José M. Porcel

Tuberculous Pleural Effusion

Tuberculous pleural effusion is one of the most common forms of extrapulmonary tuberculosis (TB). The immediate cause of the effusion is a delayed hypersensitivity response to mycobacterial antigens in the pleural space. For this reason microbiological analyses are often negative and limited by the lengthy delay in obtaining results. In areas with high TB prevalence, pleural fluid adenosine deaminase (ADA) levels greater than 40 U/l argue strongly for TB; in contrast, low levels of pleural ADA have high negative predictive value in low-prevalence countries. The specificity of this enzyme increases if only lymphocytic exudates are considered. The shortcoming of the ADA test is its inability to provide culture and drug sensitivity information, which is paramount in countries with a high degree of resistance to anti-TB drugs. Sputum induction (in addition to pleural fluid) for acid-fast bacilli and culture is a recommended procedure in all patients with TB pleurisy. The microscopic-observation drug-susceptibility assay performed on pleural fluid or pleural tissue increases by two to three times the detection of TB over conventional cultures, and it allows for the identification of multidrug-resistant TB. A reasonable management strategy for pleural TB would be to initiate a four-drug regimen and perform a therapeutic thoracentesis in patients with large, symptomatic effusions.

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

OBJECTIVE To determine the diagnostic utility of adenosine deaminase (ADA) in a large series of pleural effusions of different etiologies. METHODS A 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. RESULTS Pleural tuberculosis (TB) accounted for 221 (10.5%) effusions. Pleural fluid ADA >35U/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- (111.6U/L) than in lymphocyte-rich (62.4U/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 250U/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%). CONCLUSION Where 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.

Biomarkers of infection for the differential diagnosis of pleural effusions

We aimed to investigate whether pleural fluid concentrations of biomarkers for bacterial infection, namely triggering receptor expressed on myeloid cells (sTREM-1), procalcitonin (PCT), lipopolysaccharide-binding protein (LBP) and C-reactive protein (CRP), might identify infectious effusions and discriminate between complicated (CPPEs) and uncomplicated parapneumonic effusions (UPPEs). Stored pleural fluid samples from 308 patients with different causes of pleural effusion were used to measure the four biomarkers. Receiver-operating characteristic analysis determined the accuracy of the new tests. Median pleural fluid levels of CRP, sTREM-1 and LBP were significantly higher in CPPE compared with those in other aetiologies. The area under the curve for distinguishing infectious (parapneumonics and tuberculosis) from noninfectious effusions was 0.87 for CRP, 0.86 for sTREM-1, 0.57 for PCT and 0.87 for LBP. Regarding the discrimination of nonpurulent CPPE versus UPPE, a multivariate analysis found that pleural fluid glucose ≤60 mg·dL−1, LBP ≥17 μg·mL−1 and CRP ≥80 mg·L−1 were the best parameters. Individually, none of the new biomarkers achieved better performance characteristics than pH, glucose or lactate dehydrogenase in labelling CPPE. In conclusion, elevated pleural fluid levels of CRP, sTREM and LBP identify patients with infectious effusions, particularly those with CPPE. PCT has no value for the differential diagnosis of pleural effusions.

Pearls and myths in pleural fluid analysis.

Virtually all patients with a newly discovered pleural effusion should undergo thoracentesis to aid in diagnosis and management. The routine pleural fluid (PF) evaluation usually includes the following: cell count and differential; tests for protein, LDH, glucose, adenosine deaminase, cytology and, if infection is a concern, pH and bacterial and mycobacterial cultures. Distinguishing transudates from exudates with Lights criteria is a pragmatic first step. If the effusion is an exudate, various PF tests have proven diagnostic utility: adenosine deaminase levels >35 IU/L usually indicate tuberculosis in lymphocyte‐predominant PF; pH < 7.2 or glucose less than 60 mg/dL allow the clinician to identify complicated parapneumonic effusions; and conventional cytology may reveal malignant cells in 60% of the patients with malignant effusions. A number of optional PF tests may complement the diagnostic approach to an undiagnosed pleural effusion. For example, natriuretic peptide assays significantly improve the accuracy of a diagnosis of cardiac pleural effusion, whereas PF mesothelin levels greater than 20 nmol/L are highly suggestive of mesothelioma.

Etiología del derrame pleural: análisis de más de 3.000 toracocentesis consecutivas

OBJECTIVE To investigate the etiology of pleural effusions (PE) in adults and the accuracy of pleural fluid (PF) cytology and cultures in malignant and infectious PE, respectively. PATIENTS AND METHODS Retrospective analysis of all consecutive patients with PE undergoing diagnostic thoracentesis during the last 19 years in a university hospital. RESULTS The leading causes of PE among the 3,077 patients were: cancer (27%), heart failure (21%), pneumonia (19%), tuberculosis (9%), abdominal surgery (4%), pericardial diseases (4%) and cirrhosis (3%). Tuberculosis was the most common etiology in patients <34 years of age (52%), whereas heart failure predominated in octogenarians (45%). The most common primary tumors in malignant PE were lung (37%) and breast (16%). The overall accuracy of PF cytology was 59%, although it was significantly lower in mesotheliomas (27%) and squamous cell lung cancer (25%). In infectious PE, only 30% of cultures yielded positive results, a percentage which increased two-fold (66%) in purulent fluids (empyemas). Viridans streptococci were the most commonly isolated pathogens (25.5%). The sensitivity of solid media cultures of PF for Mycobacterium tuberculosis was low (18.5%). CONCLUSIONS Three-quarters of patients with PE in whom a diagnostic thoracentesis was indicated had cancer, heart failure, pneumonia or tuberculosis. PF cytology and cultures give false negative results in a significant number of cases.

