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Therapeutic Advances in Respiratory... 2018The use of biomarkers on pleural fluid (PF) specimens may assist the decision-making process and enhance clinical diagnostic pathways. Three paradigmatic examples are... (Review)
Review
The use of biomarkers on pleural fluid (PF) specimens may assist the decision-making process and enhance clinical diagnostic pathways. Three paradigmatic examples are heart failure, tuberculosis and, particularly, malignancy. An elevated PF concentration of the amino-terminal fragment of probrain natriuretic peptide (>1500 pg/ml) is a hallmark of acute decompensated heart failure. Adenosine deaminase, interferon-γ and interleukin-27 are three valuable biomarkers for diagnosing tuberculous pleurisy, yet only the first has been firmly established in clinical practice. Diagnostic PF biomarkers for malignancy can be classified as soluble-protein based, immunocytochemical and nucleic-acid based. Soluble markers (e.g. carcinoembryonic antigen (CEA), carbohydrate antigen 15-3, mesothelin) are only indicative of cancer, but not confirmatory. Immunocytochemical studies on PF cell blocks allow: (a) to distinguish mesothelioma from reactive mesothelial proliferations (e.g. loss of BAP1 nuclear expression, complemented by the demonstration of p16 deletion using fluorescence in situ hybridization, indicate mesothelioma); (b) to separate mesothelioma from adenocarcinoma (e.g. calretinin, CK 5/6, WT-1 and D2-40 are markers of mesothelioma, whereas CEA, EPCAM, TTF-1, napsin A, and claudin 4 are markers of carcinoma); and (c) to reveal tumor origin in pleural metastases of an unknown primary site (e.g. TTF-1 and napsin A for lung adenocarcinoma, p40 for squamous lung cancer, GATA3 and mammaglobin for breast cancer, or synaptophysin and chromogranin A for neuroendocrine tumors). Finally, PF may provide an adequate sample for analysis of molecular markers to guide patients with non-small cell lung cancer to appropriate targeted therapies. Molecular testing must include, at least, mutations of epidermal growth-factor receptor and BRAF V600E, translocations of rat osteosarcoma and anaplastic lymphoma kinase, and expression of programmed death ligand 1.
Topics: Biomarkers; Biomarkers, Tumor; Heart Failure; Humans; Pleural Diseases; Pleural Effusion; Pleural Effusion, Malignant; Tuberculosis, Pleural
PubMed: 30354850
DOI: 10.1177/1753466618808660 -
Current Opinion in Pulmonary Medicine May 2024Tuberculous pleuritis (TBP) is one of the most common types of extrapulmonary tuberculosis. We highlight the latest epidemiology of TBP, the heterogeneity of its... (Review)
Review
PURPOSE OF REVIEW
Tuberculous pleuritis (TBP) is one of the most common types of extrapulmonary tuberculosis. We highlight the latest epidemiology of TBP, the heterogeneity of its presentation and the performance of different diagnostic strategies.
RECENT FINDINGS
There are differential trends in the incidences of TBP worldwide. Its incidence increased in China but decreased in the United States in the past decade. The presentation of TBP is heterogeneous regarding clinical symptoms, radiological findings and pleural fluid analysis results. Conventional microbiological tests have low sensitivities to diagnose TBP. Recent research focused on various diagnostic tools with better yield. The sensitivity of nucleic acid amplification tests (NAAT) in pleural fluid, including the latest generation of PCR and sequencing-based techniques for detecting tuberculosis, remains suboptimal. Various pleural fluid biomarkers have been explored, but there is a lack of consensus on their clinical utility and cutoff levels.
SUMMARY
The heterogeneity of clinical presentation poses obstacles to diagnosing TBP. Further development of diagnostic tools, including more robust NAAT and biomarkers with additional validation, is needed before incorporation into routine clinical practice.
