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Lookup NU author(s): Dr Saskia Bos, Dr Pauline Pradere, Dr Bart Vanaudenaerde, Professor Andrew FisherORCiD
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Copyright © 2023 by The American Society for Pharmacology and Experimental Therapeutics. Chronic lung rejection, also called chronic lung allograft dysfunction (CLAD), remains the major hurdle limiting long-term survival after lung transplantation, and limited therapeutic options are available to slow the progressive decline in lung function. Most interventions are only temporarily effective in stabilizing the loss of or modestly improving lung function, with disease progression resuming over time in the majority of patients. Therefore, identification of effective treatments that prevent the onset or halt progression of CLAD is urgently needed. As a key effector cell in its pathophysiology, lymphocytes have been considered a therapeutic target in CLAD. The aim of this review is to evaluate the use and efficacy of lymphocyte depleting and immunomodulating therapies in progressive CLAD beyond usual maintenance immunosuppressive strategies. Modalities used include anti-thymocyte globulin, alemtuzumab, methotrexate, cyclophosphamide, total lymphoid irradiation, and extracorporeal photopheresis, and to explore possible future strategies. When considering both efficacy and risk of side effects, extracorporeal photopheresis, anti-thymocyte globulin and total lymphoid irradiation appear to offer the best treatment options currently available for progressive CLAD patients. SIGNIFICANCE STATEMENT: Effective treatments to prevent the onset and progression of chronic lung rejection after lung transplantation are still a major shortcoming. Based on existing data to date, considering both efficacy and risk of side effects, extracorporeal photopheresis, anti-thymocyte globulin, and total lymphoid irradiation are currently the most viable second-line treatment options. However, it is important to note that interpretation of most results is hampered by the lack of randomized controlled trials.
Author(s): Bos S, Pradere P, Beeckmans H, Zajacova A, Vanaudenaerde BM, Fisher AJ, Vos R
Publication type: Review
Publication status: Published
Journal: Pharmacological Reviews
Year: 2023
Volume: 75
Issue: 6
Pages: 1200-1217
Print publication date: 01/11/2023
Online publication date: 17/10/2023
Acceptance date: 05/06/2023
ISSN (print): 0031-6997
ISSN (electronic): 1521-0081
URL: https://doi.org/10.1124/pharmrev.123.000834
DOI: 10.1124/pharmrev.123.000834
PubMed id: 37295951
