José Manuel Valle

Value of adenosine deaminase in the diagnosis of tuberculous pleural effusions in young patients in a region of high prevalence of tuberculosis.

BACKGROUND--Pleural biopsy is usually considered important for the diagnosis of pleural effusions, especially for distinguishing between tuberculosis and neoplasia, even though tuberculous pleural fluid contains sensitive biochemical markers. In regions with a high prevalence of tuberculosis, and in patient groups with a low risk of other causes of pleurisy, the positive predictive value of these markers is increased. The criteria for performing a pleural biopsy under these circumstances have been investigated, using adenosine deaminase (ADA) as a pleural fluid marker for tuberculosis. METHODS--One hundred and twenty nine patients with a pleural effusion aged < or = 35 years (mean (SD) 25.2 (4.9) years) were studied. Seventy three were men. Eighty one effusions (62.8%) were tuberculous, 12 (9.3%) parapneumonic, and 10 (7.7%) neoplastic, five were caused by pulmonary thromboembolism, four by systemic lupus erythematosus, seven by empyema, three following surgery, one was the result of asbestosis, and one of nephrotic syndrome. In five cases no definitive diagnosis was reached. ADA levels were determined by the method of Galanti and Giusti. RESULTS--The diagnostic yield of procedures not involving biopsy was 94.5% (122/129). Pleural biopsy provided a diagnosis in a further two cases, but not in the remaining five. All tuberculous cases had pleural fluid levels of ADA of > 47 U/l (mean (SD) 111.1 (36.6) U/l). The only other cases in which ADA exceeded this level were six of the seven patients with empyema. Cytological examination of the pleural fluid diagnosed eight of the 10 neoplastic cases, compared with six diagnosed by pleural biopsy. CONCLUSIONS--In a region with a high prevalence of tuberculosis procedures not involving pleural biopsy have a very high diagnostic yield in patients with a pleural effusion aged < or = 35 years, making biopsy necessary only in cases in which pleural levels of ADA are below 47 U/l, pleural fluid cytology is negative and, in the absence of a positive basis for some other diagnosis, neoplasia is suspected.

Utility of tumour markers in the diagnosis of neoplastic pleural effusion

Approximately 20% of pleural effusions are caused by neoplastic processes. Although cytology is the most specific routine diagnostic procedure, its sensitivity of 50-60% is insufficient, and thus diagnosis is usually carried out by more invasive techniques such as pleural biopsy, thoracoscopy or thoracotomy. The object of this study is to evaluate the use of determining some tumour markers in pleural fluid obtained by thoracocentesis for diagnosis of neoplastic pleural effusion. Patients (271) with pleural effusions were classified in five groups: I: neoplasms n = 88; II: tuberculosis n = 63; III: parapneumonics n = 53; IV: miscellaneous exudates n = 39 and V: transudates n = 28. The tumour markers studied were: carcinoembryonic antigen (CEA), CA 125, squamous cell carcinoma antigen (SCC), and neuron specific enolase (NSE). The tumour makers had the following diagnostic efficiencies for neoplastic origin of the pleural effusion: CEA 76% (sensitivity 31%, specificity 93%); CA 125 66% (70% and 61%); SCC 65% (48% and 80%) and NSE 53% (30% and 89%). The diagnostic efficiencies for pulmonary neoplastic origins were 68% for NSE (sensitivity 83%, specificity 53%); 65% for SCC (54% and 75%); 63% for CEA (80% and 48%) and 61% for CA 125 (79% and 42%). We believe that the routine testing of tumour markers in pleural fluid obtained by thoracocentesis would greatly increase diagnostic effectiveness and could avoid the practice of more aggressive diagnostic techniques on the patient.

Diagnostic value of interleukin-12 p40 in tuberculous pleural effusions.

The diagnosis of tuberculous pleural effusion (TBPE) is frequently problematic. Several markers of TBPE in pleural fluid have been evaluated, with different results. Pleural effusions from 96 patients were classified on the basis of definitive diagnosis as tuberculous (n = 39), neoplastic (n = 42) or parapneumonic (n = 15). Adenosine deaminase (ADA), ADA isoform ADA-2, interferon (IFN)-γ, CD3+/DR+ T-lymphocytes and interleukin (IL)-12 p40 were determined in all 96 effusions. The efficiency of IL-12 p40 for diagnosis of TBPEs was evaluated, in comparison with those of the other parameters, by comparing the areas under their receiver operating characteristics. With the threshold value of 550 pg·mL−1, IL-12 p40 had a sensitivity of 92.3% (36 out of 39) and specificity of 70.2% (17 false positives). The misclassification rate of IL-12 p40 was significantly greater than those of ADA-2 and ADA. Among TBPEs, ADA correlated significantly with ADA-2, and IFN-γ with ADA and IL-12 p40. Although tuberculous pleural effusions show values of interleukin-12 p40 that are significantly higher than neoplastic and parapneumonic fluids, this parameter is less efficient than adenosine deaminase, adenosine deaminase isoform 2 and interferon-γ. Its routine determination is, accordingly, not justified.

