Pleural Loculation Research Articles

Complications of indwelling pleural catheter use and their management

The growing utilisation of indwelling pleural catheters (IPCs) has put forward a new era in the management of recurrent symptomatic pleural effusions. IPC use is safe compared to talc pleurodesis,...

Intrapleural Fibrinolysis for the Treatment of Indwelling Pleural Catheter-Related Symptomatic Loculations: A Multicenter Observational Study

Indwelling pleural catheters (IPCs) are an effective option in the management of malignant pleural effusion. Up to 14% of patients with IPCs develop symptomatic pleural loculations causing ineffective fluid drainage and breathlessness. To our knowledge, this is the first study to describe intrapleural fibrinolytic therapy for IPC-related symptomatic loculations. All patients who received intrapleural fibrinolytic therapy for symptomatic loculations between January 1, 2002, and June 30, 2014, in four established IPC centers were retrospectively included. Patient outcomes, treatment effectiveness, and adverse events were recorded. Sixty-six patients (mean age, 64.7 ± 14.2 years; 52% women) were included. Lung cancer (31.3%) and malignant pleural mesothelioma (20.3%) were the most common malignancies. Fibrinolytic instillation was performed in outpatient (61%) and inpatient settings. Tissue-plasminogen activator (n = 52), urokinase (n = 12), and streptokinase (n = 2) were used. The majority (69.7%) received only one fibrinolytic dose (range, one to six). Pleural fluid drainage increased in 93% of patients, and dyspnea improved in 83% following therapy. The median cumulative pleural fluid volume drained at 24 h posttreatment was 500 mL (interquartile range 300-1,034 mL). The area of opacity caused by pleural effusion on chest radiograph decreased from (mean, SD) 52% (14%) to 31% (21%) of the hemithorax (n = 13; P = .001). There were two cases of nonfatal pleural bleed (3%). Intrapleural fibrinolytic therapy can improve pleural fluid drainage and symptoms in selected patients with IPC and symptomatic loculation, but it carries a small risk of pleural bleeding. There is significant heterogeneity in its use currently, and further studies are needed to determine patient selection and optimal dosing regimen and to define its safety profile.

Derivation and Validation of a CT Scan Scoring System for Discriminating Malignant From Benign Pleural Effusions

Chest CT scanning has become an integral part of the workup for undiagnosed pleural effusions. We aimed to develop a CT scan-based scoring system for differentiating between benign and malignant pleural effusions. A number of chest CT scan abnormalities were compared between 228 patients with benign and 115 with malignant effusions (derivation cohort). A logistic regression analysis was used to identify the independent predictors of malignancy and generate CT scan scores, with more points assigned to those findings associated with higher β-coefficient values. The diagnostic accuracy of the CT scan scoring system was calculated for the derivation cohort and further evaluated in two independent populations (n = 80 and 42, respectively) by two radiologists. CT scan scores predicting malignancy included any pleural lesion (ie, nodule, mass, or thickening) ≥ 1 cm (5 points); the presence of liver metastases, an abdominal mass, or a lung mass or nodule ≥ 1 cm (3 points each); and the absence of either pleural loculations, pericardial effusions, or cardiomegaly (2 points each). In the first validation cohort, a sum score of ≥ 7 yielded a sensitivity of 88% (95% CI, 73%-95%), specificity of 94% (95% CI, 83%-98%), likelihood ratio positive of 13.8 (95% CI, 4.6-41.5), likelihood ratio negative of 0.13 (95% CI, 0.05-0.33), and area under the receiver operating characteristics curve of 0.919 (95% CI, 0.849-0.990). Moreover, 69% of 42 patients with pathologically unconfirmed malignant effusions from a second independent cohort would have been correctly labeled by the predictive score. A simple CT scan-based scoring system can help physicians to separate malignant from benign pleural effusions.

