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.     

Diagnostic tools in tuberculous pleurisy: a direct comparative study.

Thoracoscopy is the most accurate yet most expensive tool for establishing the diagnosis of tuberculous (TB) pleurisy. However, most high TB-incidence regions have limited financial resources, lack the infrastructure needed for routine thoracoscopy and require an alternative, cost-effective diagnostic approach for pleural effusions. Altogether, 51 patients with undiagnosed exudative pleural effusions were recruited for a prospective, direct comparison between bronchial wash, pleural fluid microbiology and biochemistry (adenosine deaminase (ADA) and cell count), closed needle biopsy, and medical thoracoscopy. The final diagnosis was TB in 42 patients (82%), malignancy in five (10%) and idiopathic in four patients (8%). Sensitivity of histology, culture and combined histology/culture was 66, 48 and 79%, respectively for closed needle biopsy and 100, 76 and 100%, respectively for thoracoscopy. Both were 100% specific. Pleural fluid ADA of > or = 50 U x L(-1) was 95% sensitive and 89% specific. Combined ADA, lymphocyte/neutrophil ratio > or = 0.75 plus closed needle biopsy reached 93% sensitivity and 100% specificity. A combination of pleural fluid adenosine deaminase, differential cell count and closed needle biopsy has a high diagnostic accuracy in undiagnosed exudative pleural effusions in areas with high incidences of tuberculosis and might substitute medical thoracoscopy at considerably lower expense in resource-poor countries.     

Carcinomatous and tuberculous pleural effusions. Comparison of tumor markers

As an aid in the differential diagnosis of exudative pleural effusions, tumor markers were investigated. We measured immunosuppressive acidic protein (IAP), carbohydrate antigen 19-9 (CA 19-9), tissue polypeptide antigen (TPA), carcinoembryonic antigen (CEA), adenosine deaminase (ADA), and alpha 1-acid glycoprotein (AGP) in the pleural fluid of 36 patients with carcinomatous pleural effusions and of 35 patients with tuberculous pleurisy because we have frequently found these diseases to be associated with exudative pleuritis. Tuberculous pleural effusions had significantly higher levels of IAP, ADA, and AGP than carcinomatous effusions (p less than 0.005). On the other hand, CEA, CA 19-9, and TPA were significantly higher in carcinomatous pleural fluids than in tuberculous fluids (p less than 0.05). There was a correlation between IAP and AGP levels, and their specificity was low. Therefore, combined assays of CEA, CA 19-9, and ADA may be useful in distinguishing pleural effusions due to malignancies from those of tuberculous origin.     

Pleural SC5b-9 in differential diagnosis of tuberculous, malignant, and other effusions.

A monoclonal antibody against soluble phase-terminal complement complex (SC5b-9) was used to try to differentiate pleural effusions of tuberculous vs malignant and other origin. Effusions of tuberculous origin showed a significantly higher SC5b-9 level than did plasma, suggesting activation of complement in the pleural space. All 26 patients with tuberculous effusions showed SC5b-9 levels in pleural fluid exceeding 2.0 mg/L, while 20 with malignant effusions had levels less than 2.0 mg/L. However, rheumatoid, some parapneumonic, and treated malignant effusions showed SC5b-9 levels above 2.0 mg/L. Considering a value exceeding 2.0 mg/L, the specificity and sensitivity of the SC5b-9 estimation in tuberculosis were 0.74 and 1.0, respectively. The mean values for C4d and Bb fragments of complement were significantly (p < 0.05) higher in the tuberculous than in the malignant effusions. However, the values for Bb in 16 (62 percent) of the 26 patients with tuberculous or malignant effusions were in the same range. The activity of adenosine deaminase (ADA) was higher in the tuberculous than in the malignant effusions. While 18 of 26 patients with tuberculous effusions showed an ADA value exceeding 50 mU/ml, the estimated cutoff point (sensitivity = 0.69), 35 of the 36 nontuberculous effusions showed a true negative value (specificity = 0.97). A correlation between ADA and SC5b-9 values was observed in pleural effusions. These observations suggest that the estimation of SC5b-9 in pleural fluid presents a new approach to differentiating tuberculous vs malignant effusions.     

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.     

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.     

