Letter to the Editor
Pleural adenosine deaminase in the diagnostic workup of tuberculous pleural effusion
Adenosina deaminase do liquido pleural na abordagem diagnóstica do derrame pleural tuberculoso
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Reis, A.S. Costa, B. Conde" "autores" => array:3 [ 0 => array:4 [ "nombre" => "R." "apellidos" => "Reis" "email" => array:1 [ 0 => "ricardomcreis@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "A.S." "apellidos" => "Costa" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "B." "apellidos" => "Conde" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Respiratory Department, Centro Hospitalar de Trás-os-Montes e Alto Douro, Vila Real, Portugal" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Respiratory Department, Centro Hospitalar do Alto Ave, Portugal" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Adenosina deaminase do liquido pleural na abordagem diagnóstica do derrame pleural tuberculoso" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Adenosine deaminase (ADA) has been promoted as a quick, efficient and cost-effective method in the diagnosis of tuberculous effusions.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> However, the predictive parameters of ADA, in the diagnostic workup of tuberculous effusions, depend on the prevalence of the disease in the population<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> and no such analysis has been published in Portugal, a country of intermediate tuberculosis (TB) incidence (25.9 per 100,000 in 2010).<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In response to this situation, we carried out a cross-sectional analysis over a 4-year period, beginning in January 2006, in which we evaluated pleural fluid results from all patients admitted to our department with a pleural effusion of unknown etiology. Only the results obtained from the first thoracocentesis were included and samples from empyema were excluded from our analysis. Pleural ADA was measured using Giusti's colorimetric method. Mann–Whitney test was performed to compare medians and a Receiver Operating Curve (ROC) was used to determine the predictive parameters of different cutoffs. Prism 6 from Graphpad Software was used for the statistical analysis.</p><p id="par0015" class="elsevierStylePara elsevierViewall">A total of 107 pleural samples were analyzed, including TB (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>20), malignant (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>54), parapneumonic (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>20) and idiopathic (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>13) effusions. Of the 107 patients, 57.9% were males, median age was 72.5 (interquartile range: 59.7; 80.2) and all the patients were of European ethnicity. TB pleural effusions were found to have the highest median ADA value (98.55<span class="elsevierStyleHsp" style=""></span>U/L), which were significantly higher than malignant effusions (17.99<span class="elsevierStyleHsp" style=""></span>U/L) (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.0001) – the group with second highest median ADA value. Using the ROC curve we found that an ADA cutoff of 40.5<span class="elsevierStyleHsp" style=""></span>U/L had the best performance in the diagnosis of pleural TB (see <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>), with a sensitivity of 95%, specificity of 91.55%, positive predictive value (PPV) of 73.08% and negative predictive value (NPV) of 98.77%. Seven nontuberculous exudates (8.0%) reached the diagnostic cutoff. Using a >50% lymphocyte count criteria in the diagnostic workup, only 4.5% nontuberculous exudates were misclassified – 2 malignant (plasmocytoma and lymphoma) and 2 parapneumonic. The association of these two criteria increased specificity (95.40%) and PPV (82.61%). Using an ADA cutoff level of 74.6<span class="elsevierStyleHsp" style=""></span>U/L and the >50% lymphocyte criteria further increased specificity (98.85%) and PPV (93.75%), and only one (1.1%) nontuberculous exudate was misclassified.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">The diagnosis of tuberculous pleural effusion is a common diagnostic challenge due to low mycobacterial detection rates and to the frequent need for invasive, sometimes technically difficult, operator dependent techniques like the pleural biopsy or thoracoscopy.