Plasminogen-Plasmin System in the Pathogenesis and Treatment of Lung and Pleural Injury

Lung and pleural injuries are characterized by inflammation, fibrinous transitional matrix deposition, and ultimate scarification. The accumulation of extravascular fibrin is due to concurrently increased local coagulation and decreased fibrinolysis, the latter mainly as a result of increased plasminogen activator inhibitor-1 (PAI-1) expression. Therapeutic targeting of disordered fibrin turnover has long been used for the treatment of pleural disease. Intrapleural fibrinolytic therapy has been found to be variably effective in clinical trials, which likely reflects empiric dosing that does not account for the wide variation in pleural fluid PAI-1 levels in individual patients. The incidence of empyema is increasing, providing a strong rationale to identify more effective, nonsurgical treatment to improve pleural drainage and patient outcomes. Therapeutics designed to resist inhibition by PAI-1 are in development for the treatment of pleural loculation and impaired drainage. The efficacy and safety of these strategies remains to be proven in clinical trial testing. Fibrinolytic therapy administered via the airway has also been proposed for the treatment of acute lung injury, but this approach has not been rigorously validated and is not part of routine clinical management at this time. Challenges to airway delivery of fibrinolysins relate to bioavailability, distribution, and dosing of the interventional agents.

Clinical Importance of Angiogenic Cytokines, Fibrinolytic Activity and Effusion Size in Parapneumonic Effusions

ObjectiveTo investigate the relationship among angiogenic cytokines, fibrinolytic activity and effusion size in parapneumonic effusion (PPE) and their clinical importance.MethodsFrom January 2008 through December 2010, 26 uncomplicated (UPPE) and 38 complicated (CPPE) PPE were studied. Based on chest ultrasonography, there were non-loculated in 30, uni-loculated in 12, and multi-loculated effusions in 22 patients. The effusion size radiological scores, and effusion vascular endothelial growth factor (VEGF), interleukin (IL)-8, plasminogen activator inhibitor type-1 (PAI-1) and tissue type plasminogen activator (tPA) were measured on admission. Treatment outcome and pleural fibrosis, defined as radiological residual pleural thickening (RPT), were assessed at 6-month follow-up.ResultsThe effusion size and effusion VEGF, IL-8 and PAI-1/tPA ratio were significantly higher in CPPE than in UPPE, and significantly higher in multi-loculated PPE than in non-locualted and uni-loculated PPE, respectively. VEGF (cutoff value 1975 pg/ml) and IL-8 (cutoff value 1937 pg/ml) seemed best to discriminate between UPPE and CPPE. VEGF, IL-8 and effusion size correlated positively with PAI-1/tPA ratio in both UPPE and CPPE. Moreover, the level of VEGF, but not IL-8, correlated positively with effusion size in all patients (r = 0.79, p<0.001) and in UPPE (r = 0.64, p<0.001) and CPPE (r = 0.71, p<0.001) groups. The patients with higher VEGF or greater effusion were prone to have medical treatment failure (n = 10; VEGF, odds ratio 1.01, p = 0.02; effusion size, odds ratio 1.26, p = 0.01). Additionally, ten patients with RPT had larger effusion size and higher levels of VEGF and PAI-1/tPA ratio than did those without.ConclusionsIn PPE, VEGF and IL-8 levels are valuable to identify CPPE, and higher VEGF level or larger effusion is associated with decreased fibrinolytic activity, development of pleural loculation and fibrosis, and higher risk of medical treatment failure.

Intrapleural streptokinase for the treatment of complicated parapneumonic effusion and empyema in 2 newborns

The management of complicated parapneumonic effusions by conventional first-line treatment with closed intercostal tube drainage and antibiotic therapy may fail because of thick viscous fluid and multiple pleural space loculations. Intrapleural fibrinolytic treatment is a non-invasive therapeutic option. In this report, we present successful use of intrapleural streptokinase for complicated parapneumonic effusion and empyema in 2 newborns. Intrapleural fibrinolytic therapy with streptokinase appears to be a safe and effective adjunctive therapy of choice and may have significant benefit even in newborns with complicated parapneumonic effusion and empyema, and thus, it can obviate surgical intervention.

