Soluble leukocyte selectin in the analysis of pleural effusions

STUDY OBJECTIVES: To determine if soluble leukocyte selectin (sL-selectin) levels in serum and pleural fluid (PF) are an inflammatory marker that differentiates pleural effusion transudates from exudates. DESIGN: sL-selectin PF and serum levels were measured in consecutive patients and compared to established criteria. SETTING: A tertiary-care military medical center. PATIENTS: One hundred twenty patients undergoing diagnostic or therapeutic thoracentesis. INTERVENTIONS: PF and serum samples were collected during thoracentesis and analyzed separately for sL-selectin levels. Results were compared with clinical diagnosis and established PF criteria including the criteria of Light et al, cholesterol ratio, total bilirubin ratio, and albumin gradient. Measurements and results: sL-selectin levels in PF and serum were determined in 109 patients. By clinical diagnosis, mean +/- SD PF sL-selectin levels were 200.2 +/- 124.3 ng/mL in transudates and 496.8 +/- 379.2 ng/mL in exudates (p < 0.001). By the criteria of Light et al, mean PF sL-selectin levels were 195.7 +/- 105.2 ng/mL in transudates and 448.2 +/- 367.6 ng/mL in exudates (p < 0.001). Mean sL-selectin PF to serum ratios were 0.31 +/- 0.17 in transudates and 0.72 +/- 0.31 in exudates (p < 0.001) by clinical criteria, and 0.31 +/- 0.18 in transudates and 0.64 +/- 0.33 in exudates (p < 0.001) by the criteria of Light et al. No significant difference was noted with serum sL-selectin levels between groups. CONCLUSIONS: sL-selectin is an inflammatory marker that differentiates transudates from exudates in pleural effusions and is a sensitive indicator for PF analysis.     

How accurate is spirometry at predicting restrictive pulmonary impairment?

OBJECTIVE: To determine the accuracy with which spirometric measurements of FVC and expiratory flow rates can diagnose the presence of a restrictive impairment. DESIGN: The pulmonary function tests of 1,831 consecutive white adult patients who had undergone both spirometry and lung volume measurements on the same visit over a 2-year period were analyzed. The probability of restrictive pulmonary impairment, defined as a reduced total lung capacity (TLC) below the lower limit of the 95% confidence interval, was determined for each of several categoric classifications of the spirometric data, and additionally for each of several interval levels of the FVC and the FEV1/FVC ratio. SETTING: A large clinical laboratory in a university teaching hospital using quality-assured and standardized spirometry and lung volume measurement techniques according to American Thoracic Society standards. RESULTS: Two hundred twenty-five of 1,831 patients (12.3%) had a restrictive defect. The positive predictive value of spirometry for predicting restriction was relatively low; of 470 patients with a low FVC on spirometry, only 41% had restriction confirmed on lung volume measurements. When the analysis was confined to the 264 patients with a restrictive pattern on spirometry (ie, low FVC and normal or above normal FEV1/FVC ratio), the positive predictive value was 58%. Conversely, spirometry had a very favorable negative predictive value; only 2.4% of patients (32 of 1,361) with a normal vital capacity (VC) on spirometry had a restrictive defect by TLC measurement. The probability of a restrictive defect was directly and linearly related to the degree of reduction of FVC when the FVC was < 80% of predicted (p = 6.002). Combining the FVC and the FEV1/FVC ratio improved the predictive ability of spirometry; for all values of FVC < 80% of the predicted amount, the likelihood of restrictive disease increased as the FEV1/FVC ratio increased. CONCLUSIONS: Spirometry is very useful at excluding a restrictive defect. When the VC is within the normal range, the probability of a restrictive defect is < 3%, and unless restrictive lung disease is suspected a priori, measurement of lung volumes can be avoided. However, spirometry is not able to accurately predict lung restriction; < 60% of patients with a classical spirometric restrictive pattern had pulmonary restriction confirmed on lung volume measurements. For these patients, measurement of the TLC is needed to confirm a true restrictive defect.     

