Abstract
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.
Keywords
pleura - lung - injury and fibrinolysis - fibrinolytic therapy - plasminogen activator
inhibitor-1
