性分別為73.3%和80.0%,WBC則為70.0%和80.0%。結(jié)論 各參數(shù)均可以用于新生兒感染診斷,但靈敏度與特異性均較高的是PCT和hs-CRP,其次為TNF-α;IL-6和IL-8敏感性雖高,但其特異性不甚滿意;WBC診斷價(jià)值雖最小,但卻是臨床必不可少的常規(guī)觀察指標(biāo)。
新生兒感染; 降鈣素原;ROC曲線
新生兒感染無(wú)特異性表現(xiàn),是造成新生兒發(fā)病率和病死率增高的主要原因。診斷需靠微生物檢查,但其結(jié)果需要幾天的時(shí)間,常常錯(cuò)過(guò)治療最佳時(shí)機(jī),因此,對(duì)于新生兒感染的早期診斷非常重要,目前有多種實(shí)驗(yàn)室指標(biāo)可提示新生兒感染,但這些指標(biāo)的臨床應(yīng)用價(jià)值有待研究,本研究應(yīng)用ROC曲線對(duì)這些指標(biāo)的臨床應(yīng)用價(jià)值進(jìn)行評(píng)價(jià)。
1.1 研究對(duì)象 2013年9月至2014年3月臨床確診新生兒感染的住院患兒30例,另選擇同期30例未發(fā)生感染的新生兒作為對(duì)照組。
1.2 實(shí)驗(yàn)儀器和試劑 上轉(zhuǎn)化學(xué)發(fā)光儀及配套試劑為北京熱景公司產(chǎn)品,i-CHROMA免疫熒光分析儀及其配套試劑購(gòu)自南寧康洋公司,血細(xì)胞五分類分析儀及配套試劑為Sysmex公司產(chǎn)品,流式細(xì)胞儀及其配套試劑為BD公司產(chǎn)品。
1.3 方法 陸續(xù)搜集30例臨床確診新生兒感染患者,在靜息狀態(tài)下空腹抽血,及時(shí)檢測(cè)血降鈣素原(PCT)、超敏C反應(yīng)蛋白(hs-CRP)、白細(xì)胞介素-6(IL-6)、白細(xì)胞介素-8(IL-8)、腫瘤壞死因子-α(TNF-α)和白細(xì)胞計(jì)數(shù)(WBC)。對(duì)照組同樣條件抽血、檢測(cè)。各結(jié)果判讀以高于參考值上限為陽(yáng)性,在參考值之內(nèi)為陰性。所測(cè)結(jié)果與對(duì)照組比較,并用ROC曲線分析其臨床價(jià)值。
2.1 新生兒感染組血漿PCT、hs-CRP、IL-6、IL-8、TNF-α和WBC 由表1可知,新生兒感染組均各指標(biāo)均高于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。
2.2ROC曲線 見(jiàn)圖1,各參數(shù)見(jiàn)表2。由ROC曲線可知,診斷新生兒感染PCT和hs-CRP敏感度和特異性都近乎達(dá)100.0%,其次為TNF-α;IL-6和IL-8敏感度均較高,但特異性不甚滿意,而WBC診斷價(jià)值雖小,但也是臨床的常規(guī)觀察指標(biāo)。
表1 各參數(shù)檢測(cè)結(jié)果及陽(yáng)性率±s)
注:與對(duì)照組比較,*P<0.05;Median為平均熒光強(qiáng)度。
表2 各指標(biāo)ROC曲線參數(shù)
圖1 ROC曲線
新生兒感染的發(fā)生率和病死率都較高,尤其是早產(chǎn)、侵入性的醫(yī)療操作以及長(zhǎng)時(shí)間住院的患兒感染發(fā)生率更高。然而由于新生兒感染的早期臨床表現(xiàn)的非特異性,血培養(yǎng)作為診斷的金標(biāo)準(zhǔn),其培養(yǎng)時(shí)間過(guò)長(zhǎng)及陽(yáng)性率低等問(wèn)題,使得診斷不及時(shí),以致延誤治療甚至導(dǎo)致死亡。近年來(lái),隨著醫(yī)療技術(shù)的發(fā)展,免疫學(xué)和基因診斷學(xué)等研究的不斷深入,對(duì)于新生兒感染的診斷指標(biāo)也有了許多新的進(jìn)展。
PCT是近年來(lái)發(fā)現(xiàn)的用于診斷感染的重要血清標(biāo)志物,與炎癥程度有較好的相關(guān)性。Lencot等[1]的研究表明,PCT不僅是預(yù)測(cè)新生兒感染的靈敏指標(biāo),還是指導(dǎo)臨床使用抗生素的良好指標(biāo),在發(fā)生新生兒感染的患兒中,抗生素使用后PCT明顯降低[2]。hs-CRP是全身炎癥反應(yīng)的早期指標(biāo)之一,外科手術(shù)、病毒感染及非感染因素均可使其增高,Matuszczak等[3]建議在新生兒感染的診斷和治療中應(yīng)用CRP水平作為指標(biāo),CRP一旦恢復(fù)正常,應(yīng)停止抗生素的使用[4]。在炎癥反應(yīng)時(shí),一些細(xì)胞因子,如IL-6、IL-8和TNF-α都會(huì)在初期就升高或降低。有研究發(fā)現(xiàn),IL-6和IL-8在新生兒感染患者明顯高于正常,而IL-10卻低于正常,IL-10的分泌和釋放還具有組織特異性[5-10]。在炎癥發(fā)生時(shí),巨噬細(xì)胞和樹(shù)突狀細(xì)胞等抗原遞呈細(xì)胞也可分泌和釋放多種細(xì)胞因子,包括IL-1及TNF-α。另外Th2細(xì)胞還可分泌釋放IL-25來(lái)調(diào)節(jié)炎癥進(jìn)程。Prashant等[11]更進(jìn)一步發(fā)現(xiàn)IL-6的敏感性更高,但升高時(shí)間很短,無(wú)法動(dòng)態(tài)觀察。而Su等[12]卻認(rèn)為CRP和WBC用于預(yù)示新生兒感染足以。
然而每個(gè)診斷指標(biāo)均具有各自的臨床及實(shí)驗(yàn)室特性。目前還沒(méi)有一種診斷指標(biāo)可以令臨床完全滿意。如今檢測(cè)技術(shù)的發(fā)展使得檢測(cè)僅需要微量的標(biāo)本就可進(jìn)行,這為聯(lián)合檢測(cè)提供了方便和可能,是今后診斷感染性疾病的方向。