Intrapleural Therapy in Empyema Thoracis: A Contemporary Solution to an Age-Old Problem?

p c a Infection within the pleural space has posed a management dilemma for physicians since the time of Hippocrates. Despite advances in medical treatment for pneumonia, the incidence of both complicated parapneumonic effusion and empyema is increasing in both the United States and the United Kingdom.1,2 The impact of the problem is significant; with up to one-third of patients progressing to surgical decortication and drainage and overall mortality ranging from 10%-20%.1,3 Complete drainage of the infection is the key management principle. Systemic antibiotic therapy and drainage of the pleural space via tube thoracostomy constitute first-line management, with surgical drainage reserved for those with complicated effusions, development of a pleural “peel or rind,” or uncontrolled pleural sepsis. Adjunctive administration of pleural fibrinolytic agents, such as tissue plasminogen activator (t-PA), through an indwelling thoracostomy tube has been well-described. The intent of treatment is to dissolve the fibrinous septa forming pleural loculation. Although several retrospective series reported improved therapeutic efficacy, the first randomized trial of this approach, the Multicenter Intrapleural Sepsis Trial (MIST1), showed no benefit to the addition of intrapleural streptokinase in this patient population.4 A subsequent meta-analysis assessing the use of intrapleural fibrinolytic agents also identified no benefit over traditional pleural drainage.5 These findings, coupled with increased experience with thoracoscopic techniques for decortication and pleural drainage, resulted in a shift toward early surgical management of patients with complicated effusions. In contrast to the poor success by using a single

Regulation of intrapleural fibrinolysis by urokinase-α-macroglobulin complexes in tetracycline-induced pleural injury in rabbits

The proenzyme single-chain urokinase plasminogen activator (scuPA) more effectively resolved intrapleural loculations in rabbits with tetracycline (TCN)-induced loculation than a range of clinical doses of two-chain uPA (Abbokinase) and demonstrated a trend toward greater efficacy than single-chain tPA (Activase) (Idell S et al., Exp Lung Res 33: 419, 2007.). scuPA more slowly generates durable intrapleural fibrinolytic activity than Abbokinase or Activase, but the interactions of these agents with inhibitors in pleural fluids (PFs) have been poorly understood. PFs from rabbits with TCN-induced pleural injury treated with intrapleural scuPA, its inactive Ser195Ala mutant, Abbokinase, Activase, or vehicle, were analyzed to define the mechanism by which scuPA induces durable fibrinolysis. uPA activity was elevated in PFs of animals treated with scuPA, correlated with the ability to clear pleural loculations, and resisted (70-80%) inhibition by PAI-1. Alpha-macroglobulin (alphaM) but not urokinase receptor complexes immunoprecipitated from PFs of scuPA-treated rabbits retained uPA activity that resists PAI-1 and activates plasminogen. Conversely, little plasminogen activating or enzymatic activity resistant to PAI-1 was detectable in PFs of rabbits treated with Abbokinase or Activase. Consistent with these findings, PAI-1 interacts with scuPA much slower than with Activase or Abbokinase in vitro. An equilibrium between active and inactive scuPA (k(on) = 4.3 h(-1)) limits the rate of its inactivation by PAI-1, favoring formation of complexes with alphaM. These observations define a newly recognized mechanism that promotes durable intrapleural fibrinolysis via formation of alphaM/uPA complexes. These complexes promote uPA-mediated plasminogen activation in scuPA-treated rabbits with TCN-induced pleural injury.

Plasmin Enhances Cell Surface Tissue Factor Activity without Increasing Tissue Factor Antigen Levels at the Cell Surfaces of Mesothelial and Endothelial Cells.

