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.     

Exudative effusions in congestive heart failure

OBJECTIVES: Pleural effusions due to congestive heart failure (CHF) typically are transudates, but an occasional patient with CHF is found to have an exudate in the absence of an apparent cause other than CHF. We sought to determine the incidence and clinical significance of such exudative effusions. DESIGN: Patients with CHF and effusions seen during the 7-year period from January 1994 through December 2000 were identified from their hospital discharge diagnoses and radiographs, while those who had undergone thoracentesis were identified from a review of the laboratory logs. The presenting symptoms and clinical course were determined from a review of the medical records. The effect of RBC contamination on pleural fluid lactate dehydrogenase (LDH) levels was determined by measuring the LDH activity of mock pleural fluid containing known amounts of RBC. RESULTS: Seven hundred seventy patients had CHF with an effusion, but only 175 patients underwent a thoracentesis. In this select group, 86 patients had transudates and 89 had exudates. A noncardiac cause for the exudate was readily identified in 59 patients by hospital discharge, and 7 more patients had an etiology found during follow-up. Eleven of the remaining 23 patients had undergone coronary artery bypass graft (CABG) surgery > or = 1 year prior to presentation, and 50% of the effusions in patients who had undergone CABG surgery were exudates. Thus, CHF-related exudates were identified in only 12 patients, and in 4 of these patients the exudates could be explained by RBC contamination of the pleural fluid. The clinical presentation of patients with CHF-associated exudates was similar to that of CHF patients with transudates. CONCLUSION: In most patients who have CHF and an exudative effusion, there is a noncardiac cause for the pleural effusion. The high frequency of exudates in patients with a history of CABG indicates a persistent impairment in lymphatic clearance from the pleural cavity. Exudative effusions due solely to CHF are rare.     

Eosinophilic pleural effusions

Eosinophilic pleural effusions, defined as a pleural effusion that contains at least 10% eosinophils, may be caused by almost every condition that can cause pleural disease. Eosinophilic pleural effusion occurs most commonly during conditions associated with the presence of blood or air in the pleural space, infections, and malignancy. Drug-induced pleural effusions, pleural effusions accompanying pulmonary embolism, and benign asbestos pleural effusions are also among the common causes of eosinophilic pleural effusion. No etiology is found in as many as one third of patients. Because studies evaluating different diagnostic approaches with eosinophilic pleural effusions are lacking, the authors suggest that certain noninvasive and invasive diagnostic tools must be used based on the patient's clinical characteristics.     

Malignant pleural effusions

Various diseases of the gastrointestinal tract at times are accompanied by an exudative pleural effusion. The exudative pleural effusions resulting from esophageal perforation, pancreatic disease, subphrenic abscess, intrahepatic abscess, splenic abscess, abdominal operations, and diaphragmatic hernia are discussed in this article.     

Tuberculous pleural effusions

While a number of recent reports have documented the changing clinical and radiographic spectrum of parenchymal tuberculosis, relatively little attention has been paid to changes in the patterns of pleural tuberculosis. We therefore reviewed the clinical, laboratory, and radiographic characteristics of 26 adult patients with tuberculous pleural effusions. We found that pleural tuberculosis has become a disease of older adults (median age, 56 years) and that 19 percent (5/26) of the cases were due to postprimary (reactivation) disease. This shift in age led to problems in diagnosis, since many of these older patients had underlying or coexisting disease that could have caused a pleural effusion. Both specimens of pleural fluid and pleural biopsy were useful in establishing the diagnosis. Examination of sputum was less helpful. All patients who were not anergic had positive cutaneous reactions to first-strength purified protein derivative of tuberculin. Lymphocytosis of the pleural fluid was not a uniform finding; only 62 percent of our patients had greater than 50 percent lymphocytes on their initial examinations of pleural fluid, and four patients had greater than 90 percent polymorphonuclear cells. All of the effusions were exudates, and four had glucose levels in the pleural fluid that were less than 30 mg/dl. Pleural tuberculosis is an important diagnostic consideration in adult or elderly patients with exudative pleural effusions.     

