Abstract：
BACKGROUND: This meta-analysis examines the comparative diagnostic performance of polymerase chain reaction (PCR) for the diagnosis of Pneumocystis pneumonia (PCP) on different respiratory tract samples, in both human immunodeficiency virus (HIV) and non-HIV populations.
METHODS: A total of 55 articles met inclusion criteria, including 11 434 PCR assays on respiratory specimens from 7835 patients at risk of PCP. QUADAS-2 tool indicated low risk of bias across all studies. Using a bivariate and random-effects meta-regression analysis, the diagnostic performance of PCR against the European Organisation for Research and Treatment of Cancer-Mycoses Study Group definition of proven PCP was examined.
RESULTS: Quantitative PCR (qPCR) on bronchoalveolar lavage fluid provided the highest pooled sensitivity of 98.7% (95% confidence interval [CI], 96.8%-99.5%), adequate specificity of 89.3% (95% CI, 84.4%-92.7%), negative likelihood ratio (LR-) of 0.014, and positive likelihood ratio (LR+) of 9.19. qPCR on induced sputum provided similarly high sensitivity of 99.0% (95% CI, 94.4%-99.3%) but a reduced specificity of 81.5% (95% CI, 72.1%-88.3%), LR- of 0.024, and LR+ of 5.30. qPCR on upper respiratory tract samples provided lower sensitivity of 89.2% (95% CI, 71.0%-96.5%), high specificity of 90.5% (95% CI, 80.9%-95.5%), LR- of 0.120, and LR+ of 9.34. There was no significant difference in sensitivity and specificity of PCR according to HIV status of patients.
CONCLUSIONS: On deeper respiratory tract specimens, PCR negativity can be used to confidently exclude PCP, but PCR positivity will likely require clinical interpretation to distinguish between colonization and active infection, partially dependent on the strength of the PCR signal (indicative of fungal burden), the specimen type, and patient population tested.
METHODS: A total of 55 articles met inclusion criteria, including 11 434 PCR assays on respiratory specimens from 7835 patients at risk of PCP. QUADAS-2 tool indicated low risk of bias across all studies. Using a bivariate and random-effects meta-regression analysis, the diagnostic performance of PCR against the European Organisation for Research and Treatment of Cancer-Mycoses Study Group definition of proven PCP was examined.
RESULTS: Quantitative PCR (qPCR) on bronchoalveolar lavage fluid provided the highest pooled sensitivity of 98.7% (95% confidence interval [CI], 96.8%-99.5%), adequate specificity of 89.3% (95% CI, 84.4%-92.7%), negative likelihood ratio (LR-) of 0.014, and positive likelihood ratio (LR+) of 9.19. qPCR on induced sputum provided similarly high sensitivity of 99.0% (95% CI, 94.4%-99.3%) but a reduced specificity of 81.5% (95% CI, 72.1%-88.3%), LR- of 0.024, and LR+ of 5.30. qPCR on upper respiratory tract samples provided lower sensitivity of 89.2% (95% CI, 71.0%-96.5%), high specificity of 90.5% (95% CI, 80.9%-95.5%), LR- of 0.120, and LR+ of 9.34. There was no significant difference in sensitivity and specificity of PCR according to HIV status of patients.
CONCLUSIONS: On deeper respiratory tract specimens, PCR negativity can be used to confidently exclude PCP, but PCR positivity will likely require clinical interpretation to distinguish between colonization and active infection, partially dependent on the strength of the PCR signal (indicative of fungal burden), the specimen type, and patient population tested.
摘要：
背景：这项荟萃分析检查了聚合酶链反应（PCR）在不同呼吸道样本上诊断肺孢子虫肺炎（PCP）的比较诊断性能，在人类免疫缺陷病毒（HIV）和非HIV人群中。
方法：共有55篇文章符合纳入标准，包括对7835例有PCP风险的患者的呼吸道标本进行的11434PCR检测。QUADAS-2工具表明所有研究的偏倚风险较低。使用双变量和随机效应荟萃回归分析，针对欧洲癌症研究和治疗组织-真菌病研究小组对已证实的PCP的定义,研究了PCR的诊断性能.
结果：支气管肺泡灌洗液的定量PCR（qPCR）提供了98.7%的最高合并灵敏度（95%置信区间[CI]，96.8%-99.5%），足够的特异性为89.3%（95%CI，84.4%-92.7%），负似然比（LR-）为0.014，正似然比（LR+）为9.19。对诱导痰的qPCR提供了类似的99.0％（95％CI，94.4％-99.3％）的高灵敏度，但降低了81.5％（95％CI，72.1％-88.3％）的特异性，LR-为0.024，LR+为5.30。qPCR对上呼吸道样本的灵敏度较低，为89.2%（95%CI，71.0%-96.5%），高特异性90.5%（95%CI，80.9%-95.5%），LR-为0.120，LR+为9.34。根据患者的HIV状况，PCR的敏感性和特异性没有显着差异。
结论：在较深的呼吸道标本上，PCR阴性可用于可靠地排除PCP，但PCR阳性可能需要临床解释来区分定植和活动性感染，部分取决于PCR信号的强度（指示真菌负荷），试样类型,和患者人群测试。
方法：共有55篇文章符合纳入标准，包括对7835例有PCP风险的患者的呼吸道标本进行的11434PCR检测。QUADAS-2工具表明所有研究的偏倚风险较低。使用双变量和随机效应荟萃回归分析，针对欧洲癌症研究和治疗组织-真菌病研究小组对已证实的PCP的定义,研究了PCR的诊断性能.
结果：支气管肺泡灌洗液的定量PCR（qPCR）提供了98.7%的最高合并灵敏度（95%置信区间[CI]，96.8%-99.5%），足够的特异性为89.3%（95%CI，84.4%-92.7%），负似然比（LR-）为0.014，正似然比（LR+）为9.19。对诱导痰的qPCR提供了类似的99.0％（95％CI，94.4％-99.3％）的高灵敏度，但降低了81.5％（95％CI，72.1％-88.3％）的特异性，LR-为0.024，LR+为5.30。qPCR对上呼吸道样本的灵敏度较低，为89.2%（95%CI，71.0%-96.5%），高特异性90.5%（95%CI，80.9%-95.5%），LR-为0.120，LR+为9.34。根据患者的HIV状况，PCR的敏感性和特异性没有显着差异。
结论：在较深的呼吸道标本上，PCR阴性可用于可靠地排除PCP，但PCR阳性可能需要临床解释来区分定植和活动性感染，部分取决于PCR信号的强度（指示真菌负荷），试样类型,和患者人群测试。
