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Low density lipoproteins and immunoglobulins in human pleural effusions.

Pleural effusions in patients with bacterial pleurisy contain low density lipoproteins (33 per cent of the blood serum LDL-concentration on average) but almost no very-low density lipoproteins (about 1 percent of the blood serum VLDL-concentration on average). Immunoglobulins are present in large amounts forming a series declining from the IgG (70 per cent of the blood serum concentration, found in effusions) to the IgM (50 per cent of the blood serum concentration). The observations are discussed in relation to morphological aspects of molecular transport through the capillary wall, and the consequences of the LDL- and IgL-accumulation in pleural fluids are briefly discussed.

Cholesterol

Primary coccidioidomycosis in children presenting with massive pleural effusion.

Large pleural effusion as the presenting feature of coccidioidomycosis in childhood has not previously been reported and may cause significant diagnostic difficulty. Three children are described who required prolonged hospitalization and therapy with amphotericin B. Primary coccidioidomycosis should be included in the differential diagnosis of large pleural effusions in pediatric patients who have been in the endemic area. Such effusions suggest a severe form of the disease and may represent evidence of acute dissemination.

Child

Management of malignant pleural effusion.

A pleural effusion is a frequent complication of malignant disease. Essential to the care of oncology patients is a fundamental knowledge of the pathophysiology and treatment of such effusions. This article discusses the current thoughts concerning the occurrence of malignant effusions, outlines the current available methods and agents employed for control, and presents a modification of the thoracostomy procedure that appears to be more effective than the standard procedure.

Bleomycin

Malignant pleural effusions.

Recurrent malignant pleural effusion is a relatively common problem that often occurs many months before the terminal stages of a patient's malignant disease. Despite careful evaluation, it is often impossible to identify the exact physiologic cause of an effusion and difficult to identify a pragmatic course of therapy. Aggressive management including chest tube drainage, with or without instillation of inflammation-inducing drugs, and radiotherapy or surgery in selected cases is indicated for palliative treatment and probably for increased survival. In formulating a treatment plan, attention should be given to a variety of factors including pathogenic forces in the formation of malignant pleural effusion, tissue type of the metastatic malignancy, general clinical status of the patient, the presence of pleural loculations and adhesions, and the exclusion of other non-malignant causes of pleural effusion.

Antineoplastic Agents

Myelomatous pleural effusion: clinical course and immunologic characterization of the pleural fluid cells.

Multiple myeloma is a disease that infrequently involves nonreticuloendothelial tissues and rarely causes pleural effusion. A 59-year-old woman had pleural effusion as the major manifestation of multiple myeloma. Light microscopy of her pleural fluid with Wright stained preparations showed all cells to be bizarre and often multinucleated plasmacytes. Electron microscopy confirmed these results. Intracellular immunofluorescence revealed IgG-kappa immunoglobulin (Ig) in greater than 90% of these cells. Surface immunofluorescence using anti-Ig sera was seen on less than 5% of the pleural fluid cells. 3H leucine incorporation into Ig in vitro was measured for these cells, and secretory curves were obtained that have the typical secretory kinetics of bone marrow plasmacytes. This demonstrates that such cells are viable and are able to synthesize and release immunoglobulin. Treatment of our patient with prednisone, melphalan, and cyclophosphamide resulted in symptomatic improvement and complete resolution of her pleural effusion. Pleural effusion is an unusual but important complication of multiple myeloma and does not necessarily carry the grave prognosis implied in previous reports.

Female

Pleural effusion from malignancy.

Pleural effusion from metastatic malignancy can cause major impairment of respiratory function and eventual death. Although cure is not possible, successful palliative treatment allows months to years of productive life, obviating the need for continuous hospitalization and repeated thoracenteses. Successful palliative treatment requires obliteration of the pleural space. Literature survey indicates that a wide variety of medical agents and surgical methods have been used with variable success. Medical methods include instillation of antineoplastic agents, antimicrobial agents, or colloidal radioisotopes into the pleural space; quinacrine and tetracycline are moderately to highly effective agents, but the toxicity of the former is substantial. Bedside talc poudrage with thoracostomy-tube drainage is a safe and highly effective alternative. Pleurectomy is the definitive method of preventing reaccumulation of pleural fluid that results from metastatic malignancy, even when other methods have failed, but thehigh morbidity and mortality of the procedures mandate careful patient selection.

