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In high-burden settings, the diagnosis of pleural tuberculosis (TB) is frequently inferred in patients who present with lymphocyte predominant exudative effusions and high adenosine deaminase (ADA) levels. Two recent small retrospective studies suggested that the lactate dehydrogenase (LDH)/ADA ratio is significantly lower in TB than in non-TB pleural effusions and that the LDH/ADA ratio may be useful in differentiating pleural TB from other pleural exudates. We compared the pleural LDH/ADA ratios, ADA levels, and lymphocyte predominance of a prospectively collected cohort of patients with proven pleural TB (n = 160) to those with a definitive alternative diagnosis (n = 68). The mean pleural fluid LDH/ADA ratio was lower in patients with pleural TB than alternative diagnoses (6.2 vs. 34.3, p < 0.001). The area under the receiver operating characteristic curve was 0.92 (p < 0.001) for LDH/ADA ratio and 0.88 (p < 0.001) for an ADA ≥40 U/L alone. A ratio of ≤12.5 had the best overall diagnostic efficiency, while a ratio of ≤10 had a specificity of 90% and a positive predictive value of 95%, with a sensitivity of 78%, making it a clinically useful “rule in” value for pleural TB in high incidence settings. When comparing the LDH/ADA ratio to an ADA level ≥40 U/L in the presence of a lymphocyte predominant effusion, the latter performed better. When lymphocyte values are unavailable, our data suggest that the LDH/ADA ratio is valuable in distinguishing TB effusions from other pleural exudates.

Chylothorax is characterized by the accumulation of chyle in the pleural space, of which the most common cause is trauma or neoplasm. Although chylothorax accounts for a small proportion of clinical pleural effusions, prompt recognition is needed to avoid malnutrition, immunodeficiency, and fibrothorax. We report 2 patients with superior vena cava obstruction caused by tunneled venous catheters resulting in chylothorax and demonstrate the potential safety of tunneled pleural catheters for prolonged chylothorax drainage in an outpatient setting with rigorous follow-up. Changes in pleural fluid chemistries of the effusions and the possible pathophysiology were assessed with a review of the literature on pleural fluid chemistries in superior vena cava obstruction.

Background: Pleural fluid pH measured by a blood gas analyzer is the only recommended method of pH measurement to guide management for patients with parapneumonic pleural effusions. Not all hospitals use blood gas analyzers for pleural fluid pH determination and it is unknown if physicians are aware of this problem. Objective: To determine if a discrepancy exists between the modality used for measuring pleural fluid pH and how physicians believe it is measured. Methods: We surveyed pulmonologists randomly across the USA by e-mail inquiring how they thought pleural fluid pH was measured at their laboratory. We then independently contacted the laboratory and asked how pleural fluid pH was actually measured. Results: Two hundred and sixty-seven pulmonologists completed the survey. Eighty-six percent of the pulmonologists use pleural fluid pH to manage complicated parapneumonic effusions. Forty-three percent did not recognize blood gas analyzer solely as the most accurate and validated method. Thirty-nine percent of the physicians who use pleural pH to manage effusions and believe that blood gas analyzers are the most accurate were wrong in their assumption that their laboratory was using this tool for pleural pH measurement. Conclusions: Whether it is due to inaccurate knowledge or a perception of how pleural fluid pH is tested, a significant number of pulmonologists, when treating complicated parapneumonic effusions, may be making management decisions based on erroneous information.

Background: Eosinophilic pleural effusion (EPE) is defined by an eosinophil count of ≧10% in the pleural fluid and often caused by air or blood in the pleural space. The diagnostic significance of EPEs is still a matter of debate. Objective: The objective of this study was to systematically review the medical literature to evaluate the diagnostic significance of EPEs. Methods: Electronic databases were searched from 1950 to April 2010 to perform a meta-analysis. Data were extracted using standardized forms, and pooled odds ratios with 95% confidence intervals were calculated. A logistic regression analysis was also performed to evaluate the association between the pleural eosinophil counts and the likelihood of underlying causes of EPEs. Results: We identified a total of 687 cases of EPE. The most common cause of EPEs was malignancy (26%) followed by idiopathic (25%) and parapneumonic (13%) effusions. The likelihood of malignancy or tuberculosis was somehow lower in EPEs than in non-EPEs, but the differences were not statistically significant. The prevalence of malignancy was significantly lower in the group of patients that required a pathologic confirmation (21 vs. 30%; p = 0.01). The likelihood of malignancy was inversely correlated with the pleural fluid eosinophil counts. The likelihood of idiopathic effusion was significantly higher in EPEs than in non-EPEs. Conclusions: Malignancy was the most common cause of EPEs. EPEs appeared to be a negative predictor of malignancy when a pleural fluid eosinophil count was extremely high. EPEs were more likely to be idiopathic as compared with non-EPEs.

