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Transforming the Future of Lung Transplantation by Improving Access and Outcomes

In This Article

  • Physicians at Massachusetts General Hospital are rapidly growing the Lung Transplant Program to address an underserved population in New England
  • The program has increased transplant volume by capitalizing on a perfect storm of technological advances and new guidelines for national donor organ allocation
  • Mass General is leading the largest lung transplant clinical trial ever performed to improve protocols for post-transplant immunosuppression and graft survival

Physicians at Massachusetts General Hospital are transforming the Lung Transplant Program by capitalizing on foundational changes across the landscape of organ transplantation. As one of only two such programs in the region, they aim to provide specialized care for patients with advanced lung disease and those for whom transplantation is the only remaining option.

"Recent innovations have expanded access to suitable organs for ever-growing pools of potential recipients," explains Brian Keller, MD, PhD, medical director of the Lung Transplant Program at Mass General. "These developments continue to move us closer to achieving our vision of providing transplants to every appropriate candidate."

Seizing the Moment

Despite therapeutic advances, lung transplantation remains the only option for patients with end-stage respiratory failure associated with chronic pulmonary diseases. However, the number of waitlisted candidates continues to outpace transplants performed annually, resulting in waitlist mortality rates historically ranging from 13% to 37% worldwide.

A transition in program leadership at Mass General led to a philosophical shift in how to approach this challenge. The resulting changes in infrastructure and protocols streamlined how transplant candidates are evaluated, and an aggressive but measured approach to identifying and using donor lungs was implemented. This approach included increased utilization of donation after circulatory death (DCD) lungs and those from donors positive for hepatitis C virus (HCV). These collectively constitute approximately 40% of the program's transplanted lungs, significantly exceeding national averages.

"Becoming a resource for lung transplantation in the region required a commitment to decisions that would optimize both transplant opportunities and outcomes," says Nathaniel Langer, MD, MSc, surgical director of the Lung Transplant Program. "Establishing protocols for lungs from DCD or HCV-positive donors expedited their safe, successful utilization and maximized transplant opportunities."

For HCV-positive donors, development of direct-acting antiviral (DAA) medications effective against HCV-related disease shifted ethical considerations involving use of their organs in HCV-naïve patients. Second-generation DAAs administered pre- or post-transplant to recipients currently demonstrate up to 100% efficacy in eradicating all HCV genotypes, resulting in widespread use of HCV-positive organs as a safe option.

"The therapy's effectiveness rapidly and substantially expanded the donor pool, which immediately translated into higher transplant volumes with no adverse effect on outcomes," says Dr. Keller.

Capitalizing on Paradigm Shifts and Technological Advances

Recent changes in donor organ acquisition and distribution by the Organ Procurement and Transplantation Network (OPTN) also significantly impacted the program's vision. Lung allocation, which classifies candidates according to medical urgency and compatibility with donor characteristics (e.g., donor age, identical vs. compatible blood type, etc.), previously included geographic restrictions as well, where candidates within a 250-nautical mile radius from the donor were prioritized, even if higher urgency candidates existed elsewhere in the country.

"These classifications created boundaries that severely limited transplant programs' ability to proactively identify and acquire suitable organs, particularly programs on the coasts where the geographic radius was more limiting," says Dr. Keller.

In March 2023, the OPTN initiated a continuous distribution system that evaluates donor-candidate compatibility according to a composite allocation score assigned to all waitlisted patients. The score prioritizes need, eliminates geographic boundaries, and reinforces equity and flexibility in organ allocation.

Within the first three months of implementation, lung allocation via this approach led to:

  • 15.9% increase in the number of transplants
  • About 42% decrease in the number of candidates removed from the waitlist due to death or being too sick for transplant
  • About 43% increase in the median distance from the donor hospital to the transplant hospital

The elimination of geographic boundaries also coincided with advances in methods for donor lung preservation, including ex vivo lung perfusion (EVLP) and controlled hypothermic storage. Lung preservation systems offer a consistent thermal environment capable of protecting donor lungs for extended periods of time. By contrast, EVLP uses a ventilator, pump, and filters to mimic the lungs' normal physiological state, allowing physicians both the time and additional data necessary to assess transplant suitability.

