Diagnostic value of adenosine deaminase in nontuberculous lymphocytic pleural effusions.

Adenosine deaminase (ADA) can aid in the diagnosis of tuberculous pleural effusions, but false-positive findings from lymphocytic effusions have been reported. The purpose of this study is to assess the ADA levels in nontuberculous lymphocytic pleural effusions (lymphocyte count > 50%) of different aetiologies. Altogether, 410 nontuberculous lymphocytic pleural fluid samples were consecutively selected. These included malignant effusions (n = 221), idiopathic effusions (n = 76), parapneumonic effusions (n = 35), postcoronary artery bypass graft surgery effusions (n = 6), miscellaneous exudative effusions (n = 21) and transudative effusions (n = 51). The ADA level reached the diagnostic cut-off for tuberculosis (40 U x L(-1)) in seven of the 410 cases (1.71%). The negative predictive value of ADA for the diagnosis of pleural tuberculosis was 99% (403 of 407 cases) in the group of lymphocytic pleural effusions. In five of these seven patients ADA1 and ADA2 were measured, and in all these cases (100%) ADA1/ADA(p) correctly classified these lymphocytic effusions as nontuberculous (ratio < 0.42). This prospective study provides additional evidence that adenosine deaminase levels in nontuberculous lymphocytic pleural effusions seldom exceed the cut-off set for tuberculous effusions. The pleural fluid adenosine deaminase levels were significantly higher in different types of exudative effusions than in transudates. An adenosine deaminase level < 40 IU x L(-1) virtually excluded a diagnosis of tuberculosis in lymphocytic pleural effusions. Adenosine deaminase1/adenosine deaminase(p) correctly classified all nontuberculous lymphocytic pleural effusions with high adenosine deaminase levels.     

Der tuberkulöse Pleuraerguss

Approximately one third of the world’s population is infected with Mycobacterium tuberculosis and among communicable diseases tuberculosis is the second leading cause of death. The most common type of tuberculosis is pulmonary tuberculosis. Among the extrapulmonary manifestations, tuberculous pleuritis ranks second only after lymphatic tuberculosis. Tuberculous pleuritis is most commonly a disease with acute onset which is self-limiting in the majority of cases. A large proportion of patients though develop some form of active tuberculosis after a latency period. Therefore the correct diagnosis and the initiation of treatment are of the utmost importance. The easiest way to establish the diagnosis of tuberculous pleuritis is to demonstrate an elevated ADA (adenosine deaminase) in a lymphocytic effusion. Should pleural fluid analysis be nondiagnostic, the diagnosis of tuberculous pleuritis can be established with percutaneous closed needle biopsy in over 80% of cases. All patients with an undiagnosed pleural effusion after closed needle biopsy require thoracoscopy with selected biopsies taken under direct vision. The diagnostic yield of thoracoscopy is close to 100% in tuberculous pleuritis.     

Evolution of semi-rigid thoracoscopy

Pleural effusions despite being so common, there is no much literature available regarding definite diagnosis for pleural effusions. Application of Light's criteria changed the approach to pleural effusion and till date remains a very useful step in the diagnosis of pleural effusions. Pleural fluid biochemistry and adenosine deaminase (ADA) enzyme levels play a significant role in the diagnosis of tubercular effusion. Studies have shown that levels of ADA are more often higher in tubercular effusion than in any other cause for it. But ADA levels can also be elevated in other types of parapneumonic effusions (PPEs), especially complicated PPEs. Hence it is difficult to distinguish a tubercular pleural effusion (TPE) from other PPEs based on pleural fluid ADA levels alone. LDH/ADA ratio as an indicator for ruling out tuberculosis was analyzed in few studies with high sensitivity and specificity. The pleural fluid cytology has a varying sensitivity, with a maximum of only 60% and it may increase with subsequent tapping. Closed pleural biopsy using a Cope or Abrams needle has a sensitivity up to 80% in cases of tuberculous effusion and 40%–73% in cases of Malignancies.Semi-rigid thoracoscopy not only allows for visualization of the pleura but also helps in procuring the biopsies under direct visualization from the abnormal looking areas. In cases of primary pleural malignancies like mesothelioma, pleurodesis can also be done in the same setting after taking the biopsy, hence reducing the number of procedures. Limitation of the semi-rigid thoracoscopy is smaller sample size and more superficial sampling of the pleura. Cryobiopsy and Electrocautery guided pleural biopsy using the IT knife are the modifications in the semi-rigid thoracoscopy to overcome the drawback of smaller sample size. While navigation band image guided pleuroscopy helps in better visualization of the vasculature of pleura during the biopsy.Management of pleural effusions has evolved over a period of time. Starting with a single criterion based on pleural fluid proteins to semi-rigid thoracoscopy. The inexhaustible research in this field suggests the desperate need for a gold standard procedure with cost effectiveness in the management of undiagnosed pleural effusions. Semi-rigid thoracoscopy has revolutionized the management of undiagnosed pleural effusions, but it has its own limitations. Various modifications have been proposed and tried to overcome the limitations to make it a cost-effective procedure.     

