Angiogenic Cytokines and Fibrinolytic Activity in Parapneumonic Effusions

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 Overview

• Status: Unknown
• Conditions: Pleural Effusion
• Intervention / Treatment: Device: pleural pigtail drainage

Detailed 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.

• Study Type: Observational
• Enrollment (Anticipated): 80

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 110
    • Recruiting
    • Division of Pulmonary Medicine, Taipei Medical University Hospital
    • Contact: Chi-Li Chung, MD, PhD; Phone Number: 3903 886-2-27372181; Email: d102092009@tmu.edu.tw
    • Principal Investigator: Chi-Li Chung, MD, PhD
    • Sub-Investigator: Shih-Hsin Hsiao, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with pleural effusions of unknown causes admitted to Taipei Medical University Hospital were included.

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

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.; Other Names: chest drain; chest tube drainage; tube thoracostomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Response to treatment including improvement in vital signs and chest radiography	5 days after treatment within admission

Secondary Outcome Measures

Outcome Measure	Time Frame
Chest radiography and pulmonary function testing with spirometry.	At discharge, and at 6 months

Collaborators and Investigators

• Sponsor: Taipei Medical University Hospital
• Collaborators: National Science Council, Taiwan
• Investigators: Principal Investigator: Chi-Li Chung, MD, PhD, Division of Pulmonary Medicine, Taipei Medical University, Taipei, Taiwan

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Anticipated): June 1, 2011
• Study Completion (Anticipated): December 1, 2011

Study Registration Dates

• First Submitted: March 23, 2011
• First Submitted That Met QC Criteria: March 28, 2011
• First Posted (Estimate): March 29, 2011

Study Record Updates

• Last Update Posted (Estimate): March 29, 2011
• Last Update Submitted That Met QC Criteria: March 28, 2011
• Last Verified: March 1, 2011

More Information

Terms related to this study

• Keywords: Pleural effusion; angiogenic cytokine; fibrinolytic activity
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Pleural Diseases; Pleural Effusion
• Other Study ID Numbers: TMUH-PARAPNEUMONIC STUDY