Objective: To evaluate Brazilian studies by summarizing the accuracy of adenosine deaminase in the diagnosis of the pleural tuberculosis, with the objective of lending support to the movement to make the test part of the routine in the investigation of pleural effusions. Methods: A search for Brazilian studies related to the determination of adenosine deaminase levels in the pleural liquid was carried out. These studies were evaluated and included in this study. The data were analyzed using summary receiver operating characteristic (SROC) curves, which enabled the studies to be collected and evaluated regarding the accuracy of the diagnosis. As for the global values of sensitivity and specificity, the Bayes' theorem was applied to calculate the post-test probabilities in different prevalences of the disease. Results: Twenty-five studies dating from 1987 to 2005 and including enough information to be used in the meta-analysis were identified. After evaluation, nine studies were included, totaling 1674 patients. According to the SROC curve, a sensitivity of 91.8% (95% CI: 89.8‑93.6%) and a specificity of 88.4% (95% CI: 86.0-90.5%) were found, with an area of 0.969 below the curve. The overall odds ratio was 112.0 (95% CI: 51.6-243.2). Considering a prevalence of tuberculosis of 50% (considered neutral), the post-test probability was 88.7% for a positive test and 91.5% for a negative test. Conclusion: Despite the differences found among studies, it is possible to conclude that the determination of adenosine deaminase levels has high accuracy in the diagnosis of the pleural tuberculosis and should be used as a routine test in its investigation.

Keywords: Pleural effusion; Tuberculosis; Diagnosis; Adenosine deaminase; Meta-analysis.

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.

Keywords: Adenosine deaminase; Pleural effusion; Tuberculosis, pleural/diagnosis; Child; Adolescent.

Background: The diagnosis of pleural tuberculosis continues to be a challenge due to the low sensitivity of traditional diagnostic methods. Histopathological examination of pleural tissue is the most accurate method, with a sensitivity of up to 80%. Determination of adenosine deaminase levels is a recently introduced method, although its usefulness in the diagnosis of pleural tuberculosis in Brazil has yet to better elucidated. Objective: To verify the sensitivity and specificity of an experimental method of measuring adenosine deaminase activity in pleural fluid in a series of patients with pleural effusion patients evaluated between August 1998 and November 2002 in Rio de Janeiro (RJ). Results: Out of 137 cases, 111 pleural fluid samples were available. Of those, 83 were from pleural tuberculosis patients. Among the 67 pleural tuberculosis patients tested, 10 (14.9%) presented human immunodeficiency virus. The adenosine deaminase cutoff value of 35U/L was determined by a receiver operator characteristic curve. The sensitivity, specificity and likelihood ratios (positive and negative) were 92.8%, 93.3%, 25.8 and 13.9, respectively. Mean adenosine deaminase in the pleural tuberculosis group was 84.7 ± 43.1 U/L, versus 15.9 ± 11.1 U/L in the group with other diseases. There was no significant difference in adenosine deaminase activity between patients with and without human immunodeficiency virus co-infection. Conclusions: Adenosine deaminase measurement in pleural fluid is a sensitive and specific method for the diagnosis of pleural tuberculosis and its use can preclude the need for pleural biopsy in the initial workup of pleural effusion patients. An adenosine deaminase cutoff value of 35U/L is recommended.

Keywords: Pleural fluid. Adenosine deaminase. Diagnosis. Tuberculosis. HIV

Abstract Objective: The incidence of tuberculosis worldwide has emphasized the need for better assays designed to diagnose the disease, principally the extrapulmonary form. The objective of the present study was to validate the performance of an automated method for the determination of adenosine deaminase (ADA) activity in pleural fluid (PF) and cerebrospinal fluid (CSF), comparing it with a conventional method (the modified Giusti method). Methods: In total, 134 samples were selected from among those tested in our laboratory: 94 PF samples and 40 CSF samples. The ADA activity was determined using the two methods. Inter- and intra-assay precision was determined, linear regression analysis was performed, simple concordance tests were conducted, and the means of the differences were calculated. Results: The correlation coefficients for PF and CSF samples were, respectively, 0.96 and 0.95. Inter-assay precision was determined using 21 replicates at 3 different activity levels: low, medium and high. The percentage coefficient of variation (%CV) was, respectively, 5.9, 8.1 and 5.8 for PF samples, compared with 21.9, 18.6 and 13.8 for CSF samples. Intra-assay precision in %CV was 1.3 and 11.7, respectively, for PF and CSF samples. The concordance between the methods in PF and CRF samples was, respectively, 96.8% and 100%, considering the reference values for the diagnosis of TB to be 40 U/L (conventional) and 30 U/L (automated) in PF samples, versus 9 U/L (for both methods) in CSF samples. Conclusions: The results validate the use of the automated method of determining ADA activity in PF and CSF samples as an alternative to the conventional method.

