TY - JOUR T1 - First histopathological evidence of irreversible pulmonary vascular disease in dasatinib-induced pulmonary arterial hypertension JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.01694-2017 SP - 1701694 AU - Cécile Daccord AU - Igor Letovanec AU - Patrick Yerly AU - Jonathan Bloch AU - Adam Ogna AU - Laurent P. Nicod AU - John-David Aubert Y1 - 2018/01/01 UR - http://erj.ersjournals.com/content/early/2018/01/05/13993003.01694-2017.abstract N2 - We read with interest the article by Weatherald et al. on the long-term outcomes of pulmonary arterial hypertension (PAH) induced by dasatinib [1]. The authors reported 21 incident cases of PAH confirmed by right heart catheterisation (RHC) and associated with dasatinib. Although a majority of patients improved after dasatinib discontinuation, PAH persisted in over one-third of cases during long-term follow-up and two additional patients had persistent exercise pulmonary hypertension despite normalisation of resting haemodynamic measures. Similarly, Shah et al. reported 41 cases of dasatinib-induced PAH confirmed by RHC with complete resolution of PAH in only 58% of patients, provided that follow-up RHC or echocardiography was most often not documented [2]. As mentioned by Weatherald and colleagues, these data suggest that dasatinib is likely to cause irreversible pulmonary vascular dysfunction and remodelling. An experimental model in rats and human pulmonary endothelial cells supports this hypothesis as it showed that dasatinib causes dose-dependent pulmonary endothelial dysfunction and apoptosis through the production of mitochondrial reactive oxygen species, a phenomenon that was not observed with imatinib [3]. To date, there is no published evidence of such pathological abnormalities on human lung. We report the case of a patient who developed dasatinib-induced severe PAH that progressed in spite of drug cessation and aggressive PAH-specific therapy and ultimately underwent lung transplantation.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. ER -