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> In this context, a rational interpretation of pleural fluid characteristics, particularly ADA level and differential leukocyte count, is essential to the diagnostic workup. In our research, an ADA level<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>40<span class="elsevierStyleHsp" style=""></span>U/L can virtually exclude pleural TB with a NPV of 98.7%, while an ADA level<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>74.6<span class="elsevierStyleHsp" style=""></span>U/L with >50%lymphocyte has a very high PPV of 93.75 and can thus be used to safely confirm pleural TB with a very small error rate of 1.1%. The performance of the cutoff value of 40<span class="elsevierStyleHsp" style=""></span>U/L and the error rate of 4.5% (for ADA<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>40<span class="elsevierStyleHsp" style=""></span>U/L and >50% lymphocytes) and 1.1% (for ADA<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>74.6<span class="elsevierStyleHsp" style=""></span>U/L and >50% lymphocytes) is in line with other publications.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,5,6</span></a> In our analysis, one patient with pleural TB had an ADA level<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>40<span class="elsevierStyleHsp" style=""></span>U/L; however, in a sample collected just 3 days later, ADA level was now 90<span class="elsevierStyleHsp" style=""></span>U/L which reaffirms the diagnostic utility of ADA. Also, as we have shown, hematological malignancies are frequent causes of error, and they should be excluded by this analysis of the pleural lymphocyte populations.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,6</span></a> However, the usefulness of ADA in the diagnosis of tuberculous effusions depends on the prevalence of the disease in the population.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> If tuberculosis is highly prevalent, as in the African continent and Southeast Asia, then a high value of pleural ADA is more likely to be due to tuberculosis, thus increasing the PPV of pleural ADA in the diagnosis of pleural TB. If, however, the disease is less prevalent, the probability of a high ADA being due to other causes, such as cancer, increases, and PPV of pleural ADA is lower. This is most evident in countries with a low prevalence of tuberculosis and an aging population, as it is in old age that malignant effusions are more prevalent.</p><p id="par0025" class="elsevierStylePara elsevierViewall">In conclusion, pleural ADA is a valuable tool in the diagnostic workup of pleural TB in Portugal and should routinely be used in the exclusion or confirmation of TB in the differential diagnosis of patients with a pleural effusion of unknown cause. Furthermore, in order to make a correct interpretation of its values, we have highlighted: potential false-positives; the usefulness of different ADA cutoffs for the exclusion or confirmation of TB; and the impact of TB prevalence on the predictive parameters of this tool.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">PPV: positive predictive value; NPV: negative predictive value; lymph.: lymphocytes.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">40<span class="elsevierStyleHsp" style=""></span>U/L \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">40<span class="elsevierStyleHsp" style=""></span>U/L<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>>50%lymph. \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">74.6<span class="elsevierStyleHsp" style=""></span>U/L<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>>50%lymph. \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Sensitivity (%, 95%CI) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">95.24 (76.11–99.21) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">95.00 (75.05–99.17) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">75.00 (50.89–91.25) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Specificity (%, 95%CI) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">91.95 (84.12–96.69) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">95.40 (88.63–98.71) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">98.85 (93.74–99.81) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">PPV (%, 95% CI) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">74.07 (53.71–88.84) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">82.61 (61.20–94.94) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">93.75 (69.69–98.86) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">NPV (%, 95%CI) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">98.77 (93.29–99.79) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">98.81 (93.52–99.80) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">94.51 (87.63–98.17) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab888032.