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Translating Basic Research Into Clinical Practice |

Translational Research in Pleural Infection and Beyond

Y. C. Gary Lee, PhD; Steven Idell, MD; Georgios T. Stathopoulos, MD
Author and Funding Information

FUNDING/SUPPORT: Y. C. G. L. is a National Health and Medical Research Council (NHMRC) Career Development Fellow and receives research project grant funding from the NHMRC, New South Wales Dust Disease Board, Sir Charles Gairdner Research Advisory Committee, Westcare, and the Cancer Council of Western Australia. S. I. is supported by National Institutes of Health (NIH), National Heart, Lung, and Blood Institute grants RO-1HL118401-01A1 and UO-1 HL121841-01A1, and by NIH SMARTT contract No. HHSN268201100014C, and by funds from the Texas Lung Injury Institute and the Temple Chair of Pulmonary Fibrosis. G. T. S. is supported by European Research Council 2010 Starting Independent Investigator and 2015 Proof of Concept grants [#260524 and #679345, respectively].

aDepartment of Respiratory Medicine, Sir Charles Gairdner Hospital, University of Western Australia, Perth, Australia

bSchool of Medicine and Pharmacology, University of Western Australia, Perth, Australia

cPleural Medicine Unit, Institute of Respiratory Health, Perth, Australia

dDepartment of Cellular and Molecular Biology and the Texas Lung Injury Institute, University of Texas Health Science Center at Tyler, Tyler, TX

eLaboratory for Molecular Respiratory Carcinogenesis, Department of Physiology, Faculty of Medicine, University of Patras, Rio, Achaia, Greece

fComprehensive Pneumology Center, University Hospital, Ludwig Maximilian University and Helmholtz Zentrum München, Member of the German Center for Lung Research, Munich, Germany

CORRESPONDENCE TO: Y. C. Gary Lee, PhD, 533 Harry Perkins Building, QE II Medical Centre, Perth, WA 6009, Australia


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;150(6):1361-1370. doi:10.1016/j.chest.2016.07.030
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The incidence of pleural infection has been rising in recent years. Intrapleural therapy with tissue plasminogen activator (tPA) and deoxyribonuclease (DNase) has significantly reduced the need for surgery, and its impact on clinical care is rising worldwide. Efforts are underway to optimize the delivery regimen and establish the short and longer term effects of this therapy. The complex interactions of bacterial infection within the pleura with inflammatory responses and clinical interventions (antibiotics and tPA/DNase or other fibrinolysins) require further studies to improve future treatment options. Intrapleural instillation of tPA potently induces pleural fluid formation, principally via a monocyte chemotactic protein (MCP)-1 dependent mechanism. Activation of transcriptional programs in pleural resident cells and infiltrating cells during pleural infection and malignancy results in the local secretion of a cocktail of proinflammatory signaling molecules (including MCP-1) within the pleural confines that contributes to effusion formation. Understanding the biology of these molecules and their interaction may provide novel targets for pleural fluid control.

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