Therapy options for chronic lung allograft dysfunction - Bronchiolitis obliterans syndrome following first-line immunosuppressive strategies: A systematic review

Abstract Background Long-term success of lung transplantation is limited by the development of chronic lung allograft dysfunction (CLAD), of which bronchiolitis obliterans syndrome (BOS) is the most common form. This systematic review seeks to identify the current evidence base for CLAD-BOS therapies following initial immunosuppressive treatment strategies. Methods Searches of MEDLINE, Embase and Cochrane Library databases from inception to May 3, 2016 were constructed using keywords relating to CLAD-BOS, study designs, and treatments of interest, including extracorporeal photopheresis (ECP), aerosolized cyclosporine, total lymphoid irradiation (TLI), alemtuzumab, and montelukast. Titles, abstracts, and full texts were screened by two independent reviewers to identify studies of CLAD-BOS second-line therapy in adult lung transplant patients. Quality was assessed according to the Downs and Black checklist. Results Of the 936 individual citations identified, 47 reports of 40 studies met inclusion criteria, including 17 full publications, 11 recent (2015–2016), and 12 older (pre-2015) congress proceedings. The majority of full publications and recent abstracts investigated ECP (11), TLI (5), alemtuzumab (4) and montelukast (2). Most studies were uncontrolled and retrospective. Compared to standard therapy alone, improved lung function and survival was reported for ECP in two studies without randomization, with lower quality evidence for improved lung function for TLI, montelukast, and aerosolized cyclosporine. Conclusions As most identified studies were of retrospective and uncontrolled design, comparison of treatment effects was limited. Available evidence suggests stabilized lung function following ECP in combination with established immunosuppressive regimens in late-line CLAD-BOS treatment, with fewer data for TLI, montelukast, and aerosolized cyclosporine.