Evaluating the Diagnostic Validity of Inflammation-associated Markers for Tuberculous Pleurisy

Tuberculosis (TB) remains a global health problem even though it has nearly been eradicated in some developed countries. Because of variable manifestations and the difficulty in collecting clinical samples, extra-pulmonary TB is usually difficult to early diagnose. Tuberculous pleurisy (TP) is one of the most common extra-pulmonary infection and accounts for approximately 5% of all forms of TB. The gold standard for diagnosing TP is mycobacterial culture of pleural effusion (PE), pleura tissue, which requires weeks to yield. The treatment could thus be delayed, resulting in an increased mortality rate. In addition, mycobacterial culture is not so sensitive for PE and with positivity in less than two thirds of cases with TB pleurisy.

For diagnosing TP, PE biomarkers are required to be investigated in addition to traditional PE cell counting and biochemistry. In particularly, inflammation-associated cytokines and apoptosis-associated markers may be important because the two pathways involve in TB infection/defense mechanism. For inflammation-association markers, current literature is not comprehensive except IFN-gamma and IFN-gamma release assay (IGRA). However, the result of IGRA using PE is disappointed. We should study other PE inflammation markers such as IFN-induced protein-10, interleukin [IL]-2, IL-12 and so on. On the other hand, apoptosis suppression is one of escape mechanisms in TB pathogenesis. Macrophage, dendritic cell, and neutrophil are reportedly inhibited for apoptosis in TB infection. But the apoptosis of PE neutrophil are rarely studied. Moreover, the role of apoptosis-associated markers (Fas ligand [FasL], decoy receptor 3, lipoxin, prostaglandin E2, caspases) in PE has rarely been investigated in diagnosing TP except FasL. Therefore, we conduct a prospective study to investigate inflammation/apoptosis-associated markers in exudative PE and apoptosis of PE neutrophil to analyze their diagnostic usefulness for TP.