Anti-Bacterial Agents

Eosinophilic pleural effusions.

Forty-three pleural fluids from 30 patients with eosinophilic pleural effusion (EPE) were examined and correlated with biochemical and clinical findings. The percentage of eosinophiles ranged from 12% to 83%, averaged 38% and was accompanied by a high lymphocyte count, averaging 34%. The fluids were shown to be exudates. A history of allergy or immune disorders was elicited from seven patients and allergy to drug from one patient. Eight patients gave a history of thoracic trauma unrelated in time to the effusion. Three patients received transvenous pacemakers. In the remaining 11 patients the presence of the eosinophilic pleural effusion could not be correlated with any clinical data. Regardless of clinical setting, which in six patients included a past history of cancer, EPE proved to be a self-limiting disease with a favorable outcome. Thus, this diagnosis by cytologic examination of the sediment is of considerable prognostic significance even in patients with a history of other disorders that may give rise to effusions. Possibly the most significant observation recorded was the presence of a large population of lymphocytes in EPE. The role of these cells in the mechanism of EPE is discussed.

Adolescent

Haemorrhagic pleural effusion in Nigerians.

Experience with haemorrhagic pleural effusion in Nigerians is described. Sixty three cases selected from 283 cases of pleural effusion over a 15-year period were analysed. Haemorrhagic pleural effusion accounted for 22% of all cases of pleural effusion. Malignant cells were found in haemorrhagic fluid in 21% of cases. The commonest cause of haemorrhagic effusion was neoplasm followed by tuberculosis and trauma. Among neoplasms carcinoma of the bronchus was responsable for about half of such cases.

Adult

Antenatal phenotype associated with PAK2 pathogenic variants: bilateral pleural effusion as a warning sign.

Fetal pleural effusions can arise in various contexts with different prognosis. They have been reported in fetuses presenting with hereditary or acquired conditions. One particularly rare genetic disorder, known as Knobloch syndrome, seems to emerge as a potential new cause of fetal pleural effusions, associated with severe outcomes. Knobloch syndrome 1 can be caused by biallelic variants in COL18A1. It is primarily characterized by its ophthalmic features, including severe vitreoretinal degeneration with retinal detachment and macular abnormalities. Neurological defects such as encephalocele and developmental delay, along with skeletal and renal malformations, are also associated with the syndrome. The Knobloch syndrome 2 is caused by monoallelic variants in the kinase domain of PAK2. It is less described and seems to also be associated with cardiac and respiratory damage in addition to the Knobloch syndrome 1 phenotype. PAK2 is a ubiquitous protein with a major implication in regulation and remodeling of the cytoskeleton and numerous other cellular pathways. Knobloch-associated variants seem to cause a loss of the kinase function of the protein. Even if the ophthalmic defects are almost constant, PAK2-associated Knobloch syndrome has slightly different features from Knobloch syndrome 1 in which pulmonary and lymphatic damages are still unseen. In a prenatal trio exome sequencing, we identified a novel de novo PAK2 missense variant, NM_002577.4:c.836 A > C, p.(Gln279Pro), classified as likely pathogenic in a 24 weeks of gestation fetus whose only sign was severe bilateral pleural effusion. From a literature review of patients, we recognize this sign as an important antenatal indicator of Knobloch syndrome 2, as it was the first sign identifiable in 2 out of 5 patients. This adds new evidence for the implication of this gene in fetal pleural effusions, with potentially severe outcomes.

Female

Pleural effusion in multiple myeloma.

Two patients with multiple myeloma are described in whom an unusual complication developed: pleural effusion containing myeloma cells. There are 7 previously reported cases of myeloma in the English literature with this type of effusion. Pleural effusion in myeloma may be due to plasma cell infiltration of the pleura, congestive heart failure, pulmonary embolism, nephrotic syndrome, and second neoplasms. In view of these multiple etiologies, diagnostic thoracentesis should be performed in order to treat the effusion appropriately.

