CHEST Guidelines-Failure-of-Fibrinolytic-Therapy-in-Empyema

Failure-of-Fibrinolytic-Therapy-in-Empyema_chest

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This correspondence revolves around a published article in "CHEST" by Barrett et al., focusing on the role of neutrophil elastase in the ineffectiveness of fibrinolytic therapy for empyema. Florova and Komissarov comment on potential issues with the study, such as the selection of patients with low plasminogen levels and the activity of plasminogen activator inhibitor 1 (PAI-1). They argue that the findings might not represent standalone elastase activity due to potential interference with a2-macroglobulin complexes. They emphasize that elevated PAI-1 levels are detrimental to pleural injury treatment and advocate for research to improve therapeutic strategies, suggesting the importance of further preclinical trials.<br /><br />Barrett et al. respond, clarifying that patient selection was not random but rather part of a sequential enrollment in a prospective trial. The authors acknowledge the apparent mismatch between PAI-1 antigen levels and its activity but insist that their study's approach was rigorous. They mention that elastase effectively cleaves PAI-1, disabling its interaction with tissue plasminogen activator (tPA). They also challenge the assumption that PAI-1 is the main barrier to fibrinolytic efficacy due to the prolonged need for tPA dosing. Barrett and colleagues present data showing rapid reduction in PAI-1 activity after treatment initiation, suggesting other factors might contribute to the duration of treatment required for patient improvement.<br /><br />Both parties agree on the necessity for ongoing research but differ on interpretations and methodologies concerning fibrinolytic therapy for empyema. Florova and Komissarov call for comparative clinical trials and development of preclinical models, while Barrett et al. defend their study's conclusions and methodologies, emphasizing biochemical explanations for their outcomes.

Keywords

neutrophil elastase

fibrinolytic therapy

empyema

plasminogen levels

PAI-1 activity

a2-macroglobulin complexes

tissue plasminogen activator

preclinical trials

comparative clinical trials

biochemical explanations