Mesothelial cells that line the thoracic and peritoneal cavities play an important role in protecting the heart, lungs and internal organs and keeping the surfaces free of friction and non-adhesive. Although human mesothelial cells in culture express low levels of tissue factor (TF), TF expression was not detected in vivo in the mesothelial lining of normal pleura but was detected in the mesothelium overlying injured or inflamed lung tissue. Inflammation in the lung parenchyma predisposes to the development of inflammatory exudative pleural effusions and pleural loculation, but the mechanism(s) responsible for TF expression in mesothelial cells under such conditions remains unclear. In the present study, we investigated whether plasmin and thrombin, two major proteases present in exudative pleural effusions, induce TF expression in cultured primary human pleural mesothelial cells (HMC). Confluent monolayers of HMC were treated with plasmin (50 nM) and thrombin (5 nM) for varying time periods. TF expression was analyzed by measurement of cell surface TF activity in FX activation assay, TF antigen by Western blotting and TF mRNA by Northern blot analysis. Both plasmin and thrombin increased cell surface TF activity by 3–4 fold. Thrombin markedly increased TF antigen levels. Surprisingly, only a minimal increase in TF antigen levels was seen in the plasmin-treated cells and no increase in TF mRNA was observed in these cells. Interestingly, 75% of the increase in TF activity was observed within 30 min of plasmin treatment. In thrombin-stimulated cells, TF activity increased slowly, reaching maximum at 4–6 h. Treatment of HMC with actinomycin-D or cycloheximide prior to the addition of the protease failed to inhibit the plasmin-induced TF activity whereas they completely attenuated the thrombin-induced TF activity. These data suggest that plasmin and thrombin enhance TF activity in HMC by different mechanisms, and that plasmin-induced TF activity is independent of de novo synthesis of TF. We also examined the effect of plasmin on TF activity in human umbilical vein endothelial cells (HUVEC). Although plasmin had a minimal effect on naive HUVEC, 30 min plasmin treatment increased cell surface TF activity of thrombin-stimulated endothelial cells by more than two-fold. In our earlier studies, we showed that proteases could mobilize intracellular TF to the cell surface of fibroblasts and thus enhance TF activity independent of de novo synthesis of TF. However, FACS analysis and 125I-FVIIa binding to cell surface TF revealed no significant differences in TF antigen levels at the surfaces of control and plasmin-stimulated HMC. Since exposure of anionic phospholipids at the outer cell surface membrane can increase cell surface TF activity, we next sought to determine if plasmin increases anionic phospholipids on the outer bilayer of the HMC cell membrane. Prothrombin activation assays showed no increase in anionic phospholipids at the surface in plasmin-treated cells. Although recent studies suggest that disulfide bond formation of cysteines in TF enhances TF procoagulant activity, our recent studies in other cell model systems suggest that this mechanism is unlikely to account for plasmin-mediated induction of cell surface TF activity in HMC. While further studies are required to exclude this possibility, our present data indicate that plasmin enhances cell surface TF activity of HMC and HUVEC by a novel mechanism that is yet to be elucidated.

Thoracoscopy in pediatric pleural empyema: a prospective study of prognostic factors

Purpose The indications for thoracoscopy remain imprecise in cases of pleural empyema. This study aimed to identify preoperative prognostic factors to help in the surgical decision. Methods From 1996 to 2004, 50 children with parapneumonic pleural empyema underwent thoracoscopy either as the initial procedure (n = 26) or after failure of medical treatment (n = 24). Using multivariate analysis, we tested the prognostic value of clinical and bacteriological data, the ultrasonographic staging of empyema, and the delay before surgery. Outcome measures were technical difficulties, postoperative complications, time to apyrexia, duration of drainage, and length of hospitalization. Results The clinical and bacterial data did not significantly predict the postoperative course. Echogenicity and the presence of pleural loculations at ultrasonography were not independent significant prognostic factors. A delay between diagnosis and surgery of more than 4 days was significantly correlated ( P < .05) with more frequent surgical difficulties, longer operative time, more postoperative fever, longer drainage time, longer hospitalization, and more postoperative complications, such as bronchopleural fistula, empyema relapse, and persistent atelectasia. Conclusion The main prognostic factor for thoracoscopic treatment of pleural empyema is the interval between diagnosis and surgery. A 4-day limit, corresponding to the natural process of empyema organization, is significant. The assessment of loculations by ultrasonography alone is not sufficient to predict the postoperative course.