The relation among pulmonary function, chest roentgenographic abnormalities, and smoking status in an asbestos-exposed cohort

To clarify the clinical value of the International Labor Office (ILO) roentgenographic classification of pneumoconiosis in assessing asbestos-exposed persons, we determined the relationships among spirometric values, radiographic evidence of parenchymal pulmonary fibrosis and/or pleural thickening, and cigarette smoking history in 684 consecutively enrolled male plumbers and pipefitters participating in a larger cross-sectional prevalence study. The subjects were mainly marine pipefitters (35%), plumbers (24%), and steamfitters/welders (23%); 28% had never smoked, 39% were ex-smokers, and 33% currently smoked cigarettes. Mean values for FVC and FEV1 were 95.0 and 91.9% of predicted, respectively, with mean FEV1/FVC ratio 77.7%; by standard criteria, 7.8% had restrictive impairment, and 21.7%, obstructive defects. Chest radiographs were normal in 63% and showed pleural abnormalities only in 17%, parenchymal abnormalities only in 7%, and both pleural and parenchymal abnormalities in 12%. Both FVC and FEV1 correlated with the degree of small opacity profusion, as assessed by ILO grade. Pleural abnormalities were associated with lower FVC values, independently of ILO profusion grade for Grades less than or equal to 1/0, and were unexplained by smoking status. In addition, there was a positive association between smoking history and degree of ILO parenchymal abnormality, particularly in those with the heaviest cumulative smoking history. Our results suggest that the ILO classification of pneumoconiosis, although a useful epidemiologic tool, should be applied with caution in persons with asbestos exposure, and that pleural abnormalities may be associated with physiologic impairment in such persons.     

Limited additive value of pleural fluid carcinoembryonic antigen level in malignant pleural effusion

OBJECTIVE: To assess the additive value of pleural fluid carcinoembryonic antigen (CEA.PF) level in the diagnosis of malignant pleural effusion. METHODS: Thoracentesis and closed pleural biopsy were performed in consecutive patients with pleural effusions. CEA.PF, cell analysis, and biochemical, cytopathologic and microbiologic studies were carried out. Further diagnostic interventions were undertaken if initial tests were inconclusive. RESULTS: A total of 176 patients were evaluated. The effusions proved malignant in 78 patients (44%). Benign etiologies were diagnosed in 89 cases, comprising 51 tuberculous pleurisies, 12 empyemas, 26 others. The cause was unknown in 9 patients. Median (range) in ng/ml of CEA.PF were 233 (1-12,500) in malignant vs. 2.5 (0.3-9) in tuberculosis, 1.4 (0.1-2) in transudates, 19.4 (0.6-312) in empyemas, p < 0.001. Receiver operating characteristic curve identified 10 ng/ml as the best cut-off for CEA.PF, yielding a sensitivity of 0.77, a specificity of 0.94, a positive and negative predictive value of 0.92 and 0.82, respectively. Among the 78 patients with malignant effusions, CEA.PF was elevated but initial cytopathologic study was nondiagnostic in 14 patients (18%). Prompted by the raised CEA.PF, further diagnostic interventions were undertaken and secured the diagnosis of malignancy in all of these 14 patients. CONCLUSIONS: CEA.PF level adds limited value on cytopathologic study in the diagnosis of malignant pleural effusions. It potentially identifies 18% of patients with malignant effusions who require further investigations despite negative initial cytopathologic study.     

