付文龍 張娟娟 代繼宏
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·論著·
支氣管鏡介導(dǎo)標(biāo)本對(duì)兒童結(jié)核病診斷價(jià)值的系統(tǒng)評(píng)價(jià)和Meta分析
付文龍1,2張娟娟1代繼宏2
目的定量評(píng)估支氣管鏡介導(dǎo)標(biāo)本對(duì)兒童結(jié)核病(TB)的診斷價(jià)值。方法 檢索PubMed、EMBASE、Ovid、Cochrane圖書(shū)館、中國(guó)生物醫(yī)學(xué)文獻(xiàn)數(shù)據(jù)庫(kù)、中國(guó)知網(wǎng)和萬(wàn)方數(shù)據(jù)庫(kù),檢索起止時(shí)間為建庫(kù)至2016年2月,并回溯納入文獻(xiàn)的參考文獻(xiàn)。2名研究者根據(jù)納入與排除標(biāo)準(zhǔn)篩選文獻(xiàn),采用QUADAS-2量表行文獻(xiàn)偏倚風(fēng)險(xiǎn)評(píng)估。以臨床診斷和實(shí)驗(yàn)室診斷作為T(mén)B診斷的金標(biāo)準(zhǔn),評(píng)估支氣管鏡介導(dǎo)標(biāo)本(支氣管肺泡灌洗液、支氣管黏膜組織及支氣管黏膜刷檢)及不同檢測(cè)方法診斷兒童TB的敏感度和特異度,并以胃液作為對(duì)照標(biāo)本。采用Meta-Disc 1.4軟件進(jìn)行Meta分析,建立匯總受試者工作特征(SROC)曲線,并計(jì)算曲線下面積 (AUC)等。采用Stata 12.0軟件繪制Deek′s漏斗圖評(píng)估發(fā)表偏倚。結(jié)果14篇文獻(xiàn)進(jìn)入Meta分析,納入2 781份(1 082例患兒)的支氣管鏡介導(dǎo)標(biāo)本。①14篇文獻(xiàn)報(bào)道了支氣管鏡介導(dǎo)所有標(biāo)本對(duì)兒童TB的診斷,匯總敏感度和特異度分別為0.38(95%CI:0.35~0.41)和1.00(95%CI:0.99~1.00);按照標(biāo)本及檢測(cè)方法行亞組分析,支氣管黏膜組織活檢的敏感度為0.51(95%CI:0.40~0.61),特異度為1.00(95%CI:0.81~1.00);支氣管肺泡灌洗液培養(yǎng)、涂片和PCR的敏感度分別為0.36(95%CI:0.32~0.40)、0.21(95%CI:0.15~0.28)和0.58(95%CI:0.46~0.69),特異度分別為1.00(95%CI:0.99~1.00)、1.00(95%CI:0.98~1.00)和1.00(95%CI:0.84~1.00)。②10篇文獻(xiàn)報(bào)道胃液對(duì)兒童TB的診斷,胃液培養(yǎng)敏感度為0.52(95%CI:0.47~0.57),特異度為1.00(95%CI:0.98~1.00);涂片敏感度為0.25(95%CI:0.16~0.36),特異度為1.00(95%CI:0.95~1.00)。③支氣管肺泡灌洗液所有檢測(cè)方法診斷TB的SROC AUC為0.883 9;胃液所有檢測(cè)方法診斷TB的SROC AUC為0.873 7。④支氣管肺泡灌洗液培養(yǎng)、涂片和胃液診斷TB文獻(xiàn)的Deeks′檢驗(yàn)P分別為0.005、0.014和0.147。結(jié)論支氣管鏡介導(dǎo)的標(biāo)本對(duì)兒童TB的診斷價(jià)值是肯定的,但支氣管肺泡灌洗液作為最常用的標(biāo)本采用培養(yǎng)和涂片對(duì)TB診斷的敏感度不優(yōu)于胃液。
支氣管鏡;兒童;結(jié)核??;診斷價(jià)值;敏感度;特異度;系統(tǒng)評(píng)價(jià);Meta分析
AbstractObjectiveTo systematically evaluate the diagnostic value of specimens via bronchoscopy for tuberculosis(TB) detection in children.MethodsThe PubMed,EMBASE, Ovid, Cochrane Library, CBM, CNKI and Wanfang database were systematically searched up to February 2016, and relevant references were manual screened. Two