Intrapleural activation, processing, efficacy, and duration of protection of single-chain urokinase in evolving tetracycline-induced pleural injury in rabbits

Intrapleural fibrinolysins have been used to treat pleural loculations. However, the efficacy of clinically available agents has recently been questioned, providing a rationale for investigation of new interventions. Single-chain urokinase plasminogen activator resists inhibition by serpins, and repeated, daily intrapleural administration of this agent prevents intrapleural loculation more effectively than complexes of this proenzyme with its receptor (Idell S, Mazar A, Cines D, Kuo A, Parry G, Gawlak S, Juarez J, Koenig K, Azghani A, Hadden W, McLarty J, Miller E. Am J Respir Crit Care Med 166: 920-926, 2002). Understanding of the protective mechanism and intrapleural processing remains unclear. We speculated that single-chain urokinase could induce sustained local fibrinolysis and protection by selective administration either before, during, or following loculation after pleural injury induced by tetracycline in rabbits. Enzymography, immunoassays, histology, immunohistochemistry, morphology, and morphometry were used to test the efficacy, duration of protective effect, and processing of single-chain urokinase. Intrapleural single chain urokinase prevented loculation at 72 h after injury (P < 0.01) if given either before or during adhesion formation and was converted to two-chain high-molecular-weight urokinase, which remained active for at least 24 h within pleural fluids. The effect was dose dependent, and established loculations at 72 h after tetracycline-induced injury were reversed at 96 h by single-dose treatment. Single-chain urokinase bound and saturated intrapleural plasminogen activator inhibitory (PAI)-1-like activity and urokinase-related immunoreactivity of the mesothelium was comparable in treatment or vehicle-control groups. Adhesions recurred by 2 wk after treatment with recurrence of excess local PAI activity. Single-chain urokinase induces sustained local fibrinolysis and reversibly prevents pleural loculation for up to 48 h after intrapleural administration after tetracycline-induced injury.

Thorax ultrasound in the management of pediatric pneumonias complicated with empyema

The aim of this work is to prospectively study the value of thoracic ultrasound (US) before pleural drainage in children with parapneumonic effusion (PPE). All children hospitalized for PPE, identified by thoracic radiography, underwent US to assess pleural loculation, echogenicity, and pleural fluid quantity. From August 2001 to July 2003, 52 children were examined. US was performed on 48 of these children, of whom 35 received chest tube drainage and 13 only received clinical treatment. US identified 38 patients with free flowing and 10 with loculated pleural fluid. About 25 of the free flowing (65.8%) and 10 (100%) of the loculated patients received chest tube drainage. Echogenicity was anechoic in 13, echoic without septations in 17 and echoic with septations in 18. Chest tube drainage was required in 6 anechoic (46.15%), 14 echoic without septations (82.35%), and 15 echoic with septations (83.33%). Quantity of fluid estimated by US varied from 20 to 860 ml. Effusion volume was higher in patients that were echoic with septations and loculated effusions. Pleural glucose and pH were lower, and LDH was higher in loculated PPE patients. In conclusion, US is an auxiliary exam for determining whether thoracic drainage is needed in parapneumonic effusion; loculated or echoic effusion should be drained, and free anechoic fluid needs further investigation.

