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Pleural macrophage recruitment and activation in asbestos-induced pleural injury.

The pathogenesis of asbestos-induced pleural fibrosis is poorly understood. Moreover, there has been a long-standing controversy regarding the relative potential of different commercial types of asbestos to cause pleural disease. We postulated that inhaled asbestos fibers translocate to the pleural space where they stimulate the recruitment and activation of pleural macrophages. To test this hypothesis, and to determine whether there are differences between inhaled amphibole and serpentine asbestos, Fischer 344 rats were exposed by intermittent inhalation (6 hr/day for 5 days/week over 2 weeks) to either National Institute of Environmental Health Sciences (NIEHS) crocidolite (average concentration 7.55 mg/m3) or NIEHS chrysotile fibers (average concentration 8.51 mg/m3). Comparisons were made with sham-exposed rats. The rats were sacrificed at 1 and 6 weeks after the cessation of exposure. More pleural macrophages were recovered at 1 and 6 weeks after crocidolite and chrysotile exposure than after sham exposure. Small numbers of crocidolite fibers (approximately 1 per 4000 cells) were detected in the pleural cell pellet of one crocidolite-exposed rat by scanning electron microscopy. Pleural macrophage supernatants were assayed for production of nitric oxide (NO) (by the Griess reaction) and tumor necrosis factor alpha (TNF-alpha) (by an enzyme-linked immunosorbent assay method). Significantly greater amounts of NO as well as TNF-alpha were generated by pleural macrophages at 1 and 6 weeks after either crocidolite or chrysotile inhalation than after sham exposure. Conceivably, translocation of asbestos fibers to the pleural space may provide a stimulus for persistent pleural space inflammation, cytokine production, and the generation of toxic oxygen and nitrogen radicals. Enhanced cytokine secretion within the pleural space may in turn upregulate adhesion molecule expression and the synthesis of extracellular matrix constituents by pleural mesothelial cells. Thus, our findings may have significance for the development of asbestos-induced pleural injury.

Animals↗

Standard pleural biopsy versus CT-guided cutting-needle biopsy for diagnosis of malignant disease in pleural effusions: a randomised controlled trial.

BACKGROUND: Over 200000 pleural effusions are attributable to cancer in the UK and USA every year. Cytological examination of pleural fluid classifies about 60% of malignant effusions. Pleural biopsy needs to be done in the remaining cases. We aimed to assess whether CT-guided biopsy is an improvement over standard pleural biopsy in this setting. METHODS: 50 consecutive patients with cytologically negative suspected malignant pleural effusions were recruited. All had a contrast-enhanced thoracic CT scan to assess pleural thickening. Patients were randomly allocated, stratified by baseline pleural thickening, to either Abrams' pleural biopsy (standard care; n=25) or CT-guided cutting needle biopsy (n=25). Sensitivity for pleural malignancy from the biopsy specimen was the primary endpoint, with the patient's clinical outcome after 1 year being the diagnostic gold standard. Analysis was per protocol. FINDINGS: Three patients did not undergo biopsy. Abrams' biopsy correctly diagnosed malignancy in eight of 17 patients (sensitivity 47%, specificity 100%, negative predictive value 44%, positive predictive value 100%). CT-guided biopsy correctly diagnosed malignancy in 13 of 15 (sensitivity 87%, specificity 100%, negative predictive value 80%, positive predictive value 100%; difference in sensitivity between Abrams' and CT-guided 40%, 95% CI 10-69, p=0.02). Diagnostic advantage was similar in patients proving to have mesothelioma. INTERPRETATION: Primary use of CT-guided biopsy would avoid doing at least one Abrams' biopsy for every 2.5 CT-guided biopsies undertaken. In cytology-negative suspected malignant pleural effusions, CT-guided pleural biopsy is a better diagnostic test than Abrams' pleural biopsy.

Adenocarcinoma↗

Diagnostic utility of pleural fluid IFN-gamma in tuberculosis pleural effusion.

