First there was the "heart in a box," a revolutionary experimental technology that allows donor hearts to be delivered to transplant recipients warm and beating rather than frozen in an ice cooler.
Now that same technology is being used to deliver "breathing lungs."
The lung transplant team at Ronald Reagan UCLA Medical successfully performed the nation's first "breathing lung" transplant in mid-November. The patient, a 57-year-old who suffered from pulmonary fibrosis - a disease in which the air sacs of the lungs are gradually replaced by scar tissue - is recuperating from the seven-hour surgery.
The groundbreaking transplant involved an experimental organ-preservation device known as the Organ Care System (OCS), which keeps donor lungs functioning and "breathing" in a near-physiologic state outside the body during transport. The current standard involves transporting donor lungs in a non-functioning, non-breathing state inside an icebox.
With the OCS, the lungs are removed from a donor's body and are placed in a high-tech OCS box, where they are immediately revived to a warm, breathing state and perfused with oxygen and a special solution supplemented with packed red-blood cells. The device also features monitors that display how the lungs are functioning during transport.
"Organs were never meant to be frozen on ice," said Dr. Abbas Ardehali, a professor of cardiothoracic surgery and director of the heart and lung transplantation program at Ronald Reagan UCLA Medical Center. "Lungs are very sensitive and can easily be damaged during the donation process. The cold storage method does not allow for reconditioning of the lungs before transplantation, but this promising 'breathing lung' technology enables us to potentially improve the function of the donor lungs before they are placed in the recipient."
UCLA is currently leading the U.S. arm of the international, multicenter phase 2 clinical INSPIRE study of the OCS, developed by medical device company TransMedics; Ardehali is the principal investigator for UCLA. The purpose of the trial is to compare donor lungs transported using the OCS technology with the standard icebox method. The INSPIRE trial is also underway at lung transplant centers in Europe, Australia and Canada and will enroll a total of 264 randomized patients.
According to Ardehali, the technology could also improve donor-lung function and could potentially help transplant teams better assess donor lungs, since the organs can be tested in the device, over a longer period of time.
In addition, it could help expand the donor pool by allowing donor lungs to be safely transported across longer distances.
"For patients with end-stage lung disease, lung transplantation can dramatically improve the patient's symptoms and offer relief from severe shortness of breath," said Dr. David Ross, professor of medicine and medical director of UCLA's lung and heart-lung transplantation program and UCLA's pulmonary arterial hypertension and thromboendarterectomy program. "The 'breathing lung' technology could potentially make the transplantation process even better and improve the outcomes for patients suffering from lung disease."
The "breathing lung" device follows on the heels of TransMedics' "heart in a box" technology which delivers donor hearts in a similar manner. The multi-center national study of the heart technology, also led by UCLA, is ongoing.
Results of a preliminary OCS lung study conducted in Europe were published in the Oct. 10 edition of the journal Lancet. The findings showed good lung transplantation outcomes following preservation using the OCS system. Read the Lancet study.
UCLA's lung and heart-lung transplant program is the largest lung transplantation program on the West Coast and leads the nation in patient outcomes. The program pioneers novel technologies in lung preservation, recipient immune monitoring and immunosuppression and is responsible for significant advances in transplantation for extremely ill and high-risk transplant candidates.
INSPIRE is an international, multi-center, large clinical trial that is actively randomizing subjects. The INSPIRE trial will evaluate the success of lung preservation using TransMedics' Organ Care SystemTM technology as compared to traditional cold-storage preservation.
The INSPIRE trial is approved under the US FDA for an IDE, and it is currently enrolling patients in leading lung transplant centers in Europe, US, Australia, and Canada. For more information, please visit http://clinicaltrials.gov/ct2/show/NCT01630434
An organ transplant is often the last therapy option for patients with severe organ failure and the only way of saving these people's lives. If a donor organ is available and a suitable recipient has been identified, then the transplant process begins with the removal of the organ. As soon as the organ is cut off from the blood supply, all possible efforts must be made to maintain the organ's ability to function. The current standard method for achieving this is to cool the organ, storing it on ice. However, in the cold storage method the organ cannot be supplied with blood and nutrients, and this means that the condition of the organ continually and progressively deteriorates.
The lung - a highly sensitive organ
This situation is particularly complicated in the case of the lung because its condition starts to deteriorate immediately after the brain death of the donor. Moreover, it suffers greater damage than other organs. This creates major problems for the recipient: already debilitated by the initial illness and the operation, then they also have to compensate deficits of the donated organ.
As a result, dysfunctions of the lung frequently occur in the first weeks after the operation, and these can have negative consequences for the short-term and long-term success of the therapy. In some cases this can even lead to a potentially fatal organ failure. Transplantation medicine is thus seeking ways of improving the state of donor lungs before implantation.
Treatment of donor lungs outside the human body
One highly promising option for improving the function of donor lungs is provided by systems for artificial perfusion. The OCS Lung from TransMedics is one such system. This system enables the donor lung to be preserved at body temperature and to be provided with nutrients through a specially formulated solution while continuing to breathe. Moreover, OCS allows continual monitoring and reconditioning of the lung outside the human body. A range of problems can thus be dealt with before transplantation, such as the removal of fluid accumulations.
Only a few of the ex-vivo perfusion systems currently in use have been developed beyond the experimental stage. Of the all the available systems, only the OCS Lung system is portable. Stationary systems still require cold storage of the donor lung on the route from the donor to the translation center. Only after this phase can the functional parameters of the organ be improved.
The problem of cold storage
Due to the ongoing damage incurred by the organs during cold storage, the time available for transplantation is limited and no organ reconditioning is possible. When an organ is placed in cold storage, in most cases a transplantation is no longer possible after five hours. If it is nonetheless carried out, then the prognosis for the patient is significantly poorer.
OCS reduces organ damage
The portable OCS Lung allows donor lungs to be maintained in an almost physiological environment immediately after explantation. This reduces ischemic time: with use of OCS this period is approximately 60 minutes (time for explantation, connection to OCS and implantation). At the same time, the time window from the donor lung retrieval to implantation maybe extended.
During this time, the function improvement of the donor organ can be immediately initiated. The donor lung reaches the recipient in a significantly better state than with cold storage and the transplanting physicians know exactly what condition the organ is in. OCS thus has the potential to decisively improve the treatment success of lung transplantations
Structure and functioning of the OCS
OCS Lung comprises of three essential components:
The OCSTM Lung Initial European Clinical Experience Featured in The Lancet Journal (Oct 10, 2012)