Tuberculous pleural effusions: advances and controversies

On a global scale, tuberculosis (TB) remains one of the most frequent causes of pleural effusions. Our understanding of the pathogenesis of the disease has evolved and what was once thought to be an effusion as a result of a pure delayed hypersensitivity reaction is now believed to be the consequence of direct infection of the pleural space with a cascade of events including an immunological response. Pulmonary involvement is more common than previously believed and induced sputum, which is grossly underutilised, can be diagnostic in approximately 50%. The gold standard for the diagnosis of tuberculous pleuritis remains the detection of Mycobacterium tuberculosis in pleural fluid, or pleural biopsy specimens, either by microscopy and/or culture, or the histological demonstration of caseating granulomas in the pleura along with acid fast bacilli (AFB). In high burden settings, however, the diagnosis is frequently inferred in patients who present with a lymphocytic predominant exudate and a high adenosine deaminase (ADA) level, which is a valuable adjunct in the diagnostic evaluation. ADA is generally readily accessible, and together with lymphocyte predominance justifies treatment initiation in patients with a high pre-test probability. Still, false-negative and false-positive results remain an issue. When adding closed pleural biopsy to ADA and lymphocyte count, diagnostic accuracy approaches that of thoracoscopy. The role of other biomarkers is less well described. Early pleural drainage may have a role in selected cases, but more research is required to validate its use and to define the subpopulation that may benefit from such interventions.     

Pleural Lavage: A Novel Diagnostic Approach For Diagnosing Exudative Pleural Effusion

Patients with pleural effusions frequently present a diagnostic and therapeutic challenge. The diagnosis is based on the interpretation of the results of thoracentesis or pleural biopsy. When a malignant tumor metastasizes to the pleura, tumor cells can be seeded over the mesothelial surface or in the subserous layer. In the former situation, tumor cells are abundant in pleural fluid, but in the latter, few malignant cells are exfoliated into the pleural cavity, and microscopic deposits may not be visualized at thoracoscopy. Pleural lavage cytologic study at the time of thoracoscopy has not been studied. The purpose of this study was to assess the value of thoracoscopic pleural lavage as an adjuvant in the diagnostic workup of patients with exudative pleural effusions. Fifty patients with exudative pleural effusions were investigated by pleural fluid cytologic findings, Abram's pleural biopsy, thoracoscopy, and pleural lavage cytologic findings. After aspiration of all pleural fluid, 300 mL saline was instilled into the pleural cavity and then recovered for cytologic analysis. The final diagnoses were 32 malignant (64%), 15 tuberculous (30%), and 3 idiopathic (6%) effusions. In the malignant group, thoracoscopic biopsy had the highest yield (94%) followed by lavage cytologic analysis (84%), fluid cytologic analysis (62%), and biopsy with Abram's needle (50%). The sensitivity of combined thoracoscopy and lavage cytologic analysis was 96%. In the patients with tuberculous pleuritis, the yield from the pathologic examination of the biopsy specimen was 93% with thoracoscopy and 60% with the Abrams needle. The diagnostic yield with cytologic analysis on pleural lavage fluid is significantly higher than that on pleural fluid. This is probably because the cells in the lavage fluid are fresher and better preserved than those in the regular pleural fluid, which may have undergone degenerative changes, yielding false-negative results. Pleural lavage cytologic analysis should be performed in patients with suspected malignant pleural effusion who are subjected to diagnostic thoracoscopy, because it may provide additional information to thoracoscopic biopsy. Accepted for publication: 21 November 2000     