Pleural fluid interferon-gamma (IFN-gamma) levels are increased in patients with tuberculosis (TB) pleural effusion. Recent studies from the west have found that estimation of pleural fluid IFN-gamma levels is an excellent diagnostic strategy for these patients. The diagnostic utility of pleural effusion IFN-gamma level estimation has not been evaluated in patients from developing countries, however. This work was carried out to study the diagnostic utility of IFN-gamma level estimation in patients with TB pleural effusion and to define the best cutoff of IFN-gamma for diagnosis TB pleural effusion. We studied 101 patients with pleural effusion. Of these, 64 were found to have a TB etiology, established by means of various conventional modalities. Measurement of pleural fluid IFN-gamma levels was done by ELISA technique. The median value of pleural fluid IFN-gamma levels in patients with TB (1480 pg/ml, range 3-14,000 pg/ml) was significantly higher (p < 0.001) compared with the non-TB group (3 pg/ml, range 0-900 pg/ml). The receiver operator characteristic (ROC) curve for IFN-gamma showed an area under the curve (AUC) value of 0.954, and the best cutoff was computed to be 138 pg/ml. Using this cutoff for IFN-gamma levels in pleural fluid for the diagnosis of TB, sensitivity, specificity, negative predictive value, and positive predictive value were found to be 90.2%, 97.3%, 85.7%, and 98.3%, respectively. Estimation of IFN-gamma levels in pleural fluid is a useful diagnostic modality for TB pleural effusion. A cutoff of 138 pg/ml provides the best sensitivity and specificity for diagnosis of TB.

Adult↗

Volume of pleural fluid required for diagnosis of pleural malignancy.

STUDY OBJECTIVES: To determine if the diagnosis of pleural malignancy is dependent on the volume of pleural fluid sampled. DESIGN AND SETTING: Single-center retrospective chart review. PATIENTS: Two hundred eighty-two patients who underwent diagnostic thoracentesis between October 1, 1998, and June 30, 1999. INTERVENTIONS: Charts were analyzed for volume of fluid, pathologic and clinical diagnoses, and demographics. Patients were classified into quartiles based on the volume of pleural fluid collected. Sensitivity and negative predictive value (NPV) were calculated for each quartile for diagnosis of pleural malignancy by cytology of pleural fluid. Further analyses were done regarding the effect of sex, race, age, smoking history, and personal history of malignancy on diagnosis. RESULTS: In total, 374 samples from 282 patients were identified (140 men and 142 women). Pleural malignancy within 6 months of initial thoracentesis was diagnosed in 99 patients (35.1%). No differences were detected for sensitivity and NPV for diagnosis of pleural malignancy between any two quartiles (p > 0.05). Samples collected from women had a higher sensitivity for predicting pleural malignancy (p = 0.0011), and those collected from nonsmokers had a slightly higher but not statistically significant sensitivity for predicting pleural malignancy (p = 0.057). Samples collected from subjects with no history of malignancy had a significantly higher NPV than samples collected from subjects with a history of malignancy (p < 0.001). After adjusting for these demographic and medical history factors, the associations of the pleural fluid volume quartiles with sensitivity and NPV did not change. CONCLUSION: The sensitivity for diagnosis of pleural malignancy is not dependent on the volume of pleural fluid extracted during thoracentesis.

Aged↗

The role of Abrams percutaneous pleural biopsy in the investigation of exudative pleural effusions.

INTRODUCTION: Blind percutaneous pleural biopsy has traditionally been performed to investigate the etiology of exudative pleural effusion in which the initial thoracentesis has been nondiagnostic. In view of the increasing use of image-guided and thoracoscopic pleural biopsies, this study examines the role of blind Abrams pleural biopsy in the investigation of pleural effusion in a large urban hospital. METHOD: Patients undergoing blind Abrams needle biopsy between January 1997 and 2003 were identified from the hospital pathology database. The case notes and pathology records of these patients were analyzed retrospectively. All patients had presented to respiratory teams with an exudative pleural effusion and had initial nondiagnostic thoracentesis. RESULTS: Seventy-five patients undergoing blind biopsy were identified. Pleural tissue was obtained in 59 biopsies (79%), with no statistically significant difference in pleural yield between respiratory specialist registrars (equivalent to pulmonary fellows in training) and senior house officers/preregistration house officers (equivalent to junior residents and interns, respectively) performing the biopsy (chi(2) test, p = 0.43). When up to three samples were obtained per episode, sufficient pleural tissue was obtained in 18 of 25 patients (72%) compared to 80% (32 of 40 patients) in whom four to six samples were taken (chi(2) test, p = 0.55 [not significant]). For all diagnoses, blind biopsy had a sensitivity of 38%, which rose to 43% when reviewing patients in whom sufficient pleural tissue was obtained (for malignant diagnosis alone, sensitivity values were 43% and 51%, respectively; specificity, 100%; negative and positive predictive values, 51%). No fatalities were reported, and pneumothorax was seen in eight patients (11%), with only two patients requiring specific intervention. CONCLUSIONS: Blind Abrams needle biopsy obtaining pleural tissue was diagnostic in approximately 50% of patients presenting with malignant effusion in the sample, and can be performed safely by all grades of medical staff with due attention to technique and supervision. The data support the continued use of the Abrams needle in the investigation of malignant pleural disease.