reviewers independently screened literatures according to the inclusion and exclusion criteria and extracted data, and assessed the risk of bias of included studies by QUADAS-2 tool. The sensitivity and specificity of test methods and specimens (bronchoalveolar lavage, bronchial brushing and tissue biopsy) via bronchoscopy were evaluated by gold standard(clinical and laboratory diagnosis). Meta-analysis was performed using Meta-Disc 1.4 software, and summary receiver operating characteristic curve (SROC) was drawn and area under the curve (AUC) and Q index were calculated. Deek′s funnel plots were drawn using Stata 12.0 software.ResultsA total of 14 studies were included involving 2 781 specimens (1 082 patients). ①Fourteen literatures reported bronchoscopy for the diagnosis of TB. The pooled sensitivity and specificity of bronchoscopy for tuberculosis detection were 0.38(95%CI:0.35-0.41)and 1.00(95%CI:0.99-1.00), respectively. Then subgroup analysis was made by the types of specimens and test methods. The pooled sensitivity and specificity of tissue biopsy were 0.51(95%CI:0.40-0.61)and 1.00(95%CI:0.81-1.00) , respectively; The pooled sensitivity and specificity of culture, acid fast bacilli on smear and PCR for bronchoalveolar lavage were 0.36(95%CI:0.32-0.40)vs1.00(95%CI:0.99-1.00), 0.21(95%CI:0.15-0.28)vs1.00(95%:0.98-1.00)and 0.58(95%CI:0.46-0.69)vs1.00(95%CI:0.84-1.00), respectively. ②Ten literatures reported gastric lavage for the diagnosis of tuberculosis, which exhibited heterogeneity(I2=93.3%). The pooled sensitivity and specificity of gastric lavage for tuberculosis detection were 0.45(95%CI:0.40-0.49)and 1.00(95%CI:0.99-1.00), respectively. The pooled sensitivity and specificity of smear for gastric lavage were 0.52(95%CI:0.47-0.57)and 1.00(95%CI:0.98-1.00), respectively. ③The SROC AUC of bronchoalveolar lavage and gastric lavage were 0.883 9 and 0.873 7, respectively; ④Pvalues of the Deek′s test of culture and smear for