Search

As the burden of tuberculosis (TB) in South Korea decreases while that of malignancy increases with an aging society, the composition of etiology for pleural effusion is changing. The aim of this study was to investigate the diagnostic value of adenosine deaminase (ADA) for diagnosis of tuberculous pleural effusion (TPE) in this circumstance. Medical records of patients who underwent medical thoracoscopy from May 2015 to September 2020 in Incheon St. Mary Hospital, Korea were retrospectively reviewed. TPE was diagnosed if one of the following criteria was met: (1) granuloma in pleura, (2) positive TB polymerase chain reaction or culture in pleural fluid or tissue with non-specific pathologic findings in pleura, or (3) bacteriologically confirmed pulmonary TB with non-specific pathologic findings in pleura. A total of 292 patients, including 156 with malignant pleural effusion (MPE), 52 with TPE, and 84 with other benign effusion, were analyzed. Among 206 patients with lymphocyte dominant pleural effusion, the area under receiver characteristic curve of ADA for diagnosis of TPE was 0.971. The sensitivity and specificity of a current cutoff value of 40 IU/L were 1.00 and 0.61, respectively, whereas those of a raised cutoff value of 70 IU/L were 0.93 and 0.93, respectively. Among 54 patients with ADA levels of 40-70 IU/L, 30 (55.6%) patients were diagnosed as MPE, 21 (38.9%) as other benign effusion, and only 3 (5.6%) as TPE. Caution is needed in clinical diagnosis of TPE with current ADA cutoff value in countries with decreasing TB incidence, due to many false positive cases., (© 2022. The Author(s).)

Lung cancer patients with malignant pleural effusions (MPE) have a particular poor prognosis. It is crucial to distinguish MPE from benign pleural effusion (BPE). The present study aims to develop a rapid, convenient and economical diagnostic method based on FTIR near-infrared spectroscopy (NIRS) combined with machine learning strategy for clinical pleural effusion classification. NIRS spectra were recorded for 47 MPE samples and 35 BPE samples. The sample data were randomly divided into train set (n = 62) and test set (n = 20). Partial least squares, random forest, support vector machine (SVM), and gradient boosting machine models were trained, and subsequent predictive performance were predicted on the test set. Besides the whole spectra used in modeling, selected features using SVM recursive feature elimination algorithm were also investigated in modeling. Among those models, NIRS combined with SVM showed the best predictive performance (accuracy: 1.0, kappa: 1.0, and AUC ROC : 1.0). SVM with the top 50 feature wavenumbers also displayed a high predictive performance (accuracy: 0.95, kappa: 0.89, AUC ROC : 0.99). Our study revealed that the combination of NIRS and machine learning is an innovative, rapid, and convenient method for clinical pleural effusion classification, and worth further evaluation.

Surgical intervention use is common in the management of childhood pleural tuberculosis (TB), however, its associated risk factors remain unclear. Between January 2006 and December 2019, consecutive children patients (≤ 15 years old) who had a diagnosis of pleural TB were included for the analysis. Surgical intervention was defined as debridement (such as breaking loculations), decortication, and thoracic surgery (such as lobectomy or segmental resection). Patients undergoing surgery were included as surgical group, without surgery were classified as non-surgical group, surgical risk factors were then estimated. Univariate and multivariate logistic regression analysis were performed to evaluate the risk factors for surgical interventions. A total of 154 children diagnosed as pleural TB (definite, 123 cases; possible, 31 cases) were included in our study. Of them, 29 patients (18.8%) were classified as surgical group and 125 patients (81.2%) were classified as non-surgical group. Surgical treatments were analyzed in 29 (18.8%) patients, including debridement (n = 4), decortication (n = 21), and thoracic surgery (n = 4). Further multivariate analysis revealed that empyema (age- and sex-adjusted OR = 27.3, 95% CI 8.6, 87.1; P < 0.001) and frequency of hospitalization (age- and sex-adjusted OR = 1.53, 95% CI 1.11, 2.11; P < 0.01) were associated with the use of surgical interventions in children with pleural TB. In China, surgical interventions are still required in a significant proportion of children with pleural TB, and the surgical risk is found to be associated with the frequency of hospitalization and empyema. These findings may be helpful to improve the management of children with pleural TB and minimize the risk of poor outcomes.