Aged↗

Pleural macrophages differentially alter pleural mesothelial cell glycosaminoglycan production.

Glycosaminoglycans are produced in abundance by the pleural mesothelium and likely participate in the inflammatory response to pleural injury. Because intrapleural tetracycline (TCN) results in pleural macrophage influx and pleural fibrosis, this study attempted to define the role of pleural macrophage products on mesothelial glycosaminoglycan (GAG) production. Pleural macrophages were isolated 72 h after intrapleural TCN or intrapleural carrageenan (CAR), a substance that recruits pleural macrophages without producing pleural fibrosis. Macrophage cultured for 24 h produced a conditioned medium that was added to pleural mesothelial cell culture containing [3H]-glucosamine and was compared to control cultures treated with RPMI culture media alone or with the addition of TCN or CAR. After 72 h, GAGs were isolated by pronase digestion, cetyl pyridinium precipitation, and MgCl2 and ethanol extraction. The majority of GAGs were found in the culture media as compared to the combined mesothelial cell and basement membrane fractions of control mesothelial cells (883 +/- 33 vs. 216 +/- 16, cpm, counts per minute), TCN-treated (792 +/- 48 vs. 204 +/- 18 cpm), CAR-treated (849 +/- 45 vs. 223 +/- 13 cpm), and macrophage-conditioned media-treated mesothelial cells (TCN macrophage-conditioned media: 1420 +/- 42 vs. 356 +/- 11 cpm; CAR macrophage-conditioned media: 1241 +/- 38 vs. 339 +/- 10 cpm) (all p < .05). Media samples were enzymatically digested and individual GAG species were separated by Sephadex G-50 column chromatography. TCN macrophage-conditioned media induced more GAG production by the mesothelial cell into the cell media (1420 +/- 42 cpm) than CAR macrophage-conditioned media (1241 +/- 38 cpm) (p < .05), which was predominantly a difference in hyaluronate production (342 +/- 53 cpm vs. 186 +/- 7 cpm) (P. < .05). The results show that pleural macrophages modulate mesothelial GAG production during tetracycline pleural injury. Increases in mesothelial cell hyaluronate production may be important in the fibrotic response to chemical pleural injury.

Animals↗

Cell-free DNA concentration in pleural fluid and serum: quantitative approach and potential prognostic factor in patients with cancer and pleural effusions.

PURPOSE: The presence of pleural effusions in patients with tumors is often indicative of locally advanced or metastatic disease, and detection of malignancy in effusion samples frequently leads to a disease upstaging. Our purpose was to quantify the DNA in pleural effusion and serum in patients presenting pleural effusion in order to assess the potential prognostic impact. PATIENTS AND METHODS: The DNA level was determined by amplifying hRNase P in paired samples of serum and pleural fluid in 70 consecutive patients with cancer showing pleural effusion. A group of 30 patients without cancer was included. The correlation between serum and pleural DNA was calculated. Survival curves according to serum and pleural DNA were analyzed. RESULTS: Median DNA concentrations were greater in patients with neoplasia than in patients without malignancy: 105 ng/mL versus 40 ng/mL (P = 0.001) in serum samples, respectively; 93 ng/mL versus 21 ng/mL (P = 0.001) in pleural fluids, respectively. A positive correlation between serum and pleural levels was confirmed (r = 0.3; P < 0.05). Median survival time for patients with serum DNA < or = 105 ng/mL was 11.03 months in contrast to only 3.63 months for patients with higher values (P = 0.036). Accordingly, median survival time for patients with pleural DNA < or = 93 ng/mL was 12.3 months versus only 4.63 months in case of higher levels (P = 0.027). CONCLUSION: This study shows that there is a strong correlation between higher levels of free DNA in pleural fluid or serum and malignancy. Survival is worse for patients with higher DNA levels in serum and pleural fluid.