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Diagnostic parameters of different pleural fluid characteristics.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:6 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Novel tests for diagnosing tuberculous pleural effusion: what works and what does not?" 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Antunes" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:2 [ "fecha" => "2010" "editorial" => "Direcção Geral de Saúde, Ministério da Saúde" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnostic tools in tuberculous pleurisy: a direct comparative study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.H. Diacon" 1 => "B.W. Van de Wal" 2 => "C. Wyser" 3 => "J.P. Smedema" 4 => "J. Bezuidenhout" 5 => "C.T. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 8 | 8 | 16 |
| 2024 October | 62 | 31 | 93 |
| 2024 September | 75 | 41 | 116 |
| 2024 August | 70 | 49 | 119 |
| 2024 July | 75 | 42 | 117 |
| 2024 June | 51 | 23 | 74 |
| 2024 May | 51 | 32 | 83 |
| 2024 April | 62 | 25 | 87 |
| 2024 March | 59 | 25 | 84 |
| 2024 February | 52 | 23 | 75 |
| 2024 January | 44 | 41 | 85 |
| 2023 December | 37 | 19 | 56 |
| 2023 November | 41 | 38 | 79 |
| 2023 October | 49 | 49 | 98 |
| 2023 September | 41 | 28 | 69 |
| 2023 August | 53 | 15 | 68 |
| 2023 July | 53 | 30 | 83 |
| 2023 June | 41 | 10 | 51 |
| 2023 May | 48 | 28 | 76 |
| 2023 April | 74 | 21 | 95 |
| 2023 March | 56 | 26 | 82 |
| 2023 February | 36 | 20 | 56 |
| 2023 January | 27 | 17 | 44 |
| 2022 December | 24 | 19 | 43 |
| 2022 November | 59 | 42 | 101 |
| 2022 October | 57 | 27 | 84 |
| 2022 September | 23 | 65 | 88 |
| 2022 August | 42 | 44 | 86 |
| 2022 July | 40 | 37 | 77 |
| 2022 June | 40 | 34 | 74 |
| 2022 May | 50 | 40 | 90 |
| 2022 April | 55 | 26 | 81 |
| 2022 March | 69 | 38 | 107 |
| 2022 February | 55 | 37 | 92 |
| 2022 January | 31 | 27 | 58 |
| 2021 December | 23 | 37 | 60 |
| 2021 November | 34 | 41 | 75 |
| 2021 October | 40 | 45 | 85 |
| 2021 September | 29 | 36 | 65 |
| 2021 August | 39 | 22 | 61 |
| 2021 July | 41 | 16 | 57 |
| 2021 June | 45 | 32 | 77 |
| 2021 May | 60 | 27 | 87 |
| 2021 April | 152 | 67 | 219 |
| 2021 March | 166 | 24 | 190 |
| 2021 February | 140 | 21 | 161 |
| 2021 January | 99 | 35 | 134 |
| 2020 December | 89 | 14 | 103 |
| 2020 November | 83 | 26 | 109 |
| 2020 October | 69 | 13 | 82 |
| 2020 September | 69 | 21 | 90 |
| 2020 August | 76 | 29 | 105 |
| 2020 July | 103 | 23 | 126 |
| 2020 June | 77 | 22 | 99 |
| 2020 May | 94 | 20 | 114 |
| 2020 April | 69 | 19 | 88 |
| 2020 March | 74 | 19 | 93 |
| 2020 February | 67 | 16 | 83 |
| 2020 January | 75 | 14 | 89 |
| 2019 December | 56 | 20 | 76 |
| 2019 November | 74 | 18 | 92 |
| 2019 October | 85 | 15 | 100 |
| 2019 September | 70 | 17 | 87 |
| 2019 August | 92 | 22 | 114 |
| 2019 July | 136 | 18 | 154 |
| 2019 June | 114 | 16 | 130 |
| 2019 May | 110 | 38 | 148 |
| 2019 April | 103 | 37 | 140 |
| 2019 March | 176 | 19 | 195 |
| 2019 February | 140 | 15 | 155 |
| 2019 January | 161 | 28 | 189 |
| 2018 December | 95 | 6 | 101 |
| 2018 November | 33 | 1 | 34 |
| 2018 October | 60 | 14 | 74 |
| 2018 September | 26 | 6 | 32 |
| 2018 August | 85 | 8 | 93 |
| 2018 July | 48 | 13 | 61 |
| 2018 June | 55 | 22 | 77 |
| 2018 May | 66 | 11 | 77 |
| 2018 April | 60 | 22 | 82 |
| 2018 March | 74 | 27 | 101 |
| 2018 February | 24 | 8 | 32 |
| 2018 January | 46 | 16 | 62 |
| 2017 December | 57 | 13 | 70 |
| 2017 November | 30 | 16 | 46 |
| 2017 October | 20 | 12 | 32 |
| 2017 September | 18 | 23 | 41 |
| 2017 August | 32 | 16 | 48 |
| 2017 July | 28 | 14 | 42 |
| 2017 June | 34 | 20 | 54 |
| 2017 May | 41 | 16 | 57 |
| 2017 April | 13 | 1 | 14 |
| 2017 March | 17 | 3 | 20 |
| 2017 February | 11 | 3 | 14 |
| 2017 January | 10 | 8 | 18 |
| 2016 December | 20 | 11 | 31 |
| 2016 November | 13 | 5 | 18 |
| 2016 October | 15 | 8 | 23 |
| 2016 September | 9 | 2 | 11 |
| 2016 August | 12 | 4 | 16 |
| 2016 July | 5 | 5 | 10 |
| 2016 May | 1 | 0 | 1 |
| 2016 April | 21 | 2 | 23 |
| 2016 March | 43 | 20 | 63 |
| 2016 February | 29 | 24 | 53 |
| 2016 January | 31 | 14 | 45 |
| 2015 December | 30 | 21 | 51 |
| 2015 November | 24 | 16 | 40 |
| 2015 October | 23 | 15 | 38 |
| 2015 September | 23 | 15 | 38 |
| 2015 August | 23 | 12 | 35 |
| 2015 July | 33 | 9 | 42 |
| 2015 June | 14 | 7 | 21 |
| 2015 May | 23 | 5 | 28 |
| 2015 April | 30 | 20 | 50 |
| 2015 March | 28 | 8 | 36 |
| 2015 February | 22 | 19 | 41 |
| 2015 January | 31 | 21 | 52 |
| 2014 December | 37 | 10 | 47 |
| 2014 November | 25 | 17 | 42 |
| 2014 October | 43 | 25 | 68 |
| 2014 September | 40 | 23 | 63 |
| 2014 August | 75 | 41 | 116 |
| 2014 July | 80 | 53 | 133 |
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