Tuberculous empyema (TE) is associated with high mortality and morbidity. In the retrospective cohort study, we aimed to find risk factors for TE among pleural tuberculosis (TB) patients. Between July 2011 and September 2015, all culture-confirmed pleural TB patients (474 cases) were enrolled in our study. Empyema was defined as grossly purulent pleural fluid. Demographic and epidemiological data were collected for further analysis. Multivariate logistic regression analysis was used to evaluate risk factors of TE in pleural TB, age-adjusted odds ratio (OR) and 95% confidence interval (CI) were calculated to show the risk. The mean age was 35.7 ± 18.1 years old, males comprised 79.1% of the participants (375 cases). Forty-seven patients (9.9%) were multidrug-resistant TB (MDR-TB), 29 (6.1%) had retreatment TB, 26 (5.5%) had diabetes mellitus. The percentage of empyema patients was 8.9% (42 cases). Multivariate analysis revealed that male (adjusted OR = 4.431, 95% CI: 1.411, 13.919), pleural adenosine deaminase (ADA, >88 U/L) (adjusted OR = 3.367, 95% CI: 1.533, 7.395) and white blood cell (WBC, >9.52 10 9 /L) (adjusted OR = 5.763, 95% CI: 2.473, 13.431) were significant risk factors for empyema in pleural TB, while pulmonary TB (adjusted OR = 0.155, 95% CI: 0.072, 0.336) was the protective factor for the patients. TE remains a serious threat to public health in China. Male sex is a significant risk factor for TE while the presence of pulmonary TB is protective, and high levels of pleural ADA and WBC count could aid in early diagnosis of TE. This finding would help towards reducing the mortality and morbidity associated with TE.

Currently, the diagnostic role of medical thoracoscopy in childhood pleural tuberculosis remains uncertain. Therefore, this retrospective study was conducted to evaluate the diagnostic performance of histological examination of tissue samples obtained by medical thoracoscopy in childhood pleural tuberculosis. Hospitalized children who underwent medical thoracoscopy between May 2012 and March 2016 were included in the study. Tissue samples obtained by thoracoscopy were submitted for histological examination (hematoxylin and eosin staining). Descriptive statistical methods were used for data interpretation, and the data were expressed as the mean ± standard deviation. The childhood tuberculosis patients had the following characteristics: 11 had pleural tuberculosis and 9 had pleural tuberculosis + pulmonary tuberculosis, the average age was 13.0 ± 2.2 years old, 60% were male, 26.3% (5/19) of patients tested positive for acid-fast bacilli positive in smears, 21.1% (4/19) of patients were positive for TB-PCR, and 90% (18) of pleural tuberculosis patients were positive in the culture for Mycobacterium tuberculosis. The sensitivity of histological examinations of tissue samples obtained by thoracoscopy in the detection of pleural tuberculosis was 80% (16/20). Complications were reported in 15 cases, and all complications disappeared spontaneously without any specific treatment. Therefore, we concluded that medical thoracoscopy was a sensitive and safe tool for the detection of childhood pleural tuberculosis.

Pleural macrophages play critical roles in pathogenesis of tuberculous pleuritis, but very little is known about their response to anti-tuberculosis antibiotics treatment. Here, we examined whether and how pleural macrophages change in phenotype, transcription and function following antibiotics treatment in patients with tuberculous pleuritis. Results show pro-inflammatory cytokines were down-regulated significantly post antibiotic treatment in the pleural effusions and pleural macrophages up-regulated markers characteristic of M2 macrophages such as CD163 and CD206. Differential expression analysis of transcriptomes from four paired samples before and after treatment identified 230 treatment-specific responsive genes in pleural macrophages. Functional analysis identified interferon-related pathway to be the most responsive genes and further confirmed macrophage polarization to M2-like phenotype. We further demonstrate that expression of a significant fraction of responsive genes was modulated directly by antibiotics in pleural macrophages in vitro. Our results conclude that pleural macrophages polarize from M1-like to M2-like phenotype within a mean of 3.5 days post antibiotics treatment, which is dependent on both pleural cytokine environment and direct modulatory effects of antibiotics. The treatment-specific genes could be used to study the roles of pleural macrophages in the pathogenesis of tuberculous pleuritis and to monitor the response to antibiotics treatment.

The functions of MAIT cells at the site of Mycobacterium tuberculosis infection in humans are still largely unknown. In this study, the phenotypes and immune response of MAIT cells from tuberculous pleural effusions and peripheral blood were investigated. MAIT cells in tuberculous pleural effusions had greatly enhanced IFN-γ, IL-17F and granzyme B response compared with those in peripheral blood. The level of IFN-γ response in MAIT cells from tuberculous pleural effusions was inversely correlated with the extent of tuberculosis infection (p = 0.0006). To determine whether cytokines drive the immune responses of MAIT cells at the site of tuberculosis infection, the role of IL-1β, IL-2, IL-7, IL-12, IL-15 and IL-18 was investigated. Blockade of IL-2, IL-12 or IL-18 led to significantly reduced production of IFN-γ and/or granzyme B in MAIT cells from tuberculous pleural effusions. Majority of IL-2-producing cells (94.50%) in tuberculous pleural effusions had phenotype of CD3(+)CD4(+), and most IL-12p40-producing cells (91.39%) were CD14(+) cells. MAIT cells had significantly elevated expression of γc receptor which correlated with enhanced immune responses of MAIT cells. It is concluded that MAIT cells from tuberculous pleural effusions exhibited highly elevated immune response to Mtb antigens, which are controlled by cytokines produced by innate/adaptive immune cells.