Transudative pleural effusions

A transudative pleural effusion develops when the systemic factors influencing the formation or absorption of the pleural fluid are altered. The pleural surfaces are not involved by the primary pathologic process. The diagnosis of transudative effusion is simple to establish by examining the characteristics of the pleural fluid. Transudates have all of the following three characteristics: The ratio of the pleural fluid to the serum protein is less than 0.5. The ratio of the pleural fluid to the serum LDH is less than 0.6. The pleural fluid LDH is less than two thirds the upper limit of normal for the serum LDH. Among the conditions that produce transudative pleural effusion, congestive heart failure is by far the most common. Pulmonary embolism, cirrhosis of the liver with ascites, and the nephrotic syndrome are the other common causes. Management of transudative pleural effusions involves managing the primary disease. Refractory, massive effusions can be controlled by tetracycline pleurodesis.     

Lipid pleural effusions

Traditionally, a lipid pleural effusion has been described as milky or turbid appearing. However, lipid effusions may have varied presentations making a diagnosis by appearance problematic. Distinguishing between a chylothorax and a cholesterol effusion, the 2 types of lipid effusions, is essential. A chylothorax develops after injury or obstruction of the thoracic duct, leading to a chyle leak into the pleural space that is characterized by an increased triglyceride concentration and the presence of chylomicrons. In contrast, a cholesterol effusion is a long-standing effusion associated with an elevated cholesterol concentration, usually greater than 250 mg/dL, a thick pleural rind, and represents a form of lung entrapment.     

Tuberculous pleural effusions

Tuberculosis is the most frequent cause of death due to infectious diseases. In Europe, it is one of the most frequent types of pleural effusions in young patients. Tuberculosis is caused by the rupture of a pulmonary subpleural caseous focus, which releases mycobacterium into the pleural cavity, thereby triggering an immune response involving mainly macrophages, CD4+ T lymphocytes, and the cytokines released by these cells (especially interleukin 1, interleukin 2, and ?-interferon). In recent years, classical microbiological and histological methods of diagnosis have been joined by biochemical analyses of pleural fluid, which are faster and can be more sensitive. In particular, tuberculous effusions have high adenosine deaminase (ADA) activity, apparently due to high levels of the ADA isoenzyme ADA2, which is only found in monocytes and macrophages (although certain data suggest the possible involvement of activated T cells, too). It has been recommended that treatment for tuberculosis be initiated if analysis of pleural fluid shows high ADA activity, a lymphocyte/neutrophil ratio greater than 0.75, and no malignant cells. Another highly efficient marker is ?-interferon, which is released by activated CD4+ T cells, but its high price is an obstacle to its routine determination in clinical practice. Identification of mycobacterial DNA by means of the polymerase chain reaction (PCR) is less efficient, apparently because its sensitivity depends heavily on mycobacterium concentration. No other biochemical parameters currently appear to be of marked relevance for the diagnosis of tuberculous pleural effusion (TPE). TPE responds well to the standard treatment for tuberculosis. However, 50% of TPE patients have a thickened pleura as a result of the accumulation of fluid, and in 16% the quantity of effusion increases during treatment, even if corticosteroids are administered. It therefore seems reasonable for treatment with antituberculous drugs to be preceded by therapeutic thoracocentesis to remove as much fluid as possible.     

Malignant pleural effusions

The estimated annual incidence of malignant pleural effusions in the United States is 150,000 cases. Patients most commonly present with dyspnea, initially on exertion and later at rest. Chemical pleurodesis is the most common modality of therapy for patients with recurrent, symptomatic, malignant pleural effusion. Talc is the most successful pleurodesis agent, and talc poudrage and slurry have equal efficacy. Although a number of cases of acute respiratory failure have been associated with talc pleurodesis, the incidence is < 1% and many of these episodes cannot be clearly attributed to talc alone. Although a low pleural fluid pH is associated with a decreased survival and less successful pleurodesis, pH should not be the sole criterion for recommending or withholding pleurodesis. Other factors that need to be considered before recommending pleurodesis include relief of dyspnea after therapeutic thoracentesis, general health of the patient, performance status, presence of trapped lung, and the primary malignancy. Pleuroperitoneal shunt or chronic indwelling catheter should be considered for patients who fail pleurodesis or who have a trapped lung.     

