LAUSR

Malignant pleural effusion (MPE) affects an estimated 150 000 patients and accounts for 126 000+ hospital admissions a year in the USA alone. In many MPE patients, the lung is unable to expand to the chest wall after drainage of the effusion, either because of endobronchial obstruction or visceral pleural encasement by tumour. This phenomenon is called nonexpandable (or trapped) lung. Non-expandable lung (NEL) is a significantly understudied topic. Its incidence, best diagnostic method and relation to clinical outcomes, especially pleurodesis success and survival, are poorly understood. The work by Martin et al., recently published in Respirology, represents an important early step in providing data on NEL. This study included 214 patients with MPE (larger than most previous series on NEL) at two separate UK centres which add strength to the findings. The incidence of NEL varies significantly in published literature. Clinical practice guidelines citing historical data suggest that one-third of MPE patients have NEL. Most studies of pleurodesis for MPE specifically target patients with expandable lung, and not surprisingly report a low rate of NEL. How and where the patients are recruited may also influence the rates reported. Martin et al. found a two-fold difference in the incidence of NEL— 34% (33/97) and 17% (15/86) — between the two tertiary units. The study included only post-pleuroscopy patients, and the differences may, among other reasons, reflect differences in patient selection for the procedure. The incidence of NEL also critically depends on how it is defined, including cut-off values and mode of detection. Martin et al. defined NEL as apposition of the lung to <50% of the lateral chest wall on chest radiographs (CXR), although other studies used more stringent cut-off values (<25%). NEL from malignant causes are often not uniformly trapped. Two-dimensional images (e.g. CXR) can significantly underestimate the total area of nonapposition of visceral and parietal pleura. However, routine use of three-dimensional imaging (e.g. computed tomography (CT)) is not clinically practical. Inter-observer variation compounds the difficulty in defining the true incidence of NEL. Martin et al. is the first to illustrate this point and found only a fair-tomoderate level of concordance between a primary and secondary reader (all experienced specialists) in determining if CXR shows >50% of NEL. It is noteworthy that without CT verification, even a concordant reading does not necessarily mean the decision is accurate. Traditionally, the clinical importance of defining NEL in MPE is in candidate selection for pleurodesis where apposition of the two pleural layers is needed for success. Critically, however, no data exist on what extent of trapped lung should contraindicate pleurodesis. Without such information, no recommendation can be drawn even if better ways of defining NEL are developed. The ideal definitive study of NEL therefore needs to include large cohorts (to encompass the disease heterogeneity) of all-comers with MPE, assessed with threedimensional imaging and followed up for pleurodesis success. This would also help further explore an observation from Martin et al.: that NEL was associated with a poorer prognosis, presumably a result of more advanced malignancies. Many clinical myths exist concerning NEL. First, not all NEL will remain trapped. Response to cancer therapy can allow NEL to re-expand. Very often, the lung may appear non-expandable immediately after evacuation of MPE but will expand fully over a few days, especially if the effusion has accumulated over a long period of time. In the Australasian Malignant PLeural Effusion trial-2, patients with NEL could develop autopleurodesis especially if drained daily via an indwelling pleural catheter (IPC). Clinicians must also discard the old belief that patients with NEL will not derive symptom benefits from fluid drainage (reviewed elsewhere). How should clinicians approach NEL knowing it may require years, if not decades, for research studies to provide a full picture of how best to define, assess and employ NEL for selecting patients for pleurodesis? Research in MPE care has been progressing rapidly in the past decade and the latest finding raises the possibility of bypassing the need of defining NEL. Use of IPC has emerged from several multicentred randomized controlled trials (RCT) and clinical guidelines to be the first-choice definitive therapy for MPE. Treatment with IPC significantly cuts hospitalization days and need for further invasive pleural drainage compared with conventional bedside chest tube talc pleurodesis while providing similar benefits in quality-oflife and dyspnoea. A recent multicentred RCT by Bhatnagar et al. showed the feasibility and benefits of combining IPC placement and talc slurry instillation and provides a paradigm shift: that IPC and talc pleurodesis are not mutually exclusive but can be complementary. The EPIToME (Early Pleurodesis via IPC and Talc pleurodesis for Malignant Effusion) protocol, which combines the wisdom of the above-mentioned studies, is being evaluated in a pragmatic observational study. Patients with symptomatic MPE are treated with IPC (unless contraindications exist) and, if the underlying lung expands after fluid evacuation, talc slurry pleurodesis via the IPC followed by daily drainages. For patients with NEL, this approach ensures early IPC placement (current recommended therapy for NEL). The EPIToME approach circumvents our inability to