Adult↗

Use of pleural fluid C-reactive protein in laboratory diagnosis of pleural effusions.

OBJECTIVES: C-reactive protein (CRP) which is synthetized by hepatocytes is an acute phase protein and its serum level increases within 6-9 hours after infection or tissue damage. We investigated its usefulness as a marker of bacterial infection in patients with pleural effusion. METHODS: We studied the usefulness of pleural fluid C-reactive protein measurement in a population of 72 patients with pleural effusion, by means of an immunoturbidimetric method (Hitachi 717, Boheringer Mannheim). A comparison of serum and pleural effusion C-reactive protein levels in different subgroups of patients with effusion was made. RESULTS: According to preset diagnostic criteria, 19 patient effusions were classified as transudates and the mean (+/- 5 D) pleural fluid CRP [5.3 (+/- 7.8) mg per liter, p < 0.001] were significantly lower than those in the exudate effusions group. Among the 53 patients with exudate effusion, eight were caused by neoplastic disease and the pleural fluid CRP mean (29.3 +/- 16.1 mg per liter, p < 0.001) were significantly lower than those in exudates from parapneumonic effusions (122.7 +/- 48.0 mg per liter, p < 0.001) and than those in the exudates from patients with effusion associated with tuberculosis (67.8 +/- 32.1 mg per liter, p < 0.001). Moreover, all but two transudates had a C-reactive protein lower than 10 mg/L, whereas only two exudates with tuberculosis origin had a C-reactive protein value lower than 10 mg/L, instead all pleural-fluid C-reactive protein from exudates with pneumonia were greater than 10 mg/L. We had found a correlation between the pleural and serum C-reactive protein (r = 0.6884, p < 0.0001). And transudates tended to have lower ratios of pleural to serum CRP (0.26) than exudates (0.55), and malignant effusions had lower ratios (0.37) than pneumonic and tuberculous effusions (0.52, 0.58). CONCLUSIONS: Pleural fluid CRP > 10 mg per liter had good sensitivity (82%), specificity (87.5%) and predictive value of positivity (95.5%) in the diagnosis of exudate effusions and higher CRP-levels may prove to be a practical, accurate and rapid method for differentiating pneumonic effusions and effusions associated with tuberculosis from others. It can be considered that quantitative immunoturbidimetric assay of pleural-fluid C-reactive protein will be a useful diagnostic tool to differentiate pleural effusions with bacterial origin from others.

Albumins↗

Closed pleural needle biopsy: predicting diagnostic yield by examining pleural fluid parameters.

OBJECTIVE: Pleural fluid parameters that predict a diagnostic closed pleural needle biopsy were investigated. DESIGN: A retrospective analysis. SETTING: The Institute of Pulmonology, Hadassah University Hospital. PATIENTS AND METHODS: Forty-four patients who underwent closed pleural needle biopsies were included in this study. Pleural fluid values of protein, glucose, lactate dehydrogenase (LDH), pH, and white blood cell count with differential cell counts, from patients with diagnostic and non-diagnostic pleural biopsies were compared. RESULTS: Thirteen patients (29%) had diagnostic biopsies. Malignancy was identified in 10 patients (23%), of whom 70% had adenocarcinoma. Three other patients had non-malignant specific diagnosis. LDH levels in pleural fluid from patients with diagnostic pleural biopsy were higher than in patients with non-diagnostic pleural biopsies (1436 +/- 333 U l(-1) vs. 775 +/- 109 U l(-1); P < 0.05). LDH levels less than 510 U l(-1) were highly predictive of a negative biopsy (negative predictive value of 86.6%). Follow up revealed malignancy including mesothelioma and lymphoma, in 10 of 30 (33%) patients with non-diagnostic biopsies, and one patient died of unrelated cause, while the pleural effusion either resolved, remained stable or an alternative benign process was identified in 19 patients (63%). CONCLUSIONS: Low levels of LDH (< 510 U l(-1)) were highly predictive of a negative pleural needle biopsy. Thus, LDH may serve as a useful guide in deciding whether to perform closed pleural biopsy or to proceed to thoracoscopically guided biopsy.

Adult↗

Lupus pleuritis. Clinical features and pleural fluid characteristics with special reference to pleural fluid antinuclear antibodies.