bronchoalveolar lavage were 0.005 and 0.014.Pvalue of the Deek′s test of gastric lavage was 0.147.ConclusionThe value of bronchoscopy for the diagnosis of tuberculosis was definitive in children. Bronchoalveolar lavage for bronchoscopy was the most common specimen, but in terms of culture and smear, it wasn′t better than gastric lavage for tuberculosis detection.
兒童是結(jié)核病(TB)高危人群,近年發(fā)病率有增高的趨勢(shì)[1~3]。據(jù)WHO統(tǒng)計(jì),每年有53萬(wàn)~100萬(wàn)兒童診斷為T(mén)B,每年有13.6萬(wàn)兒童死于TB,至少占全球疾病負(fù)擔(dān)的6%[4~7]。 由于兒童TB臨床表現(xiàn)多樣且不典型,排菌量少、痰涂片陽(yáng)性率低,導(dǎo)致診斷困難[8,9]。TB實(shí)驗(yàn)室診斷常用的標(biāo)本有痰、胃液及血液等,傳統(tǒng)TB診斷方法包括痰涂片和培養(yǎng)。痰涂片診斷TB的陽(yáng)性率較低[4,10~12],結(jié)核分枝桿菌培養(yǎng)耗時(shí)需3~4周。
支氣管鏡對(duì)于兒童TB的診斷優(yōu)勢(shì)在于可直觀病變部位,且可從病變部位直接取材獲取病原學(xué)和(或)病理學(xué)標(biāo)本。支氣管肺泡灌洗液、支氣管黏膜刷檢及組織活檢為T(mén)B診斷提供了幫助,其中支氣管肺泡灌洗液是胸內(nèi)TB診斷的最佳標(biāo)本,可顯著提高診斷陽(yáng)性率[10,13~15]。目前關(guān)于支氣管鏡對(duì)TB診斷已有較多的關(guān)注[9,16],Zhen等[17]在2015年的Meta分析探討了以成人支氣管肺泡灌洗液為標(biāo)本的酶聯(lián)免疫斑點(diǎn)試驗(yàn)(ELISPOT)對(duì)TB的診斷;也有關(guān)于支氣管鏡對(duì)兒童TB診斷的定性系統(tǒng)綜述[18],但未發(fā)現(xiàn)相關(guān)定量的評(píng)價(jià)。本文系統(tǒng)檢索相關(guān)文獻(xiàn),評(píng)估支氣管鏡介導(dǎo)標(biāo)本和檢測(cè)方法對(duì)兒童TB的診斷價(jià)值,以期為臨床應(yīng)用提供參考。
1.1支氣管鏡介導(dǎo)的標(biāo)本及檢測(cè)方法①標(biāo)本類(lèi)型:支氣管肺泡灌洗液、支氣管黏膜組織、支氣管黏膜刷檢;②檢測(cè)方法:結(jié)核分枝桿菌培養(yǎng)、抗酸桿菌涂片、PCR、活檢和Xpert 結(jié)核分枝桿菌/利福平試驗(yàn)(MTB/RIF)。
1.2文獻(xiàn)納入標(biāo)準(zhǔn)①入選病例均經(jīng)支氣管鏡介導(dǎo)的標(biāo)本診斷TB,且能獲取診斷試驗(yàn)四格表數(shù)據(jù),即真陽(yáng)性值(TP )、假陽(yáng)性值(FP)、假陰性值(FN) 、真陰性值(TN); ②TB診斷金標(biāo)準(zhǔn)為臨床診斷或?qū)嶒?yàn)室診斷;③對(duì)照標(biāo)本為胃液;④年齡0~18歲; ⑤中文和英文語(yǔ)種。
1.3文獻(xiàn)排除標(biāo)準(zhǔn)未報(bào)道相關(guān)檢測(cè)方法的文獻(xiàn)。
1.4文獻(xiàn)檢索策略計(jì)算機(jī)檢索PubMed、EMBASE、Cochrane圖書(shū)館、Ovid、中國(guó)生物醫(yī)學(xué)文獻(xiàn)數(shù)據(jù)庫(kù)(CBM)、中國(guó)知網(wǎng)和萬(wàn)方數(shù)據(jù)庫(kù),檢索起止時(shí)間為建庫(kù)至2016年2月1日。同時(shí)回溯納入文獻(xiàn)的參考文獻(xiàn)。