"These systems enable preservation of lungs outside the body for extended periods," explains Dr. Langer. "This facilitates verification of donor lung quality and decisions concerning their safe transport from potentially anywhere in the world." In 2023, these methods enabled the program to successfully transplant donor lungs transported 2,900 nautical miles from Alaska.

Mass General's strategy for exploiting these opportunities has paid dividends for patients throughout New England who need lifesaving lung transplants. In 2023, Mass General performed a site record of 53 transplants and is on track for 70 in 2024, constituting an approximately 500% increase in volume since 2021.

"Our strategy during this period involved a consistent willingness to say yes to referrals while generating outcomes that solidified our reputation and justified our approach," explains Dr. Keller. "Moving forward, we want to expand outreach efforts to underserved areas where these opportunities can have the greatest impact."

Driving Innovation to Improve Transplant Outcomes

Immunosuppression is a common requirement following solid organ transplantation to offset host rejection of the graft. Immunosuppression after lung transplantation presents unique challenges by the lungs' constant exposure to contaminants from both the external atmosphere and blood circulation. In this regard, transplanted lungs need to initiate immune responses to protect the host and also avoid becoming the target of those responses.

"This complicated relationship makes development of new therapeutics difficult and explains why the same immunosuppressive medications have been used for three decades," says Dr. Keller.

Mass General is currently leading an international clinical trial enrolling 350 patients across 15 transplant centers to evaluate a novel immunosuppressive regimen.

"The low number of lung transplants at single centers requires a concerted and collaborative effort for meaningful discovery," he explains. "We're confident that this large-scale study will offer new insight into how to improve post-transplant immunosuppression and graft survival."

The Mass General team is also in the early stages of research to evaluate the efficacy of extracorporeal photopheresis (ECP) to treat chronic lung allograft dysfunction (CLAD), which affects up to 60% of recipients. In this context, ECP involves extracting a patient's white blood cells and treating them with a photosensitizer, followed by exposure to ultraviolet A radiation and reintroduction to the patient. The result essentially downregulates the immune reaction responsible for CLAD.

Evidence suggests that ECP benefits up to 70% of patients, although few studies outline the mechanisms and long-term outcomes. "Given the limited treatment options for chronic rejection, it's important to confirm the efficacy of ECP therapy," says Dr. Keller. "We also want to identify biomarkers capable of predicting patient response to ECP and the likelihood that the therapy will restore graft function."

Navigating the Future of Lung Transplantation

Drs. Keller and Langer emphasize that the program's success to this point is only the beginning. Plans are currently in place to finalize protocols that will offer all types of lung/multi-organ transplants, as well as lung transplants for recipients living with human immunodeficiency virus.

They also highlight the benefits of Mass General and its ecosystem tailored toward answering difficult questions and solving challenging problems. Dr. Langer notes that when breaking new ground, it helps to be surrounded by talented and motivated people eager to advance the field and open to novel ways of getting there.

"There's a degree of tolerance for the risks necessary to advance not only the field of lung transplantation, but also medicine in general," says Dr. Keller. That culture permeates the multidisciplinary team responsible for the program's rapid evolution. "People here are actively engaged in improving transplant outcomes and opportunities because they're genuinely excited about what we've accomplished and where we're headed."

Dr. Langer also acknowledges the magnitude of scientific and technological changes in the field during the previous five years, but suggests that the best is likely yet to come. "It feels like we're at an inflection point in the history of transplantation that will be remembered for exponential leaps in progress," he explains. "It's incredibly exciting to participate in that transformation."

To refer a patient to the Lung Transplant Program, please call 800-876-5864 or email

Read more about the Lung Transplant Program

Visit the Division of Pulmonary & Critical Care Medicine


Massachusetts General Hospital's Heart Transplant Program completed its first bloodless heart transplant on a Jehovah's Witness patient using blood-conserving methods.


David A. D'Alessandro, MD, and colleagues found that six-month survival was similar in patients who received donor hearts that were reanimated and assessed with extracorporeal nonischemic perfusion after circulatory death and those whose donor hearts were preserved with cold storage after brain death.