腺苷脱氨酶诊断结核性胸膜炎价值的再评价

目的 探讨胸腔积液和血清中腺苷脱氨酶(ADA)对鉴别结核性胸膜炎及恶性胸腔积液的临床价值.方法 回顾性分析91例经内科胸腔镜胸膜活检病理确诊为结核性胸腔积液(结核组49例)和恶性胸腔积液(恶性组42例)患者的胸腔积液及血清中ADA活性,应用受试者工作曲线(ROC曲线)确定结核性胸膜炎患者胸腔积液ADA的最佳临界值.结果 结核组胸腔积液ADA活性和胸腔积液ADA与血清ADA比值分别为(46±26)U/L和4.1±4.0,明显高于恶性组的(16±8)U/L和1.7±1.2,差异均有统计学意义(t值分别为7.383和3.852,均P＜0.01),结核组和恶性组的血清ADA活性分别为(13±5)U/L和(12±6)U/L,差异无统计学意义(t=1.582,P＞0.05).应用ROC曲线确定胸腔积液ADA诊断结核性胸膜炎的最佳临界值为28.7 U/L,灵敏度为75.5%,特异度为95.2%.结论 胸腔积液ADA活性可以作为鉴别结核性和恶性胸腔积液的重要指标,对结核性胸膜炎有较高的临床诊断价值,而血清ADA活性对鉴别两者无临床意义.     

High adenosine deaminase activity in the pleural effusion of a patient with Legionnaires' disease

Abstract:   Although Legionnaires' disease (LD) is frequently accompanied by pleural effusion, the characteristics of pleural effusions in LD have not been well studied. Levels of adenosine deaminase (ADA) activity in pleural fluid >40 IU/L have a high sensitivity (81–100%) and specificity (83–100%) for tuberculosis. ADA activity in pleural effusions due to LD has not been previously reported. The case of a patient with LD complicated by a pleural effusion with high ADA activity is reported. In countries where the prevalence of tuberculosis is high and pleural fluid ADA activities are frequently measured, LD should be included in the differential diagnosis of an exudative pleural effusion with high ADA activity.     

Diagnostic significance of gamma-interferon in tuberculous pleurisy

We studied ADA and gamma interferon (gamma-IFN) levels in pleural fluid of 45 cases presenting with pleural effusion to the Ankara University School of Medicine Chest Diseases Hospital between September 2001 and September 2002. Fifteen patients had TB pleurisy, 20 patients had malignant pleurisy and 10 patients had transudative pleural effusion. The cut-off value for pleural fluid gamma-IFN levels were 12 pg/mL. According to this, all patients with transudative effusions, 19 of 10 patients with malignant effusions and 2 of 15 patients with tuberculous (TB) effusions had pleural fluid gamma-IFN levels under the cut-off value. In exudative effusions, sensitivity and specificity of gamma-IFN were 87% and 95% respectively. The sensitivity of pleural fluid ADA levels was 86% and specificity of pleural fluid ADA levels was 100%. Pleural fluid ADA levels in TB effusions were significantly higher than the non-TB effusions. Also there were no statistically significant differences between pleural fluid ADA and g-IFN levels according to sensitivity and specificity. As a result, we have shown that gamma-IFN is a valuable test in diagnosis of TB pleurisy. We think that when it is used routinely, it will be a good alternative to the conventional invasive diagnostic tests.     

Pleural controversy: Closed needle pleural biopsy or thoracoscopy—Which first?