Topics: Humans; Pleural Effusion; Tuberculosis, Pleural; Exudates and Transudates; Biomarkers; Pleurisy; Sensitivity and Specificity
PubMed: 38323466
DOI: 10.1097/MCP.0000000000001052 -
BMC Infectious Diseases Aug 2019Due to the similar clinical, lung imaging, and pathological characteristics, talaromycosis is most commonly misdiagnosed as tuberculosis. This study aimed to identify... (Comparative Study)
Comparative Study
BACKGROUND
Due to the similar clinical, lung imaging, and pathological characteristics, talaromycosis is most commonly misdiagnosed as tuberculosis. This study aimed to identify the characteristics of talaromycosis pleural effusion (TMPE) and to distinguish TMPE from tuberculosis pleural effusion (TPE).
METHODS
We enrolled 19 cases each of TMPE and TPE from Guangxi, China. Patients' clinical records, pleural effusion tests, biomarker test results, and receiver operating characteristic curves were analyzed.
RESULTS
In total, 39.8% (65/163) of patients exhibited serous effusion, of whom 61 were non-human immunodeficiency virus (HIV)-infected patients; 68.85% of the non-HIV-infected patients (42/61) had TMPE. Thoracentesis was performed only in 19 patients, all of whom were misdiagnosed with tuberculosis and received long-term anti-tuberculosis treatment. In four of these patients, interleukin (IL)-23, IL-27, and interferon-gamma (IFN-γ) measurements were not performed since pleural effusion samples could not be collected because the effusion had been drained prior to the study. In the remaining 15 patients, pleural effusion samples were collected. Talaromyces marneffei was isolated from the pleural effusion and pleural nodules. Most TMPEs were characterized by yellowish fluid, with marked elevation of protein content and nucleated cell counts. However, neutrophils were predominantly found in TMPEs, and lymphocytes were predominantly found in TPEs (both p < 0.05). Adenosine deaminase (ADA) and IFN-γ levels in TMPEs were significantly lower than those in TPEs (all p < 0.05) and provided similar accuracies for distinguishing TMPEs from TPEs. IL-23 concentration in TMPEs was significantly higher than that in TPEs (p < 0.05), and it provided similar accuracy for diagnosing TMPEs. IL-27 concentrations in TMPEs were significantly lower than those in TPEs (all p < 0.05) but was not useful for distinguishing TMPE from TPE.
CONCLUSIONS
Talaromycosis can infringe on the pleural cavity via the translocation of T. marneffei into the pleural space. Nonetheless, this phenomenon is still commonly neglected by clinicians. TMPE is a yellowish fluid with exudative PEs and predominant neutrophils. Higher neutrophil counts and IL-23 may suggest talaromycosis. Higher lymphocyte counts, ADA activity, and IFN-γ concentration may suggest tuberculosis.
Topics: Adenosine Deaminase; Adolescent; Adult; Aged; Biomarkers; Child; Child, Preschool; Cohort Studies; Female; Humans; Infant; Interferon-gamma; Interleukin-23 Subunit p19; Interleukins; Lymphocytes; Male; Middle Aged; Mycoses; Neutrophils; Pleural Effusion; ROC Curve; Talaromyces; Tuberculosis, Pleural
PubMed: 31455239
DOI: 10.1186/s12879-019-4376-6 -
Monaldi Archives For Chest Disease =... Aug 2021Treating tuberculosis (TB) is not the end of the disease because of the wide spectrum of post TB sequelae associated with the disease. There is insufficient data on post...
Treating tuberculosis (TB) is not the end of the disease because of the wide spectrum of post TB sequelae associated with the disease. There is insufficient data on post TB radiological sequelae. The aim of this study is to evaluate the post TB radiological sequelae on chest x-rays in patients who had completed the treatment for pulmonary and pleural TB at a tertiary care hospital of a high TB burden country. This is a retrospective cross-sectional study conducted on patients treated for pulmonary and pleural TB. Adult patients (18 years or above) with a clinical or microbiological diagnosis of pulmonary or pleural TB were included. Patients were classified on the basis of site of TB into pulmonary and pleural TB. Post-treatment radiological sequelae on chest x-ray were evaluated and divided into three main types i.e. fibrosis, bronchiectasis and pleural thickening. During the study period a total of 321 patients were included with a mean age of 44(SD±19) years. Only 17.13% (n=55) patients had normal chest x-rays at the end of treatment and 82.87% (n=266) patients had post-TB radiological sequelae with fibrosis being the most common followed by pleural thickening. The post TB radiological sequelae were high in patients who had diabetes mellitus (78.94%), AFB smear-positive (90.19%), AFB culture-positive (89.84%), Xpert MTB/Rif positive (88.40%) and with drug-resistant TB (100%). As a clinician, one should be aware of all the post TB sequelae so that early diagnosis and management can be facilitated.
