We agree that the European cohort study by Janssen et al is a high quality study providing strong evidence for greater safety with large particle talc,1 as stated clearly in our editorial.2 However, to assume that these results prove complete safety is an extrapolation beyond the data, and risks overlooking milder or rarer (but important) adverse events.

We agree with the authors’ paper that “the small increases in temperature and oxygen use after talc pleurodesis … might be due to mild systemic and lung inflammation caused by talc”. In their European cohort, 60.7% of the patients were using oxygen on day 1 and 56.8% still required supplementation 48 h after pleurodesis. A rise in the volume of supplemental oxygen of 0.25 l/min (p = 0.001) on day 1 and 0.21 l/min (p = 0.025) on day 2 was noted. We recognise that oxygen therapy was not included in the protocol for this study, so it is difficult to know if supplementation was “needed” or just “given”. However, this means the dataset is uninformative about talc-induced hypoxaemia; it does not exclude it. In a randomised comparison of talc types (in which oxygen therapy was included in the protocol), 12/21 patients (57%) had an increase in their alveolar-arterial oxygen gradient after large talc (in 4/21 (19%) this was by >2 kPa), and 17% had an arterial oxygen tension of <8 kPa.3

We believe that carefully executed studies of pleurodesis, such as the European cohort study, have begun to cast light on the details of what happens to patients receiving talc pleurodesis, to the great benefit of clinical care. This growing evidence base is identifying yet more questions (such as whether and how large particle talc may produce hypoxaemia), and further large studies will help clarify these questions.