The most efficient and cost-effective approach to the diagnosis of pleural exudates remains controversial. Important considerations include the respective diagnostic yields of thoracocentesis, closed pleural biopsy and thoracoscopy; the incremental gain in diagnostic yield when sequentially combining these investigations; and the role of various image modalities. The diagnostic yield of thoracocentesis is in the order of 60% for malignancy and >90% for tuberculosis. A second aspiration may increase the yield for malignancy, but a third is generally superfluous. Many authorities consider thoracoscopy the investigation of choice in exudative pleural effusions where a thoracocentesis was nondiagnostic and particularly when malignancy is suspected. It allows for the direct inspection of the pleura and for talc poudrage. Thoracoscopy has a diagnostic yield of 91-95% for malignant disease and as high as 100% for pleural tuberculosis. Access to thoracoscopy is, however, limited in many parts of the world, as significant resources and expertise are required. Blind closed pleural biopsy has a yield of 80% for tuberculosis and <60% for pleural malignancy. Recent studies suggest that CT and/or ultrasound guidance may improve the yield, particularly for malignancy, where it may be as high as 88% and 83%, respectively. A second thoracocentesis combined with an image-assisted pleural biopsy with either an Abrams needle or cutting needle, depending on the setting, may therefore be an acceptable alternative to thoracoscopy. With such an approach, thoracoscopy may potentially be reserved for cases not diagnosed by means of closed pleural biopsy.     

ADA1/ADAp ratio in pleural tuberculosis: an excellent diagnostic parameter in pleural fluid

We analysed the efficacy of pleural adenosine deaminase (ADAp) and the ADA1/ADAp ratio in the diagnosis of pleural tuberculosis in 103 pleural effusions, 27 of which were tuberculosis (TB) and 76 other diagnoses (non-TB). Smears, cultures and pleural biopsies were carried out in all cases, and were used for final diagnosis. The diagnostic yield of the parameters under study were as follows: smears/cultures of mycobacteria in fluid 11.1%/33.3%; biopsy 33.3%/51.8% and tuberculosis granulomas 85.1%. The levels of ADAp and ADA1/ADAp ratio in TB and non-TB groups showed very significant differences (P < 0.00001); in the TB group: ADAp 54.7 +/- 23.5 IU and ADA1/ADAp 0.27 +/- 0.08; in the non-TB group: ADAp 18.3 +/- 43.2 IU and ADA1/ADAp 0.64 +/- 0.14. The assay established ADA levels in pleural fluid > or = 40 IU and an ADA1/ADAp ratio < or = 0.42 as cut-off levels to identify individuals in the TB group, with a sensitivity of 88.8%/100%, a specificity of 92%/98.6%, a positive predictive value (PPV) of 80%/96.4%, a negative predictive value (NPV) of 95.8%/100% and an accuracy of 91.2%/99.02%. The ADAp levels in 27 patients with TB, showed close correlation with the number of monocyte macrophages (P = 0.001), but not with the number of lymphocytes (P = n.s.). The ADA1/ADAp ratio overcomes the limitations of ADAp (false positives and negatives), and is the most useful parameter for diagnosis on account of a high diagnostic yield, low cost and speed of the assay for identifying a pleural tuberculosis diagnosis, when compared with traditional methods.     

Pleural tuberculosis: A concise clinical review

Tuberculosis (TB) is the leading infectious cause of death worldwide, and the commonest cause of death in people living with HIV. Globally, pleural TB remains one of the most frequent causes of pleural exudates, particularly in TB‐endemic areas and in the HIV positive population. Most TB pleural effusions are exudates with high adenosine deaminase (ADA), lymphocyte‐rich, straw‐coloured and free flowing, with a low yield on mycobacterial culture. TB pleurisy can also present as loculated neutrophil‐predominant effusions which mimic parapneumonic effusions. Rarely, they can present as frank TB empyema, containing an abundance of mycobacteria. Up to 80% of patients have parenchymal involvement on chest imaging. The diagnosis is simple if M. tuberculosis is detected in sputum, pleural fluid or biopsy specimens, and the recent advent of liquid medium culture techniques has increased the microbiological yield dramatically. Where the prevalence of TB is high the presence of a lymphocyte‐predominant exudate with a high ADA has a positive predictive value of 98%. In low prevalence areas, the absence of an elevated ADA and lymphocyte predominance makes TB very unlikely, and pleural biopsy should be performed to confirm the diagnosis. Pleural biopsy for liquid culture and susceptibility testing must also be considered where the prevalence of drug resistant TB is high. Treatment regimens are identical to those administered for pulmonary TB. Initial pleural drainage may have a role in symptom relief and in hastening the resolution of the effusion. Surgical intervention may be required in loculated effusions and empyemas.     