Tuberculous pleural effusion. Twenty-year experience

We reviewed the records of 1,738 cases of tuberculosis seen during the period from 1968 to 1988 in Mobile, Alabama. Seventy cases of tuberculous pleural effusion were identified and constituted 4.9 percent of all disease due to Mycobacterium tuberculosis during this period. Tuberculous pleural effusion was diagnosed if the patient had M tuberculosis cultured from sputum, pleura, or pleural fluid and had a roentgenographic pleural effusion without an alternative explanation for the presence of the effusion. The diagnosis of tuberculous pleural effusion was made in the absence of a positive culture if the patient had an undiagnosed lymphocytic exudative pleural effusion and all clinical and roentgenographic abnormalities resolved on antimycobacterial chemotherapy. The mean age of all patients was 47 +/- 18.4 years. The 70 cases were evenly divided between 35 that were accompanied by roentgenographic pulmonary parenchymal infiltrates and 35 that occurred in the absence of parenchymal infiltrates. We conclude that cultures of all potentially diagnostic specimens (sputum, pleural fluid, and pleura) and an intermediate-strength skin test, are sensitive tests for the diagnosis of tuberculous pleural effusion. In addition, the age of patients with tuberculous pleural effusion appears to be increasing.     

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.     

Asbestos-induced pleural fibrosis and impaired lung function

To assess the clinical significance of asbestos-induced pleural fibrosis, we evaluated the relationship between radiographic evidence of pleural fibrosis and spirometric values in 1,211 sheet metal workers. Of those with pleural fibrosis (n = 334), 78% had circumscribed plaques and 22% had diffuse pleural thickening involving the costophrenic angle. Factors that were found to be associated with the presence and type of pleural fibrosis included increased age (p less than 0.001), more years in the trade (p less than 0.0001), more years since first exposure to asbestos (p less than 0.0001), more pack-years of cigarette smoking (p less than 0.01), and the presence and degree of interstitial fibrosis (p less than 0.0001). After controlling for these potential confounders (age, years in the trade, latency, pack-years of smoking, and ILO profusion category), linear multivariate regression models demonstrated that both circumscribed plaques (p = 0.007) and diffuse pleural thickening (p = 0.008) were independently associated with decrements in FVC but not with decrements in the FEV1/FVC ratio. Furthermore, our data indicate that the effect of diffuse pleural thickening on decrements in FVC is approximately twice as great as that seen with circumscribed pleural plaques. We conclude that the presence and type of pleural fibrosis among asbestos-exposed workers is independently associated with a pattern of spirometry that is suggestive of an underlying restrictive defect in lung function.     

Poor interpretation of pulmonary function tests in patients with concomitant decreases in FEV1 and FVC

Background and objective:   A new interpretative strategy for pulmonary function tests (PFT) has been proposed by the American Thoracic Society/European Respiratory Society (ATS/ERS) Task Force. To assess the accuracy of this strategy, clinical diagnosis was compared with the PFT interpretation in patients showing concomitant decreases in FEV₁ and FVC.
Methods:   A retrospective study was conducted of 681 patients with normal FEV₁/FVC and low FVC who underwent lung volume measurements and spirometry on the same date between July and November 2005 at Asan Medical Center, Seoul, Korea. Patients were clinically diagnosed by the consensus decision of two respiratory physicians, and the kappa coefficient was calculated to compare the clinical diagnosis with the PFT interpretation using the ATS/ERS strategy.
Results:   The PFT interpretation showed an obstructive pattern in 205 patients and a restrictive pattern in 476. Of the 205 patients with an obstructive pattern on PFT, 44 were clinically diagnosed with obstructive, 97 with restrictive and 17 with mixed disease, whereas 47 patients had no disease. Of the 476 patients with a restrictive pattern on PFT, 11 were clinically diagnosed with obstructive, 369 with restrictive and 60 with mixed disease, whereas 36 patients had no disease. The kappa coefficient was 0.35 (95% confidence interval: 0.26–0.44; P  < 0.0001).
Conclusions:   The weak agreement between the clinical diagnosis and the PFT interpretation in patients showing concomitant decreases in FEV₁ and FVC suggests that other clinical findings should be assessed in addition to PFT.     