Topics: Adult; Cross-Sectional Studies; Humans; Mycobacterium tuberculosis; Pakistan; Retrospective Studies; Sensitivity and Specificity; Sputum; Tuberculosis, Pleural; Tuberculosis, Pulmonary
PubMed: 34340298
DOI: 10.4081/monaldi.2021.1814 -
The Cochrane Database of Systematic... Mar 2017Corticosteroids used in addition to antituberculous therapy have been reported to benefit people with tuberculous pleurisy. However, research findings are inconsistent... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Corticosteroids used in addition to antituberculous therapy have been reported to benefit people with tuberculous pleurisy. However, research findings are inconsistent and raise doubt as to whether such treatment is worthwhile. There is also concern regarding the potential adverse effects of corticosteroids, especially in HIV-positive people.
OBJECTIVES
To evaluate the effects of adding corticosteroids to drug regimens for tuberculous pleural effusion.
SEARCH METHODS
In April 2016, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (the Cochrane Library), MEDLINE, Embase, LILACS, Current Controlled Trials, and the reference lists of articles identified by the literature search.
SELECTION CRITERIA
Randomized controlled trials (RCTs) and quasi-RCTs that compared any corticosteroid with no treatment, placebo, or other active treatment (both groups should have received the same antituberculous drug regimen) in people diagnosed with tuberculous pleurisy.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the search results, extracted data from the included trials, and assessed trial methodological quality using the Cochrane 'Risk of bias' tool. We analysed the data using risk ratios (RR) with 95% confidence intervals (CIs). We applied the fixed-effect model in the absence of statistically significant heterogeneity.
MAIN RESULTS
Six trials with 590 participants met the inclusion criteria, which were conducted in Asia (three trials), Africa (two trials), and Europe (one trial). Two trials were in HIV-negative people, one trial was in HIV-positive people, and three trials did not report HIV status.Corticosteroids may reduce the time to resolution of pleural effusion. Risk of residual pleural effusion on chest X-ray was reduced by 45% at eight weeks (RR 0.54, 95% CI 0.37 to 0.78; 237 participants, 2 trials, low certainty evidence), and 65% at 24 weeks (RR 0.35, 95% CI 0.18 to 0.66; 237 participants, 2 trials, low certainty evidence).Compared with control, corticosteroids may reduce the risk of having pleural changes (such as pleural thickening or pleural adhesions), on chest X-ray at the end of follow-up by almost one third (RR 0.72, 95% CI 0.57 to 0.92; 393 participants, 5 trials,low certainty evidence), which translates to an absolute risk reduction of 16%.One trial reported deaths in people that were HIV-positive, with no obvious difference between the groups; the trial authors' analysis suggests that the deaths observed in this trial were related to HIV disease rather than pleural TB (RR 0.91, 95% CI 0.64 to 1.31; 197 participants, 1 trial).We found limited data on long-term functional respiratory impairment on 187 people in two trials, which reported that average percentage predicted forced vital capacity was similar in the group receiving prednisolone and in the control group (very low certainty evidence).The risk of adverse events that led to discontinuation of the trial drug was higher in people with pleural TB receiving corticosteroids (RR 2.78, 95% CI 1.11 to 6.94; 587 participants, 6 trials, low certainty evidence). The trial in HIV-positive people reported on six different HIV-related infections, with no obvious differences. However, cases of Kaposi's sarcoma were only seen in the corticosteroid group (with 6/99 cases in the steroid group compared to 0/98 in the control group) (very low certainty evidence).