Adenosine deaminase levels in nontuberculous lymphocytic pleural effusions

OBJECTIVES: Adenosine deaminase (ADA) can aid in the diagnosis of tuberculous pleural effusions, but false-positive findings from lymphocytic effusions have been reported. We studied the ADA levels in a variety of nontuberculous lymphocytic effusions and analyzed the relationships between ADA and conventional hematologic and biochemical parameters. METHODS: One hundred six lymphocytic pleural fluid samples (lymphocyte count > 50%) were analyzed. These included post-coronary artery bypass grafting (CABG) effusions (n = 45), malignant effusions (n = 27), miscellaneous exudative effusions (n = 10), and transudative effusions (n = 24). ADA levels were determined using the Giusti method. In 22 randomly selected cases, ADA was measured again on the same sample 6 weeks later. RESULTS: The ADA level reached the diagnostic cutoff for tuberculosis (40 U/L) in only three cases (2.8%): two lymphomas and one complicated parapneumonic effusion. There was no significant correlation between effusion ADA levels and the total leukocyte (r = 0.08), differential lymphocyte (r = 0.18) or monocyte (r = - 0.18) counts. ADA levels were significantly lower in the transudative effusions (7.2 +/- 3.5 U/L) than in post-CABG (16.6 +/- 7.2 U/L), malignant (15.3 +/- 11.2 U/L), and other exudative (15.4 +/- 13.1 U/L) effusions (p < 0.001). ADA measurements were consistent when assayed 6 weeks apart (r = 0.95; p < 0.00001; coefficient of variation, 14%). CONCLUSIONS: ADA levels in nontuberculous lymphocytic effusions seldom exceeded the diagnostic cutoff for TB. Effusion ADA levels cannot be predicted from total or differential leukocyte counts. Post-CABG pleural fluids had ADA levels similar to other nontuberculous lymphocytic effusions. ADA is stable in effusion fluids, and its measurement is reproducible.     

Investigation of pleural effusion: comparison between fibreoptic thoracoscopy, needle biopsy and cytology

Twenty-eight patients with exudative pleural effusion have been investigated by fibreoptic thoracoscopy, Abrams needle biopsy and pleural fluid cytology. Sixteen patients had previously had negative pleural biopsies and cytology. Twenty effusions were malignant (16 mesothelioma, four metastatic carcinoma), seven were due to nonspecific inflammation and in one case no abnormality was found. The diagnostic yield for all three techniques combined was 85%, for thoracoscopy alone 65%, Abrams biopsy 60% and cytology 45%. In 12 patients presenting without previous investigation all eight malignant effusions were correctly diagnosed by at least one of the techniques with individual sensitivities of 75% for thoracoscopy, 63% for Abrams and 38% for cytology. Of the 16 patients who had previously had negative investigations 12 had malignant effusions, nine (75%) of which were diagnosed by a combination of the techniques. In this group, the individual sensitivities were 58% for both thoracoscopy and Abrams and 50% for cytology. A correct diagnosis of malignancy was made by a combination of needle biopsy and cytology in 75% of patients with previous investigations and 88% of those without. Fibreoptic thoracoscopy added only two diagnoses of malignancy to those obtained by Abrams and cytology. The limitations of the technique render it unsuitable for routine investigation of pleural effusions.     

Diagnostic performance of adenosine deaminase activity in pleural fluid: A single-center experience with over 2100 consecutive patients

ObjectiveTo determine the diagnostic utility of adenosine deaminase (ADA) in a large series of pleural effusions of different etiologies.MethodsA retrospective study of 2104 consecutive patients presenting with pleural effusion was carried out at a Spanish university hospital. ADA levels in pleural fluid were determined using a non-Giusti automatic kinetic assay, and a receiver operating characteristics curve analysis was applied to estimate their discriminative properties.ResultsPleural tuberculosis (TB) accounted for 221 (10.5%) effusions. Pleural fluid ADA > 35 U/L yielded 93% sensitivity, 90% specificity, a positive likelihood ratio (LR) of 10.05 and a negative LR of 0.07 for the diagnosis of TB among lymphocytic exudates. The ADA activity was significantly higher in neutrophil- (111.6 U/L) than in lymphocyte-rich (62.4 U/L; p = 0.002) TB effusions. Overall, more than 40% of parapneumonics and half of lymphomatous effusions exceeded the cutoff set for TB. These were the only causes of ADA activity above 250 U/L. When the prevalence of TB as a cause of exudative effusions is low (e.g., 1%), the estimated positive predictive value of the ADA test may be as low as 7%, although the negative predictive value remains high (99.9%).ConclusionWhere available, pleural ADA should be routinely used to rule TB in or out in areas with moderate to high or low TB prevalence, respectively. A high ADA level is a characteristic not only of lymphocytic, but also of neutrophilic TB effusions. An extremely high ADA activity should raise suspicion of empyema or lymphoma.     