Keywords: Adenosine deaminase; Tuberculosis/diagnosis; Pleural effusion; Cerebrospinal fluid.

Objective: To present epidemiological data on patients diagnosed with tuberculosis, as well as on associated factors, and to determine the efficacy of the National Tuberculosis Control Program in Bagé, Brazil. Methods: A retrospective study was carried out at the Pablo Barcellos Center, analyzing cases of tuberculosis reported from January 2001 to December 2004. Data were collected through the review of clinical charts and from the National Case Registry database. Results: During this period, of the 4468 sputum smear microscopies performed, 131 were positive, with higher prevalence among males aged 26 to 35 years old. Prevalence was lower among those aged 65 and above. Over 50% of the patients were Caucasian, had only 1 to 3 years of schooling and worked in low-income jobs (mean salary, 265 Brazilian reals/month). There was no significant difference between smokers and former smokers/nonsmokers, and only one of the 131 cases was HIV positive. Conclusion: The number of sputum smear microscopies performed in Bagé increased in the past four years. In 2003 and 2004, it exceeded the goal of the National Tuberculosis Control Program. However, the number of new cases decreased, demonstrating the efficacy of the active search for tuberculosis cases in the city.

Keywords: Tuberculosis; Epidemiology; Communicable disease control.

Background: In Brazil, tuberculosis is the major cause of pleural effusion. In more than 50% of cases, treatment has been initiated prior to confirmation of the diagnosis. Our objective was to identify factors that can contribute to the diagnosis. Method: We studied 215 consecutive patients with pleural effusion: 104 from tuberculosis (TB) and 111 from other causes (41 were from malignancies, 29 involved transudation, 28 were parapneumonic and 13 were from other etiologies). Clinical, radiological and laboratorial variables were evaluated for differences between the two groups, individually or in combination. Results: Male gender and PPD > 10 mm were significantly more frequent in the tuberculosis group. Radiological features were similar in both groups. Among the continuous variables, adenosine deaminase (ADA), percentile of cells, protein and age performed better as isolated diagnostic criteria. Between the group with tuberculosis and that with pleural effusion from other causes, no significant differences were found in Lactate dehydrogenase, total leukocytes or duration of disease. The correlation of ADA with any other welldeveloped continuous variable showed an LR+ > 10 and an LR- < 0.1, which effectively confirmed or ruled out a diagnosis of tuberculous pleural effusion. Conclusions: In patients with ADA levels > 39 at 95% sensitivity, the specificity can be improved to more than 90% if we consider non purulent effusion or effusion with a predominance of lymphocytes (> 50%).

Keywords: Tuberculosis, pleural/diagnosis. Adenosine deaminase/diagnosis use. Sensitivity and specificity.

Objective: To evaluate the quality of diagnosis and the epidemiological profile of patients with pleural tuberculosis in the state of Roraima, Brazil, in order to provide technical support for the development and implementation of public policies to combat the disease. Methods: This was a cross-sectional study designed to determine the prevalence of pleural forms of tuberculosis in Roraima between 2005 and 2013 and to evaluate the diagnostic criteria used, as well as their determinants. This study was based on secondary data from the Brazilian Case Registry Database, including all reported cases of pleural tuberculosis in the state during the study period. Diagnoses based on bacteriological or histopathological confirmation were defined as high-quality diagnoses. Results: Among the 1,395 cases of tuberculosis reported during the study period, 116 (8.3%) were cases of pleural tuberculosis, accounting for 38.9% of all cases of extrapulmonary tuberculosis in the sample. The incidence rate of pleural tuberculosis did not follow the downward trend observed for the pulmonary form of the disease during the same period. The prevalence of cases with a high-quality diagnosis was 28.5% (95% CI: 20.4-37.6%). In a univariate analysis, none of the demographic or clinical characteristics collected from the database were found to have a significant impact on the outcome (as explanatory variables). Conclusions: The quality of the diagnoses in our study sample was considered unsatisfactory. Limited access to specific diagnostic methods might have contributed to these results.

