From donor to durable graft: modern paradigms in lung transplantation

Lung transplantation is the only definitive therapy for selected patients with end-stage respiratory disease. Although survival after lung transplantation has improved over recent decades, long-term outcomes remain inferior to those of other solid organ transplants, largely because of chronic lung allograft dysfunction and infection-related complications. In this review, we synthesize contemporary practice across the lung transplant continuum, from donor identification and optimization to long-term survivorship. We first examine donor selection, management, and expansion strategies, including extended-criteria and donation-after-circulatory-death donors, ex vivo lung perfusion, uncontrolled DCD, and living-donor lobar transplantation. We then review current allocation frameworks, with emphasis on the U.S. composite allocation score, and highlight key candidate-level factors such as frailty, nutritional status, comorbidities, and the unique considerations for pediatric candidates and those bridged with extracorporeal support. Advances in operative techniques, intraoperative mechanical support, enhanced recovery pathways, and early extubation are discussed in the context of primary graft dysfunction and perioperative morbidity. We outline contemporary maintenance immunosuppressive regimens, infection prophylaxis strategies, and the spectrum of early and late alloimmune events, as well as post-transplant malignancies and their impact on long-term outcomes. Finally, we address functional recovery, health-related quality of life, reproductive health, and preventive care, and explore emerging frontiers including precision immunomonitoring with donor-derived cell-free DNA, cell-based immunotherapies, and lung xenotransplantation. Together, these developments underscore the substantial progress achieved and the opportunities that remain to extend allograft survival, reduce treatment-related toxicity, and improve the lived experience of lung transplant recipients.