Tunneled Pleural Catheters for Palliation of Malignant Pleural Effusions

Tunneled Pleural Catheters for Palliation of Malignant Pleural Effusions

Utilidad de la urocinasa intrapleural en el tratamiento del derrame pleural paraneumónico

Intrapleural fibrinolytic instillation has been used in the treatment of loculated pleural effusions and empyemas and has reduced the need for surgical intervention. Currently, the most commonly used fibrinolytic is urokinase, although the doses have not yet been standardized in children. The aim of the present study was to evaluate the utility of urokinase in the treatment of infectious pleural effusions in children. A retrospective study was performed of children with infectious pleural effusions admitted to the pediatric intensive care unit (PICU) between January 2000 and December 2003. Age, sex, clinical features, laboratory tests, response to urokinase treatment and clinical course during hospital stay were analyzed. Thirty-one children were treated. The mean age was 38.1 months (SD: 22). There were 18 boys and 13 girls. The most frequent month of diagnosis was November and the number of admission significantly increased from 2002 onwards. The most frequent antibiotic therapy used before admission to the PICU was cefotaxime associated with vancomycin (41 %), followed by cefotaxime alone (16 %). Positive cultures for Streptococcus pneumoniae were found in 11 patients (35 %). Pleural loculation was found in 14 patients (45 %). Treatment with intrapleural urokinase was used in 23 patients (74 %). The mean chest tube drainage was 140 ml (SD: 175) in the 24 hours before urokinase instillation and was 406 ml (SD: 289) in the 48 hours after fibrinolytic therapy (p < 0.05). Twenty-one patients (91 %) who received urokinase treatment had a good response. There were no complications during the treatment. The mean length of stay in the PICU was 5.8 days (SD: 2.6). The incidence of complicated pleural effusions due to S. pneumoniae has increased in the last few years, despite antibiotic therapy. Intrapleural urokinase is an effective treatment, including in empyemas without loculation. None of our patients required thoracotomy and there were few adverse effects.

Coagulation, fibrinolysis, and fibrin deposition in acute lung injury.

To review: a) the role of extravascular fibrin deposition in the pathogenesis of acute lung injury; b) the abnormalities in the coagulation and fibrinolysis pathways that promote fibrin deposition in the acutely injured lung; and c) the pathways that contribute to the regulation of the fibrinolytic system via the lung epithelium, including newly recognized posttranscriptional and urokinase-dependent pathways. Another objective was to determine how novel anticoagulant or fibrinolytic strategies may be used to protect against acute inflammation or accelerated fibrosis in acute lung injury. Published medical literature. Alveolar fibrin deposition is characteristic of diverse forms of acute lung injury. Intravascular thrombosis or disseminated intravascular coagulation can also occur in the acutely injured lung. Extravascular fibrin deposition promotes lung dysfunction and the acute inflammatory response. In addition, transitional fibrin in the alveolar compartment undergoes remodeling leading to accelerated pulmonary fibrosis similar to the events associated with wound healing, or desmoplasia associated with solid neoplasms. In acute lung injury, alveolar fibrin deposition is potentiated by consistent changes in endogenous coagulation and fibrinolytic pathways. Procoagulant activity is increased in conjunction with depression of fibrinolytic activity in the alveolar compartment. Initiation of the procoagulant response occurs as a result of local overexpression of tissue factor associated with factor VII. Depression of fibrinolytic activity occurs as a result of inhibition of urokinase plasminogen activator (uPA) by plasminogen activators, or series inhibition of plasmin by antiplasmins. Locally increased amplification of plasminogen activator inhibitor-1 (PAI-1) is largely responsible for this fibrinolytic defect. Newly described pathways by which lung epithelial cells regulate expression of uPA, its receptor uPAR, and PAI-1 at the posttranscriptional level have been identified. These pathways operate by cis-trans interactions between mRNA binding proteins; regulatory sequences within these mRNAs control their stability. The regulatory mechanisms seem to involve multiple protein-mRNA interactions, and the phosphorylation state of the proteins appears to determine whether complex formation of, or dissociation from, the regulatory sequences occurs. uPA is capable of inducing its own expression in lung epithelial cells as well as that of uPAR and PAI-1-the effects involve posttranscriptional regulatory components. These and related observations have led to the implementation of anticoagulant or fibrinolytic strategies to protect the lung against acute lung injury. The success of new fibrinolytic strategies to block pleural loculation suggests that a similar approach might be used to prevent accelerated pulmonary fibrosis, which can occur in association with many forms of acute lung injury. Disordered coagulation and fibrinolysis promote extravascular fibrin deposition in acute lung injury. It is this deposition that characterizes acute lung injury and repair. Expression of uPA, uPAR, and PAI-1 by the lung epithelium, as well as the ability of uPA to induce other components of the fibrinolytic system, involves posttranscriptional regulation. These pathways may contribute to disordered fibrin turnover in the injured lung. The success of anticoagulant or fibrinolytic strategies designed to reverse the abnormalities of local fibrin turnover in acute lung injury supports the inference that abnormalities of coagulation, fibrinolysis, and fibrin deposition have a critical role in the pathogenesis of acute lung injury.