Keywords: Tuberculosis/diagnosis; Tuberculosis/epidemiology; Tuberculosis, pleural.

Objective: To evaluate the accuracy of bacteriological methods and of polymerase chain reaction (with primers specific for IS6110 of the Mycobacterium tuberculosis complex) in testing sputum samples from indigenous (Amerindian) and non-indigenous patients. Methods: A total of 214 sputum samples (154 from indigenous patients and 60 from non-indigenous patients) were analyzed in order to determine the accuracy of smear microscopy (direct and concentrated versions) for acid-fast bacilli, culture, and polymerase chain reaction. Results: Both microscopy methods presented low sensitivity in comparison with culture and polymerase chain reaction. Specificity ranged from 91% to 100%, the concentrated acid-fast smear technique being the least specific. Nontuberculous mycobacteria were isolated three times more frequently in samples from indigenous patients than in those from non-indigenous patients. False-positive and false-negative polymerase chain reaction results were more common in the indigenous population. Conclusion: Positivity and isolation of nontuberculous mycobacteria in the acid-fast smear in conjunction with polymerase chain reaction positivity raise the following hypotheses: nontuberculous mycobacteria species with DNA regions homologous to, or even still possessing, the M. tuberculosis IS6110 exist in the Amazon; colonization of the oropharynx or of a tuberculous lesion accelerates the growth of the nontuberculous mycobacteria present in the sputum samples, making it impossible to isolate M. tuberculosis; A history of tuberculosis results in positivity for M. tuberculosis DNA. The absence of bacteriological positivity in the presence of polymerase chain reaction positivity raises questions regarding the inherent technical characteristics of the bacteriological methods or regarding patient history of tuberculosis.

Keywords: Tuberculosis, pulmonary/diagnosis; Mycobacterium tuberculosis, Polymerase chain reaction/methods; Indians, south american

For diagnostic purposes of pleural tuberculosis, three pleural fragments are routinely obtained from a single site by needle biopsy. The objective of this study is to compare the diagnostic yield of the routine procedure with two different approaches: harvesting five fragments on a single site (A), and collection of fragments at an additional site (B); from the same cutaneous orifice, the needle was partially removed up to the subcutaneous tissue and redirected at a 45o angle. The authors performed a prospective study in 115 patients submitted to pleural biopsy. The first three pleural fragments were placed in a vial (VA1-3), the 5 subsequent fragments obtained at the same site were placed in a second vial (VA4-8), and the five fragments from the second site were placed in a third vial (VB1-5). Analysis of fragments from VA1-3 revealed granuloma in 72/92 tuberculosis cases (78.3%), whereas in fragments VA5-8 and VB1-5, granuloma was observed in 74/92 cases (80.5%). In 6/92 patients the diagnosis at VA1-3 was non-specific pleuritis, but granuloma was found in VA4-8, resulting in a diagnosis increment of 8.3% (adding six to the 72 patients). In 7/92 patients (7.6%) the histopathological examination at site A led to a non-specific result but granuloma was found at site B, leading to a diagnostic increment of 9.0% (7 to 78 patients). Histological concordance of two examinations by the same pathologist had a kappa index of 0.62 (0.54 to 0.7) whereas concordance between two different pathologists had a kappa index of 0.64 (0.56 to 0.72). The performance of multiple biopsies at two different sites at the pleural surface led to an additional diagnosis of 13 patients, i.e., an increase of 18% (13 to 72) relative to the routine procedure. Considering the low cost increase of obtaining the fragments, adoption of this method is recommended in routine pleural tuberculosis diagnosis.

Keywords: Tuberculosis, pleural tuberculosis, biopsy, diagnosis.