以PubMed為例的檢索式為(bronchoscopy OR bronchoscope) AND ("Bronchoalveolar Lavage" OR "Bronchoscopy biopsy" OR "bronchial brushing") AND (children OR paediatric OR pediatric OR infant) AND (tuberculosis OR TB) AND (sensitivity OR specificity OR false negative OR false positive OR diagnosis)。
以CBM為例的檢索式為("嬰兒"[常用字段:智能] OR "幼兒"[常用字段:智能] OR "兒童"[常用字段:智能]) AND "支氣管鏡"[常用字段:智能] AND ( "肺泡灌洗液"[常用字段:智能] OR "支氣管黏膜刷檢"[常用字段:智能] OR "支氣管鏡活檢"[常用字段:智能]) AND ("結(jié)核"[常用字段:智能]) AND ("診斷"[常用字段:智能] OR "特異性"[常用字段:智能] OR "敏感性"[常用字段:智能] OR "靈敏度"[常用字段:智能] OR "預(yù)測(cè)值"[常用字段:智能])。
1.5文獻(xiàn)篩選和資料提取由付文龍和張娟娟根據(jù)納入標(biāo)準(zhǔn)篩選文獻(xiàn),制定資料提取表格行資料提取和錄入,交叉核對(duì)。提取的內(nèi)容包括: 作者、發(fā)表時(shí)間、國(guó)家、樣本量、性別比、標(biāo)本類(lèi)型、檢測(cè)方法、納入標(biāo)本數(shù)及診斷試驗(yàn)數(shù)據(jù)等。如文獻(xiàn)報(bào)道的數(shù)據(jù)不完整,通過(guò)郵件與作者聯(lián)系索取。
1.6文獻(xiàn)偏倚風(fēng)險(xiǎn)采用QUADAS-2量表[19]行偏倚風(fēng)險(xiǎn)評(píng)價(jià),包括①病例的選擇(3項(xiàng)內(nèi)容),②待評(píng)價(jià)試驗(yàn)(2項(xiàng)內(nèi)容),③金標(biāo)準(zhǔn)(2項(xiàng)內(nèi)容),④病例流程和進(jìn)展(3項(xiàng)內(nèi)容),每一條標(biāo)準(zhǔn)以“是”、“否”、“不清楚”評(píng)價(jià)。由付文龍和張娟娟獨(dú)立評(píng)價(jià),遇到分歧討論解決。
1.7統(tǒng)計(jì)學(xué)方法采用Meta-Disc 1.4軟件行Meta分析。采用χ2檢驗(yàn)行統(tǒng)計(jì)學(xué)異質(zhì)性分析,P≤0.1為文獻(xiàn)間存在顯著異質(zhì)性;采用I2對(duì)異質(zhì)性進(jìn)行定量,I2≤50%為中至低度異質(zhì)性,采用固定效應(yīng)模型描述;I2>50%為高度異質(zhì)性,采用隨機(jī)效應(yīng)模型描述。根據(jù)標(biāo)本類(lèi)型和檢測(cè)方法行亞組分析。對(duì)無(wú)法合并效應(yīng)量文獻(xiàn)行描述性分析。建立匯總受試者工作特征(SROC)曲線,并計(jì)算曲線下面積 (AUC)和Q*指數(shù)。以Stata 12.0軟件繪制Deek′s漏斗圖評(píng)估發(fā)表偏倚。P<0.05為差異有統(tǒng)計(jì)學(xué)意義。
2.1文獻(xiàn)檢索結(jié)果共檢索到文獻(xiàn)651篇,圖1顯示文獻(xiàn)篩選流程,14篇文獻(xiàn)進(jìn)入Meta分析[18,20~32]。
圖1文獻(xiàn)篩選流程圖
2.2納入文獻(xiàn)的基本特征14篇文獻(xiàn)來(lái)自7個(gè)國(guó)家(中國(guó)5篇,印度3篇,南非2篇,土耳其1篇,美國(guó)1篇,英國(guó)1篇,法國(guó)1篇)。共納入1 082例患兒,2 781份支氣管鏡介導(dǎo)的標(biāo)本。TB的種類(lèi):肺結(jié)核9篇[18,20,22,24,27~30,32],支氣管內(nèi)膜結(jié)核2篇[21,23],復(fù)雜胸內(nèi)結(jié)核1篇[31],未分類(lèi)2篇[25,26]。納入文獻(xiàn)的基本信息見(jiàn)表1,診斷參數(shù)見(jiàn)表2,支氣管鏡介導(dǎo)和胃液任一標(biāo)本陽(yáng)性即認(rèn)為病例實(shí)驗(yàn)室陽(yáng)性,診斷4格表數(shù)據(jù)均以例數(shù)表示。