Adult

Immune complex vasculitis as a cause of ascites and pleural effusions in systemic lupus erythematosus.

A patient is described with systemic lupus erythematosus and large painless ascites and pleural effusions. Pleural and peritoneal fluid complement levels were depressed, and DNA binding was elevated in the presence of normal serum values. Immunoglobulin and complement deposits were demonstrated in vessels of the pleura, peritoneum, and skin, along with histologic evidence of vasculitis. The relation of the ascites and pleural effusions to the presence of widespread vasculitis and local immune complex formation is discussed. These complications responded poorly to corticosteroid therapy but slowly resolved following the addition of an immunosuppressive agent.

Adult

Exploratory proteomic and metabolomic profiling of pleural effusions identifies histone H4 and alanine as promising complementary markers for pleural tuberculosis.

The diagnosis of pleural tuberculosis (Pl-TB) remains challenging. Histopathological analysis and pathogen detection in pleural biopsies are informative but limited. We investigated differentially expressed proteins and metabolites in pleural effusions from patients with Pl-TB, malignancies, and other pathologies. A proteomic analysis of pooled pleural effusions identified 45 proteins exclusively detected or upregulated in Pl-TB samples, many linked to infectious processes. Conversely, 18 proteins were uniquely found or upregulated in malignant pleural effusions, mainly associated with detoxification and hemostasis. To validate these findings, we employed targeted proteomics in individual samples. Eight proteins were validated: S100-A9, histone H4, insulin-like growth factor-binding protein 2, fibrinogen beta chain, ficolin-3, immunoglobulin heavy constant alpha 1, sulfhydryl oxidase 1, and histidine-rich glycoprotein. Additionally, NMR-based metabolomics identified 13 metabolites with differential abundance between Pl-TB and non-TB samples. Notably, N-acetyl-glycoprotein and the branched-chain amino acids, alanine and lysine differed between groups. Proteomic and metabolomic analyses revealed distinct molecular profiles between Pl-TB and non-TB patients, despite intra-group variability. To address this, we applied classification models. Histone H4 and alanine consistently emerged as discriminative features. Overall, this study provides novel insights into the molecular landscape of Pl-TB. The combined quantification of proteins and metabolites may improve differential diagnosis, although should be further validated in larger, independent cohorts before clinical application.

Humans

Diagnostic value of biochemical analysis of pleural effusions. Carcinoembryonic antigen and beta 2 microglobulin.

Pleural effusions from 105 patients with malignant and nonmalignant diseases were examined for tumor cells, content of CEA, beta2 microglobulin, ceruloplasmin, alpha2 macroglobulin, orosomucoid, lysozyme, and hexosaminidase. Only CEA and beta2 microglobulin determinations were of diagnostic value. CEA concentrations greater than 11 ng/ml were found only in malignant effusions. Beta 2 microglobulin values were increased in pleural effusions due to lymphoma or immune diseases. Measurement of CEA and beta2 microglobulin in addition to the cytologic examination could increase the diagnostic significance of the analysis of pleural effusions.

Beta-Globulins

Pleural effusions.

Many different conditions result in the accumulation of pleural fluid. A diagnostic thoracentesis should be performed on all patients with pleural effusion from whom pleural fluid can be easily obtained. Empirically we have found that when the pleural effusion is more than 10 mm thick on the lateral decubitus roentgenogram, pleural fluid is easily obtained. At least 30 cc fluid should be obtained and distributed to the various laboratories as outlined in Table 2. The results of these tests will show whether the fluid is a transudate or an exudate. If the fluid is a transudate, no further diagnostic procedures need be directed towards the pleura. If the fluid is an exudate, the diagnosis will frequently be made by these original tests and therapy for the pleural disease can be instituted. If the diagnosis has not been made, the results of these tests should lead to a rational diagnostic attack.

Amylases

Pleural effusion in Wilms' tumor.