AUTHORS' CONCLUSIONS
Long-term respiratory function is potentially the most important outcome for assessing the effects of adjunctive treatments for people with pleural TB. However, the information on the impact of pleural TB on long-term respiratory function is unknown and could be eclipsed by other risk factors, such as concurrent pulmonary TB, smoking, and HIV. This probably needs to be quantified to help decide whether further trials of corticosteroids for pleural TB would be worthwhile.
Topics: Adrenal Cortex Hormones; Antitubercular Agents; HIV Seronegativity; HIV Seropositivity; Humans; Pleura; Randomized Controlled Trials as Topic; Tuberculosis, Pleural; Tuberculosis, Pulmonary
PubMed: 28290161
DOI: 10.1002/14651858.CD001876.pub3 -
The Korean Journal of Internal Medicine Jan 2022Pleural fluid adenosine deaminase (ADA) levels are useful in discriminating tuberculous pleural effusions (TPEs) from malignant pleural effusions (MPEs). However, some...
BACKGROUND/AIMS
Pleural fluid adenosine deaminase (ADA) levels are useful in discriminating tuberculous pleural effusions (TPEs) from malignant pleural effusions (MPEs). However, some patients with MPE exhibit high-ADA levels, which may mimic TPEs. There is limited data regarding the differential diagnosis between high-ADA MPE and high-ADA TPE. This study aimed to identify the predictors for distinguishing high-ADA MPEs from high-ADA TPEs.
METHODS
Patients with TPE and MPE with pleural fluid ADA levels ≥ 40 IU/L were included in this study. Clinical, laboratory, and radiological data were compared between the two groups. Independent predictors and their diagnostic performance for high-ADA MPEs were evaluated using multivariate logistic regression analysis and receiver operating characteristic curve.
RESULTS
A total of 200 patients (high-ADA MPE, n = 30, and high-ADA TPE, n = 170) were retrospectively included. In the multivariate analysis, pleural fluid ADA, pleural fluid carcinoembryonic antigen (CEA), and pleural nodularity were independent discriminators between high-ADA MPE and high-ADA TPE groups. Using pleural ADA level of 40 to 56 IU/L (3 points), pleural CEA level ≥ 6 ng/mL (6 points), and presence of pleural nodularity (3 points) for predicting high-ADA MPEs, a sum score ≥ 6 points yielded a sensitivity of 90%, specificity of 96%, positive predictive value of 82%, negative predictive value of 98%, and area under the receiver operating characteristic curve of 0.965.
CONCLUSION
A scoring system using three parameters may be helpful in guiding the differential diagnosis between high-ADA MPEs and high-ADA TPEs.
Topics: Adenosine Deaminase; Carcinoembryonic Antigen; Diagnosis, Differential; Humans; Pleural Effusion; Pleural Effusion, Malignant; Retrospective Studies; Sensitivity and Specificity; Tuberculosis; Tuberculosis, Pleural
PubMed: 33045810
DOI: 10.3904/kjim.2020.246 -
Jornal Brasileiro de Pneumologia :... 2021Pleural tuberculosis (PlTB) diagnosis is a challenge due to its paucibacillary nature and to the need of invasive procedures. This study aimed to identify easily... (Observational Study)
Observational Study
OBJECTIVES
Pleural tuberculosis (PlTB) diagnosis is a challenge due to its paucibacillary nature and to the need of invasive procedures. This study aimed to identify easily available variables and build a predictive model for PlTB diagnosis which may allow earlier and affordable alternative strategy to be used in basic health care units.
METHODS
An observational cross-sectional study compared PlTB and non-TB patients followed at a tertiary Brazilian hospital between 2010 and 2018. Unconditional logistic regression analysis was performed and a Decision Tree Classifier (DTC) model was validated and applied in additional PlTB patients with empiric diagnosis. The accuracy (Acc), sensitivity (Se), specificity (Sp), positive and negative predictive values were calculated.