本研究選取了臨床常用的一些感染指標(biāo)進(jìn)行評(píng)估,篩選出敏感性和特異性均較高的指標(biāo)用以指導(dǎo)臨床診斷、治療和監(jiān)測(cè),以早期了解感染的嚴(yán)重程度和預(yù)后,并指導(dǎo)抗生素的應(yīng)用。研究結(jié)果顯示,新生兒感染組高于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(P<0.05),說(shuō)明眾參數(shù)均可預(yù)測(cè)新生兒感染;由ROC曲線可知,PCT和hs-CRP敏感度和特異性達(dá)100.0%,TNF-α敏感度為96.7%,特異性為99.3%;IL-6和IL-8敏感度均為93.3%,但特異性分別為73.3%和80.0%,WBC則為70.0%和80.0%。由此可見(jiàn),診斷新生兒感染靈敏度與特異性均較高的是PCT和hs-CRP,其次為TNF-α;IL-6和IL-8敏感性雖高,但其特異性不甚滿意;WBC診斷價(jià)值雖最小,但卻是臨床必不可少的常規(guī)觀察指標(biāo)。此結(jié)果可供臨床作為早期診斷新生兒感染的依據(jù),也可為臨床實(shí)驗(yàn)室檢測(cè)項(xiàng)目的設(shè)置提供參考。但單個(gè)指標(biāo)的診斷陽(yáng)性率均不甚滿意,建議聯(lián)合檢測(cè)。
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Diagnostic value of multi-parameter evaluation by ROC curve for neonatal infection*
MENGFan-ping1,HAOPo2△
(1.DepartmentofClinicalLaboratory,ChongqingThreeGorgesCentralHospital,Chongqing404000,China; 2.DepartmentofMedicalTechnique,ChongqingThreeGorgesMedicalCollege,Chongqing404020,China)
Objective To investigate the early diagnosis value of multiple laboratory indicators for neonatal infection.Methods 30 hospitalized neonates with infection were selected and 30 normal neonates were selected as the controls.The blood PCT,hs-CRP,IL-6,IL-8,TNF-α and WBC were detected.The levels of above indicators were compared between the two group.The clinical application value of these indicators for the diagnosis of neonatal infection was evaluated by using theROCcurves.Results The various parameters in the neonatal infection group were higher than those in the control group(P<0.05);theROCcurves indicated that the sensitivity and specificity of PCT and hs-CRP reached 100.0%,which of TNF-α were 96.7% and 99.3% respectively; the sensitivity of IL-8 and IL-6 were 93.3% and their specificity was 73.3% and 80.0% respectively; the sensitivity and specificity of WBC were 70.0% and 80.0% respectively.Conclusion The above parameters can be used to diagnose neonatal infection,PCT and hs-CRP have the higher sensitivity and specificity,followed by TNF-α; although IL-8 and IL-6 have higher sensitivity,but their specificity is unsatisfactory; WBC has the minimal diagnostic value,but is an indispensable routine observation indicator in clinic.
neonatal infection ; PCT;ROCcurve
重慶市衛(wèi)生局醫(yī)學(xué)科技計(jì)劃項(xiàng)目(2011-2-411);重慶市萬(wàn)州區(qū)科技計(jì)劃項(xiàng)目(201203060)。
孟凡萍,女,主管檢驗(yàn)師,在讀博士,主要從事脂代謝和血液學(xué)檢驗(yàn)方面的工作和研究。
△通訊作者,E-mail:hpo1979@126.com。
10.3969/j.issn.1672-9455.2015.01.011
A
1672-9455(2015)01-0028-03
2014-05-05
2014-10-08)