Advances in the management of pleural disease

Abstract

Pleural disease affects over 3000 people per million population annually. Consequently, it represents a significant proportion of the respiratory physician’s workload and can present to clinicians of all backgrounds in primary and secondary care. Pleural effusions have been reported in association with over 50 different conditions; some related to specific pulmonary pathologies, but many being manifestations of multisystem disease. The burden that conditions such as pleural infection; malignant pleural disease; and pneumothorax impose on patients and health care systems is enormous and growing. As such, a clear understanding of these key conditions is crucial to any physician regardless of the specialty. This article addresses a number of areas relating to pleural disease, providing an overview of the diagnostic and therapeutic advances that have been made in our understanding of pleural pathology in recent years. The directions that future research in this important area of respiratory medicine might take will also be discussed.

Keywords::

• empyema
• mesothelioma
• pleural disease
• pleural effusion
• pleural infection
• pneumothorax

Financial & competing interests disclosure

JP Corcoran is a Clinical Research Fellow funded by a grant from the UK Medical Research Council to the Oxford Respiratory Trials Unit (ORTU) and University of Oxford. R Hallifax is an Academic Clinical Fellow funded by the UK National Institute for Health Research (NIHR) and University of Oxford. Both JP Corcoran and R Hallifax have received a travel award from the British Lung Foundation (supported by Napp Pharmaceuticals) to support attendance at the American Thoracic Society International Conference 2013. NM Rahman is supported by the UK NIHR Oxford Biomedical Research Centre based at the Oxford University Hospitals NHS Trust and University of Oxford. NM Rahman was the corresponding author for the MIST2 study and is the current clinical director of the ORTU, which also published the MIST1 and TIME2 studies. The ORTU received an unrestricted educational grant from Roche UK to the University of Oxford for the conduct of the MIST2 study. The TIME2 study was supported by an unrestricted educational grant to the University of Oxford from the British Lung Foundation and the Robert Luff Foundation, London, UK; equipment for the TIME2 study was supplied by Rocket Medical, Washington, UK. NM Rahman has acted as a consultant to Rocket Medical for device development. The authors have no other relevant affiliations or financial involvement AQ2 with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Pleural infection is on the increase in both adult and pediatric populations without clear explanation or cause. Despite advances in our understanding of this condition alongside new diagnostic and therapeutic strategies, 1-year mortality in adults with pleural infection has remained consistently above 20% for over 20 years.

• • Pleural infection is distinct from parenchymal lung infection, with growing acceptance that the latter is not necessary to cause the former, and recognition that the microbiology of pleural infection is both unique and variable according to local and global factors.

• • The recently described use of combination intrapleural therapy with tPA and DNase in adults as part of the MIST2 study potentially provides a novel approach to improve outcomes in pleural infection although further research is necessary to confirm its benefits along with how and when it should be utilized.

• • Further research is needed to try and identify baseline factors at clinical presentation that might predict poor outcomes in pleural infection so that the place of more aggressive therapeutic strategies – including surgical intervention – can be more accurately defined.

• • Malignant pleural mesothelioma while comparatively rare is still on the increase in a number of Western countries including the UK. More worryingly, it is also becoming more common in Asia, Africa and South America where asbestos remains in widespread use – potentially laying the foundations for a disease epidemic in years to come.

• • Mesothelioma remains universally fatal, and supportive care is the mainstay of treatment. Different modalities including surgery, radiotherapy and chemotherapy have proven of extremely limited success either in isolation or combination; further research in these areas alongside more novel strategies such as intrapleural therapeutics is needed to improve on a median survival that remains below 12 months following diagnosis.

• • Malignant pleural effusions are becoming more common as the number of patients diagnosed with cancer and surviving for prolonged periods following treatment increases. A number of therapeutic approaches can be considered dependent on the patient’s physical condition and wishes, with definitive in- and outpatient management options available.

• • The management of pneumothorax remains somewhat controversial with highly variable practice; limited consensus across guideline statements; and debate ongoing regarding how and when to intervene in the immediate episode and to prevent recurrence. There is the potential for advances through the development of new approaches such as ambulatory treatment although these require robust studies that have up to now been sadly lacking.