Eighteen patients with lupus erythematosus (LE) and pleural effusions were evaluated. Fourteen patients had lupus pleuritis and four had pleural effusions of other etiologies. All patients were symptomatic, and the presenting signs and symptoms did not help distinguish between lupus pleuritis and pleural effusions of other causes. The presence of LE cells confirmed the diagnosis of lupus pleuritis in seven of eight patients. In 11 of 13 patients with lupus pleuritis, the pleural fluid antinuclear antibody (ANA) titer was greater than or equal to 1:160, and in nine of 13 patients with lupus pleuritis, the pleural fluid to serum (PF/S) ANA ratio was greater than or equal to 1. In the four patients with LE and a pleural effusion of another etiology, the pleural fluid ANA titer was negative in two and low titer in two (1:40, 1:80); the pleural fluid to serum ANA titer was always less than one. Of 67 patients with pleural effusions of other etiologies, the pleural fluid ANA was negative. The signs and symptoms of lupus pleuritis are nonspecific, however; the findings of LE cells in pleural fluid confirms the diagnosis and a high pleural fluid ANA titer (greater than or equal to 1:160) and a PF/S ANA ratio of greater than or equal to 1 strongly supports the diagnosis.

Adolescent↗

Diagnostic yield of closed pleural biopsy in exudative pleural effusion.

OBJECTIVE: Closed pleural biopsy is known to be diagnostic in approximately 75% of pleural effusion undiagnosed by thoracocentesis or pleural fluid evaluation. The purpose of this study was to determine the efficacy of closed pleural biopsy in a Saudi tertiary care teaching hospital. METHODS: We retrospectively reviewed the diagnostic utility of all closed pleural biopsies performed from January 1988 to December 1997 at the King Fahad National Guard Hospital, Riyadh, Kingdom of Saudi Arabia. RESULTS: One hundred and twenty-two pleural biopsies were performed in 116 patients using cope needle in 39, Abram's needle in 82, and Trucut needle in one patient. Twelve cases were excluded due to transudative effusion (N=6) and obtaining no pleural tissue (N=6). Specific diagnoses were obtained in 54 cases giving a diagnostic yield of 49.1%. Of these 10 revealed neoplasia, 35 tuberculosis, and 9 empyema. A non-specific diagnosis was obtained in 56 (50.9%) cases. CONCLUSION: By closed pleural biopsy 49.1% of undiagnosed exudative pleural effusions could be diagnosed. This shows that closed pleural biopsy is still of value as a diagnostic procedure, and should be carried out prior to invasive procedures such as thoracoscopy or open pleural biopsy.

Adult↗

[Radiographic visualization of pleural space under negative pleural pressure].

Although many imaging modalities have developed in the area of pulmonary medicine, information about the condition of pleural surface is limited. In this study, we carried out contrast pleurography under negative pleural pressure in dogs and humans to evaluate the condition of the pleural space including adhesion between the two pleural layers, incomplete fissure and features of the pleural surface. After insertion of a flower-type catheter into the pleural space under ultrasonic guidance, contrast material (60% Meglumine iotalamate, Conray 60, 0.5-1.0 ml/kg) was injected into the pleural space through the catheter. In dogs with intact pleura, contrast material distributed to the pulmonary surface, including interlobar spaces, rapidly. In dogs with pleural adhesion which was induced artificially with talc, affected areas were visualized as defects of contrast material. In humans, this contrast pleurography provided information about pleural adhesion, pulmonary lobulation, extent of cancer to neighbouring lobes, irregular pleural surface due to bullae formation and pleural indentation by cancerous lesion. There was no serious complication in dogs and human studies. This contrast pleurography is unique because it is possible to evaluate the pleural space physiologically under negative pressure condition. It may be concluded that this method of pleurography is useful for the clinical evaluation of the condition of the pleura in various lung diseases.

Adult↗

Useful tests on the pleural fluid in the management of patients with pleural effusions.