Pleural fluid pH as a predictor of survival for patients with malignant pleural effusions

STUDY OBJECTIVES: To assess the accuracy of pleural fluid (PF) pH in predicting duration of survival of patients with malignant pleural effusions. DESIGN: Analysis of patient-level data from nine sources retrieved from a MEDLINE search and correspondence with primary investigators. STUDY SELECTION: Published and unpublished studies that report PF pH values and duration of survival of patients with malignant pleural effusions. DATA COLLECTION AND ANALYSIS: Primary investigators supplied patient-level data (n = 417), which was examined by receiver operating characteristic (ROC) analysis, logistic regression, and survival time modeling to determine the utility of PF pH for predicting survival compared with other clinical factors. The primary investigations were graded for study design. MEASUREMENTS AND RESULTS: Median survival (n = 417) was 4.0 months: PF pH (p < 0.0039) was an independent predictor of survival duration. A PF pH test threshold < or = 7.28 had the highest accuracy for identifying poor 1-, 2-, and 3-month survivals. The predictive accuracies of PF pH (area under the ROC curve range, 0.571 to 0.662) and a PF pH-high-risk tumor (lung, soft tissues, renal, ovary, gastrointestinal, prostate, and oropharynx) model (odds ratio range, 2.91 to 6.67), however, were modest for predicting 1-, 2-, and 3-month survival. Only 54.4% and 62.7% of patients identified by PF pH < or = 7.28 or the PF pH-high-risk tumor model to die within 3 months were correctly classified. Weaknesses of the primary data were identified. CONCLUSIONS: PF pH has insufficient predictive accuracy for selecting patients for pleurodesis on the basis of estimated survival.     

The role of fiberoptic bronchoscopy in evaluating the causes of pleural effusions

To evaluate the diagnostic merit of fiberoptic bronchoscopy in pleural effusions, we performed fiberoptic bronchoscopy in addition to thoracocentesis and closed pleural biopsy in 140 patients who were admitted for diagnostic investigation of the causes of pleural effusions. The patients were divided into subgroups based on clinical features and roentgenographic findings of chest x-ray films. In 39 patients, the pleural effusions were due to various nonneoplastic disorders and in 95 patients it was caused by malignancy. In six patients, the causes of the pleural effusions remained undetermined. A final diagnosis was made by pleural examination in 68 patients, by fiberoptic bronchoscopy in 58 patients, and by either one or both in 100 patients. In 82 patients who had no hemoptysis, a final diagnosis was made by pleural examination in 57 cases and by fiberoptic bronchoscopy in 11 cases only. The diagnostic yield of fiberoptic bronchoscopy (47/58) was superior to that of pleural examination (11/58) in 58 patients presenting with hemoptysis. In 74 patients who had pleural effusions as the sole roentgenographic abnormality, the final entity was established by pleural examination in 45 and by fiberoptic bronchoscopy in 12. The diagnostic merit of fiberoptic bronchoscopy was significantly higher in 59 patients who had concurrent pulmonary abnormalities on their chest roentgenograms. A final diagnosis was made in 43 cases by fiberoptic bronchoscopy in comparison with 21 cases by pleural examination. For patients with unknown pleural effusions, fiberoptic bronchoscopy was more likely to yield a diagnosis than thoracocentesis with closed pleural biopsy in those who had hemoptysis or pulmonary abnormality on chest x-ray films, whereas the reverse applied when these features were absent.     