Predictive models for diagnosis of pleural effusions secondary to tuberculosis or cancer

Background and objective:   Tuberculosis (TB) and cancer are two of the main causes of pleural effusions which frequently share similar clinical features and pleural fluid profiles. This study aimed to identify diagnostic models based on clinical and laboratory variables to differentiate tuberculous from malignant pleural effusions.
Methods:   A retrospective study of 403 patients (200 with TB; 203 with cancer) was undertaken. Univariate analysis was used to select the clinical variables relevant to the models composition. Variables β coefficients were used to define a numerical score which presented a practical use. The performances of the most efficient models were tested in a sample of pleural exudates (64 new cases).
Results:   Two models are proposed for the diagnosis of effusions associated with each disease. For TB: (i) adenosine deaminase (ADA), globulins and the absence of malignant cells in the pleural fluid; and (ii) ADA, globulins and fluid appearance. For cancer: (i) patient age, fluid appearance, macrophage percentage and presence of atypical cells in the pleural fluid; and (ii) as for (i) excluding atypical cells. Application of the models to the 64 pleural effusions showed accuracy higher than 85% for all models.
Conclusions:   The proposed models were effective in suggesting pleural tuberculosis or cancer.     

内科胸腔镜检查对胸腔积液鉴别诊断的价值

目的探讨内科胸腔镜检查对胸膜积液病因诊断的重要价值,了解结核性与癌性胸腔积液的差异。方法回顾性分析经胸腔镜检查的231例胸腔积液患者的病因构成,重点比较结核性胸腔积液104例（结核组）和癌性胸腔积液114例（癌性组）患者临床资料与胸腔镜检查结果。结果①病因构成：231例胸腔积液患者中,结核性与癌性所占比例最大（45．02％,47．62％）;②临床资料：结核组患者年龄较癌性组年轻,病程较癌性组短（P〈0．001）,发热症状更多;结核组黄色胸水较多见（73．08％）,癌性组血性胸水较多见（76．36％）。两者胸腔积液量（超声测值）无显著性差异（P=0．351）。结核组腺苷脱氨酶（ADA）、乳酸脱氢酶（LDH）较癌性组高,癌胚抗原（CEA）较癌性组低（P〈0．001）;③内科胸腔镜下表现：结核组以胸膜粟粒结节、广泛粘连较多见;癌性组胸膜大小不等弥漫结节较多见。结论结核性及癌性胸水是胸腔积液的常见病因,内科胸腔镜检查联合临床症状及胸水生化检测,可大大提高胸腔积液病因的诊断率,其创伤小,安全性好,值得广泛推广。     

Evaluation of polymerase chain reaction, adenosine deaminase, and interferon-gamma in pleural fluid for the differential diagnosis of pleural tuberculosis

STUDY OBJECTIVES: Pleural tuberculosis (TB) is a diagnostic challenge because of its nonspecific clinical presentation and paucibacillary nature. The inefficiency of conventional laboratory methods and the reliance on pleural biopsy have motivated the evaluation of alternative diagnostic strategies. We have evaluated polymerase chain reaction (PCR) directed to the IS6110 sequence of Mycobacterium tuberculosis, the determination of adenosine deaminase (ADA) activity, and measurement of interferon (IFN)-gamma levels in pleural fluid in the diagnosis of pleural TB. PATIENTS: ADA activity, IFN-gamma levels, and PCR were evaluated in 140 cases of pleural effusion, 42 with confirmed pleural TB, 19 with probable pleural TB, 70 with a nontuberculous etiology, and 9 having an undetermined etiology. RESULTS: ADA activity, IFN-gamma levels, and PCR were 88%, 85.7%, and 73.8% sensitive, respectively, and 85.7%, 97.1%, and 90% specific, respectively, for pleural TB that had been confirmed by either culture or pleural biopsy specimens. The combination of PCR, IFN-gamma measurement, and ADA activity determination allowed the selective increase of sensitivity and specificity for probable and confirmed cases compared to individual methods. Positive and negative predictive values for these individual or combined methods were maintained over a wide range of prevalence of pleural TB in the patient population presenting with pleural effusions. Fever and younger age were associated with tuberculous pleural effusion (p < 0. 0001), while blood in sputum and older age were associated with malignant etiology (p < 0.008). CONCLUSIONS: These clinical variables together with the use of ADA activity determination, PCR, and measurement of IFN-gamma levels provide the basis for the rapid and efficient diagnosis of pleural TB in different clinical settings.     