The association of pleural effusion and Wilms' tumor is uncommon. We report three patients who developed pleural effusion as a result of different mechanisms, all of which were related to Wilms' tumor or to its treatment.

Child, Preschool

Diagnostic performance of machine learning models for malignant and non-malignant pleural effusion: Systematic review and meta-analysis.

BACKGROUND: Accurately distinguishing malignant pleural effusion (MPE) from non-malignant pleural effusion is clinically important, but the generalisability and methodological quality of machine-learning (ML) models remain uncertain. METHODS: We searched eight databases to 23 April 2026. Diagnostic performance was pooled using random-effects and Reitsma bivariate models, and study quality was assessed using PROBAST+AI. RESULTS: Forty-two studies were included; 17 contributed to the AUC meta-analysis and 14 to the bivariate analysis. The pooled AUC was 0.90 (95 % CI 0.85-0.94; 95 % prediction interval 0.62-0.98), with sensitivity of 0.80 (95 % CI 0.77-0.83) and specificity of 0.87 (95 % CI 0.79-0.92). Only nine studies reported external, temporal or independent validation. Externally validated studies had a lower pooled AUC than studies without external validation (0.83 vs 0.92), with lower specificity observed in the two externally validated studies contributing sensitivity and specificity data. All 42 development assessments had high overall quality concerns, and all 42 model evaluations were judged at high risk of bias. CONCLUSIONS: ML models showed good apparent accuracy for distinguishing MPE from non-MPE, but the evidence was limited by substantial heterogeneity, high risk of bias and scarce external validation. The pooled estimates reflect the average performance of different selected models rather than the expected accuracy of a single clinical test. ML models should be regarded as adjuncts to existing diagnostic pathways until they are confirmed by rigorous multicentre prospective external validation and clinical-impact studies.

Humans

Decreased heat-labile opsonic activity and complement levels associated with evidence of C3 breakdown products in infected pleural effusions.

Heat-labile opsonic activity was measured simultaneously in serum and pleural fluid of patients with transudates, infectious exudates (with positive or negative bacterial culture) and neoplastic exudates, using two different complement-dependent phagocytic tests: the killing of Staphylococcus aureus Wood 46 variant strain (K50 opsonic titers) and the assessment of ingestion rate of endotoxin-coated paraffin particles (Oil Red 0 uptake test). K50 opsonic titers were lower in culture-positive pleural effusions as compared to culture-negative (P < 0.002) or neoplastic effusions (P < 0.002). These results were corroborated by the Oil Red 0 uptake test. The data obtained with the two assays showed a significant correlation (P < 0.001). The hemolytic activity of complement (CH50) as well as the levels of C3 breakdown product, C3d, were measured in the same sera and pleural fluid samples and in an additional group of patients with pleural effusions of the same etiology. Effusions with positive cultures showed lower CH50 values (P < 0.01) and higher C3d values (P < 0.05) when compared to culture-negative pleural fluids. Finally, evidence for immune complexes in pleural effusions and sera was looked for by determination of Clq binding activity. Levels were higher in culture-positive effusions when compared to culture-negative fluids (P = 0.005).K50 opsonic titers showed a positive correlation with CH50 values (P < 0.001) for all fluids tested. Similarly Clq binding activity correlated with C3d levels in effusions of infectious origin (P = 0.05). Recovery experiments using the various bacterial species isolated from culture-positive pleural effusions showed evidence of complement inactivation upon incubation with pooled sera at concentrations of 10(7)-10(8) microorganisms/ml. These results indicate that one important reason for bacterial persistence in empyema may be decreased opsonization secondary to local consumption of complement.

Adult

Mediastinal herniation of the pleural sac: occurrence in massive pleural effusion.

In a review of 50 patients with massive pleural effusion, mediastinal herniation of the pleural sac occurred in 16 patients (32 percent). Right-to-left herniation (ten patients) was more common than left-to-right (six patients). Herniation occurred only in the posteroinferior mediastinum (D5-D11). Fourteen patients had displacement of the mediastinum away from the side of pleural effusion. Disappearance of herniated sac in every patient following thoracocentesis confirmed the diagnosis.

Hernia