Efeitos da idade e do sexo sobre os limites de decisão clínica de um método automatizado de adenosina desaminase em uma amostra da população brasileira com tuberculose pleural

Contém tabelas e ilustraçõesIntrodução: A adenosina desaminase (ADA) é um biomarcador diagnóstico para a tuberculose (TB) utilizando líquido pleural (ADA-P). Alguns estudos têm relatado que diferentes fatores podem afetar o valor de corte da ADA-P para o diagnóstico de derrame pleural por TB. Objetivo: Estabelecer o novo valor de referência de ADA-P para o diagnóstico da tuberculose pleural, cuja atividade foi medida utilizando um ensaio cinético automatizado. Outros objetivos foram avaliar a influência da idade e do sexo sobre o valor de corte de ADA-P para a tuberculose pleural em uma amostra da população brasileira. Desenho do estudo: Estudo observacional, descritico e analítico. Período de estudo: março de 2012 a janeiro de 2015. Métodos: Foram realizados exames clínicos: físicos, de imagem, laboratoriais e cirúrgicos para avaliação da síndrome de derrame pleural (SDP). Um ensaio automatizado de ADA foi realizado por um kit comercial onde a ADA catalisa irreversivelmente a conversão de adenosina em inosina com H2O2 produzido na reação enzimática final. Resultados: Um total de 121 pacientes. No grupo TB (n = 26), 11 pacientes eram do sexo masculino (42%) e 15 do sexo feminino (58%). As medianas das idades dos pacientes com TB, não-TB, derrames pleurais no geral foram 46,0 ± 18,98, 64,0 ± 17,88 anos e 62,0 ± 19,14, respectivamente (KW = 5,33, P = 0,0569). A correlação entre os valores dos níveis de adenosina desaminase entre os pacientes com TB pleural para ambos os sexos não foi significativa (U = 72,0, P = 0,89025), assim como não tuberculose e em geral. No entanto, quando os níveis de ADA foram dicotomizados pela idade mediana (62 anos), o valor de P foi significativo apenas no grupo geral (U = 1307,0, P = 0,0047). Para o diagnóstico de TB pleural, o melhor valor de corte estabelecido pelo nosso estudo na curva ROC para ADA-P foi ≥ 31,1 IU / L (AUC = 88,2, P = 0,0001), para ambos os sexos e independentemente da idade, por ensaio automático de adenosina desaminase. Conclusões: A ADA-P pode ser considerado útil como biomarcador adjuvante no manejo integrado da síndrome de derrame pleural. A idade e o sexo não foram significativos para influenciar o limite de decisão clínica para o diagnóstico. O valor de corte do ADA-P foi ≥ 31,1 UI/L entre a população brasileira para o derrame pleural por TB através do ensaio automatizado utilizadoBackground: The adenosine deaminase (ADA) is a diagnostic biomarker for tuberculosis (TB) using pleural fluid (P-ADA). A few studies have reported that different factors can affect a cut-off value of P-ADA for diagnosis of TB pleural effusion. Aim: To establish the new ADA-P reference value for the diagnosis of pleural tuberculosis, whose activity was measured using an automated kinetic assay. Other objectives were to evaluate the influence of age and sex on the cutoff value of ADA-P for pleural tuberculosis in a sample of the Brazilian population. Study design: Prospective study. Study period: March 2012 to January 2015. Methods: Clinical exams were performed: physical, image, laboratory, and surgical procedures were carry out for pleural effusion syndrome (PES) evaluations. An automated ADA assay was performed by a commercial kit where ADA irreversibly catalyzes the conversion of adenosine to inosine with H2O2 produced in the final enzymatic reaction. Results: A total of 121 patients. In TB group (n=26), 11 patients were male (42%) and 15 patients were female (58%). The median ages of the patients with TB, non-TB, overall pleural effusions were 46.0 ± 18.98, 64.0±17.88 years, and 62.0 ±19.14, respectively (KW=5.33, P=0.0569). Correlation between values of adenosine deaminase levels among the patients with pleural TB for both the sexes were not significant (U=72.0, P=0.89025), as well as non-TB and overall. However, when ADA levels was dichotomised by median age (62 years old) the p value was significant only in overall group (U=1307.0, P=0.0047). For pleural TB diagnosis, the best cut-off value established by our study on ROC curve for P-ADA was ≥31.1 IU/L (AUC=88.2, P=0.0001) for both sexes and independent of age by automated adenosine deaminase assay. Conclusions: The P-ADA may be helpful as an adjunctive biomarker in the integrated management of pleural effusion syndrome. The age and sex were not significant to influence on clinical decision limit for the diagnostic. The P-ADA cut-off value was ≥ 31.1 UI/L among Brazilian population for TB pleural effusion by automated assay.48 f

