Although it is curable, tuberculosis remains one of the most frequent causes of pleural effusions on a global scale, especially in developing countries. Tuberculous pleural effusion (TPE) is one of the most common forms of extrapulmonary tuberculosis. TPE usually presents as an acute illness with fever, cough and pleuritic chest pain. The pleural fluid is an exudate that usually has predominantly lymphocytes. The gold standard for the diagnosis of TPE remains the detection of Mycobacterium tuberculosis in pleural fluid, or pleural biopsy specimens, either by microscopy and/or culture, or the histological demonstration of caseating granulomas in the pleura along with acid fast bacilli, Although adenosine deaminase and interferon-γ in pleural fluid have been documented to be useful tests for the diagnosis of TPE. It can be accepted that in areas with high tuberculosis prevalence, the easiest way to establish the diagnosis of TPE in a patient with a lymphocytic pleural effusion is to generally demonstrate a adenosine deaminase level above 40 U/L. The recommended treatment for TPE is a regimen with isoniazid, rifampin, and pyrazinamide for two months followed by four months of two drugs, isoniazid and rifampin.
The complex interactions among different immune cells have important functions in the development of malignant pleural effusion (MPE). Here we perform single-cell RNA sequencing on 62,382 cells from MPE patients induced by non-small cell lung cancer to describe the composition, lineage, and functional states of infiltrating immune cells in MPE. Immune cells in MPE display a number of transcriptional signatures enriched for regulatory T cells, B cells, macrophages, and dendritic cells compared to corresponding counterparts in blood. Helper T, cytotoxic T, regulatory T, and T follicular helper cells express multiple immune checkpoints or costimulatory molecules. Cell-cell interaction analysis identifies regulatory B cells with more interactions with CD4+ T cells compared to CD8+ T cells. Macrophages are transcriptionally heterogeneous and conform to M2 polarization characteristics. In addition, immune cells in MPE show the general up-regulation of glycolytic pathways associated with the hypoxic microenvironment. These findings show a detailed atlas of immune cells in human MPE and enhance the understanding of potential diagnostic and therapeutic targets in advanced non-small cell lung cancer.
Objective Although the values of soluble mesothelin-related peptides (SMRPs), including mesothelin and megakaryocyte potentiating factor, in serum and/or pleural fluid for diagnosing malignant pleural mesothelioma (MPM) have been extensively studied, the exact diagnostic accuracy of these SMRPs remains controversial. The purpose of the present meta-analysis is to update the overall diagnostic accuracy of SMRPs in serum and, furthermore, to establish diagnostic accuracy of SMRPs in pleural fluid for MPM. Design Systematic review and meta-analysis. Methods A total of 30 articles of diagnostic studies were included in the current meta-analysis. Sensitivity, specificity and other measures of accuracy of SMRPs in serum and pleural fluid for the diagnosis of MPM were pooled using random effects models. Summary receiver operating characteristic curves were used to summarise overall test performance. Results The summary estimates of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic OR were 0.61, 0.87, 5.71, 0.43 and 14.43, respectively, for serum and 0.79, 0.85, 4.78, 0.30 and 19.50, respectively, for pleural fluid. It was also found that megakaryocyte potentiating factor in serum had a superior diagnostic accuracy compared with mesothelin for MPM. Conclusions SMRPs in both serum and pleural fluid are helpful markers for diagnosing MPM with similar diagnostic accuracy. The negative results of SMRP determinations are not sufficient to exclude non-MPM, and the positive test results indicate that further invasive diagnostic steps might be necessary for the diagnosis of MPM.
Background Accurate differentiating diagnosis is essential for choosing treatment for exudative pleural effusions. Objective To establish the diagnostic accuracy of interleukin 27 for tuberculous pleural effusion (TPE). Methods First, the concentrations of pleural interleukin 27, interferon-gamma and adenosine deaminase were compared between 51 patients with TPE and 103 with non-TPEs (Beijing cohort), and their diagnostic values were evaluated. These were further verified in another independent population (Wuhan cohort, n=120). In the second part of the study, we performed a meta-analysis. Results With a cut-off value of 591.4 ng/L in the Beijing cohort, the area under the curve, sensitivity, specificity, positive predictive value and negative predictive value of interleukin 27 to diagnose TPE were 0.983 (95% CI 0.947 to 0.997), 96.1% (86.5% to 99.5%), 99.0% (94.7% to 100%), 98.0 (89.4 to 99.9) and 98.1 (93.3 to 99.8), respectively. Excellent diagnostic accuracy of interleukin 27 was also found in the Wuhan cohort and was further confirmed in the meta-analysis. The diagnostic performance of interleukin 27 was comparable to that of interferon-gamma and was more accurate than that of adenosine deaminase. Since the post-test probability of a negative result was always <0.1%, a negative test was considered to exclude TPE in all tuberculosis prevalence settings. Conclusions Interleukin 27 can be used to diagnose TPE in a high prevalence setting, and a negative result can also be reliably used to rule out TPE in all prevalence settings.