Angiogenic Cytokines and Fibrinolytic Activity in Parapneumonic Effusions

Pleural Effusion Clinical Trial

Official title:

Angiogenic Cytokines and Fibrinolytic Activity in Parapneumonic Effusions

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01325454
• Other study ID #: TMUH-PARAPNEUMONIC STUDY
• Status: Recruiting
• Phase: N/A
• First received: March 23, 2011
• Last updated: March 28, 2011
• Start date: January 2008
• Est. completion date: December 2011

Study information

• Verified date: March 2011
• Source: Taipei Medical University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Taiwan: Department of Health
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: December 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

• 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).

Exclusion Criteria:

• History of chest trauma or invasive procedures directed into the pleural cavity; bleeding disorder or anticoagulant therapy

• Use of streptokinase in the previous 2 years; and likely survival less than 6 months.

Study Design

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

• Pleural Effusion

Intervention

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.

Locations

Country	Name	City	State
Taiwan	Division of Pulmonary Medicine, Taipei Medical University Hospital	Taipei

Sponsors (2)

Lead Sponsor	Collaborator
Taipei Medical University Hospital	National Science Council, Taiwan

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response to treatment including improvement in vital signs and chest radiography		5 days after treatment within admission	No
Secondary	Chest radiography and pulmonary function testing with spirometry.		At discharge, and at 6 months	No