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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

Financial support: YCGL is a National Health & 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.

SI is supported by the National Institutes of Health, National Heart Lung and Blood Institute Grants RO-1HL118401-01A1, UO-1 HL 121841-01A1 and NIH SMARTT contract No. HHSN268201100014C, funds from the Texas Lung Injury Institute and the Temple Chair of Pulmonary Fibrosis.

GTS is supported by European Research Council 2010 Starting Independent Investigator and 2015 Proof of Concept Grants (#260524 and #679345, respectively).

Conflict of Interest: YCGL is the lead investigator of AMPLE-2, a multicenter randomized trial for which Rocket Medical provides free drainage equipment for participants. YCGL has served on the advisory board of CareFusion, Lung Therapeutic Inc and Sequana Med Ltd and has received an unrestricted educational grant from Rocket Medical UK for research.

SI serves as Chief Scientific Officer for Lung Therapeutics Inc and serves on the Board of Directors. He has grant support from the National Heart Lung and Blood Institute of the National Institutes of Health as Principal Investigator: RO-1HL118401-01A1 Airway Delivery of Fibrinolytic Therapy for ISALI, UO-1 HL 121841-01A1 Single chain urokinase plasminogen activator (scuPA) for treatment of loculated complicated parapneumonic effusions and empyema. And the NHLBI SMARTT program contract No. HHSN268201100014C (completed) for manufacturing of single chain urokinase, toxicology and regulatory support.

GST has no conflict of interests to declare.

1Department of Respiratory Medicine, Sir Charles Gairdner Hospital, University of Western Australia, Perth, Australia

2Pleural Medicine Unit, Institute of Respiratory Health, Perth, Australia

3School of Medicine & Pharmacology, University of Western Australia, Perth, Australia

4Dept of Cellular and Molecular Biology and the Texas Lung Injury Institute, The University of Texas Health Science Center at Tyler (UTHSCT), Tyler, Texas, USA

5Laboratory for Molecular Respiratory Carcinogenesis, Department of Physiology, Faculty of Medicine, University of Patras, Rio, Achaia, Greece

6Comprehensive Pneumology Center (CPC), University Hospital, Ludwig-Maximilians University and Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany

Corresponding author: Professor Y.C. Gary Lee, 533 Harry Perkins Building, QE II Medical Centre, Perth, WA 6009, Australia. .


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


Chest. 2016. doi:10.1016/j.chest.2016.07.030
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Abstract

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 of surgery and its impact on clinical care is rising worldwide. Efforts are underway to optimize the delivery regime 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) 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 pro-inflammatory signalling 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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