Pleural Fluid Analysis in Tuberculous Pleurisy Progressing into Severe Pleural Thickening Underwent Pleural Decortication

Background : Although most patients with tuberculous pleurisy respond well to anti-tuberculous drugs, some are known to progress into severe pleural thickening which needs decortication despite adequate anti-tuberculous treatment. Therefore, the purpose of this study was to identify factors associated with the development of severe pleural thickening in patients who finally underwent pleural decortication in tuberculous pleurisy. Patients and Methods : From retrospective medical records review, 121 patients initially diagnosed as tuberculous pleurisy without initial pleural fluid loculation were enrolled between January 1998 and December 2002. They were separated into two groups: 85 patients in group 1 who improved by anti-tuberculous drugs only, and 36 patients in group 2 who had progressed into pleural adhesion and finally underwent pleural decortication despite adequate (more than 6 months) anti-tuberculous treatment. Results : Males were more common in group 2 (M/F=31/5) than in group 1 (M/F=53/32) (p=0.010). Group 2 patients tended to have lower pleural fluid glucose level (58±4 mg/dL) than group 1 (89±3 mg/dL) (p=0.001) and higher pleural fluid adenosine deaminase level (86±5 IU/L) than group 1 (76±

Derrame pleural y empiema complicado en niños: Evolución y factores pronósticos

Complicated pleural empyema has a torpid and longer clinical evolution, requiring in some patients surgical management. The predictive factors for surgical treatment are not well known. To search for clinical, laboratory or radiological predictors for the requirement of surgical treatment in pediatric patients with empyema. A retrospective review of the charts of 108 patients hospitalized for pneumonia plus pleural effusion at the Pediatric Service of the Catholic University Hospital between January 1985 and July 2000. Eighty one patients had complete radiological evaluation and pleural fluid biochemical analysis. Forty nine (60%) fulfilled the criteria for empyema and 32 (40%) for an exudate. Thirteen patients with empyema required surgery and 36 were treated medically. The mean age was 3 years (range 9 months-6 years) for the surgically treated and 4 years (range 12 months-14 years) for the non-surgical group. The male/female ratio was 5:1 in the surgical group and 1:1 for the non-surgical group. Pleural fluid cultures were positive in 21 of 79 patients. Streptococcus pneumonia was the most frequently isolated agent. No significant differences were found between groups for the average days of fever prior to the diagnosis or total days of fever, days of hospital stay, pleural fluid pH (6.8 and 7.0 respectively) and glucose (21 and 31 mg/dl respectively). No differences were either observed for pleural fluid risk factors (pH < 7 and glucose < 20 mgdl), the presence of extensive pleural effusions, pleural loculations or bands on pleural ultrasonography and positive Gram stain or cultures in the pleural fluid. Surgical patients required oxygen for more days than medical patients (7.7 and 5.1 days; p = 0.037). This study failed to find predictive clinical, radiological or pleural fluid parameters, for the requirement of surgical treatment of empyema.