The use of adenosine deaminase and interferon-gamma as diagnostic tools for tuberculous pericarditis

BACKGROUND: Traditional diagnostic tests for pericardial tuberculosis (TB) are insensitive and often require long culture periods, and this has led to more emphasis being placed on biochemical tests such as the pericardial adenosine deaminase (ADA) test. However, controversy exists as to its diagnostic utility. In addition, the use of interferon (IFN)-gamma, which is a reliable indicator of pleural and peritoneal TB, has not been explored in pericardial effusions. We investigated ADA and IFN-gamma levels in pericardial effusions of different etiologies. METHODS AND RESULTS: A prospective study was carried out from February 1995 to February 1998 at Tygerberg Hospital (South Africa), with pericardial taps being performed under echocardiographic guidance. During this period, 110 consecutive patients presenting with large pericardial effusions were included in the study. Diagnoses were made according to predetermined criteria, and they included TB (n = 64), malignancy (n = 12), nontuberculous infections (n = 5), other effusions (n = 19), and effusions of uncertain origin (n = 10). The median ADA level in the tuberculous group was 71.7 U/L (range, 10.3 to 303.6 U/L), which was significantly higher than that in any other group (p < 0.05). With a cutoff level for ADA activity of 30 U/L, sensitivity was 94%, specificity was 68%, and positive predictive value was 80%. IFN-gamma levels were determined in 30 subjects. The median IFN-gamma concentration in the tuberculous group was > 1,000 pg/L, which was significantly higher than in any other diagnostic group (p < 0.0005). A cutoff value of 200 pg/L for IFN-gamma resulted in a sensitivity and specificity of 100% for the diagnosis of pericardial TB. CONCLUSION: Pericardial fluid levels of ADA and IFN-gamma are useful in the diagnosis of tuberculous pericarditis.     

ADA检测在淋巴细胞性胸腔积液中的应用价值

目的 研究不同病因产生的淋巴细胞性胸腔积液腺苷脱氨酶(ADA)值的差异，及其与传统的血液生化学参数之间的相互关系。方法 分析l05例淋巴细胞性胸水中的ADA值，其中包括结核性50例、恶性肿瘤性40例、漏出性l5例。结果 以40U/L作为诊断结核的阳性分割值，其特异性为98．2％、敏感性为89．0％；ADA值与白细胞总数、淋巴细胞百分比、中性粒细胞百分比、LDH、蛋白的含量无关。恶性胸水的ADA值与漏出性胸水比较无差异。结论 ADA检测对结核性胸腔积液具有相当高的特异性(98．2％)，但敏感度较低为(89．0％)。血液生化学参数与ADA值的大小无明显相关性。     

Tumour necrosis factor-alpha in comparison to adenosine deaminase in tuberculous pleuritis

BACKGROUND: Adenosine deaminase (ADA) is already used for the differential diagnosis of tuberculosis pleurisy. Tumour necrosis factor-alpha (TNF) is another marker which has been investigated for this purpose. OBJECTIVE: We evaluated the diagnostic value of pleural fluid and serum TNF concentrations in tuberculous pleuritis and compared them to ADA. METHODS: Sixty-two patients (24 tuberculous pleuritis, 38 non-tuberculous pleuritis) with exudative pleurisy were included. Serum and pleural fluid TNF concentrations were determined in all patients and ADA activity in 54 patients. Pleural fluid TNF concentrations and pleural fluid/serum TNF were compared to pleural fluid ADA activity and pleural fluid/serum ADA. RESULTS: When the tuberculous and non-tuberculous groups were compared, pleural fluid TNF concentrations (65.4 +/- 136.9 pg/ml vs. 54.5 +/- 144.2 pg/ml, respectively; p < 0.001), pleural fluid ADA activity (74.2 +/- 33.3 U/l vs. 23 +/- 16.3 U/l; p < 0.0001), pleural fluid/serum TNF (2.55 +/- 5.23 vs. 0.26 +/- 0.2; p < 0.001) and pleural fluid/serum ADA (4.58 +/- 8.14 vs. 1.15 +/- 0.7; p < 0.0001) were significantly higher in the tuberculous group. When cut-off points were assessed, 8 pg/ml and 40 U/l were found for pleural fluid TNF concentrations and pleural fluid ADA activity, respectively. Sensitivity, specificity, area under the curve were 87.5%, 76.3%, 0.772 for pleural fluid TNF concentrations and 90.9%, 89.5%, 0.952 for pleural fluid ADA activity, respectively; the difference between these areas under the curves was significant (p < 0.05). CONCLUSIONS: Pleural fluid TNF levels and pleural fluid/serum TNF were higher in tuberculous effusions than in other exudates, but their diagnostic value appears to be poorer than that of ADA.     