Background: Pleural fluid (PF) pH measurement is important for establishing a diagnosis and for guiding clinical management. The current standard practice is to collect PF samples for pH measurement in heparinized syringes at room temperature and to instantaneously process these samples. Objective: The purpose of this study is to investigate the effect of collecting PF in heparinized versus non-heparinized syringes at room temperature on PF pH measurements when processed at various time intervals. Methods: From 50 consecutive thoracenteses, 1 ml of PF was collected anaerobically in each of six 3-ml syringes. Only three syringes were coated with heparin. The samples were processed for PF pH measurements at time 0 (T₀) and 1 h (T1) and 2 h (T2) after collection. All specimens were preserved at room temperature, until the measurements were carried out in duplicates by a calibrated blood gas analyzer. Results: PF pH values were significantly lower with heparinized versus non-heparinized syringes at all time intervals (T₀: pH heparinized = 7.378 ± 0.107 vs. pH non-heparinized = 7.390 ± 0.108; T1: pH heparinized = 7.378 ± 0.115 vs. pH non-heparinized = 7.389 ± 0.111; T2: pH heparinized = 7.367 ± 0.105 vs. pH non-heparinized = 7.389 ± 0.121). In the heparinized syringes, there was a significant decrease in PF pH values at T2 versus T₀ and T1. There were no significant changes in PF pH values over time in the non-heparinized syringes. Conclusions: For serial PF pH measurements, the same type of syringes (either heparinized or non-heparinized) should be consistently used. With heparinized syringes, processing of PF pH measurements should be performed within 1 h after collection.

Background: Although clinical practice guidelines endorse the use of pleural fluid pH to select patients with parapneumonic effusions for pleural drainage, no studies have reported likelihood ratios for pleural fluid pH. Objectives: We derived and tested the value of continuous likelihood ratios for selecting pneumonia patients for pleural drainage. Methods: Patient level pleural fluid pH results were obtained from a registry of primary studies that assessed the discriminative properties of pH. Multilevel likelihood ratios were calculated for four pH intervals. Continuous likelihood ratios were derived from logistic regression using discrete pH values. Binary, multilevel and continuous likelihood ratios were compared to evaluate the statistical (χ2) and clinical advantages of continuous likelihood ratios. Results: Hundred and ninety-seven pleural fluid pH results were retrieved from published reports and categorized into four pH ordinal intervals. Multilevel likelihood ratios ranged from a low of 0.13 (95% CI, 0.04–0.41) for pH values >7.40 to a high of 15.80 (95% CI, 7.04–35.45) for pH values ≤7.00. Logistic regression derived the following equation for continuous likelihood ratios: exp[–7.168(measured pH – 7.207)]. Continuous likelihood ratios offered more diagnostic information both statistically (p < 0.005) and clinically compared with binary and multilevel likelihood ratios. Conclusions: Analysis of a patient registry allows the derivation of an exponential equation that calculates continuous likelihood ratios for discrete pleural fluid pH values. Continuous likelihood ratios provide more clinically and statistically significant information compared with binary and multilevel likelihood ratios for calculating posttest probabilities of the need to drain parapneumonic effusions.

Background:C-reactive protein (CRP) pleural fluid levels have been found to be higher in tuberculosis and parapneumonic effusions than in other causes of pleural effusion. Objective:The aim of this study was to analyze whether CRP (a simple and inexpensive test) may be a diagnostic aid for tuberculosis in lymphocytic pleural effusions. Methods:One hundred and forty-four patients with a lymphocytic pleural effusion (more than 50% lymphocytes in the differential white blood cell count) were included. The patients were 93 men (65%) and 51 women (35%), aged 64 ± 18 years (mean ± SD). The diagnoses were as follows: tuberculosis, 20; pleural effusion associated with malignancy, 69; transudates, 38; other benign exudates, 17. Results: The CRP pleural fluid level was higher in tuberculous pleuritis (54 ± 24 mg/l) than in lymphocytic effusions of other origin (21 ± 16 mg/l; p < 0.001). High CRP levels (≧50 mg/l) have a high specificity for tuberculosis (95%), and low levels (Conclusions: CRP pleural fluid level determination is useful in the diagnostic workup of lymphocytic pleural effusions. High CRP levels are very suggestive of tuberculous pleuritis, and low CRP levels make this diagnosis unlikely.

