Background Lung transplantation is a therapeutic option for select patients with end-stage lung disease. However, successful lung transplantation is hampered by chronic lung allograft dysfunction (CLAD), in particular bronchiolitis obliterans syndrome (BOS). Although there is no approved or standard treatment for BOS, which may have several distinct phenotypes, extracorporeal photopheresis (ECP) has shown promising results in patients who develop BOS refractory to azithromycin treatment. Methods We reviewed all relevant clinical data indexed on PubMed from 1987 to 2017 to evaluate the role of ECP in patients with BOS. Results 7 small studies investigated the immunomodulatory effects of ECP in patients after solid organ transplant and 12 studies reported clinical data specific to ECP therapy for BOS. Studies indicate that ECP triggers an apoptotic cellular cascade that exerts various immunomodulatory effects mediated via increases in anti-inflammatory cytokines, a decrease in pro-inflammatory cytokines, and an increase in tolerogenic regulatory T cells. Clinical evidence derived from relatively small single-center studies suggests that ECP therapy is associated with improvement or stabilization in lung function and sustainable, statistically significant, decreases in the rate of lung function decline in patients with BOS. Additionally, when adverse event data were reported, ECP was generally well-tolerated. None of the comparative studies were randomized. Conclusions Immunomodulation mediated via ECP is a rational therapeutic option that may improve clinical outcomes in patients with BOS, particularly in the context of in-depth patient phenotyping as part of a stratified approach to treatment; good quality randomized controlled trials are needed to confirm observational findings. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Author correspondence: Paul Corris, MBBS, FRCP, Institute of Cellular Medicine, Newcastle University and The Newcastle upon Tyne Hospitals, NHS Foundation Trust, Newcastle upon Tyne, United Kingdom. Business Phone: +44 (0) 191 213 7462. E-mail: paul.corris@ncl.ac.uk AUTHORSHIP Ramsey Hachem participated in the design of the review search strategy, and in the interpretation, critical review and writing of this paper Paul Corris participated in the design of the review search strategy, and in the interpretation, critical review and writing of this paper CONFLICT OF INTEREST AND FUNDING SOURCES PC: No disclosures of relevance, RH: Grant support from Therakos, Inc., a Mallinckrodt Pharmaceuticals company. Financial support for medical editorial assistance was provided by Therakos, Inc., a Mallinckrodt Pharmaceuticals company. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
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