Diagnostic Accuracy with Total Adenosine Deaminase as a Biomarker for Discriminating Pleural Transudates and Exudates in a Population-Based Cohort Study

Background. An initial step in the evaluation of patients with pleural effusion syndrome (PES) is to determine whether the pleural fluid is a transudate or an exudate. Objectives. To investigate total adenosine deaminase (ADA) as a biomarker to classify pleural transudates and exudates. Methods. An assay of total ADA in pleural fluids (P-ADA) was observed using a commercial kit in a population-based cohort study. Results. 157 pleural fluid samples were collected from untreated individuals with PES due to several causes. The cause most prevalent in transudate samples (21%, n=33/157) was congestive heart failure (79%, 26/33) and that among exudate samples (71%, n=124/157) was tuberculosis (28.0%, 44/124). There was no significant difference in the proportion of either sex between the transudate and exudate groups. The median values of P-ADA were significantly different (P<0.0001) between both total exudates (18.4 U/L; IQR, 9.85-41.4) and exudates without pleural tuberculosis (11.0 U/L; IQR, 7.25-19.75) and transudates (6.85; IQR, 2.67-11.26). For exudates, the AUC was 0.820 (95% CI, 0.751-0.877; P<0.001), with excellent discrimination. The optimum cut-off point in the ROC curve was determined as the level that provided the maximum positive likelihood ratio (PLR; 14.64; 95% CI, 2.11-101.9) and was22.0 U/L. For transudates, the AUC was 0.8245 (95% CI, 0.7470-0.9020; P<0.0001). Internal validation of the AUC after 1000 resamples was evaluated with a tolerance minor than 2%. The clinical utility was equal to 92% (95% CI, 0.84 to 0.96, P<0.05).Conclusions. P-ADA is a useful biomarker for distinguishing pleural exudates from transudates

Increased Cytokeratin 19 Fragment Levels Are Positively Correlated with Adenosine Deaminase Activity in Malignant Pleural Effusions from Adenocarcinomas

Adenosine deaminase (ADA) and cytokeratin 19 (CK19) are known pleural biomarkers. Although ADA in humans functions mainly in the immune system, it also appears to be associated with the differentiation of epithelial cells. Keratin filaments are important structural stabilizers of epithelial cells and potent biomarkers in epithelial differentiation. This study aimed to investigate the simultaneous presence of the ADA enzyme and CK19 fragments to assess epithelial differentiation in malignant and benign pleural fluids. Diagnosis of the cause of pleural effusion syndrome was confirmed by means of standard examinations and appropriate surgical procedures. An ADA assay, in which ADA irreversibly catalyzes the conversion of adenosine into inosine, was performed using a commercial kit. The CK19 assay was performed using a CYFRA 21-1 kit, developed to detect quantitative soluble fragments of CK19 using an electrochemiluminescence immunoassay. One hundred nineteen pleural fluid samples were collected from untreated individuals with pleural effusion syndrome due to several causes. ADA levels only correlated with CK19 fragments in adenocarcinomas, with high significance and good correlation (rho = 0.5145, P=0.0036). However, further studies are required to understand this strong association on epithelial differentiation in metastatic pleural fluids from adenocarcinomas