Abstract
My career of research has centred on improving the understanding of the pathology of pleural diseases, and their better management. The work has focussed particularly on cancer (malignant pleural effusion, MPE) and infection causes of pleural effusions.
Pleural effusions affect an estimated 23 million people a year worldwide as it can arise from over 60 systemic or pulmonary diseases. Diagnosing the underlying cause of a pleural effusion can therefore be challenging and often requires multiple interventions (from pleural aspiration to video-assisted thoracoscopic surgery, VATS). Pleural effusions are broadly separated as transudate (arising from imbalance of hydrostatic and oncotic forces under the Starling’s equation) and exudates (most of which developed from vascular hyperpermeability and plasma extravasation). MPE and pleural infection are the two most common exudative effusions both associated with significant morbidity and healthcare costs (~US$5 billion and $500 million a year respectively in the United States alone); hence they are my research focuses.
Management of pleural effusion often involves evacuation of the fluid by invasive interventions ranging from thoracentesis, chest tube insertion/drainage to surgery (VATS or thoracotomy). All the pleural diagnostic and drainage procedures are painful and have recognized risks. Complications do occur, as highlighted by a nationwide alert issued by the UK National Patient Safety Agency on unacceptably high rates of adverse events from pleural procedures in the United Kingdom in 2008. The latest British Thoracic Society analyses in March 2025 reinforced that, although safety has improved since 2008, serious harm events persist. In addition, diagnostic and drainage procedures often necessitate hospital admissions and costs. In patients with MPE and advanced cancer, this often means taking away precious days with family.
The overarching aim of my research work is to provide diagnosis and management of common pleural effusions with fewer, and less invasive, interventions. In so doing, we can reduce morbidity, hospitalization and costs as well as promoting quality-of-life (QoL).
Using robust clinical studies, I have challenged and disproved decades-old practices in pleural disease, uncovered significant harm and redundancies and evaluated new therapies. This has been achieved using i) multicentre randomised trials that tested novel treatments and advanced clinical care while minimising invasive pleural drainages; ii) novel diagnostic techniques that improved patients' diagnostic journey; and iii) multidisciplinary (nutrition, psychology, exercise) approaches to improve QoL of patients.
This thesis represents the compilation of 47 selected scientific papers from 25 years of clinical and translational pleural research that fall within the theme of this thesis. My full list of publications is provided as an Appendix 1 at the end of this thesis.
This thesis is subdivided into three Sections:
Section 1: Malignant Pleural Effusions (MPEs): Research on Improving Clinical Care
In this Section, I provided
1 (a): selected publications that outline the shortcomings of conventional MPE treatment options especially the high rate of failure and (including lethal) complications as well as the resultant heterogeneity in clinical practice worldwide. This highlights the need for developing new management methods.
1 (b): key publications from my group on using indwelling pleural catheter (IPC) as a new therapeutic method for MPE. These papers provide clinical trial evidence on its utility, benefits and optimization of its delivery.
1 (c): landmark publications that presented data on, and best management of, common complications of IPC use.
1 (d): evidence of adoption of IPC use in major international guidelines of MPE care, for which I contributed as a panellist and co-author.
1 (e): my work on potential new predictors in MPE care to help guide patient selection, and effort to develop new drugs to control MPE.
Section 2: Pleural Infection: Improving management approaches
In this section, I provided
2 (a): highlighted translational research papers that offer insight on disease pathophysiology.
2 (b): important published epidemiology data of pleural infection with clinical implications.
2 (c): work on a novel intrapleural therapy with tissue plasminogen activator (tPA) and deoxyribonuclease (DNase) which helped transform care worldwide, and other randomized trials I conducted to further improve care.
Section 3: Improving Diagnostic Approaches and Understanding Breathlessness from Pleural Effusions
In this Section, I provided
3 (a): original physiological studies examining how pleural effusion causes breathlessness.
3 (b): original research papers examining value of novel diagnostic tests and molecules to help determine the underlying cause of pleural effusion.