Evaluation of PCR in bronchoalveolar lavage fluid for diagnosis of Pneumocystis jirovecii pneumonia: a bivariate meta-analysis and systematic review

Abstract

Background: As a promising tool, PCR in bronchoalveolar lavage fluid (BALF) has not been accepted as a diagnostic criterion for PJP.

Objective: We undertook a systematic review of published studies to evaluate the diagnostic accuracy of PCR assays in BALF for PJP.

Methods: Eligible studies from PubMed, Embase and Web of Science reporting PCR assays in BALF for diagnosing PJP were identified. A bivariate meta-analysis of the method's sensitivity, specificity, and positive and negative likelihood ratios with a 95% confidence interval (CI) were analyzed. The post-test probability was performed to evaluate clinical usefulness. A summary receiver operating characteristics (SROC) curve was used to evaluate overall performance. Subgroup analyses were carried out to analysis the potential heterogeneity.

Results: Sixteen studies published between 1994 and 2012 were included. The summary sensitivity and specificity values (95% CI) of PCR in BALF for diagnosis of PJP were 98.3% (91.3%-99.7%) and 91.0% (82.7%-95.5%), respectively. The positive and negative likelihood ratios were 10.894 (5.569-21.309) and 0.018 (0.003-0.099), respectively. In a setting of 20% prevalence of PJP, the probability of PJP would be over 3-fold if the BALF-PCR test was positive, and the probability of PJP would be less than 0.5% if it was negative. The area under the SROC curve was 0.98 (0.97-0.99).

Conclusions: The method of PCR in BALF shows high sensitivity and good specificity for the diagnosis of PJP. However, clinical practice for the diagnosis of PJP should consider the consistent respiratory symptoms, radiographic changes and laboratory findings of the suspected patients.

Figure 1. Flow diagram of the process of selecting included studies.

This flow-diagram shows 398 references identified, after screening all of the titles and abstracts, 71 articles were selected for full-text review. Ultimately, 16 studies that were included in the meta-analysis, 55 studies were excluded for various reasons.

Figure 2. Summary of the methodological quality assessment of the included studies according to QUADAS-2 criteria.

Data was carried out using a bar graph showing the percentages of the 16 studies that met the criteria (Yes), did not meet the criteria (No), and did not provide adequate relevant data (Unclear).

Figure 3. Forest plots of the sensitivity and specificity of BALF-PCR for the diagnosis of PJP.

The circles in squares and the horizontal lines represent the point estimate and 95% confidence interval for each included study and the diamond represents the pooled estimate.

Figure 4. SROC curve shows summary operating sensitivity and specificity with confidence and prediction contours.

SROC curve with confidence and prediction regions around mean operating sensitivity and specificity point analyses of PCR assays in BALF for the diagnosis of PJP. Abbreviations: AUC, area under curve; SENS, sensitivity; SPEC, specificity; SROC curve, summary receiver operating (SROC) curve.

Figure 5. Fagan’s nomogram for calculating post-test probabilities (PTPs).

Lines were drawn from the prior probability on the left through the likelihood ratios in the center and extended to the posterior probabilities on the right, which demonstrates that BALF-PCR is very informative raising probability of PJP to over 3-fold when positive from 20% and lowering the probability of disease to as low as 0.5% when negative.