2.3文獻(xiàn)偏倚評(píng)價(jià)結(jié)果QUADAS-2量表評(píng)估結(jié)果顯示,①病例選擇:5篇文獻(xiàn)[22,23,26,27,31]納入病例非連續(xù)或隨機(jī),有高度偏倚,余9篇文獻(xiàn)為低度偏倚;②待評(píng)價(jià)試驗(yàn):4篇[18,21,29,30]文獻(xiàn)采用雙盲法評(píng)估結(jié)果,為低度偏倚,10篇文獻(xiàn)[20,22~28,31,32]為高度偏倚;③金標(biāo)準(zhǔn):13篇文獻(xiàn)[18,20~31]為低度偏倚,文獻(xiàn)[32]為不清楚;④病例流程和進(jìn)展:14篇文獻(xiàn)均為低度偏倚。
2.4Meta分析結(jié)果
2.4.1支氣管鏡介導(dǎo)所有標(biāo)本對(duì)TB的診斷價(jià)值14篇文獻(xiàn)報(bào)道了支氣管鏡介導(dǎo)標(biāo)本對(duì)TB的診斷。異質(zhì)性檢驗(yàn)P<0.001,I2=83.0%,文獻(xiàn)間具異質(zhì)性,隨機(jī)效應(yīng)模型Meta分析結(jié)果顯示,匯總敏感度0.38(95%CI:0.34~0.41),特異度為1.00(95%CI:0.99~1.00)。
2.4.2支氣管肺泡灌洗液對(duì)TB的診斷14篇文獻(xiàn)報(bào)道
表2 支氣管鏡介導(dǎo)標(biāo)本和胃液對(duì)兒童結(jié)核病診斷的參數(shù)信息
了支氣管肺泡灌洗液對(duì)TB的診斷。異質(zhì)性檢驗(yàn)P<0.001,I2=86.0%,采用隨機(jī)效應(yīng)模型合并結(jié)果。Meta分析結(jié)果顯示,匯總敏感度0.37(95%CI:0.34~0.40),特異度為1.00(95%CI:0.99~1.00)。
根據(jù)標(biāo)本和檢測(cè)方法不同行亞組分析(圖2), 11篇文獻(xiàn)[20~23,25,26,28~32]報(bào)道了支氣管肺泡灌洗液培養(yǎng),異質(zhì)性檢驗(yàn)P<0.001,I2=79.5%,采用隨機(jī)效應(yīng)模型,匯總敏感度0.36(95%CI:0.32~0.40),特異度1.00(95%CI:0.99~1.00);5篇文獻(xiàn)[18,22,30~32]報(bào)道了支氣管肺泡灌洗液涂片,異質(zhì)性檢驗(yàn)P<0.001,I2=91.3%,采用隨機(jī)效應(yīng)模型,匯總敏感度0.21(95%CI:0.15~0.28),特異度1.00(95%CI:0.98~1.00);3篇文獻(xiàn)[22,25,28]報(bào)道了支氣管肺泡灌洗液PCR,異質(zhì)性檢驗(yàn)P<0.001,I2=0,固定效應(yīng)模型匯總敏感度0.58(95%CI:0.46~0.69),特異度1.00(95%CI:0.84~1.00);2篇文獻(xiàn)報(bào)道了支氣管肺泡灌洗液Xpert MTB/RIF,異質(zhì)性檢驗(yàn)P=0.430,I2=0,固定效應(yīng)模型的匯總敏感度0.55(95%CI:0.44~0.65),特異度1.00(95%CI:0.98 ~1.00)。
2.4.3組織活檢對(duì)TB的診斷4篇文獻(xiàn)[22,26~28]報(bào)道了支氣管鏡黏膜組織活檢(圖2),異質(zhì)性檢驗(yàn)P=0.062,I2=59.1%,采用隨機(jī)效應(yīng)模型,匯總敏感度0.51(95%CI:0.40~0.61),特異度1.00(95%CI:0.81~1.00)。
圖2支氣管鏡介導(dǎo)不同標(biāo)本和檢測(cè)方法對(duì)兒童結(jié)核病診斷的匯總敏感度和特異度
2.4.4支氣管黏膜刷檢對(duì)TB的診斷文獻(xiàn)[24]顯示支氣管黏膜刷檢培養(yǎng)、涂片及PCR診斷TB的敏感度分別為0.33(95%CI:0.17~0.54),0.30(95%CI:0.14~0.50)和0.33(95%CI:0.17~0.54),特異度均為1.00(95%CI:0.86~1.00)。3種檢測(cè)方法匯總敏感度為0.32(95%CI:0.22~0.43),特異度1.00(95%CI:0.95~1.00)。
2.4.5胃液對(duì)TB的診斷價(jià)值納入10篇文獻(xiàn)[17,18,20,21,23,25,26,29~31],異質(zhì)性檢驗(yàn)P<0.001,I2=93.3%,隨機(jī)效應(yīng)模型匯總敏感度為0.45(95%CI:0.40~0.49),特異度1.00(95%CI:0.99~1.00)。