Examination of the pleural fluid is useful in establishing the etiology of a pleural effusion. Transudative pleural effusions can be differentiated from exudative pleural effusions by measuring the levels of protein and lactic acid dehydrogenase in the pleural fluid and serum. If a patient clinically appears to have a transudative pleural effusion, but the pleural fluid meets exudative criteria, demonstration that the albumin levels is more than 1.2 gm/dl higher in the serum than in the pleural fluid provides evidence that the effusion is transudative. The gross appearance of the pleural fluid should always be noted. Other tests that routinely should be obtained on exudative pleural fluids are Gram stain and cultures, cell counts and differential, glucose, amylase, lactic acid dehydrogenase, cytology, and a marker for tuberculous pleuritis. The diagnosis of tuberculous pleuritis is strongly suggested by a pleural fluid adenosine deaminase level above 45 IU/L or a gamma interferon level above 3.7 U/ml.

Diagnosis, Differential↗

CT of pleural abnormalities in lymphangioleiomyomatosis and comparison of pleural findings after different types of pleurodesis.

OBJECTIVE: The objective of our article was to describe the spectrum and frequency of pleural abnormalities on CT in patients with lymphangioleiomyomatosis (LAM) and the pleural findings associated with different types of pleurodesis (talc, mechanical, and chemical) performed to treat the complications of pleural disease in these patients. MATERIALS AND METHODS: Two hundred fifty-eight patients with LAM underwent CT of the chest. Pleural abnormalities assessed included pleural thickening, presence of a pleural mass, areas of high attenuation, effusion, and pneumothorax. In patients who had had pleurodesis, the CT findings were correlated with the type of procedure performed. RESULTS: One hundred thirty-three (52%) of 258 patients had pleurodesis (unilateral, 68/133; bilateral, 65/133). Pleural abnormalities were more common in patients who had pleurodesis (101/133, 76%) than in those who had not (47/125, 38%) and were more prevalent on the operated side than on the unoperated side of those 68 patients who had unilateral pleurodesis. The frequencies of findings for the group without pleurodesis versus the group with pleurodesis were pleural thickening (26% vs 65%), effusion (10% vs 13%), loculated effusion (2.4% vs 11%), pneumothorax (1.6% vs 10%), areas of high attenuation (1.6% vs 23%), and mass (0.8% vs 14%), respectively. Areas of high attenuation in the pleura were present in all types of pleurodesis (mechanical, 8%; chemical, 13%; talc, 40%) and in two patients who had had repeated thoracentesis or pleurectomy. Pleural masses were present in patients who had had all types of pleurodesis (mechanical, 10%; chemical, 9%; talc, 24%) and in one patient who had had thoracentesis and thoracostomy; the masses commonly enhanced and did not change in size over time. CONCLUSION: Pleural abnormalities are common in patients with LAM as complications of the disease itself and as sequelae of pleurodesis and other pleura manipulations. Pneumothorax and pleural effusion result from the underlying pathophysiology of LAM, whereas areas of high attenuation and masses develop after all types of pleurodesis and other manipulations of the pleura (i.e., thoracentesis, thoracostomy).

Adult↗

Use of pleural fluid C-reactive protein in diagnosis of pleural effusions.

The aims of the study were to assess whether C-reactive protein (CRP) is a sensitive marker for discriminating between transudative and exudative and pleural effusions to evaluate whether it can be used to distinguish inflammatory pleural effusions from other types of effusion. Pleural fluid and serum CRP levels were obtained in 97 patients with pleural effusion, using an immunoturbidimetric method (Olympus AU-600 autoanalyser). We compared CRP levels between transudates and exudates, inflammatory effusions and other types of effusion. According to the criteria used, 16 patients were included in the transudate group and 81 patients in the exudate group. Pleural fluid CRP levels were significantly lower in the transudate group (P<0.04; 14.9 +/- 4.9 mg l(-1) and 35.5 +/- 4.9 mg l(-1) respectively). Also, the ratio of pleural fluid to serum was significantly lower in the transudate group (P<0.009; 0.8 +/- 0.5 mg l(-1) and 2.8 +/- 0.7 mg l(-1), respectively). In the exudate group, 35 patients had neoplastic effusions, 10 chronic non-specific pleurisy, 19 tuberculous pleurisy, 16 parapneumonic effusion and one Dressler Syndrome. When these sub-groups were compared, the parapneumonic effusion subgroup CRP levels (mean 89 +/- 16.3 mg l(-1)) were significantly higher than those in the other subgroups, other exudate of neoplastic effusion, tuberculous pleurisy and chronic non-specific effusion and the transudate group (P<0.0001; P<0.0001; P<0.0004 and P<0.0001, respectively). The ratio between pleural fluid and serum CRP was significantly higher in the parapneumonic effusion subgroup than in the neoplastic subgroup (P<0.0002; 6.6 +/- 2.7 mg l(-1) and 1 +/- 0.2 mg l(-1), respectively). Pleural fluid CRP levels > 30 mg l(-1) had a high sensitivity (93.7%) and specificity (76.5%) and a positive predictive value of 98.4%. In the differential diagnosis of pleural effusions, higher CRP levels may prove to be a rapid, practical and accurate method of differentiating parapneumonic effusions from other exudate types. Although the high level of CRP obtained in the exudate group may be due to the number of patients with parapneumonic effusion who were included, the pleural CRP level may also be helpful in discriminating between exudative and transudative pleural effusions.

