Chronic rejection is the Achilles heel of modern lung transplantation, characterized by a slow, progressive decline in allograft function. Clinically, this manifests as obstructive disease, restrictive disease, or a mixture of the 2 depending on the underlying pathology. The 2 major phenotypes of chronic rejection include bronchiolitis obliterans syndrome and restrictive allograft syndrome. The last decade of research has revealed that each of these phenotypes has a unique underlying pathophysiology which may require a distinct treatment regimen for optimal control. Insights into the intricate alloimmune pathways contributing to chronic rejection have been gained from both large and small animal models, suggesting directions for future research. In this review, we explore the pathological hallmarks of chronic rejection, recent insights gained from both clinical and basic science research, and the current state of animal models of chronic lung rejection.
Chronic rejection is the Achilles’ heel of modern lung transplantation, and the authors review the pathological hallmarks of chronic rejection, recent insights gained from both clinical and basic science research, and the current state of animal models of chronic lung rejection.
1 Division of Cardiothoracic Surgery, Department of Surgery.
2 Division of Experimental Surgery, La Paz University Hospital Madrid, Spain.
3 Division of Pulmonary and Critical Care Medicine, Department of Medicine.
4 Department of Pathology and Immunology Washington University School of Medicine Saint Louis, Missouri.
Received 13 February 2018. Revision received 4 April 2018.
Accepted 9 April 2018.
D.K. is on the scientific advisory board of Compass Therapeutics. All other authors declare no conflicts of interest.
DK is supported by NIH 1P01AI116501, R01 HL094601, Veterans Administration Merit Review 1I01BX002730, and the Foundation for Barnes-Jewish Hospital.
Each author participated in the writing of this article and approved the final version for submission.
Correspondence: Daniel Kreisel, MD, PhD, Campus Box 8234, 660 South Euclid Ave, Washington University School of Medicine, St. Louis, MO 63110. (firstname.lastname@example.org).