CHEST Guidelines-Response_chest

Response_chest_34

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In this letter to the editor, the authors address feedback from Komissarov and Florova concerning their article on the role of plasminogen activator inhibitor-1 (PAI-1) in complex pleural diseases. The original study explored the inefficacies of intrapleural fibrinolysis, suggesting neutrophil-mediated inflammatory plasminogen degradation, instead of high PAI-1, as a primary cause.<br /><br />The authors contend that their method did not arbitrarily select patients but used all available subjects from a prospectively randomized trial. They reaffirm that their findings reflecting the plasma-to-pleural fluid plasminogen ratios align with existing literature, emphasizing significant reductions in detectable plasminogen in complex effusions. The study reports that the variable effectiveness of intrapleural tissue plasminogen activator (tPA) is not primarily due to PAI-1 activity, as the latter significantly decreases after tPA administration. Despite this, a typical treatment course involves multiple tPA doses over three days, prompting questions on the impact of PAI-1 inhibition alone.<br /><br />The authors address critiques about elastase's role, noting their evidence of elastase cleaving PAI-1, potentially altering its inhibitory effect on tPA. They clarify that, contrary to suggestions, they did not recommend using active plasmin but proposed plasminogen supplementation, which is common in various medical treatments and not associated with specific complications.<br /><br />The communication invites further research on plasminogen's role in pleural space diseases and implies that enhancing plasminogen levels may improve outcomes. The letter underscores the necessity of cautious advancement of therapeutics and calls for detailed clinical trials. It also acknowledges financial support from the Surgical Infection Society and related NIH grants, asserting no conflicts of interest or external influence in the study design or outcome.

Keywords

plasminogen activator inhibitor-1

complex pleural diseases

intrapleural fibrinolysis

neutrophil-mediated inflammation

plasminogen degradation

tissue plasminogen activator

elastase

plasminogen supplementation

therapeutics

clinical trials