Lymphocyte populations in tuberculous pleural effusions

Different systemic and local responses to mycobacterial antigens suggest an active compartmentalization of responsive lymphocytes to tubercular antigens. This fact, observed in pleuritic processes, raises doubts about the accuracy of information obtained in the study of cells taken solely from peripheral blood. For this reason we decided to study the concept of compartmentalization in 140 patients suffering from pleural effusions. Patients were classified into six groups according to the aetiology of the effusion: group I, tuberculous, n = 23; group II, paraneoplastic, n = 41; group III, metapneumonic empyematous, n = 5; group IV, transudate, n = 38; group V, miscellaneous exudate, n = 19; group VI, unknown aetiology, n = 14. In each group we studied the lymphocyte population by using flow cytometry with doubly fluorescent monoclonal antibodies: B [expressing human lymphocyte antigen (HLA)-DR on the surface], T (CD3 +), CD4 + and CD8 +, and the subpopulation of activated T lymphocytes (together expressing CD3 and HLA-DR on the surface) (CD3 + DR +). The study of these subpopulations in peripheral blood did not yield valuable results, but the CD3 + DR + population in pleural fluid demonstrated a diagnostic efficiency of 84% [positive predictive value (PPV) 51%, negative predictive value (NPV) 96%] at a cut-off value of 80.4 cells/mm3. The CD3 + DR + pleural fluid/peripheral blood ratio demonstrated an efficiency of 83% (PPV 50%, NPV 96%), and showed a statistically significant difference (P < 0·02) with regard to all the diagnostic groups, with the exception of the paraneoplastic effusions. The lymphocytic subpopulations study confirms the concept of compartmentalization in tuberculous pleuritis, as shown by the greater number of activated T lymphocytes present in pleural fluid in comparison with peripheral blood in tuberculous pleuritis, a 98% efficiency of adenosine deaminase (ADA) determination in pleural fluid versus a 50% value in peripheral blood, predominance of helper cells (CD4 +) in pleural fluid and suppressor cells (CD8 +) in peripheral blood, a greater CD4 + /CD8 + ratio in pleural fluid than in peripheral blood, and a significant correlation of ADA-CD3 + DR + in pleural fluid, which does not occur in peripheral blood.

Cholesterol in pleural exudates depends mainly on increased capillary permeability

Pleural fluid (PF) cholesterol is a useful parameter to differentiate between pleural transudates and exudates, although the pathophysiologic mechanisms for its increase in exudates are not fully understood. We aim to elucidate the cause of this increase by analyzing the levels of cholesterol-high-density lipoproteins (HDLs), low-density lipoproteins (LDLs), apolipoprotein A (ApoA), and apolipoprotein B (ApoB)-in PF and blood as well as the number of leucocytes and red cells in the PF. We studied 259 patients with pleural effusion (57 transudates and 202 exudates). The correlations of the pleural and serum (S) levels of these parameters were analyzed, with the pleural cholesterol fractions as the dependent variables and their levels in blood and the pleural/serum protein ratio (P/S prot ratio) as the independent variables. The pleural fluid cholesterol levels (PFCHOL) correlated with their blood levels and the capillary permeability (r=0.885). No significant differences were found between the percentage of LDL, with regard to total cholesterol in the serum [SCHOL], and the same percentage in the exudates, between the PF/S LDL ratio (0.46) and the PF/S CHOL ratio (0.48), or between the PF/S ApoB ratio and the PF/S LDL ratio. The percentage of PF cholesterol bound to HDL and LDL was significantly higher (91.9%) than in the blood (90%). No significant correlations were found between any of the lipids studied and the number of erythrocytes and leucocytes. In conclusion, the PFCHOL may be predicted from the SCHOL, and the capillary permeability may be reflected by the PF/S prot ratio.

La aspergilosis pulmonar invasiva en la enfermedad pulmonar obstructiva crónica

Invasive pulmonary aspergillosis (IPA) is a severe disease, specially among immunocompromised patients. Its frequency increases in other patients such as those with Chronic Obstructive Pulmonary Disease (COPD), mainly when steroids are prescribed. The most common form of presentation is a respiratory tract infection with poor response to antimicrobial treatment. The delay in its diagnosis is one of the main causes of its high lethality. Once suspected, respiratory secretion cultures, chest X ray examination and computed tomography should be obtained and galactomannan, a marker of hematogenous dissemination of the microorganism, should be determined. Although the repeated isolation of Aspergillus spp is suggestive of invasive disease, the definitive diagnosis requires cytopathological confirmation. Further studies should be performed in these patients, since the available information was obtained from the observations made in immunocompromised patients, and may not be applicable accurately to API among COPD patients.