Asbestos exposure and tuberculous pleurisy as developmental causes of progressive unilateral upper-lung field pulmonary fibrosis radiologically consistent with pleuroparenchymal fibroelastosis

BackgroundUnilateral upper-lung field pulmonary fibrosis (upper-PF), which is radiologically consistent with pleuroparenchymal fibroelastosis, develops after thoracic surgery. In most patients with unilateral upper-PF, aberrant intra-/extra thoracic air commonly emerges and an autopsy shows chronic pleuritis, which indicates that pleural involvement is associated with upper-PF development. If so, there may be patients with unilateral upper-PF who have a history of pleural involvement, including tuberculous pleurisy (TP) or asbestos exposure (AE). This study aimed to examine this supposition.MethodsWe examined the radiological reports of all consecutive patients from 2012 to 2018 to investigate whether there were patients having unilateral upper-PF and a history of TP or AE.ResultsEight patients were included in the study. Five patients had a history of TP, and the remaining three had that of AE. All patients were men and had respiratory symptoms, and seven patients presented with restrictive ventilatory impairment. The interval between TP or last AE and upper-PF development was long, with a median of over 20 years. The upper-PF lesion was commonly located in the right lung, and aberrant intrathoracic air was observed in five patients during their clinical course. Additionally, the upper-PF lesion transformed into a cystic lesion in six patients, which resulted in Aspergillus infection in two patients. The prognosis was poor, with a median overall survival of 38 months.ConclusionsUnilateral upper-PF developed even in patients with a history of pleural involvement. Our results indicate that pleural involvement plays an important role in the development of unilateral upper-PF.     

The role of thoracic ultrasonography for evaluation of patients with decompensated chronic heart failure

OBJECTIVES: This study examined the usefulness of thoracic ultrasonography for evaluation of fluid accumulation in patients with decompensated chronic heart failure (CHF) in comparison with physical signs, upright posteroanterior chest X-ray and echocardiography. BACKGROUND: Decompensated CHF is frequently accompanied by pleural effusion, suggesting that pleural effusion is a useful marker for confirming the diagnosis of the uncontrolled stage of CHF. Thoracic ultrasonography seems to be adequate for this purpose. METHODS: Patients with uncontrolled CHF and an interpretable physical examination, chest X-ray, ultrasonogram for the heart and thorax and thoracic X-ray computed tomographic (CT) scan were enrolled in the study (n = 60). Patients free from thoracic and cardiovascular diseases served as a control (n = 22). Thoracic CT scan was used as the gold standard for the presence or absence of pleural effusion. Variables used to predict body fluid accumulation included the following: pulmonary rales, jugular venous distension or peripheral edema, roentgenographic evidence of pulmonary edema or pleural fluid, pericardial or pleural effusion on ultrasonographic study. RESULTS: The reported incidence of pleural effusion detected by thoracic ultrasonography was high (91%). The incidence of physical signs and roentgenographic signs of body fluid accumulation, however, was modest (56%) to low (33%). The best clinical variable for identifying patients with decompensated CHF was the detection of pleural fluid by thoracic ultrasonography (91% predictive accuracy). This variable also had high interobserver agreement (95% overall agreement, kappa = 0.70). There was only 41% to 65% predictive accuracy of other clinical variables, with 72% to 95% agreement (kappa = 0.400-0.848). CONCLUSIONS: Thoracic ultrasonography is a simple, sensitive and accurate method for the evaluation of body fluid accumulation in patients with decompensated CHF. This technique can be used to assist in making the diagnosis of decompensated CHF if other causes of pleural effusion have been clinically ruled out.     

Impaired cardiac autonomic functions in patients with environmental asbestos exposure: a study of time domain heart rate variability