Objective: Previous studies have demonstrated that closed pleural biopsy (CPB) has a sensitivity of less than 60% for diagnosing malignancy. Therefore, controversy has recently emerged regarding the value of CPB as a diagnostic test. Our objective was to assess the accuracy of CPB in diagnosing malignancy in patients with pleural effusion. Methods: This was a prospective 8-year study of individuals who underwent CPB to establish the etiology of pleural effusion. Information on each patient was obtained from anatomopathological reports and medical records. When CPB findings showed malignancy or tuberculosis, the biopsy was considered diagnostic, and that was the definitive diagnosis. In cases in which biopsy histopathological findings were nonspecific, a definitive diagnosis was established on the basis of other diagnostic procedures, such as thoracoscopy, thoracotomy, fiberoptic bronchoscopy, biochemical and cellular measurements in pleural fluid, and/or microbiological tests. The accuracy of CPB was determined with 2 × 2 contingency tables. Results: A total of 1034 biopsies from patients with pleural effusion were studied. Of those, 171 (16.54%) were excluded from the accuracy analysis either because of inadequate samples or insufficient information. The results of the accuracy analysis were as follows: sensitivity, 77%; specificity, 98%; positive predictive value, 99%; negative predictive value, 66%; positive likelihood ratio, 38.5; negative likelihood ratio, 0.23; pre-test probability, 2.13; and post-test probability, 82. Conclusions: CPB is useful in clinical practice as a diagnostic test, because there is an important change from pre-test to post-test probability.

Keywords: Biopsy; Pleural effusion, malignant/diagnosis; Pleural effusion, malignant/epidemiology.

Objective: To evaluate the accuracy of determining specific IgA to HspX recombinant antigen in pleural fluid and serum samples for the diagnosis of pleural tuberculosis in patients with pleural effusion. Methods: This was a cross-sectional study. Serum and pleural fluid samples of patients with pleural effusion and suspected of having pleural tuberculosis were tested with indirect ELISA in order to determine the optical density of specific IgA to HspX. Results: We evaluated serum and pleural fluid samples from 132 patients: 97 diagnosed with pleural tuberculosis (study group) and 35 diagnosed with pleural effusion due to other causes (control group). The determination of IgA in pleural fluid satisfactorily discriminated between pleural tuberculosis patients and control patients. The sensitivity of the test in pleural fluid and in serum was 69% and 30%, respectively, whereas the specificity was 83% and 84%, respectively. Conclusions: Our data suggest that this test can be used in the diagnosis of pleural tuberculosis. Further studies, involving larger patient samples and different epidemiological scenarios, are warranted.

Keywords: Pleural effusion; Tuberculosis/diagnosis; Enzyme-linked immunosorbent assay.

Objective: To determine the levels of the tumor markers carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1) and carbohydrate antigen 15-3 (CA 15-3) in the blood and pleural fluid of patients with benign or malignant pleural effusion, evaluating the sensitivity of each marker in these fluids. Methods: We prospectively evaluated 85 patients with pleural effusion. The study of the pleural fluid observed the criteria established in the literature. Levels of the markers were determined using electrochemiluminescence. The sensitivity was determined on the condition that the specificity was ≥ 90%. Results: Of the 85 cases, 36 (42.4%) were malignant, 30 (35.3%) were benign, and the results were inconclusive in 19 (22.3%). In the malignant cases, the CEA and CYFRA21-1 levels were higher in the pleural fluid than in the blood, which was not observed for CA 15-3. In the benign cases, the CYFRA21-1 levels were higher in the pleural fluid than in the blood, whereas the opposite was found for CEA and CA 15-3. There were significant differences between malignant and benign cases for all markers, in pleural fluid and blood. In the pleural fluid, the sensitivity of CEA, CYFRA21-1 and CA 15-3 was 69.4, 69.4 and 66.7%, respectively, and the combined sensitivity was 80.6%. In the blood, the sensitivity was 57.1%, 71.4% and 48.6% for CEA, CYFRA21-1 and CA 15-3, respectively, and the combined sensitivity was 77%. Conclusion: The results suggest that these markers might be useful in the differentiation between malignant and benign pleural effusion.

Keywords: Biological tumor marker; Cyfra 21.1; CEA; CA 15.3; Pleural effusion.

In Brazil, research on pulmonology has become increasingly more visible in recent years. In addition to the Brazilian Journal of Pulmonology, other journals have contributed to that by publishing relevant articles in this area. The objective of this article was to briefly report the most relevant studies on pulmonology that were published in other important Brazilian journals between 2009 and 2010. Altogether, there were 56 articles related to the various subareas that compose the field of respiratory diseases.