腺苷脱氨酶与溶菌酶检测在诊断结核性胸腔积液中的价值

评价腺苷脱氨酶与溶菌酶检测时结核性胸腔积液的诊断价值。对108例诊断明确的胸腔积液患者进行胸水腺苷脱氨酶及胸水溶菌酶与血清溶菌酶之比值测定。结果结核性胸腔积液患者胸水中腺苷脱氨酶含量明显高于癌性胸腔积液组(P<0.05),胸水溶菌酶与血清溶菌酶之比明显高于癌性胸腔积液组(P<0.01)。     

ADA、CRP和CEA在胸腔积液诊断中的意义

目的探讨腺苷脱氨酶（ADA）、C反应蛋白（CRP）、癌胚抗原（CEA）在胸腔积液中鉴别诊断的意义。方法收集已确诊的胸腔积液标本76例（结核性胸腔积液29例、癌性胸腔积液38例和化脓性胸腔积液9例）,检测胸腔积液中ADA、CRP和CEA数值,并进行各组间统计学分析。结果ADA在结核性胸腔积液及化脓性胸腔积液明显升高,在癌性胸腔积液明显偏低（P〈0．01）。CRP在化脓性胸腔积液升高最明显,在结核性胸腔积液次之,在癌性胸腔积液中值最低,三者之间比较有显著差异（P〈0．01）。CEA在癌性胸腔积液中均值明显高于结核性胸腔积液和化脓性胸腔积液组（P〈0．01）。结论ADA、CRP和CEA联合监测对胸腔积液的鉴别诊断有较好的意义。     

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.     

结核性与癌性胸腔积液的实验室检测比较研究

目的比较研究实验室检测腺苷脱氨酶(ADA)、乳酸脱氢酶(LDH)、癌胚抗原(CEA)、蛋白(TP)、葡萄糖(GLU)等多项指标对结核性与癌性胸腔积液的鉴别诊断价值。方法对151例明确诊断为结核性或癌性胸腔积液分别测定胸水ADA、LDH、CEA、TP、GLU和血清TP,并进行统计分析。结果结核性胸腔积液中ADA、LDH、TP含量都明显高于癌性胸腔积液,其中胸水ADA以28U/L作为诊断结核性胸水的临界值则其敏感性和特异性均极高,结核性胸水中GLU含量则低于癌性胸水,癌性胸水CEA的阳性率高达76.0%,而结核性胸水CEA均阴性。结论联合检测胸水ADA、LDH、CEA、TP和GLU可以作为结核性与癌性胸腔积液的诊断和鉴别诊断依据,其中ADA28U/L可以考虑作为结核性胸腔积液的单独诊断依据。     

Comparison of six biological markers for the diagnosis of tuberculous pleuritis

STUDY OBJECTIVE: We sought a marker to differentiate tuberculous pleural effusions from nontuberculous pleural effusions, which otherwise can be difficult. PATIENTS: We studied 55 patients with pleural effusions, 20 (36%) with tuberculous pleuritis and 35 (64%) with a nontuberculous etiology. MEASUREMENTS AND RESULTS: Pleural fluid levels of adenosine deaminase, interferon (INF)-gamma, interleukin (IL)-12p40, IL-18, immunosuppressive acidic protein, and soluble IL-2 receptors were measured and were subjected to receiver operating characteristic analysis. INF-gamma had the greatest sensitivity and specificity for tuberculous pleuritis among the six biological markers studied. CONCLUSION: The determination of INF-gamma levels in pleural fluid is the most informative in the diagnosis of tuberculous effusion.     

白介素27和腺苷脱氢酶单独及联合检测对结核性胸膜炎诊断价值

目的 探讨白介素27((interleukin-27,IL-27)和腺苷脱氨酶(adenosine deaminase,ADA)单独检测及两者联合检测结果对结核性胸膜炎和恶性肿瘤所致胸腔积液的鉴别诊断价值。方法 选取2017年12月1日至2018年7月29日福建省福州肺科医院收治的胸腔积液患者101例,通过闭式胸膜活检、内科胸腔镜检查获得病理学证据或者痰/胸腔积液分枝杆菌培养阳性及菌种鉴定结果。根据诊断结果分为结核性胸膜炎患者61例(结核组);恶性肿瘤所致胸腔积液患者40例(恶性组),其中肺黏膜相关淋巴瘤1例,恶性胸膜间皮瘤1例,肺黏液表皮样癌1例,非霍奇金淋巴瘤1例,小细胞肺癌3例,肺腺癌33例。采用酶联免疫吸附法检测两组患者胸腔积液中的IL-27和ADA的含量并进行统计学分析。应用受试者工作曲线(ROC)确定IL-27和ADA检测结果对鉴别结核性胸膜炎与恶性肿瘤所致胸腔积液的最佳临界值,并进一步分析IL-27与ADA联合检测(串联试验、并联试验)对于诊断结核性胸膜炎的价值。结果 结核组患者胸腔积液中检测到的IL-27和ADA浓度分别为[409.48(229.04,954.97)]ng/L和(45.88±14.33)U/L,明显高于恶性组[分别为115.74(77.72,161.97)ng/L和10.50(7.00,15.00)U/L],差异均有统计学意义(Z=3.139,P<0.01;t=4.006,P<0.01)。绘制ROC曲线确定IL-27鉴别结核性胸腔积液与恶性胸腔积液诊断的最佳临界值为176.31ng/L,敏感度和特异度分别为85.25% (52/61)和82.50% (33/40);ADA鉴别结核性胸腔积液与恶性胸腔积液诊断的最佳临界值为28U/L,敏感度和特异度分别为93.44% (57/61)和87.50% (35/40)。串联试验方法联合检测,特异度(95.00%,38/40)较单独检测IL-27(82.50%,33/40)及单独检测ADA(87.50%,35/40)均明显升高,并有较好的敏感度(81.97%,50/61);并联试验方法联合检测,敏感度(96.72%,59/61)较单独检测IL-27(85.25%,52/61)及单独检测ADA(93.44%,57/61)均明显升高,但特异度较低(75.00%,30/40)。结论 胸腔积液中IL-27和ADA对结核性胸膜炎的诊断均有较高价值;IL-27和ADA串联试验有助于结核性和恶性肿瘤所致胸腔积液的鉴别诊断。     