RESULTS
From 1,135 TB patients, 160 were considered for analysis (111 confirmed PlTB and 49 unconfirmed PlTB). Indeed, 58 non-TB patients were enrolled as controls. Hyporexia [adjusted odds ratio (aOR) 27.39 (95% CI 6.26 - 119.89)] and cellular/biochemical characteristics on pleural fluid (PF) (polimorphonuclear in two categories: 3-14% aOR 26.22, 95% CI 7.11 - 96.68 and < 3% aOR 28.67, 95% CI 5.51 - 149.25; and protein ≥ 5g/dL aOR 7.24, 95% CI 3.07 - 17.11) were associated with higher risk for TB. The DTC constructed using these variables showed Acc=87.6%, Se=89.2%, Sp=84.5% for PlTB diagnosis and was successfully applied in unconfirmed PlTB patients.
CONCLUSION
The DTC model showed an excellent performance for PlTB diagnosis and can be considered as an alternative diagnostic strategy by using clinical patterns in association with PF cellular/biochemical characteristics, which were affordable and easily performed in basic health care units.
Topics: Brazil; Cross-Sectional Studies; Humans; Pleural Effusion; Predictive Value of Tests; Sensitivity and Specificity; Tuberculosis, Pleural
PubMed: 34909921
DOI: 10.36416/1806-3756/e20210245 -
International Journal of Infectious... Jan 2019The confirmatory diagnosis of pleural tuberculosis (pTB) remains challenging. The aim of this study was to describe the clinical and epidemiological characteristics of... (Observational Study)
Observational Study
BACKGROUND
The confirmatory diagnosis of pleural tuberculosis (pTB) remains challenging. The aim of this study was to describe the clinical and epidemiological characteristics of pTB patients and assess the yield of different diagnostic procedures in a low burden country with a high rate of immigrant population.
METHODS
All adult patients with pTB between 2007 and 2014 were studied retrospectively.
RESULTS
One hundred and three out of 843 patients with tuberculosis had pTB. Fifty-three (54.1%) were male, and the median age was 45years (range 18-87years). Fifty-two (50.49%) patients were immigrants. A confirmed diagnosis was reached in 16 patients (15.5%) by microbiological studies of pleural effusion. Lung involvement was demonstrated by sputum smear microscopy in 13/49 (26.5%), sputum GeneXpert MTB/RIF test in 13/20 (65%), and sputum culture in 16/37 (43.2%). High-resolution computed tomography (CT) showed lung involvement in 47.7% of the patients. The cure rate was 91.3% at the 1-year follow-up. Three patients died, all of them within the first month after diagnosis.
CONCLUSIONS
The detection of lung involvement increased by two-fold when lung CT was used; this correlated with the likelihood of finding a positive microbiological result on sputum sample testing. Pleural microbiological studies had a low diagnostic yield, and sputum could have a complementary role.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antitubercular Agents; Drug Resistance, Multiple, Bacterial; Emigrants and Immigrants; Female; Follow-Up Studies; Humans; Incidence; Isoniazid; Male; Middle Aged; Mycobacterium tuberculosis; Retrospective Studies; Sensitivity and Specificity; Spain; Sputum; Tuberculosis, Pleural; Young Adult
PubMed: 30449728
DOI: 10.1016/j.ijid.2018.10.005 -
Jornal Brasileiro de Pneumologia :... 2021To evaluate the accuracy of determining the adenosine deaminase (ADA) level, the 2'-deoxyadenosine/ADA ratio, and the LDH/ADA ratio in pleural fluid for the diagnosis of...
Performance of the quantification of adenosine deaminase and determination of the lactate dehydrogenase/adenosine deaminase ratio for the diagnosis of pleural tuberculosis in children and adolescents.
OBJECTIVE
To evaluate the accuracy of determining the adenosine deaminase (ADA) level, the 2'-deoxyadenosine/ADA ratio, and the LDH/ADA ratio in pleural fluid for the diagnosis of pleural tuberculosis (PT) in children and adolescents.