Keywords: Pulmonary medicine; Research; Brazil.

Objective: To determine the efficacy of the scoring system, recommended by the Brazilian National Ministry of Health (NMH), for the diagnosis of pulmonary tuberculosis (TB) in children and adolescents, regardless of their HIV status. Methods: This was a cross-sectional analytical study carried out between January of 2002 and December of 2006, involving 239 individuals less than 15 years of age. The patients were divided into four groups: latent TB (LTB group; n = 81); no-TB (NTB group; n = 41); TB group (n = 104); and TB/HIV group (n = 13). We studied the clinical, radiological and laboratory findings according to the scoring system. Results: Reports of fever, cough, asthenia and weight loss for at least two weeks were significantly higher in the TB group (p < 0.0001). The proportion of cases with a history of any contact and household contact with a TB patient was, respectively, 95.0% and 86.1% in the TB group, versus 75.0% and 58.3% in the TB/HIV group. In the TB and TB/HIV groups, respectively, chest X-rays revealed parenchymal alterations in 75.0% and 53.9%, revealing combined parenchymal/lymph node alterations in 18.2% and 30.8%. There were no significant differences among the groups regarding the tuberculin skin test results. In the TB group, 16.3% of the patients were malnourished (p < 0.005 vs. the LTB group). The mean NMH system scores in the LTB, NTB, TB and TB/HIV groups were, respectively, 24.2, 18.5, 45.3 and 41.5. Conclusions: The NMH system scores were significantly higher in the TB and TB/HIV groups than in the other two groups. Therefore, this scoring system was valid for the diagnosis of pulmonary TB in this population, regardless of HIV status.

Keywords: Tuberculosis/diagnosis; HIV seropositivity; Diagnostic techniques and procedures.

Early, accurate diagnosis of tuberculosis is one of the major pillars of the control of the disease. The purpose of this consensus statement is to provide health professionals with the most current, useful evidence for the diagnosis of tuberculosis in Brazil. To that end, the Tuberculosis Committee of the Brazilian Thoracic Association brought together 14 members of the Association with recognized expertise in tuberculosis in Brazil to compose the statement. A nonsystematic review of the following topics was carried out: clinical diagnosis, bacteriological diagnosis, radiological diagnosis, histopathological diagnosis, diagnosis of tuberculosis in children, and diagnosis of latent tuberculosis infection.

Keywords: Tuberculosis/diagnosis; Mycobacterium tuberculosis; Tuberculosis, multidrug-resistant/diagnosis; Latent tuberculosis/diagnosis.

Objective: To analyze the epidemiological characteristics of and trends regarding the incidence of pleural TB. Methods: This was a retrospective descriptive study of TB cases reported between 1998 and 2005 and compiled from the Epidemiological Surveillance Tuberculosis System (Epi-TB database). Results: A total of 144,347 new cases of TB were reported during the period studied. Pulmonary TB was the predominant form (118,575 cases; 82.2%). Among the extrapulmonary forms (25,773 cases; 17.8%), pleural TB was the form most often reported (12,545 cases; 48.7%). For all forms, the incidence (per 100,000 population) decreased (from 49.7 in 1998 to 44.6 in 2005; R2 = 0.898; p < 0.001), whereas the incidence of pleural TB remained stable (4.1 in 1998 and 3.8 in 2005; R2 = 0.433; p = 0.076). The highest incidence of pleural TB was found among males (2:1) aged from 30 to 59 years. Of the 12,545 patients with pleural TB, 4,018 (32.0%) presented comorbidities: alcoholism (9.5%); HIV (8.0%); diabetes (3.3%); and mental illness (1.2%). The diagnosis was based on bacteriological (14.2%) and histological (30.2%) methods, as well as on unspecified methods (55.6%). Conclusions: Pleural TB was the predominant extrapulmonary form of TB in the state of São Paulo, with a stable incidence between 1998 and 2005, although there was a trend toward a decrease in the incidence of the pulmonary forms. The diagnosis of pleural TB was confirmed through histology and bacteriology in 44.4% of the cases.

Keywords: Pleural effusion; Tuberculosis, pleural; HIV.