Can the prognostication and management of non-malignant pleural effusions be improved?

Abstract

Introduction

Non-malignant pleural effusions (NMPE) are a diverse group of pathological entities with limited high quality evidence to guide diagnostic and management strategies. Management frequently defaults to medical therapy plus therapeutic thoracentesis (TT), and there is a paucity of literature evaluating the effects of management on patients’ lives. This thesis evaluates multiple aspects of NMPE, from basic pathology and patient characteristics, to prognostics, management strategies and patient experience.

Methods

To understand the global burden of disease, patient characteristics, prognostics and current management, the largest study of NMPE data was performed using retrospective analysis of a global dataset of 755 individual records. To evaluate the pathological processes underlying non-malignant pleural effusions and identify potential diagnostic biomarkers, exploratory untargeted metabolomic analysis was performed of a large set (n=751) of pleural fluid samples resulting from organ failure, infection, malignancy and benign asbestos-related pleural effusion (BAPE). The risk association between post-coronary artery bypass graft (CABG) pleural effusions and asbestos exposure was explored at a population level by performing retrospective analysis of routine data from the Health Episode Statistics (HES) dataset. The feasibility of a protocol involving indwelling pleural catheter (IPC) insertion, daily IPC drainage and talc instillation for the management of medically resistant recurrent pleural effusions related to heart failure (HF) was assessed in a multi-site randomised feasibility study, REDUCE 2, which is ongoing at the time of writing. Finally, the effect of TT on patient activity levels was assessed in a single centre prospective observational study by comparing actigraphy data pre- and post-TT. Novel patient-reported outcome measures (PROMs) were also assessed for the first time in pleural disease in this study by comparison to the current standard tool, the visual analogue score for dyspnoea (VAS-D).

Results

The NMPE population was demonstrated to be elderly and frail, with high one-year mortality rates (33% in the cardiac group). Unilateral NMPE are common, and transudates are associated with higher mortality than exudates. Management is predominantly medical with TT the preferred pleural intervention. Metabolomic analysis did not identify reliable biomarkers. Valuable experience was gained of the complexities of metabolomic research in pleural fluid that may be used to inform further research. Asbestos exposure was found to cause a doubling of risk of post-CABG pleural effusion compared to unexposed individuals (OR 2.16). Delayed due to COVID-19, the feasibility study remains in recruitment. A noteworthy incidental finding suggests the incidence of HF related NMPE may be reducing, perhaps due to the effects of novel drug regimens. Patient activity levels do not change significantly following TT, and novel PROMs may be of use in future pleural research.

Conclusions

This thesis has updated our understanding of NMPE disease burden and patient characteristics, demonstrated asbestos exposure conferring a risk of post-CABG pleural effusion development and that therapeutic thoracentesis does not improve patient activity levels. Insights have been gained to guide future pleural metabolomic research. The results of REDUCE 2 will inform future NMPE management.

Date of Award	10 Dec 2024
Original language	English
Awarding Institution	University of Bristol
Supervisor	Nick A Maskell (Supervisor) & Rahul Bhatnagar (Supervisor)