The Value of Adenosine Deaminase 2 in the Detection of Tuberculous Pleural Effusion: A Meta-Analysis and Systematic Review

Abstract

Adenosine deaminase 2 (ADA₂) is reported as a novel diagnostic biomarker for tuberculous pleural effusion (TPE) in many studies. This meta-analysis was conducted to systematically evaluate the general diagnostic performance of pleural ADA₂ in TPE. After searching for relevant studies that investigated the diagnostic performance of pleural ADA₂ in TPE in several databases, we assessed and selected eligible studies to calculate pooled parameters by STATA 16.0 software. A final set of thirteen studies entirely met the inclusion standards and were used to calculate pooled parameters in our meta-analysis. Among them, there were nine English studies and four Chinese studies. The pooled parameters of pleural ADA₂ in diagnosing TPE were summarized as follows: sensitivity, 0.91 (95% CI: 0.86-0.95); specificity, 0.93 (95% CI: 0.92-0.95); positive likelihood ratio, 13.9 (95% CI: 10.6-18.3); negative likelihood ratio, 0.09 (95% CI:0.06-0.16); diagnostic odds ratio, 147 (95% CI: 76-284); and the area under the curve, 0.95 (95% CI: 0.93-0.97). Pleural ADA₂ is a reliable indicator with excellent accuracy in TPE diagnosis. However, we need to combine pleural ADA₂ with diverse examinations to diagnose TPE in clinical practice.

Figure 1

PRISMA flowchart of the selection process.

Figure 2

Summary of QUADAS-2 assessments of the included studies. QUADAS-2, Quality Assessment of Diagnostic Accuracy Studies-2. Four fields included are the patient selection methods, index test, reference standard, and flow and timing.

Figure 3

Forest plots of sensitivity and specificity for ADA2. The pooled sensitivity was 0.91 (95% CI: 0.86–0.95), and the pooled specificity was 0.93 (95% CI: 0.92–0.95).

Figure 4

The summary receiver operating characteristic (SROC) curve and the area under the curve (AUC). The AUC was 0.95 (95% CI: 0.93–0.97). AUC, area under the curve; SENS, sensitivity; SPEC, specificity.

Figure 5

Fagan's nomogram.

Figure 6

Meta-regression of the included studies. Both sensitivity and specificity were significantly affected by publication year and the cutoff value (P < 0.05), indicating that publication year, cutoff value, and other unknown covariates result in heterogeneity.

Figure 7

Deeks's funnel plot. The apparent asymmetric shape of Deeks's funnel plot and P value = 0.02 indicate that publication bias significantly existed in the study.