Biomarkers↗

Interleukin-8 induces lymphocyte chemotaxis into the pleural space. Role of pleural macrophages.

The pleural space is a potential compartment between the lung and chest wall that becomes filled with fluid and inflammatory cells in a number of respiratory diseases. In an attempt to understand one aspect of the inflammatory process in the pleural space, we compared the responses in three different diseases (congestive heart failure [CHF], tuberculosis [TB], and cancer). Large concentrations of interleukin-8 (IL-8) were detected in cancer and TB effusions, but not in CHF. Surprisingly, the concentration of IL-8 correlated best with lymphocyte recruitment and not with neutrophil recruitment. Pleural fluid from cancer and TB patients was chemotactic for lymphocytes, and this activity was partly blocked by an anti-IL-8 antibody in cancer and completely blocked in TB. To determine whether there was the potential for a chemotactic gradient into the pleural space, pleural effusion cells were analyzed for the expression of IL-8. Cells in the effusions of cancer patients expressed IL-8, whereas IL-8 could not be detected from the cells of TB and CHF effusions. To explore the possible role of pleural macrophages in the regulation of IL-8, pleural effusion cells were treated with culture supernatants from stimulated pleural macrophages. Stimulated pleural macrophages were able to induce expression of messenger RNA (mRNA) for IL-8 and IL-8 protein production, and this activity was abrogated by blocking tumor necrosis factor-alpha. These findings suggest that soluble IL-8 is an important factor for the recruitment of lymphocytes into the pleural space, and that this cytokine is produced by both pleural structural and cancer cells after their activation by macrophage-derived, cytokine-mediated signals.

Adult↗

Pleural fluid levels of vascular cell adhesion molecule-1 are elevated in eosinophilic pleural effusions.

STUDY OBJECTIVES: The mechanisms responsible for the accumulation of eosinophils in pleural fluid are not fully understood. The objective of the present study was to examine the relationship between pleural fluid eosinophilia and the levels of vascular cell adhesion molecule (VCAM)-1, eotaxin, RANTES (regulated upon activation, normal T-cell expressed and secreted), and interleukin (IL)-4 in pleural effusions. PATIENTS AND METHODS: Thirty-one patients with eosinophilic pleural effusion (EPE) [eosinophil percentage > 10% of the pleural fluid nucleated cells] and 10 patients without EPE were evaluated. VCAM-1, eotaxin, RANTES, and IL-4 in all pleural fluids were measured using enzyme-linked immunosorbent assay kits. IL-5 levels of the same fluids were measured in a previous study. RESULTS: VCAM-1, eotaxin, and RANTES but not IL-4 were detectable in the pleural fluids. The mean level of VCAM-1 in EPE (336 +/- 85 ng/mL) was significantly higher (p = 0.011) than that in the noneosinophilic effusions (260 +/- 34 ng/mL) [mean +/- SD]. VCAM-1 levels were significantly correlated with the eosinophil count and percentage in all pleural fluids (r = 0.43, p = 0.005, and r = 0.37, p = 0.019, respectively). Multiple linear regression analysis disclosed that both IL-5 (beta, 0.63; p < 0.001) and VCAM-1 (beta, 0.27, p = 0.025) are independent predictors of the number of eosinophils in all pleural fluids. RANTES and eotaxin did not differ significantly between EPEs and non-EPEs, and were not correlated with the number of pleural fluid eosinophils. CONCLUSION: The levels of VCAM-1 are increased in EPE, suggesting that VCAM-1 is important in the pathogenesis of EPE. Neither eotaxin nor RANTES is associated with pleural fluid eosinophilia.

Chemokine CCL11↗