Determination of adenosine deaminase activity and its isoenzymes for diagnosis of pleural effusions

OBJECTIVE: We aimed to investigate adenosine deaminase (ADA) activity and the activities of its ADA1 and ADA2 isoenzymes in pleural effusions and also sera with different aetiological origins. METHODOLOGY: The pleural effusions of 87 patients were examined. The patients were separated into four groups: transudates, parapneumonic, malignant, and tuberculous effusions. The cases were also designated as tuberculous or non-tuberculous group. Adenosine deaminase activity was determined by the colorimetric method described by Giusti and Galanti. RESULTS: The intermean differences were statistically significant for total ADA, ADA1 and ADA2, except for pleural fluid ADA1 in the malignant group when compared to the tuberculous effusion group. The intermean differences between the tuberculous and non-tuberculous group were statistically significant for all three parameters except for pleural fluid and serum ADA1 activity. The sensitivities of total ADA, ADA1 and ADA2 activities for tuberculosis were 91, 57 and 93%, respectively; their specificities 89, 88 and 92%, respectively; their positive predictive values 82, 70 and 86%; and their diagnostic accuracies 89, 76 and 92%, respectively, in pleural fluid. CONCLUSIONS: Determination of ADA and its isoenzymes can help to differentiate the causes of pleural effusion. Increased ADA2 activity is a striking marker of tuberculous effusions. In contrast, increased ADA1 activity was significantly elevated in parapneumonic effusions.     

Update on tuberculous pleural effusion

The possibility of tuberculous pleuritis should be considered in every patient with an undiagnosed pleural effusion, for if this diagnosis is not made the patient will recover only to have a high likelihood of subsequently developing pulmonary or extrapulmonary tuberculosis Between 3% and 25% of patients with tuberculosis will have tuberculous pleuritis. The incidence of pleural tuberculosis is higher in patients who are HIV positive. Tuberculous pleuritis usually presents as an acute illness with fever, cough and pleuritic chest pain. The pleural fluid is an exudate that usually has predominantly lymphocytes. Pleural fluid cultures are positive for Mycobacterium tuberculosis in less than 40% and smears are virtually always negative. The easiest way to establish the diagnosis of tuberculous pleuritis in a patient with a lymphocytic pleural effusion is to generally demonstrate a pleural fluid adenosine deaminase level above 40 U/L. Lymphocytic exudates not due to tuberculosis almost always have adenosine deaminase levels below 40 U/L. Elevated pleural fluid levels of γ‐interferon also are virtually diagnostic of tuberculous pleuritis in patients with lymphocytic exudates. In questionable cases the diagnosis can be established by demonstrating granulomas or organisms on tissue specimens obtained via needle biopsy of the pleura or thoracoscopy. The chemotherapy for tuberculous pleuritis is the same as that for pulmonary tuberculosis.     

Increased pleural fluid adenosine deaminase in brucellosis is difficult to differentiate from tuberculosis

Pleural involvement in brucellosis is very rare. Current knowledge on brucella pleuritis is limited to a few case studies, and pleural adenosine deaminase (ADA) in brucellosis has not been studied previously. We report the pleural fluid characteristics, including ADA, of two cases with brucella pleurisy. Analysis of the pleural fluids revealed exudative effusions with increased ADA level, decreased glucose concentration, and lymphocyte predominance. The similarity with tuberculous pleurisy was remarkable. We suggest that brucellosis should be considered in the differential diagnosis of tuberculosis, especially in regions endemic for both diseases.