Lung Transplantation: Decades of Experience and Expertise
Since the inception of the new program nearly two decades ago, the Lung Transplantation Program at NewYork-Presbyterian/
“The lung transplant program has grown into a large comprehensive multidisciplinary team,” says Dr. Arcasoy. “Over the years, we have almost triplicated the number of transplants, consistently improving our early and long-term results with the best survival in the country,” says Dr. D’Ovidio.
“Today, our program includes four surgeons, six pulmonary transplant specialists, seven clinical coordinators, who are either RNs, physician assistants, or nurse practitioners, and a large inpatient PA team that manages the care of post-transplant patients,” continues Dr. D’Ovidio. “Patients are selected, discussed, treated, and managed collegially between the surgeons and the clinicians. The two services have different roles but even weight in the overall management of our patients.”
Historically, waiting time has been the primary determinant of lung organ allocation in the United States. “Patients were listed and waited two to three years to climb to the top of the list to get a transplant,” says Dr. Arcasoy. “This meant a death sentence for late referrals who were very sick. The allocation system changed in May 2005 to incorporate a medical urgency measure. All of a sudden, we started transplanting sicker and sicker patients.”
According to Dr. Arcasoy, many patients were being admitted to the hospital and needed mechanical support devices. “For about 10 years, we have been using the ambulatory ECMO [extracorporeal membrane oxygenation] system, and we were one of the first centers to implement this kind of support for patients with end-stage lung disease. We evaluate patients, list them if eligible, and support them as a bridge to transplant until organs become available.”
“Previously, patients would go on full cardiopulmonary bypass machines during surgery, but now, almost 100 percent of the time we use ECMO,” adds Dr. D’Ovidio. “Ultimately, this allows us to minimize coagulopathy and hemodynamic instability, which can be caused by cardiopulmonary bypass. The overall management of these patients has evolved and been refined significantly, both intraoperatively and postoperatively, to accommodate the more severe conditions we treat. In recent years we’ve also created a senior lung transplant program in that now 30 to 40 percent of our patients are over 65.”
Expanding the Pool of Donor Lungs
While the absolute number of organ donors is fundamentally far lower than those in need, an even smaller percentage, just 20 to 30 percent of donor lungs, is usually deemed acceptable for transplant, notes Dr. D’Ovidio. “Most lungs sustain too much damage at the time of death, which precludes them from transplantation.”
“As our experience has grown, so has our tendency to stretch the limits of what kind of lungs we would accept for transplantation,” says Dr. Arcasoy. “We published a paper on extended donor lungs years ago that showed that donor lungs that are not perfect yield very similar outcomes to standard lungs.”
“Ex vivo lung perfusion [EVLP] allows for the assessment of donated lungs outside of the donor’s body and also serves as a platform to potentially recondition the lungs by ventilating and perfusing them before implantation,” says Dr. D’Ovidio. “The process entails warming the lungs to normal body temperature; flushing the donor blood, inflammatory cells, and potentially harmful biologic factors; and treating the lungs with antibiotics and anti-inflammatory agents. In some cases, lungs that might have previously been deemed too poor for transplant can, in fact, be successfully reassessed, rendering them usable.”
In 2011, NewYork-Presbyterian/Columbia participated in the multicenter NOVEL Trial (Normothermic Ex Vivo Lung Perfusion as an Assessment of Extended/Marginal Donor Lungs) with Dr. D’Ovidio as Principal Investigator. “We were one of the first two centers in the country to transplant from an ex vivo procurement,” says Dr. D’Ovidio. “We’ve had outstanding results with this process with best early and long-term survival in the trial.”
“EVLP is also a very powerful platform, in my opinion, for research where we could someday apply treatments to the lungs using gene therapy or another approach before transplantation,” says Dr. Arcasoy.
“We are currently developing drug delivery strategies using nanoparticles to be aerosolized to the donor lung while on EVLP,” says Dr. D’Ovidio.
The paucity of suitable lung donors has led the team to explore the utilization of donors beyond brain dead-donors, which were previously the standard. “Much more frequently, we are using donors after cardiac death, a new criterion we’ve been proactively promoting in the U.S.,” says Dr. D’Ovidio. “It requires a more in-depth and dynamic assessment of the donor before procurement because once the patient has arrested there is no circulation and we are urged to procure the organ as quickly as possible. Instead of hours of assessment, with our dedicated protocol we’re now assessing everything in a few minutes allowing us to be extremely successful. Many centers have been requiring the use of the ex vivo lung perfusion system in these donors, despite the good quality of the organ, to accommodate the assessment of the organ outside of the donor body.”
“We have also been considering donor lungs that we wouldn’t have pursued in the past,” continues Dr. D’Ovidio. “For example, over the last nine months, we have been utilizing organs from donors who had a social history of IV drug abuse. With serological testing there has been a dramatic drop in the risk of potential and unrevealed viral infections. We have already had a 15 percent increase in transplants this year due only to donors with a history of IV drug abuse.”
“We have also been advocating for broader sharing of lungs — not just local sharing, but allowing access to donors within a wider region in the United States,” says Dr. Arcasoy. “We’ve made this point about the lung allocation policy with nearly 10 publications, including, most recently, an article published in the American Journal of Transplantation in which we discussed the geographic disparities in local donor lung supply and lung transplant waitlist outcomes. We’ve shown that individuals who live in the lowest lung availability areas have an 84 percent more likelihood of death or removal from the waiting list due to clinical deterioration and a 57 percent less transplantation rate. The United Network for Organ Sharing recently changed the policy from primarily local allocation to allocation with a 250-nautical mile radius, which is a significant improvement in the system, but it’s not yet perfect.”
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