METHODS
This was a retrospective cross-sectional study conducted at a tertiary hospital in a high-tuberculosis-incidence area, between 2001 and 2018. All patients with ADA in pleural fluid and a confirmed diagnosis of PT (cPT) or parapneumonic effusion (PPE) were included.
RESULTS
The cPT and PPE groups comprised 25 and 68 individuals, respectively. At a cutoff of 40 U/L, ADA measurement showed the following: sensitivity, 88%; specificity, 31%; positive predictive value (PPV), 32%; negative predictive value (NPV), 88%; and overall accuracy, 46%. The best cutoffs were an ADA level of 125 U/L, a 2'-deoxyadenosine/ADA ratio of 0.5, and an LDH/ADA ratio of 8.3, with AUC of 0.67, 0.75, and 0.82, respectively. The sensitivity, specificity, PPV, NPV, and overall accuracy of the 125 U/L ADA cutoff were 84%, 65%, 47%, 92%, and 70%, respectively, compared with 79%, 79%, 59%, 91%, and 79%, respectively, for the 8.3 LDH/ADA ratio cutoff. Changing the LDH/ADA ratio cutoff to 3.0 increased the specificity to 98%.
CONCLUSIONS
The ADA level and the 2'-deoxyadenosine/ADA ratio are not good biomarkers for the diagnosis of PT in pediatric patients. Determination of the LDH/ADA ratio provides the best overall accuracy for the diagnosis of PT in such patients.
Topics: Adenosine Deaminase; Adolescent; Child; Cross-Sectional Studies; Humans; L-Lactate Dehydrogenase; Pleural Effusion; Retrospective Studies; Sensitivity and Specificity; Tuberculosis, Pleural
PubMed: 34008761
DOI: 10.36416/1806-3756/e20200558 -
International Journal of Clinical... 2023Tuberculosis (TB), a multisystemic disease with protean presentation, remains a major global health problem. Although concurrent pulmonary tuberculosis (PTB) and... (Observational Study)
Observational Study
Epidemiology and Association Rules Analysis for Pulmonary Tuberculosis Cases with Extrapulmonary Tuberculosis from Age and Gender Perspective: A Large-Scale Retrospective Multicenter Observational Study in China.
BACKGROUND
Tuberculosis (TB), a multisystemic disease with protean presentation, remains a major global health problem. Although concurrent pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) cases are commonly observed clinically, knowledge regarding concurrent PTB-EPTB is limited. Here, a large-scale multicenter observational study conducted in China aimed to study the epidemiology of concurrent PTB-EPTB cases by diagnostically defining TB types and then implementing association rules analysis.
METHODS
The retrospective study was conducted at 21 hospitals in 15 provinces in China and included all inpatients with confirmed TB diagnoses admitted from Jan 2011 to Dec 2017. Association rules analysis was conducted for cases with concurrent PTB and various types of EPTB using the Apriori algorithm.
RESULTS
Evaluation of 438,979TB inpatients indicated PTB was the most commonly diagnosed (82.05%) followed by tuberculous pleurisy (23.62%). Concurrent PTB-EPTB was found in 129,422 cases (29.48%) of which tuberculous pleurisy was the most common concurrent EPTB type observed. The multivariable logistic regression models demonstrated that odds ratios of concurrent PTB-EPTB cases varied by gender and age group. For PTB cases with concurrent EPTB, the strongest association was found between PTB and concurrent bronchial tuberculosis (lift = 1.09). For EPTB cases with concurrent PTB, the strongest association was found between pharyngeal/laryngeal tuberculosis and concurrent PTB (lift = 1.11). Confidence and lift values of concurrent PTB-EPTB cases varied with gender and age.
CONCLUSIONS
Numerous concurrent PTB-EPTB case types were observed, with confidence and lift values varying with gender and age. Clinicians should screen for concurrent PTB-EPTB in order to improve treatment outcomes.
Topics: Humans; Tuberculosis, Extrapulmonary; Tuberculosis, Pleural; Retrospective Studies; Tuberculosis, Pulmonary; China
PubMed: 37609664
DOI: 10.1155/2023/5562495