Over the past several decades, improvements in donor selection, organ preservation, and operative strategies have expanded the pool of candidates with advanced lung disease who are able to access lung transplantation. However, access to this life-saving therapy remains limited by geographic, socioeconomic, and systemic inequalities, while long-term survival is constrained by chronic lung allograft dysfunction (CLAD), despite improvements in immunosuppression and supportive care. This perspective will address the future of lung transplantation through the intersecting challenges of improving organ utilization, equity, and CLAD, as the success of the field depends on progress in all three areas.
Improved organ utilization
One important factor in expanding access to care is to improve the utilization of lung allografts from the existing donor pool. Lungs remain one of the lowest recovered organs.1 Despite the challenges in optimizing and sustaining donor lungs for recovery and transplant suitability, lung utilization has increased, as evidenced by a continued annual rise in the rate of lung transplantation. While increased utilization is in part due to increased access to and use of organ reperfusion and recovery technology—such as ex vivo lung perfusion (EVLP) to evaluate marginal organs, expansion of the donor pool through use of hepatitis C virus (HCV) positive donors into HCV-negative recipients (given the ability to treat and clear HCV), and increased utilization of extended criteria donors—more recent improvements in utilization can be attributed to specialized donor recovery centers and donation after circulatory death (DCD).2–6
Organ recovery centers
Traditional donor management and organ procurement occurs with donors remaining at the hospital where brain death is determined. This places the burden of donor management on small hospitals that do not have extensive experience or investment in donor optimization. That’s why a model called an organ recovery center (ORC) was created in 2001 by the organ procurement organization (OPO) Mid-America Transplant.7 Multiple studies have shown donor management at an ORC is associated with improved abdominal organ utilization, decreased cost, and increased efficiency compared with the traditional donor model.8–9 With respect to lung utilization, a lung-focused resuscitation protocol at an ORC led to improved utilization from 19.8% to 33.9%.10 Due to this success, 24 of 57 OPOs have now established some form of an ORC, with 11 OPOs having freestanding facilities, while the others use transplant centers or hospitals to utilize their intensive care beds, operating rooms, and diagnostic services for donor management.7
Donor after circulatory death
Historically, donor lungs were procured from donations after brain death (DBD), with minimal use of lung allografts from DCD due to difficulty with evaluation of lung allografts. The rate of DCD lung allograft use in the US rose from 0.1% (N = 1) in 2001 to 5.7% (N = 197) in 2019, in part due to registry studies demonstrating equivalent outcomes between allografts from DBD and DCD and in part due to the use of EVLP to assess marginal donors after organ recovery.11–13
In 2020, a technique known as thoracoabdominal normothermic regional perfusion (TA-NRP) was introduced in the US as a means to assess cardiac allografts in DCD donors.14 Early institutional experience of lung allograft utilization from TA-NRP DCD donors showed no difference in perioperative complications or short-term and long-term survival.15 However, due to the need for standardization to optimize lung allograft quality, a consensus document was created to highlight the need for pre-donation diuresis, drainage of donor blood after the right atrial drain is placed, a vent to reduce hydrostatic pressure on the lung, early reintubation and ventilation, as well as minimizing TA-NRP time to less than 60 minutes.16 The increase of DCD donors for all thoracic organ transplantation has led to continued significant growth in DCD lung transplant. As of September 2025, 18.5% (N = 431) of the 2,330 lung transplants performed this year have been recovered from DCD donors.11
Equity and access to lung transplantation
Recent studies demonstrate that inequities in access to lung transplantation in the US are both persistent and multifactorial. Despite major policy shifts, disparities remain across race, ethnicity, gender, geographic location, and socioeconomic status. For example, Black and Hispanic candidates remain less likely than White candidates to undergo transplantation, with the gaps particularly pronounced among older patients and those from higher-poverty communities.17–20
Measures of socioeconomic disadvantage, including the Area Deprivation Index and the Distressed Communities Index, are consistently associated with worse outcomes across the transplant continuum, from referral and evaluation through waitlist placement and posttransplant survival.21–22 Upstream barriers, such as lower referral rates to general pulmonologists or lung transplant centers, make it less likely that patients from the most disadvantaged neighborhoods ever reach the waiting list. Even after successful transplantation, these patients face higher five-year mortality, independent of baseline clinical risk.21–22
These disparities reflect broader social determinants of health and systemic barriers at every stage of care.23 Geographic barriers, including limited proximity to a lung transplant center combined with relocation polices, can amplify socioeconomic barriers. Transplant hospitals must maintain acceptable publicly reported outcomes. Patients who have modifiable and nonmodifiable identified risks for poorer posttransplant outcomes—whether those are socioeconomic, psychosocial, or inherent in their identified comorbidities such as degree of frailty, history of cancer, or history of nonrevascularized coronary disease—the transplant team determines their own criteria for individual cases they are capable of accepting based on risk tolerance, the team’s level of expertise, and resourcing.
