Sequential Pleural Fluid and Serum Biomarker Measurements in Patients Undergoing Medical Thoracoscopy for Persistently Undiagnosed Pleural Effusion: A Pilot Study from a TB-Endemic Tertiary Centre.

INTRODUCTION

Pleural effusion remains diagnostically challenging when standard thoracentesis does not establish an aetiology. This pilot analysis described sequential biomarker measurements in patients proceeding to medical thoracoscopy and explored their associations and discrimination across final diagnostic classifications.

METHODS

Prospectively collected data from a single-centre tertiary referral cohort were analysed. Pleural-fluid adenosine deaminase (ADA) and serum complement components 3 and 4 (C3 and C4) were obtained on day 1, whereas pleural-fluid cancer antigen 125 (CA125) and lactate dehydrogenase (LDH) were obtained at the day 7/thoracoscopy evaluation. Final classifications were based on a composite reference standard integrating thoracoscopy, histopathology, microbiology, cytology, imaging, and clinical follow-up. Analyses were exploratory.

RESULTS

Amongst 75 patients, 6 (8.0%) were classified as tuberculous pleural effusion (TB-PE), 33 (44.0%) as malignant pleural effusion (MPE) and 36 (48.0%) as other non-tuberculous, non-malignant pleural effusions. ADA differed across groups (Kruskal-Wallis P = 0.002; Benjamini-Hochberg q = 0.010) and showed exploratory discrimination for TB-PE (area under the curve [AUC] 0.934; bootstrap 95% confidence interval [CI] 0.855-0.995). At the conventional ≥ 40 U/L threshold, sensitivity was 83.3%, specificity 93.4%, positive predictive value (PPV) 55.6%, negative predictive value (NPV) 98.3%, positive likelihood ratio (LR+) 12.7, and negative likelihood ratio (LR-) 0.18. CA125, LDH, C3 and C4 did not show significant omnibus group differences after reanalysis. In a post hoc sensitivity analysis excluding 26 patients retained as non-specific pleuritis (n = 49), ADA remained significantly different across groups (P = 0.004; q = 0.022).

CONCLUSIONS

In this selected thoracoscopy cohort, day 1 pleural-fluid ADA showed the clearest exploratory signal, including after exclusion of non-specific pleuritis, but estimates were based on only six TB-PE cases and do not establish stand-alone utility or a role in avoiding thoracoscopy. The remaining biomarkers showed no robust aetiology-specific signal.

TRIAL REGISTRATION: ClinicalTrials.gov NCT06159179.