Adenosine deaminase activity in tuberculous pleural effusions: a diagnostic test

The activity of adenosine deaminase (ADA) was investigated in pleural effusions from 10 patients with tuberculous pleurisy and 76 patients with pleural effusions of other aetiology. The ADA activity in the tuberculous patients was significantly higher than in the other groups, with the exception of those with empyema. Specificity (87%) and sensitivity (100%) of this test for tuberculosis is high when a reference limit of more than 53 U/l is taken.     

腺甘脱氨酶、肿瘤坏死因子α、白细胞介素对结核性与恶性胸水鉴别诊断的价值

目的探讨胸水中腺甘脱氨酶（ADA）、肿瘤坏死因子-α[（TNF—α）、白细胞介素-2（IL-2）和IL-6水平对结核性与恶性胸水鉴别诊断的价值。方法采用酶法和化学发光法对49例结核性胸水与43例恶性胸水患者ADA、IL-2、IL-6、TNF-α水平进行检测。结果结核性胸水组患者胸水中ADA、IL-5、TNF-α含量明显高于恶性胸水组（P〈0．01）,而胸水IL-2含量在两组患者间比较无统计学意义（P〉0．05）。结论检测胸水中ADA、IL-5、TNF-α的水平对鉴别结核性与恶性胸水有较高的临床价值。     

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.     

胸水和血清ADA、TB-Ab-IgG联合检测对结核性胸膜炎的诊断探讨

目的 探讨胸水/血清腺苷脱氨酶(ADA)、结核抗体(TB-Ab-IgG)联合检测对结核性胸膜炎的诊断价值.方法 采用斑点金免疫渗滤试验(DIGFA)和酶连续监测法对234例胸腔积液进行胸水/血清ADA和TB-Ab-IgG检测结果进行分析.结果 结核性胸膜炎患者174例其胸水、血清中TB-Ab-IgG的阳性率分别为62.0%和70.1%,特异性分别为93.1%(56/60)和86.6%(52/60).ADA活性在结核性和癌性胸腔积液中分别为(59.58±29.85)U/L和(15.31±7.36)U/L(P<0.01).以P-ADA>40 U/L做为诊断结核的临界值,其敏感性为79.3%,特异性为86.4%;以P-ADA/S-ADA>1为临界值,其敏感性为97.7%,特异性为95.5%.结论 胸水和血清ADA、TB-Ab-IgG联合检测在结核性胸膜炎与非结核性胸膜炎上具有诊断与鉴别诊断价值.     

Elevated levels of soluble interleukin-2 receptors in tuberculous pleural effusions

The levels of soluble IL-2R were measured in pleural fluid from patients with tuberculosis pleurisy. There were significantly elevated soluble IL-2R values in tuberculous pleural fluid as compared with pleural fluid of nontuberculous etiology including malignant, bacterial and transudative pleural effusions. In patients with tuberculous pleurisy, the level of soluble IL-2R in pleural fluid was markedly greater than that in serum. Furthermore, a significant positive correlation was observed between soluble IL-2R levels and adenosine deaminase levels in tuberculous pleural fluid. These findings suggest that elevated levels of pleural fluid soluble IL-2R in tuberculous pleurisy could reflect the local proliferation of activated T-cells and may be clinically useful in the diagnostic procedures for patients with pleural tuberculosis.