Team resourcing in the current health care climate can factor into the number of higher-risk, high-resource cases a transplant team may accept whereas geographic proximity may limit the patient from seeking additional opinions regarding transplant candidacy following a denial by the local center. While recent policy changes seek to improve equity, the literature underscores that meaningful progress will require targeted interventions, better data collection, and intentional resource allocation to ensure equitable access and outcomes in lung transplantation.20,24
Chronic lung allograft dysfunction
Up to 50% of lung transplant recipients experience CLAD (a persistent ≥ 20% decline in FEV1 from posttransplant baseline) within five years of transplant. CLAD remains the primary cause of late morbidity and mortality in lung transplant recipients and is therefore a significant focus of research efforts within the lung transplant community. Recent studies have furthered the understanding of the mechanisms, diagnosis, prognosis, and potential treatment strategies of CLAD.
The pathogenesis of CLAD reflects complex interactions between immune injury; nonimmune insults such as infection, aspiration, and ischemia/reperfusion; and repair. A recent review by Bery and colleagues emphasized that immune-mediated injury drives pathogenesis and suggests a framework that supports precision approaches to the individual processes, including cellular and humoral immune responses; autoimmunity; innate immune activation; and environmental insults such as infection, gastrointestinal reflux, and air pollution. Independent risk factors associated with probable CLAD were identified by Todd and colleagues this year and include cytomegalovirus infection, the presence of donor-specific antibodies > 90 days following lung transplant, acute rejection, acute lung injury, and organizing pneumonia.25 This study represents an important addition to the understanding of CLAD, as patients with probable CLAD have a significantly increased risk of graft loss and earlier identification of CLAD is crucial for effective intervention. Predicting CLAD before spirometric decline is potentially on the horizon through work on molecular signatures (eg, donor-derived cell-free DNA, microRNAs), immune cell subsets, and imaging modalities, which will guide preemptive therapies.
Tailored immunosuppression management is important for prevention of CLAD. The investigators of the Clinical Study Evaluating Two Treatment Protocols for Immunosuppressive Drugs: Looking at 3-year Incidence of CLAD (ScanCLAD) trial compared once-daily tacrolimus to twice-daily cyclosporin in a Scandinavian cohort and identified a significantly reduced incidence of CLAD in the tacrolimus-treated group at three years, confirming the superiority of tacrolimus for maintenance immunosuppression.26 While Benazzo and colleagues evaluated the efficacy of extracorporeal photopheresis (ECP) for prevention of CLAD and demonstrated that patients who received ECP immediately following lung transplant had more freedom from acute cellular rejection, fewer infections, and significantly higher freedom from CLAD at three years.
Across these studies, three themes emerge: 1) early recognition of probable CLAD and immune injury predicts outcomes and creates therapeutic windows; 2) precision strategies, including biomarkers and immunomodulation, are essential for tailoring care; and 3) preventive approaches through effective immunosuppression management hold promise for delaying CLAD onset. Collectively, these findings chart a path toward improved long-term survival and quality of life for lung transplant recipients.
In summary, the future of lung transplantation depends on advancing three interconnected priorities: improving donor organ utilization, ensuring equitable access, and reducing the impact of CLAD. Progress in each area is essential in order to expand the reach of transplantation and make its benefits more durable and more just.
References
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