Environmental asbestos exposure is related to diffuse pleural disease (thickening and calcification) and restrictive pulmonary disease. To assess cardiac autonomic system, we investigated the time domain heart rate variability (HRV) by Holter monitoring and their correlation with pulmonary function tests in patients with pleural disease caused by environmental asbestos exposure. We studied 45 patients (26 men, 19 women, aged 62.67 +/- 10.1 years) and 35 healthy patients who had similar sex and age profile to the patients (24 men, 11 women, aged 59.31 +/- 8.4 years). The asbestosis group was divided into 3 subgroups according to the severity of forced vital capacity (FVC) severe (group 1) (n = 12): FVC less than 50% of expected, moderate (group 2) (n = 16): FVC 64%-51% of expected and mild (group 3) (n = 17): FVC 65%-80% of expected. HRV parameters were significantly different among all groups (P<.0001). Comparing the 4 groups (subgroups and control group), group 1 had the lowest mean HRV values and controls had the highest mean HRV values (P<.0001). Severity of autonomic dysfunction was correlated with the severity of FVC and arterial oxygen pressure. Right ventricular end-diastolic internal diameter (RVEDID) and right ventricular end-systolic internal diameter (RVESID) values were significantly increased in patients (P <.0001, P < 0.0001, respectively). Pulmonary acceleration time (AcT) values were shorter in all patient groups than control group (P <.0001). It was shortest in group 1. Group 2 and 3 had shorter AcT values than control group. HRV parameters were correlated positively with AcT values and negatively with RVEDID and RVESID values. In conclusion, patients with restrictive pulmonary disease due to environmental asbestos exposure had autonomic dysfunction, which was correlated with the severity of restriction. This was thought to be the result of chronic hypoxia, pulmonary hypertension, and right ventricular enlargement.     

Angiopoietin-2 levels are elevated in exudative pleural effusions

OBJECTIVE: To examine the pleural fluid (PF) and serum levels of angiopoietin (Ang)-1, Ang-2, and vascular endothelial growth factor (VEGF) in patients with pleural effusions (PEs). METHODS: One hundred fifteen patients, 16 with transudative PEs due to heart failure and 99 with exudative PEs (malignant, 40; para-pneumonic, 24; tuberculous, 13; miscellaneous etiologies, 22) were included in the study. PF and serum levels of the growth factors were measured using enzyme-linked immunosorbent assay. RESULTS: PF Ang-2 and VEGF levels but not Ang-1 levels were higher (p < 0.001) in exudates than in transudates. PF Ang-2 levels were higher in tuberculous PEs than in PEs of any other etiology and were lower in heart failure PEs than in PEs of any other etiology. The highest PF VEGF levels were observed in patients with malignant and parapneumonic PEs. The lowest PF VEGF levels were observed in patients with transudates. In PEs, Ang-2 levels correlate with VEGF levels (p < 0.001), RBC count (p = 0.002), nucleated cell count (p < 0.001), total protein levels (p < 0.001), and lactate dehydrogenase levels (p < 0.001). PF Ang-1 levels were lower than serum Ang-1 levels both in patients with exudates (p < 0.001) and in those with transudates (p = 0.001). PF Ang-2 levels were higher than serum Ang-2 levels both in patients with exudates (p < 0.001) and in those with transudates (p = 0.045). PF VEGF levels were higher than serum VEGF levels in patients with malignant PEs (p < 0.001) and parapneumonic PEs (p = 0.003), but lower than serum VEGF levels in heart failure PEs (p < 0.001). In patients with tuberculous PEs and exudative PEs of miscellaneous etiology, PF and serum VEGF levels did not differ significantly. CONCLUSION: Ang-2 levels but not Ang-1 levels are elevated in exudative PEs, and they correlate with levels of VEGF and markers of pleural inflammation. It is thus possible that Ang-2 along with VEGF participate in pleural inflammation and the pathogenesis of exudative PEs.     

Comprehensive investigation of novel serum markers of pulmonary fibrosis associated with systemic sclerosis and dermato/polymyositis

