Angiogenic Cytokines and Fibrinolytic Activity in Parapneumonic Effusions
Recruitment status was Recruiting
Angiogenesis is a key process in the formation of exudative pleural effusions. Fluid loculation is common in parapneumonic effusion and is associated with depressed pleural fibrinolytic activity and poor clinical outcome. However, the relationship between angiogenic cytokines and fibrinolytic activity in the pleural space remains unclear. The researchers's hypothesis is that the levels of angiogenic cytokines were increased and associated with decreased fibrinolytic activity in parapneumonic effusions which may contribute to fibrin deposition and fluid loculation in the pleural space.
|Study Design:||Observational Model: Case Control
Time Perspective: Prospective
|Official Title:||Angiogenic Cytokines and Fibrinolytic Activity in Parapneumonic Effusions|
- Response to treatment including improvement in vital signs and chest radiography [ Time Frame: 5 days after treatment within admission ] [ Designated as safety issue: No ]
- Chest radiography and pulmonary function testing with spirometry. [ Time Frame: At discharge, and at 6 months ] [ Designated as safety issue: No ]
Biospecimen Retention: Samples Without DNA
|Study Start Date:||January 2008|
|Estimated Study Completion Date:||December 2011|
|Estimated Primary Completion Date:||June 2011 (Final data collection date for primary outcome measure)|
Patients with parapneumonic effusions
Patients with pleural effusions of unknown causes admitted to Taipei Medical University Hospital were included if parapneumonic effusion was diagnosed as one associated with pneumonia according to the criteria of the American Thoracic Society (ie, patients with newly acquired respiratory symptoms, fever, and abnormal breath sounds, plus a new lung infiltrate seen on a chest radiograph).
Device: pleural pigtail drainage
With the guidance of chest US, 50 ml of pleural fluid was collected using a standard thoracentesis technique immediately or within 24 hr after hospitalization. When pleural effusion was multi-loculated, the fluid was aspirated from the largest loculus. Routine analyses of pleural fluid for total leukocytes, cell differentials of leukocytes, pH value, and levels of protein, glucose and LDH were performed in addition to cytological and microbiologic examination of pleural fluid.The rest of pleural fluid samples were mixed with 3.8 % sodium citrate in a 9:1 ratio of pleural fluid to citrate. The sodium citrate-mixed pleural fluid specimens were immersed in ice immediately and then centrifuged at 2,500 g for 10 minutes. The cell-free supernatants of pleural fluid were frozen at -70℃ immediately after centrifuge for later measurements. The commercially available enzyme-linked immunosorbent assay kits were used to measure the effusion levels of VEGF, IL-8 , tPA and PAI-1.
Formation of parapneumonic effusions (PPE) involves increased pleural vascular permeability induced by the contiguous pneumonia. It has been demonstrated that exposure of pleural mesothelial cells to bacteria or lipopolysaccharide (LPS) leads to increased release of angiogenic factors, including vascular endothelial growth factor (VEGF) and interleukin (IL)-8, which induce vascular hyperpermeability, fluid exudation, and neutrophil influx into the pleural space, and may play a pivotal role in development of PPE. With persistent inflammation and angiogenesis, amplified vascular and mesothelial permeability leads to increased plasma extravasation, activation of the coagulation cascade, and repression of fibrinolytic activity within the pleural cavity, which contribute to the development of a ''complicated'' PPE, manifested with fibrin deposition and pleural fluid loculation. Fibrin turnover in the pleural cavity is greatly affected by fibrinolytic activity mediated by plasmin, which is regulated mainly by the equilibrium between plasminogen activators (PAs) and plasminogen activator inhibitors (PAIs).VEGF induces vascular hyperpermeability and may facilitate the genesis of fibrin gel in PPE. Previous studies reported that VEGF plays a role in the modulation of tPA and PAI-1, and that anti-VEGF antibody attenuates pleurodesis induced by transforming growth factor-β2. These findings suggest that VEGF may be involved in the regulation of fibrin turnover, fluid loculation and tissue fibrosis in the pleural space. Enhanced procoagulant and depressed fibrinolytic activities have been observed in PPE. However, the relationship between angiogenic cytokines and fibrinolytic activity in PPE remains unclear.
|Division of Pulmonary Medicine, Taipei Medical University Hospital||Recruiting|
|Taipei, Taiwan, 110|
|Contact: Chi-Li Chung, MD, PhD 886-2-27372181 ext 3903 firstname.lastname@example.org|
|Principal Investigator: Chi-Li Chung, MD, PhD|
|Sub-Investigator: Shih-Hsin Hsiao, MD|
|Principal Investigator:||Chi-Li Chung, MD, PhD||Division of Pulmonary Medicine, Taipei Medical University, Taipei, Taiwan|