Why enzymatic treatment may increase access to lung transplants

By Jules Murtha | Medically reviewed by Sanja Jelic, MD
Published March 21, 2022

Key Takeaways

  • ABO blood group matchings are often necessary for successful lung transplants, which poses allocation challenges for some patients who lack blood type compatibility with available donor lungs.

  • Lung transplant allocation may change in the future due to enzymatic treatments that may blood type A donor lungs compatible to transplant into recipients with a different blood type

  • Clinicians should advise patients seeking a lung transplant to avoid alcohol and drug use—including nicotine—and to secure social support networks throughout the entirety of the transplant process.

Patients seeking lung transplants face a number of barriers, one of which is eligibility. Consider Ron Flewett, age 53, a patient with idiopathic pulmonary fibrosis, whose case was described in an article published in Breathe. He knows he may not qualify for transplantation: He is sick, but he has to be sick enough to need the transplant—yet not so sick that he will cease to be eligible.

Physicians can play a role by encouraging their patients to abide by lung transplant eligibility guidelines to raise their chances of acquiring a new lung. Balancing the health timelines can be tricky, and socioeconomic factors can influence prognosis. Also affecting eligibility and outcomes is the issue of blood type compatibility with the donor.

Recent early, experimental data suggest that blood type conversion treatments of the donor lung’s outside the human body may make some of those donor lungs acceptable or transplantation into patients with a different blood type.

Introducing enzymatic treatments

The execution of lung transplants is often complicated by the need for ABO blood group matchings, creating access issues for patients.

Researchers are looking at the potential for enzymatic treatments to play a role in increasing blood type compatibility.

A February 2022 study published by Science Translational Medicine explores the preclinical efficacy and safety of two enzymes used together—FpGalNAc deacetylase and FpGalactosaminidase—in the removal of A antigen (A-Ag) by means of ex vivo lung perfusion (EVLP). The success of this process would ensure the conversion of group A (ABO-A) red blood cells to group O (ABO-O) red blood cells in donor lungs.

To test the enzymes, researchers used five human ABO-A1 red blood cell samples and three post-static incubation human aortae. They found that the enzymes successfully withdrew more than 99% A-Ag from the red blood cells and 90% A-Ag from the aorta. The concentrations left over—some at 1 μg/ml—were low. 

Continuing their experiment, the researchers then put eight human donor lungs (ABO-A1) through the EVLP process. Over the span of 4 hours, EVLP removed more than 97% of endothelial A-AG among lungs containing enzyme perfusate, with no reported trace of acute lung toxicity.

Following this, the investigators then simulated an ABO-incompatible transplant. They used an ex vivo model of antibody-mediated rejection with the use of ABO-O plasma simulating the recipient’s circulation and  three donor lungs. When compared with control lungs, the treated lungs showed signs of reduced complement deposition, antibody binding, and injuries associated with antibodies—a promising result.

Overall, researchers found that EVLP safely and effectively removed A-Ag in donor lungs outside the human body. Thus, there appears to be potential for EVLP to make some of the ABO-incompatible lung transplants feasible.

Best practices for patients seeking eligibility

While the new enzymatic treatment research has great potential, it’s still in the experimental, nascent stages of development. 

In the meantime, physicians who have patients in need of a lung transplant may advise them to take cues from Penn Medicine’s guidelines for increased eligibility. Patients can do a lot to counter the factors outside of their control.

Above all, doctors can encourage patients to refrain from drinking alcohol and taking drugs.

Patients should also steer clear of any nicotine product—which includes vaping—for at least 6 months and provide documentation for proof. In addition, having a body mass index (BMI) of 35 or below may aid patients seeking candidacy for a lung transplant.

Finally, whether or not patients have a support system can affect eligibility. Doctors may motivate patients to secure a support system, lining up access to a group of people to depend on before, during, and after undergoing the lung transplant. 

While awaiting their transplant, patients such as Ron can profit from the advice of other transplantees. Beatriz Salgueiro, who had two lung transplants in her 20s, also told her story in the article in the aforementioned Breathe article. She advises transplant candidates to keep their bodies moving and enjoy their favorite foods pre-transplant, because dietary restrictions after the procedure may not allow this.

"Live your life the best you can for as long as you can. Provided you follow the advice of your doctors, do not let anyone else stop you."

Beatriz Salgueiro, transplant recipient

"Stop thinking of yourself as a patient or someone who is sick,” she added. “You are a person with dreams and aspirations and now your body can keep up with your head. Do not let that go to waste.”

Final thoughts

Some lung transplants hinge on the availability of ABO blood group matchings, creating accessibility issues for certain patients who lack blood type compatibility. Two enzymes—FpGalNAc deacetylase and FpGalactosam inidase—can successfully convert group A (ABO-A) red blood cells to group O (ABO-O). When applied to donor lungs, the conversion may open doors to far greater transplant accessibility among patients, as well as improvements in fairness. However, these treatments are currently in the early, experimental stages of development.

What it means for you

To raise patients’ chances of getting a lung transplant, doctors can emphasize the need to steer clear of alcohol and drugs, forgo all nicotine products for at least 6 months, maintain a BMI of 35 at most, and find a stable support group.


  1. Chan EG, Hayanga JWA, Tuft M, et al. Access to lung transplantation in the United States: the potential impact of access to a high-volume center. Transplantation. 2020;104(7):e199-e207.

  2. Penn Medicine. Lung Transplant Eligibility and Commitment. PennMedicine.org. 2022.

  3. Wang A, Ribeiro RVP, Ali A, et al. Ex vivo enzymatic treatment converts blood type A donor lungs into universal blood type lungs. Science Translational Medicine. 2022;14(632).

  4. Williams C, Flewett R, Salgueiro B. Lung transplantation: the patient view from either side of the operating table. Breathe. 2021;17(1):200305.

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