Prognostic significance of pleural fluid data in patients with malignant effusion.

BACKGROUND To determine the effects of the biochemical and cytological properties of the pleural fluid (PF) on the survival of patients with malignant pleural effusion (MPE). METHODS A retrospective study of 284 patients with MPE was performed, which measured overall survival, survival of patients with different types of primary tumors, and survival as a function of PF biochemical variables transformed into quartiles. RESULTS Median overall survival of MPE patients was 5.4 months following diagnosis. Survival varied significantly depending on the type of the primary tumor: 17.4 months for mesothelioma, 13.2 months for breast cancer, 7 months for lymphoma and 2.6 months for lung cancer. A multivariate analysis of PF biochemical parameters showed that survival was lower as the concentration of lactate dehydrogenase (LDH) increased (11.3 months if LDH was between 140 U/L and 358 U/L vs 2.8 months if LDH was between 1027 U/L and 10,110 U/L) or the concentration of pleural proteins decreased (9.4 months if proteins were between 4.92 g/dL and 7.94 g/dL vs 2.2 months if proteins were between 0.97 g/dL and 3.85 g/dL). We also found that when mesotheliomas were excluded from the analysis, survival was lower in patients with a PF pH lower than 7.3 (2.4 months vs 6.8 months, p=0.03). CONCLUSIONS Tumor type as well as some biochemical features of the pleural fluid, such as pH and concentrations of proteins and LDH, influence survival in patients with MPE.

Analysis of pleural effusions in acute pulmonary embolism: radiological and pleural fluid data from 230 patients.

Background and objective:  The aims of this study were to describe the frequency and radiographical characteristics of pleural effusions in a large population of patients with acute pulmonary embolism (PE) and characterize the pleural fluid biochemistry in those patients who underwent diagnostic thoracentesis.

Predictive factors, microbiology and outcome of patients with parapneumonic effusion

We aimed to determine the incidence, clinical consequences and microbiological findings related to the presence of pleural effusion in community-acquired pneumonia, and to identify predictive factors for empyema/complicated parapneumonic effusion. We analysed 4,715 consecutive patients with community-acquired pneumonia from two acute care hospitals. Patients were classified into three groups: no pleural effusion, uncomplicated parapneumonic effusion and empyema/complicated parapneumonic effusion. A total of 882 (19%) patients had radiological evidence of pleural fluid, of whom 261 (30%) met criteria for empyema/complicated parapneumonic effusion. The most important event related to the presence of uncomplicated parapneumonic effusion was a longer hospital stay. Relevant clinical and microbiological consequences were associated with empyema/complicated parapneumonic effusion. Five independent baseline characteristics could predict the development of empyema/complicated parapneumonic effusion: age <60 yrs (p=0.012), alcoholism (p=0.002), pleuritic pain (p=0.002), tachycardia >100 beats·min−1 (p=0.006) and leukocytosis >15,000 mm−3 (p<0.001). A higher incidence of anaerobes and Gram-positive cocci was found in this subgroup of patients. We conclude that only the development of empyema/complicated parapneumonic effusion carried relevant consequences; this condition should be suspected in the presence of some baseline characteristics and managed by using antimicrobials active against Gram-positive cocci and anaerobes.

Comparing serum and pleural fluid pro-brain natriuretic peptide (NT-proBNP) levels with pleural-to-serum albumin gradient for the identification of cardiac effusions misclassified by Light's criteria.

Background and objectives:  To assess the diagnostic performance of the amino‐terminal fragment of pro‐brain natriuretic peptide (NT‐proBNP) in pleural fluid and serum for the identification of pleural effusions owing to heart failure, and to determine if these measurements allow better categorization of cardiac effusions that have been misclassified by Lights criteria, than do serum‐pleural fluid albumin and protein gradients.

Comparative analysis of Light's criteria and other biochemical parameters for distinguishing transudates from exudates

OBJECTIVES To compare the accuracy of Lights criteria for categorizing a pleural effusion as an exudate with several alternative criteria. DESIGN Prospective evaluation of patients who underwent a diagnostic thoracocentesis. SETTING Community teaching hospital in Lleida, Spain. PATIENTS AND METHODS Medical records and pleural fluid characteristics of 241 consecutive patients with pleural effusion admitted over a 29-month period were reviewed. Forty eight of these patients were excluded for different reasons. Lights criteria and a different cutoff level for the pleural fluid cholesterol level were applied and their accuracies were calculated. RESULTS Of the 193 patients included, 38 (20%) had transudates and 155 (80%) exudates. The accuracy of Lights criteria for identifying exudates was 92% [confidence intervals (CI), 88-96%], with a sensitivity of 97% (CI, 94-100%) and specificity of 71% (CI, 57-85%). A cutoff level of 50 mg dl-1 was selected for pleural cholesterol, which yielded a sensitivity and specificity of 84% (CI, 79-90%), with an accuracy of 84% (CI, 72-96%). Overall, pleural cholesterol misclassified more exudates as transudates than Lights criteria (15 vs. 3.2%, P < 0.001). The combination of pleural cholesterol with lactate dehydroegnase (LDH) or pleural fluid/serum protein ratio revealed a comparable accuracy to that achieved with Lights criteria. CONCLUSIONS Lights criteria are just as useful as the association of pleural cholesterol and LDH to detect exudates. In the present study, no parameter, including pleural cholesterol, was superior to Lights criteria.