Dr. Albert Rizzo:
Welcome to Lungcast, the monthly respiratory health podcast series from the American Lung Association and medical news site HCPLive. I’m your host, Dr. Albert Rizzo, Chief Medical Officer of the American Lung Association.
Today’s episode is a return visit by Dr. Maryam Valapour of the Cleveland Clinic, who is Director of Lung Transplant Outcomes and a physician-scientist with a large research portfolio studying ways to better risk stratify patients for timely transplant access and maximize survival. She is also the Senior Investigator for Lung Transplantation with the United States Scientific Registry of Transplant Recipients, overseeing analyses of all U.S. lung transplant data and allocation systems.
She’s joined today by Dr. Kenneth McCurry, a cardiothoracic surgeon, Surgical Director of the Lung and Heart-Lung Transplant Program at the Cleveland Clinic, and Director of the Ex Vivo Lung Perfusion and Respiratory ECMO Programs.
Dr. Valapour, thank you for returning, and welcome Dr. McCurry.
Our first conversation back in 2021 gave us a comprehensive look at indications and experiences in lung transplantation. Today, I’d like to focus on updates to lung allocation, graft dysfunction, EVLP, and new developments since then.
Dr. Valapour, since our last discussion, lung allocation has seen changes — terms like composite allocation score and continuous distribution are now being used. How has this latest modification impacted patients seeking transplantation?
Dr. Maryam Valapour:
Thank you again for having me. In 2005, the lung transplant system transitioned to the LAS, which prioritized the sickest patients for access to transplant. Over the past 20 years, we’ve improved both patient management and donor management, so the strict geographic boundaries we once relied on were no longer necessary.
In 2017, an incremental change broadened geographic sharing of donor lungs. The new Composite Allocation Score, implemented in March 2023, represents the next step — it marries geographic reach with candidate urgency and biological difficulty in finding a match.
After a year, two important trends emerged: more candidates are being transplanted, and fewer patients are dying on the waiting list. This is largely because we now better account for biological barriers and broaden reach for the sickest patients.
Dr. Rizzo:
Thank you. Dr. McCurry, last time we also discussed primary graft dysfunction and chronic rejection. Could you update us on changes in monitoring or management?
Dr. Kenneth McCurry:
Yes, thank you. Chronic rejection remains the major challenge in transplantation. Despite advances, survival curves after one-year survival haven’t changed much in decades. In lungs, this manifests as chronic lung allograft dysfunction (CLAD).
Risk factors include both immune mechanisms (T- and B-cell mediated rejection) and non-immune ones (aspiration, reflux, primary graft dysfunction). Increasingly, inflammation is seen as the common pathogenic mechanism.
A very exciting area now is the lung microbiome. Early evidence suggests changes in microbial burden and diversity correlate with rejection risk, independent of other factors. This parallels what’s been seen in non-transplant lung disease. Research here is very promising.
Dr. Rizzo:
That’s fascinating. I had read recent studies suggesting bacterial burden and microbiome shifts may contribute to outcomes. Switching gears: Dr. McCurry, could you update us on ex vivo lung perfusion (EVLP)? I understand its use has increased significantly at the Cleveland Clinic.
Dr. McCurry:
Yes. EVLP allows us to assess and rehabilitate donor lungs outside the body. Many donor lungs are injured — from trauma, infection, or fluid overload — and would traditionally be declined. With EVLP, we can perfuse and ventilate them on a machine for several hours, assess their function, and sometimes improve them for transplant.
At our center, EVLP now accounts for 25–35% of our lung transplants each year. Nationally, only about 20% of donor lungs are used, so EVLP has tremendous potential to expand the donor pool.
There are challenges — the process is complex, requiring frequent use and expertise. Some centers have struggled with low volume. To address this, companies like United Therapeutics have centralized EVLP facilities, performing it at scale and returning suitable lungs to transplant programs.
Dr. Rizzo:
In 2021, we also discussed COVID-related respiratory failure and transplant. Has that become more common?
Dr. Valapour:
Yes. In 2021, about 1 in 10 U.S. lung transplants were for COVID-related ARDS or fibrosis. That number has since decreased, but early in the pandemic it was a significant new indication.
Dr. McCurry:
At Cleveland Clinic, we performed about 18 transplants for COVID-related ARDS. Outcomes were comparable to those for fibrotic lung disease, though these were very complex cases. For post-COVID fibrosis, we’ve only done a few so far, but outcomes have been good.
Dr. Rizzo:
Has long COVID in transplant recipients been studied?
Dr. Valapour:
Not much yet. Registries only began capturing these diagnoses in 2020. It will likely be years before we know the long-term outcomes.
Dr. Rizzo:
This past year, Northwestern performed a double lung transplant in a patient with metastatic lung cancer. What are your thoughts on this?
Dr. McCurry:
It’s a bold step. Historically, carefully selected patients with certain lung cancers — like early adenocarcinoma in situ — have had acceptable outcomes with transplant. Dr. Bharat and colleagues are pushing these boundaries further, including metastatic disease.
There’s precedent in liver transplantation for certain cancers, but much still needs to be studied in lungs, particularly ensuring disease is confined. It’s an exciting but challenging frontier.
Dr. Rizzo:
Dr. Valapour, disparities in lung transplantation have been studied for years. Your work showed Black patients have worse post-transplant survival, even after adjusting for socioeconomic status. Can you expand on this?
Dr. Valapour:
Yes. Our study found Black patients had worse survival compared to non-Hispanic whites, and socioeconomic adjustment did not fully explain it. Important unanswered questions remain: Are patients receiving differential care within the same centers? Are they delayed in referral or listing?
Allocation systems like LAS or CAS only affect patients once listed, so they can’t address inequities in referral or access. Recently, HHS directed that data collection should begin at referral, not just listing, so we can start to better study and address these gaps.
Dr. Rizzo:
Thank you. Finally, what lies ahead in transplantation?
Dr. McCurry:
This is an exciting time. We could potentially double the number of lung transplants in the next five years with better donor utilization, EVLP, and emerging technologies. We’re also looking at ways to personalize donor lungs on the device — making them less immunogenic, improving matches, and potentially reducing chronic rejection.
Artificial lung technology may also play a role in the next decade.
Dr. Valapour:
I’d add that advances in computational medicine and quantitative sciences will make us smarter at donor-recipient matching, improving survival even if organ supply doesn’t increase dramatically.
Dr. Rizzo:
That’s encouraging. Thank you, Dr. Valapour and Dr. McCurry, for sharing these updates, and thanks to our listeners for tuning in.