根據(jù)檢測(cè)方法行亞組分析(圖3), 8篇文獻(xiàn)[20,21,23,25,26,29~31]采用胃液培養(yǎng),異質(zhì)性檢驗(yàn)P<0.001,I2=95.4%,匯總敏感度0.52(95%CI:0.47~0.57),特異度1.00(95%CI:0.98~1.00);5篇文獻(xiàn)[17,18,29~31]采用涂片,異質(zhì)性檢驗(yàn)P=0.006,I2=72.5%,匯總敏感度0.25(95%CI:0.16~0.36),特異度1.00(95%CI:0.95~1.00); 1篇文獻(xiàn)[25]采用PCR,敏感度0.31(95%CI:0.22~0.42),特異度1.00(95%CI:0.95~1.00)。
圖3胃液不同檢測(cè)方法對(duì)兒童結(jié)核病診斷的匯總敏感度和特異度
2.5SROC分析支氣管鏡介導(dǎo)所有標(biāo)本及檢測(cè)方法(5種)診斷TB的SROC AUC為0.881 8,Q*為0.812 3(圖4A);其中支氣管肺泡灌洗液所有(4種)、培養(yǎng)和涂片檢測(cè)診斷TB的SROC AUC分別為0.883 9、0.864 7和0.787 2,Q*分別為0.814 5、0.795 3和0.724 8;胃液所有檢測(cè)方法診斷TB的SROC AUC為0.873 7,Q*為0.804 2(圖4B),其中胃液培養(yǎng)和涂片診斷TB的SROC AUC分別為0.892 9和0.737 8,Q*分別為0.823 7和0.683 4。
2.6發(fā)表偏倚分析支氣管鏡介導(dǎo)所有標(biāo)本及檢測(cè)方法文獻(xiàn)的漏斗圖不對(duì)稱(chēng)(圖4C),且Deek′s檢驗(yàn)P<0.05,提示存在發(fā)表偏倚;支氣管肺泡灌洗液培養(yǎng)和涂片診斷TB文獻(xiàn)的Deek′s檢驗(yàn)P分別為0.005和0.014。胃液診斷兒童TB文獻(xiàn)的漏斗圖略不對(duì)稱(chēng)(圖4D),Deek′s檢驗(yàn)P=0.147,提示發(fā)表偏倚不顯著,胃液培養(yǎng)診斷兒童TB文獻(xiàn)的Deek′s檢驗(yàn)P=0.935。其他各亞組因文獻(xiàn)數(shù)量少未行發(fā)表偏倚檢驗(yàn)。
圖4診斷兒童結(jié)核病匯總受試者工作特征曲線(SROC)和發(fā)表偏倚Deek′s漏斗圖
注A:支氣管鏡介導(dǎo)所有標(biāo)本及檢測(cè)方法診斷結(jié)核病的SROC;B:胃液所有檢測(cè)方法診斷結(jié)核病的SROC;C:支氣管鏡介導(dǎo)所有標(biāo)本及檢測(cè)方法診斷結(jié)核病文獻(xiàn)的Deek′s漏斗圖;D:胃液所有檢測(cè)方法診斷兒童結(jié)核病文獻(xiàn)的Deek′s漏斗圖
本文Meta分析納入14篇文獻(xiàn),根據(jù)QUADAS-2量表?xiàng)l目來(lái)評(píng)價(jià)文獻(xiàn)偏倚風(fēng)險(xiǎn),在金標(biāo)準(zhǔn)、病例流程和進(jìn)展的偏倚風(fēng)險(xiǎn)為低度,在病例選擇上5/14篇文獻(xiàn)為高度偏倚,待評(píng)價(jià)試驗(yàn)10/14篇為高度偏倚,總體偏倚風(fēng)險(xiǎn)為低度。同時(shí)納入文獻(xiàn)間存在一定的臨床異質(zhì)性,如標(biāo)本類(lèi)型(支氣管肺泡灌洗液、支氣管黏膜刷檢和組織)、檢測(cè)方法(培養(yǎng)、涂片、PCR、活檢及Xpert MTB/RIF)、目標(biāo)人群(年齡、感染部位及狀態(tài)不同)、研究方案(前瞻性、回顧性研究)及TB診斷參考標(biāo)準(zhǔn)(臨床、實(shí)驗(yàn)室)等均有所不同,報(bào)告敏感度的文獻(xiàn)間存在顯著的統(tǒng)計(jì)學(xué)異質(zhì)性,行亞組分析但仍不能完全消除異質(zhì)性,且支氣管鏡介導(dǎo)的所有標(biāo)本和支氣管肺泡灌洗液培養(yǎng)的文獻(xiàn)存在發(fā)表偏倚,結(jié)合GRADE證據(jù)質(zhì)量評(píng)價(jià)工具,支氣管鏡介導(dǎo)標(biāo)本及其檢測(cè)方法診斷兒童TB的證據(jù)質(zhì)量為低至中。