OBJECTIVE: To investigate the association between serum levels and clinical signs of lung fibrosis in patients with systemic sclerosis and inflammatory myopathies. METHODS: ELISA tests for a mucin-like glycoprotein KL-6, von Willebrandt factor (vWF), soluble E-selectin (sES) and surfactant protein D (SP-D) were performed in sera of 104 patients with systemic sclerosis, 31 patients with poly/dermatomyositis) and 24 patients with Raynaud's phenomenon as controls. The clinical and laboratory data were evaluated by a simple standard protocol including chest x-ray, lung function tests, echocardiography and, in selected cases, high resolution computer tomography (HRCT). Clinically significant pulmonary fibrosis (PF) defined as a simultaneous presence of radiological sign of pulmonary fibrosis and restrictive impairment. Severe PF was established if HRCT scans showed diffuse interstitial lung disease with low diffusing capacity. End stage PF was determined as severe PF with very low diffusing capacity. RESULTS: Patients with pulmonary fibrosis on chest x-ray showed significantly elevated serum levels of KL-6, SP-D and vWF. Inverse correlation was found between serum levels of KL-6/SP-D and lung function parameters, such as DLCO% and FVC. With regard to HRCT findings, patients with elevated serum level of KL-6 showed significantly more frequently ground glass opacity, diffuse and honeycombing fibrosis than patients with normal level of KL-6. The sensitivity of KL-6 for PF in SSc is increased with the severity of PF (PF on chest x-ray < severe PF < end stage of PF). Lung fibrosis occurred more frequently in patients with simultaneously elevated KL-6 and sES compared to cases with a single positivity of either KL-6 or sES. CONCLUSION: KL-6, SP-D, vWF and ES are good surrogate factors of pulmonary fibrosis but can not replace conventional diagnostic procedures. However, these markers are suitable for the assessment of progression and severity of pulmonary fibrosis in systemic autoimmune disorders once the diagnosis is established.     

ABC del líquido pleural

Virtually all patients with a pleural effusion should undergo thoracentesis to aid diagnosis and management. Routine pleural fluid (PF) evaluation usually includes differential cell count, protein, lactate dehydrogenase, glucose and adenosine deaminase determinations, cytology and, if infection is a concern, pH as well as bacterial and mycobacterial cultures. Distinguishing transudates from exudates through Light's criteria is a pragmatic first step. If the effusion is an exudate, various PF tests have proven diagnostic utility: adenosine deaminase levels >35 U/L usually indicate tuberculosis in lymphocytic-predominant PFs, or empyema in neutrophilic-predominant PFs; pH<7.2 or glucose <60 mg/dL allow the clinician to identify complicated parapneumonic effusions, and conventional cytology may demonstrate malignant cells in 60% of patients with malignant effusions. A number of optional PF tests may complement the diagnostic approach to a pleural effusion of uncertain etiology. For example, natriuretic peptide assays significantly improve the accuracy of diagnosis of cardiac pleural effusions, whereas PF mesothelin levels greater than 20 nM are highly suggestive of mesothelioma.     

Osteopontin is upregulated in malignant and inflammatory pleural effusions

Background and objective:   Osteopontin (OPN) is an important mediator of inflammation and cancer progression. In the present study, we asked whether pleural fluid (PF) and serum OPN concentrations differed between patients with pleural effusions of different aetiologies, and whether assessment of OPN levels was useful for diagnostic purposes.
Methods:   One hundred and nine consecutive patients with pleural effusions of different aetiologies were recruited prospectively during daily clinics. OPN levels were measured by ELISA.
Results:   PF OPN levels were 10-fold higher in exudates than in transudates and were significantly correlated with markers of pleural inflammation and vascular hyper-permeability, such as PF/serum LDH or protein ratios, PF protein and PF vascular endothelial growth factor levels. Patients with malignant pleural effusions had higher PF and lower serum OPN concentrations than those with benign disease. The diagnostic accuracies of PF and PF/serum OPN for malignancy were 71.5% (95% CI: 64–80) and 70.6% (95% CI: 62–80), respectively.
Conclusions:   OPN levels were elevated in exudative pleural effusions, as compared with the levels in blood or transudative pleural effusions. While PF and PF/serum OPN were higher in patients with malignancies, the diagnostic accuracy of the tests was not sufficient to permit routine use in clinical practice.     

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 Light's 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.     

Patient with bilateral pleural effusion: are the findings the same in each fluid?

