Abstract
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.
Footnotes
- Received February 3, 2023.
- Revision received April 27, 2023.
- Accepted June 5, 2023.
This work received no external funding. The following authors are supported by a research fellowship, but received no specific funding for the current review: S.B. is funded by the Paul Corris International Clinical Research Training Scholarship. B.M.V. is funded by the KU Leuven (C24/050). A.J.F. is funded in part by the National Institute for Health Research Blood and Transplant Research Unit (NIHR BTRU) in Organ Donation and Transplantation at the University of Cambridge in collaboration with Newcastle University and in partnership with NHS Blood and Transplant (NHSBT). The views expressed are those of the author(s) and not necessarily those of the NIHR, the Department of Health and Social Care or NHSBT. R.V. is a senior clinical research fellow of the Fund for Scientific Research Flanders (FWO) (1803521N) and supported by a research grant from FWO (G060322N).
No author has an actual or perceived conflict of interest with the contents of this article.
- Copyright © 2023 by The American Society for Pharmacology and Experimental Therapeutics
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