本文SROC分析顯示,支氣管鏡介導(dǎo)所有標(biāo)本和檢測(cè)方法診斷TB的AUC 為0.881 8,胃液對(duì)TB診斷AUC 0.873 7,提示兩者對(duì)兒童TB有較好的診斷價(jià)值。支氣管鏡介導(dǎo)的3種標(biāo)本對(duì)TB診斷價(jià)值,其中支氣管黏膜組織活檢的敏感度最高為0.51,支氣管刷檢的敏感度最低為0.32,特異度均為1.00,但由于這2種標(biāo)本納入文獻(xiàn)較少,結(jié)果存在不精確性,有待進(jìn)一步評(píng)估。支氣管肺泡灌洗液作為最常用的標(biāo)本,診斷總體敏感度為0.37,以其為標(biāo)本的4種檢驗(yàn)方法中,PCR對(duì)TB診斷的敏感度最高為0.58,這與既往研究結(jié)果相近。Tian等[33]在2015年以支氣管肺泡灌洗液為標(biāo)本PCR對(duì)痰涂片陰性TB診斷的Meta分析結(jié)果顯示,敏感度為0.54,而另外2篇[34,35]基于各種標(biāo)本的Meta分析結(jié)果顯示PCR診斷TB敏感度分別為0.85和0.96;本文支氣管肺泡灌洗液涂片敏感度最低為0.21,培養(yǎng)敏感度為0.36,Xpert MTB/RIF敏感度為0.55。尹青琴等[36]基于各種標(biāo)本Xpert MTB/RIF的Meta分析結(jié)果提示兒童和成人的敏感度分別為0.74和0.90。本文結(jié)果與既往研究不一致,主要考慮有2方面原因,一是與兒童攜菌率低有關(guān)[36],二是用于支氣管鏡檢查的TB多不典型。
胃液的收集與支氣管鏡的檢查均為侵入性操作,而支氣管肺泡灌洗液作為支氣管鏡檢查最常用的標(biāo)本,兩者常被用于對(duì)比。本文關(guān)于胃液對(duì)TB的診斷有3種檢測(cè)方法,其中PCR僅有1篇文獻(xiàn);培養(yǎng)和涂片的敏感度分別為0.52和0.25,均優(yōu)于支氣管肺泡灌洗液,與已報(bào)道的文獻(xiàn)結(jié)果一致[18],考慮主要有以下幾方面原因[30]:①多項(xiàng)研究中每例患兒是連續(xù)取3 d清晨的胃液標(biāo)本,而支氣管肺泡灌洗液每例患兒大多僅留取1個(gè)標(biāo)本。②兒童TB通常含菌量少,影像學(xué)有肺實(shí)質(zhì)浸潤(rùn)或淋巴結(jié)腫大,因此分離細(xì)菌相對(duì)困難。③支氣管肺泡灌洗液是注入生理鹽水后獲取的,進(jìn)一步稀釋氣道分泌物濃度,檢出少數(shù)結(jié)核分枝桿菌可能性減少。④由于技術(shù)原因,支氣管鏡不一定能到達(dá)病變的確切部位,特別是在年幼兒童的小氣道。因此,樣本可能不包含受影響段的分泌物。
本文系統(tǒng)評(píng)價(jià)的局限性:①未能獲取未發(fā)表的文獻(xiàn),因而不能排除潛在的發(fā)表偏倚;②只納入英文和中文文獻(xiàn),可能存在語(yǔ)種偏倚。
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(本文編輯:丁俊杰)
Diagnostic value of specimens via bronchoscopy for tuberculosis in children: a systematic review and meta-analysis
FUWen-long1,2,ZHANGJuan-Juan1,DAIJi-hong2
(1KeyLaboratoryofDevelopmentalDiseasesinChildhood,MinistryofEducation, 2CenterofRespiratoryDisordersofChildren′sHospital,ChongqingMedicalUniversity,Chongqing400014,China)
DAI Ji-hong,E-mail:danieljh@163.com
Bronchoscopy; Children; Tuberculosis; Diagnostic value; Sensitivity;Specificity;Systematic review;Meta-analysis
重慶醫(yī)科大學(xué)附屬兒童醫(yī)院1 兒童發(fā)育與疾病教育部重點(diǎn)實(shí)驗(yàn)室,2 呼吸中心重慶,401104
代繼宏,E-mail:danieljh@163.com
10.3969/j.issn.1673-5501.2016.03.006
2016-03-30
2016-05-17)