Background: Controversy exists regarding the clinical utility of pleural fluid parameters as prognosticators of complicated parapneumonic effusions that require drainage. Objectives: The purpose of this prospective study is to further assess the utility of these parameters in the management of a larger series of parapneumonic effusions and to determine appropriate binary decision thresholds. Methods: We studied 238 consecutive patients with parapneumonic effusions who underwent diagnostic thoracentesis. Results: We found that pleural fluid pH had the highest diagnostic accuracy (area under the curve, AUC: 0.928; 95% confidence interval, CI: 0.894–0.963) compared with pleural fluid glucose (AUC: 0.835; 95% CI: 0.773–0.897), LDH (AUC: 0.824; 95% CI: 0.761–0.887) or pleural fluid volume (AUC: 0.706; 95% CI: 0.634–0.777). The optimal binary decision threshold for pleural fluid pH identifying complicated effusions requiring drainage was 7.15. Binary, multilevel and continuous likelihood ratios (LRs) for pH were calculated to estimate the likelihood of complication of the pleural effusion. Values for the LRs were compared for each of the three strategies, and relative clinical and statistical significances were assessed. Binary LRs provided significantly less information than continuous strategies. Conclusion: The pH has the highest diagnostic accuracy for identifying complicated parapneumonic pleural effusions. The binary decision threshold determining the need for chest drainage is 7.15 in our patient series. We recommend continuous LRs to estimate the post-test probability of the complication as they provide the most information compared with binary LRs. Our results do not support the use of pleural fluid LDH as independent predictor of complicated parapneumonic effusions.

The objective of this study was the prospective evaluation of the IgG antibody levels to mycobacterial antigen 60 (A60) in serum and pleural fluid and their role in the diagnosis of tuberculous pleuritis. The level of IgG was measured by Elisa in 30 patients with tuberculous pleuritis and 48 control subjects with pleural effusion (24 with carcinoma, 10 with transudative pleural effusion, 11 with empyema or parapneumonic effusion, 1 with pulmonary embolism and 2 due to systemic lupus erythematosus). The median titers of IgG against A60 of both serum and pleural fluid from tuberculous patients [445.6 +/- 133.56 and 263 +/- 72.58 Elisa units (EU) respectively] were significantly higher than those of corresponding median values (97.3 +/- 8.35 and 41.3 +/- 4.93 EU) of the control group (p0.01 and p0.01, respectively). Considering 240 units as cutoff point for a positive test in serum, the sensitivity was 53.3% and the specificity 100%. In the pleural fluid the cutoff point value was established at 150 units, with a sensitivity of 50% and specificity of 100%. We concluded that Elisa using A60 is a reliable and rapid test with an acceptable sensitivity and magnificent specificity.

Lymphocyte subpopulations analysis by an 11-monoclonal antibody (MoAb) panel was carried out in pleural fluid and in peripheral blood in 30 patients affected by newly diagnosed, untreated pleural effusion of different etiology determinated with bacteriological, cytological or histological criteria. Lymphocytes were the predominant cell type, in pleural fluid, in neoplastic pleural effusions as well as in congestive heart failure pleural effusions and, especially, in tuberculous pleural effusions. Lymphocyte analysis in pleural fluid and in peripheral blood suggests the involvement of different mechanisms for the lymphocyte accumulation in the pleural space according to different etiologies. Tuberculous pleural effusions showed an evident CD4+ and TEC T5.9+ lymphocyte accumulation from peripheral blood. In these patients, cutaneous skin test response to purified protein derivative was strongly related to this situation. In neoplastic pleural effusions there was a lower percentage of CD4+ lymphocytes, reflecting circulating lymphocyte pool; however, in neoplastic pleural effusions, various lymphocyte patterns may be sometimes observed depending on different histologies. Passive lymphocyte accumulation seems to be the most important mechanism in congestive-heart-failure pleural effusions.