STUDY OBJECTIVES: To determine whether, in patients with bilateral pleural effusions, the main cellular and biochemical features of the pleural fluid on the right side differ from or correlate with those on the left side. We examined lactate dehydrogenase (LDH), glucose, and total protein (TP) levels, RBC count, nucleated cell count (NCC), and differential cell count. PATIENTS AND METHODS: Twenty-seven patients with bilateral pleural effusions, including 13 patients with effusions after coronary artery bypass graft surgery, 12 patients with congestive heart failure, 1 patient with malignant pericarditis, and 1 patient with renal failure, were studied retrospectively. RESULTS: The right-sided and the left-sided pleural effusions did not differ in the mean TP (p = 0.38), glucose (p = 0.31), and LDH (p = 0.39) levels, RBC count (p = 0.31), NCC (p = 0.96), and the percentage of neutrophils (p = 0.22), lymphocytes (p = 0.73), mononuclear cells (MNCs) [p = 0.49], and eosinophils (p = 0.65). The bias +/- precision was 0.1 +/- 0.64 g/dL for TP, - 2.7 +/- 23 mg/dL for glucose, 41 +/- 362 IU/L for LDH, 6,100 +/- 62,900 cells/ micro L for RBC count, - 36 +/- 1,043 cells/ micro L for NCC, - 2.9 +/- 11.6% for the percentage of neutrophils, 1.15 +/- 17% for the percentage of lymphocytes, 2.3 +/- 17% for the percentage of the MNCs, and - 0.15 +/- 5.4% for the percentage of eosinophils. Moreover, there was a close correlation between the right-sided and the left-sided pleural effusions concerning TP level (r = 0.85, p < 0.001), glucose level (r = 0.78, p < 0.001), LDH level (r = 0.71, p < 0.001), RBC count (r = 0.66, p < 0.001), NCC (r = 0.60, p = 0.001), and the percentage of neutrophils (r = 0.77, p < 0.001), lymphocytes (r = 0.77, p < 0.001), MNCs (r = 0.74, p < 0.001), and eosinophils (r = 0.84, p < 0.001). CONCLUSION: Since the pleural fluid findings tend to be similar in both sides of patients with bilateral pleural effusion, we suggest that diagnostic thoracentesis may not need to be performed on both sides, unless there is a specific clinical indication.     

Pleural determinants of restrictive lung function and respiratory symptoms in an asbestos-exposed population.

To further define the relationship between asbestos-induced pleural fibrosis and restrictive lung function, we investigated the pleural determinants of respiratory symptoms and restrictive physiology in 1,211 sheet metal workers. We evaluated the relationship between specific components of pleural fibrosis (costophrenic angle involvement, diaphragmatic plaques, width and length of pleural fibrosis, pleural calcification, and the type of fibrosis-circumscribed plaque or diffuse pleural thickening) and both forced vital capacity and respiratory symptoms. We found that costophrenic angle involvement, the width and length of pleural fibrosis, and the presence of either circumscribed plaque or diffuse pleural thickening were each significantly associated with a lower FVC. No consistent relationship was observed between FVC and either diaphragmatic plaques or pleural calcification. However, since the pleural abnormalities were highly collinear, none of these abnormalities alone or in combination predicted the reduction in FVC significantly better than a model that included circumscribed plaques and diffuse pleural thickening. We also investigated the relationship of each component of pleural fibrosis with cough, dyspnea, and chest pain. After controlling for appropriate confounders, a trend toward significance was observed between increased width and length of fibrosis and dyspnea with exertion. Otherwise, these pleural abnormalities were not consistently related to any of the three respiratory symptoms. Our results indicate that although pleural plaques and diffuse pleural thickening and their components are independently associated with a lower FVC, these components of pleural fibrosis do not substantially improve the previously defined relationship between FVC and both circumscribed plaques and diffuse pleural thickening. In addition, a trend toward significance was observed between the width and length of the pleural abnormality and dyspnea while hurrying.