Immunobiology of pleural inflammation: potential implications for pathogenesis, diagnosis and therapy.

Although infectious, inflammatory and neoplastic diseases frequently involve the pleural space and walls, little is known about the immunological and molecular mechanisms underlying pleural disorders. This article provides an overview of recent insights into immunobiological processes likely to play a role in the pathogenesis of pleural disorders. Pleural involvement in certain diseases is associated with the infiltration of a number of different types of immune cells, such as neutrophils, eosinophils or lymphocytes, in various proportions depending on both the course and the aetiology of the underlying disease. In addition to infiltrating cells, mesothelial cells have been demonstrated to actively participate in pleural inflammation via release of various mediators and proteins, including platelet-derived growth factor (PDGF), interleukin-8, monocyte chemotactic peptide (MCP-1), nitric oxide (NO), collagen, antioxidant enzymes and the plasminogen activation inhibitor (PAI). Furthermore, several inflammatory mediators have been detected at increased concentrations within pleural effusions, including lipid mediators, cytokines and proteins (adenosine deaminase, lysosyme, eosinophil-derived cationic proteins, and products of the coagulation cascade). The presence of these mediators underline the concept of pleural inflammation, and certain cytokines seem to characterize a specific aetiology of pleurisy. The understanding of these processes and the sequence of events leading to pleural loculation, pleural adhesion or repair are likely to provide the basis for early therapeutic intervention and reduce pleural-associated morbidity.

Diagnosis and management of thoracic empyemas.

Parapneumonic effusions are frequent complications of bacterial pneumonia. Depending on the severity of the underlying pneumonia, the promptness of antibiotic therapy, and the virulence of the infecting organism, 5% to 50% of patients will require pleural fluid drainage to prevent progression to an empyema. The decision to drain the pleural space depends on multiple clinical, laboratory, and radiographic factors. Delayed drainage results in pleural loculations, prolonged hospitalizations, and increased mortality. Image-guided percutaneous chest catheters provided an effective method for draining both free-flowing and loculated effusions. Fibrinolytic agents are gaining wider acceptance for promoting drainage of loculated, viscous pleural fluid although randomized studies do not exist. Patients failing a chest tube drainage method should undergo early evaluation for an open surgical procedure.

Streptococcus milleri pulmonary disease: a review and clinical description of 25 patients.

Streptococcus milleri is increasingly being recognised as an important pulmonary pathogen which may lead to the development of empyema or lung abscess. Although several small series have been reported, the clinical and laboratory features have yet to be fully characterised. Twenty five cases were identified and the clinical and laboratory data from case records were analysed. There were 16 empyemas, five lung abscesses, and four with both lung abscess and empyema. The mean age of the patients was 61 years (range 36-89) and 84% were men. The most common symptoms at presentation were shortness of breath, chest pain, cough, and weight loss; only 36% had a fever. Four of the nine patients with lung abscess required a diagnostic lobectomy because of suspected malignancy. Predisposing factors were present in 80% of patients and included the following: pneumonia, periodontal disease, excess alcohol intake, previous thoracic surgical procedures, and malignancy. Laboratory features of S milleri infection were leucocytosis, neutrophilia, anaemia, abnormal liver function tests, and hypoalbuminaemia. In the group with empyema five patients had a pneumothorax on initial presentation and pleural loculation occurred in 10 of these patients. The median stay in hospital was 34 days (range 11-88). Six patients died, five of whom had significant underlying illnesses. Pulmonary infection with S milleri may result in considerable morbidity and mortality, and is characterised by a strong male predominance, non-specific symptoms (often without toxicity), the presence of predisposing factors, pleural loculation, pneumothorax, and a protracted stay in hospital.