Accessible online at: www.karger.com/journals/res Since 1972, Light’s criteria have been accepted as the most appropriate diagnostic approach to distinguishing between exudative and transudative pleural effusions. According to Light et al. [1], a pleural fluid is an exudate if it meets the following criteria: pleural protein divided by serum protein 10.5, pleural fluid LDH divided by serum LDH 10.6 and pleural fluid LDH 1200 IU/l (12/3 of normal serum limits). In the past a number of clinical studies critically reassessed the accuracy of Light’s criteria. However, almost all reported again on an excellent sensitivity for exudates, near to 100%, whereas a somewhat lower specificity of around 80% was noted [2–5]. In this issue of Respiration, Romero et al. once more revisit Light’s criteria by comparing and classifying several chemical tests from specimens of blood and pleural fluid in 243 patients with pleural effusions. None of the tests resulted in a higher accuracy than the combination of the classic Light criteria. Therefore the authors conclude that due to their consistency, Light’s criteria still remain the standard for distinguishing exudates from transudates. In addition, the authors established that a combination of pleural fluid LDH (1307 IU/l) with pleural cholesterol (160 mg/dl) nearly meets the sensitivity (96%) and specificity (87%) of Light’s criteria. They therefore suggest considering the use of pleural fluid analysis for LDH/cholesterol as an alternative method of distinguishing transudates from exudates. Using this approach, phlebotomy can be avoided and costs may possibly be lower. So far so good. However, as Bartter et al. [6] have recently stated, the time has come that we should accept the criteria of Light and stop focussing our efforts on the elusive goal of finding an even more perfect technique for separating effusions into exudates and transudates. In fact, it is well known that every chemical analysis, as well as all derived combinations, form only one part of the clinical assessment of pleural effusions, as is true for most of the laboratory tests in clinical medicine. Whatever we measure in pleural fluids, any attempt to obtain results with an accuracy of 100% can only be illusional. For pleural fluid tests in particular there will always remain a certain number of false interpretations due to the fact that in some patients a classic exudate can sometimes be a transudate, and less frequently also a classic transudate may derive from an exudative condition [7]. Working from chemical analysis only, one would probably perform a number of unnecessary and even harmful diagnostic procedures, as may occur, for instance, in patients with congestive heart failure during treatment with diuretics. On the other hand, in a patient with bronchial cancer complicated by an atelectasis, the presence of a transudate may result in diuretic treatment instead of a bronchoscopic exploration. Nevertheless I believe that future diagnostic attempts should focus on parameters for detecting specific etiologies of exudative effusions rather than improving Light’s criteria [6]. In the meantime it is strongly recommended to assess the patient’s entire condition, and not to rely on pleural fluid analysis exclusively.

36 cases of eosinophilic pleural effusion (EPE) are reviewed. The etiologies were: traumatic 25%, congestive heart failure (CHF) 14%, infectious 8.5%, idiopathic 8.5% and miscellaneous 11%. 33% (12 patients) had a tumoral etiology, yet in only 1 patient could all additional etiologies for EPE be ruled out. Hence, the conclusion is that EPE is rarely caused by a tumoral etiology, and that other etiologies should be considered. The comparison of pleural fluid and peripheral blood findings disclosed no significant difference among the various subgroups.

106 pleural effusions or pleural opacities suggesting fluid were evaluated in a prospective study by B-mode real-time sonography and radiography. 41 cases were first investigated by means of ultrasound, 65 by the conventional erect roentgenogram. The correct diagnosis of pleural fluid was made by ultrasound in 95.3% and by radiologic examination in 86.8% of the cases. Radiography failed to distinguish between pleural effusion and solid pleural thickening in 7.5%, sonography in 1.9% of the cases. In 8 patients with normal roentgenograms, small epidiaphragmal pleural effusions were detected by means of ultrasound. In diagnosis of pleural effusion, sonography was found to be superior to the conventional radiologic technique both in sensitivity and in diagnosing the consistency. The value of the ultrasonic method both in establishing the quality of intrathoracic masses adjacent to the pleura and in sonographically guided needle puncture is emphasized

The present study contains the review of 30 patients with malignant mesothelioma of the pleura, examined and treated at our institution. In an attempt to compare various methods of diagnosis in this entity, emphasis was laid on specific abilities and limitation of investigations such as pleural biopsy, pleural fluid cytology, diagnostic thoracoscopy and thoracotomy and radiological studies including computed tomography and magnetic resonance imaging. Clinical management problems encountered in this neoplasm are also discussed.

The separation of pleural effusions into exudates and transudates is based on the pleural fluid LDH and protein content compared to the simultaneous serum LDH and protein content. A patient in biventricular failure presented with a right pleural effusion that met the criteria of a transudate. After a traumatic thoracentesis the fluid met the criteria of an exudate.