Hypothyroidism and pleural effusions

Serous effusions have been thought to be an unusual complication of hypothyroidism and most commonly have been associated with ascites, pericardial fluid and heart failure. Pleural fluid as an isolated finding in hypothyroidism is apparently rare and complete analysis of these hypothyroid-associated pleural effusions has not been described. To determine the frequency, chemical characteristics and clinical associations of hypothyroidism and pleural effusions, the medical records of 128 patients with hypothyroidism (defined by an increased serum TSH concentration) were reviewed. The majority of effusions in patients with hypothyroidism were due to other diseases. Effusions solely due to hypothyroidism appeared to be a real entity. These effusions were borderline between exudates and transudates and showed little evidence of inflammation.     

Atypical tuberculous pleural effusions

Typically, a tuberculous pleural effusion is submassive, unilateral, and has the appearance of a clear straw coloured fluid with a cellular content predominantly consisting of lymphocytes. Atypical characteristics of tuberculous pleural effusion do, however, need to be recognised to mitigate the risk of delayed diagnosis, the latter sometimes resulting in potentially avoidable deaths, and also to reduce the risk that untreated patients might transmit the disease.     

T-helper type 1/T-helper type 2 balance in malignant pleural effusions compared to tuberculous pleural effusions

STUDY OBJECTIVES: Malignant and tuberculous pleurisies are two major causes of lymphocyte-dominant pleurisy. Several studies have already reported that tuberculous pleurisy is a T-helper type 1(Th1)-dominant disease. In this study, we sought to examine the Th1/T-helper type 2 (Th2) balance, especially focusing on the polarizing status of T-cells to Th1/Th2 in malignant pleural effusions by measuring cytokines in pleural effusions and by evaluating the polarizing status of T-cells on the point of stimulation with interleukin (IL)-12 and/or IL-18. Furthermore, we evaluated inhibitors of interferon (IFN)-gamma production in effusions to rule out the possibility of direct inhibition of T-cell polarization. PATIENTS: Effusion samples were collected from 19 patients with malignant pleurisy caused by lung cancer and from 7 patients with tuberculous pleurisy. MEASUREMENTS: Concentrations of pleural fluid IFN-gamma, IL-12, and IL-4 were measured. IFN-gamma production of T-cells enriched from malignant pleural effusions in the presence of IL-12 and/or IL-18 was also examined. We further compared the inhibitory activity of malignant pleural effusions against IFN-gamma production and analyzed the expression of T-cell immunoglobulin mucin, mucin domain (Tim-3), a Th1-specific molecule in pleural fluid T-cells. RESULTS: Although malignant pleural effusions showed low levels of Th1 and Th2 cytokines and ratios of IFN-gamma and IL-12 to IL-4 were low, isolated T-cells produced a significant level of IFN-gamma in the presence of IL-12 and IL-18. Soluble factors were not found to inhibit IFN-gamma production in malignant pleural effusions. In tuberculous pleural effusion, ratios of IFN-gamma and IL-12 to IL-4 were significantly higher, and T-cells showed the expression of Tim-3 messenger RNA. CONCLUSIONS: We confirmed that T-cells in the malignant pleural effusions are mainly na?ve or not definitely polarized to Th1. Moreover, malignant tumor does not actively distort the cytokine condition through production of soluble inhibitors within effusions. The present study indicates that antitumor immunity may be enhanced by restored IFN-gamma activity through combination of IL-12 and IL-18, and that it will lead to new therapies for malignant effusion.     

胸膜活检对原因不明的渗出性胸腔积液的诊断价值

目的观察胸膜活检术在渗出性胸腔积液诊断中的价值。方法对146例渗出性胸腔积液患者行胸膜活检，同时取胸水及痰送检抗酸杆菌及癌细胞。结果146例胸膜活检第一次活检成功率71．9％，特异性病理诊断92例，病理诊断阳性率63％。恶性胸腔积液胸膜活检阳性率58％，胸水细胞学检查阳性率22％，痰找癌细胞阳性率16％。结核性胸腔积液胸膜活检阳性率66．6％，痰找抗酸杆菌阳性率5．2％。结论胸膜活检是一项安全、简单、有效的胸膜疾病的重要的内科确诊手段。