Biomarker Levels During Indwelling Pleural cAtheter Sample Testing

An alternative and emerging treatment for malignant pleural effusions is the placement of a chronic indwelling pleural catheter.

Tunneled pleural catheters (TPC) are ideal for treatment of malignant pleural effusion (MPE) associated with a trapped or non-expandable lung which will not have sufficient visceral and parietal pleura apposition for chemical pleurodesis. Transforming growth factor-Beta 1 (TGF-β) is a profibrotic cytokine, and a potent inducer of Plasminogen activator inhibitor-1 (PAI-1) in human pleural mesothelial cells. PAI-1 inhibits protease-dependent fibrinolytic activity and along with TGF-β, its concentration is increased in exudative and tuberculous pleural effusion. TGF-β levels in pleural fluid have been shown to correlate with pleural thickness in tuberculosis pleurisy and empyema in rabbits.

TGF-β is a multifunctional cytokine primarily produced by mesothelial cells in the pleural space, but can also originate from lung parenchymal macrophages that migrate to the pleural space. In humans, TGF-β consists of three isoforms (TGF-β1, TGF-β2, and TGF-β3). They share many biological activities and their actions on cells are qualitatively similar in most cases. TGF-β stimulates the extracellular matrix production and studies support that TGF-β over-production is a key regulator in pleural fibrosis and chemical pleurodesis. Moreover, TGF-β signaling for the production of PAI-1 is clearly noted in human mesothelial cells of different origins. Different inflammatory stimuli in the pleural space including malignancy and infection may activate TGF-β up-regulation and enhanced production which in turns results in PAI-1 expression.

Inclusion criteria

• Pleural effusion (etiology fulfilling one of the following criteria):

• Malignant effusion confirmed by cytology or pleural biopsy
• exudative effusion in the setting of known malignancy with no other identifiable cause
• Malignant effusion due to tumors that are historically rapidly responsive to systemic therapy (small cell lung cancer, hematological malignancies) will only be included if refractory to standard chemotherapy
• 18 years of age
• Symptoms such as shortness of breath, cough, or chest fullness/chest discomfort
• Demonstration of symptomatic improvement after therapeutic thoracentesis
• Recurrent pleural effusion after therapeutic thoracentesis
• Capacity to provide informed consent

Exclusion criteria

• Projected life expectancy less than 30 days.
• Radiographic evidence of trapped lung - persistent lung collapse with failure of the majority (>50%) of the lung to reexpand following drainage of a pleural effusion
• Previous lobectomy or pneumonectomy on the affected side
• Patient receiving intrapleural chemotherapy
• Chylothorax - pleural effusion with triglyceride levels > 110 mg/dl or chylomicrons on lipoprotein analysis, most commonly due to trauma/obstruction of the thoracic duct
• Parapneumonic effusion - pleural effusion associated with pneumonia
• Empyema - infected pleural space as defined by purulent pleural fluid, positive gram stain, or positive culture
• Inability to adequately perform pleural drainage at home
• Uncorrectable bleeding disorder
• Skin infection at the site of intended catheter insertion
• Pregnant women - detected by spot urine testing prior to the procedure