FUTURE IN TRANSPLANT - 2

1. ATTACHING AN ANTIOXIDANT -  In the case of lung transplants, the procedue is often complicated by substances known as free radicals, which can damage lungs as soon as they are removed from a donor's body.  If the damage caused by free radicals is too extensive, the recipient's immune system may attack the new organ, creating life-threatening situation.  In the journal Nature Biotechnology, Dr. Vladimir R. Muzykantov shows that attaching an antioxidant -- which fights free radicals -- onto an antibody that hones in on lung cells helps protect extracted rat lungs from free radical-linked damage.  If this technique shows similar results in humans, doctors may one day employ this mechanism to boost the success of lung transplant.  Since free radicals can start to damage lung tissue as soon as the organ is extracted from the donor, "we envision a prophylatic infusion of this targeted therapeutics just prior to organ harvest, or immediately after."
2. LIVE CELL THERAPY The treatment involves taking cells from the lungs of sheep embryos and injecting them into the patients abdomen. The theory is that the new cells travel to the damaged lungs and stimulate the regeneration of new, healthy tissue.  Cells are currently produced in laboratories in Europe, where regeneration is allowed and performed in clinics ( many for cosmetic, anti-aging reasons.) Treatment is also available in the Bahamas and Mexico.  Live Cell Therapy is not approved and not allowed in the USA. 
3. Increasing the Quantity of Lungs for Transplantation Using High-Frequency Chest Wall Oscillation The use of chest physiotherapy in donor patient management occupies an established place in most lung procurement protocols. The implementation of high-frequency chest wall oscillation as part of the donor lung procurement protocol may increase rates of successful lung recovery by providing effective clearance of obstructing pulmonary secretions containing destructive by-products of inflammation and entrapped pathogens.  High frequency chest wall oscillation may also improve arterial blood gas values, a critical factor in increasing lung procurement rates.  Although speculative, the benefits of high-frequency chest wall oscillation on donor lungs might improve perfusion and oxygenation of other organs for possible transplantation.The number of lung transplants performed annually reached a peak and then a decrease was seen in 1999. The cause of this decrease is an acute shortage of both available and suitable donors.   Current projections suggest that the supply of human donor organs, regardless of source, will never be adequate to meet the need. To increase that supply, a number of controversial solutions hae been proposed.The reasons for the plateau is three-fold: 1) public education and policy campaigns fail to aggressively recruit future donors and/or their families. 2) physicians, surgeons, and healthcare professionals do not proactively identify and place on a "donor track" suitable dying or brain dead individuals and 3) requirements for careful donor selection eliminate a significant percentage of otherwise available organs.  Since 1993, when only 10% of brain dead individuals who met criteria to donate kidneys, liver, and pancreas, were the lungs sufficiently healthy to procure for transplant.  Since then, aggressive efforts have been implemented to increase viability of lungs in ideal donors and to expand the donor pool.  Now accepted are older donors, those with a signficant smoking history, and some with marginal pulmonary functions. As a result of such modifications, viable lungs are procured from 15-20% of beating heart multiple organ donors.  Until recently, most OPO's relied on chest physiotherapy (CPT) techniques to achieve secretion clearance in donors. CPT is an airway clearance method that combines manual percussion and vibration of the chest wall by a caregiver, strategic positioning of the patient for mucus drainage, and, in unconscious patients, suctioning technigues.   Despite the intuitive rationale for administerin CPT to organ donors, the treatment is neither easily available nor ncecessarily benign.  Its safety and efficacy for use in such patients may be compromised by a number of factors: CPT is labor- intensive, time consuming, and methodologically challenging.  To overcome obstacles that limit availability, safety, and effectiveness of CPT for donors, OPO's are challenged to identify alternative modalities that are the following: equal to or more effective than CPT, less hazardous than CPT, time-efficient, and cost-effective. High- Frequency chest wall oscillation(HFCWO) technology may offer a practical solution.  the HFCWO airway clearance treatments may be administered to organ donors via a device designated as The Link System (American Biosystems, Inc.,) The Link is technologically identical to the The Vest Airway Clearance System( Advanced Respiratory Inc.,). A fitted vest, connected by hoses to an air pulse generator, inflates and deflates rapidly, applying oscillating compressive forces to the chest wall.  HFCWO applies rapidly oscillating compressive forces externally to the thorax generating forces within the airways that dislodge mucus adherent to bronchial walls. The resulting oscillating bursts of air impart shear forces to the mucus layer and have been shown to reduce the viscosity of mucus.   In studies, HFCWO was shown to be superior or equal to professionally administered CPT. (Source: Progress in Transplantation, 2002, Jane M. Braverman, PhD, North American Transplant Coordinators Organization)
4. Heme Oxygenase (HO)-1 - Heme oxygenase (HO) -1 long believed to be a cytoprotective protein, has recently been identified as a graft surival gene. A study evaluated the role of HO-1 for obliterative bronchiolitis. Conclusions from the study: HO-1 protein expression is increased in murine heterotopic airway rejection, and deficienc of HO-1 accelerates the development of the obliterative bronchiolitis- like lesion. IL-10 protein expression parallels expression of HO-1, suggesting that IL-10 may participate in the genesis of HO-1's effects on the inflammatory process triggered by allotransplantation.(Source: Transplantation 2003)
5. New Approaches to transplant immunosuppression- One strategy to develop new immunosuppressants seeks to identify targets that are critical for and specific to the adaptive immune response. Three approaches have been used to guide this enterprise; molecular design based on steric resemblance of the antagonist to the natural ligand; construction of complementary DNA oligonucleotides that hybridize with the leader sequence of messenger RNA encoding the synthesis of the specific target, thereby preventing production of that protein; and functional comparisons based on similar inhibitory profiles of candidate compounds and a probe that blocks the target nonselectively. (Source: Transplantation Proceedings, August 2003)

6. Fundoplication - Fundoplication aids lung graft.   Keep bronchiolitis obliterans at bay in GERD patients -- By David HodgesSAN ANTONIO  In lung transplant patients with known gastroesophageal reflux disease (GERD), early fundoplication leads to significant improvement in actuarial survival and freedom from the  bronchiolitis obliterans syndrome.These findings, presented at the Society of Thoracic Surgeons meeting here, emphasize the importance of non-alloimmune-mediated lung allograft injury in chronic lung failure, said the authors of the study."The prevalence of reflux in patients with end-stage lung disease is common," said lead study author Dr. Edward Canter of the Duke University Medical Centre in Durham, N.C. "We have seen a prevalence of GERD in 76% of lung cancer patients."Dr. Canter said his work adds to an increasing body of evidence that suggests non-immune mediated injury due to GERD may contribute to the development of the bronchiolitis obliterans syndrome, a process affecting the conducting airways following chronic rejection of the lung allograft. He and his colleagues had previously demonstrated late fundoplication is able to reverse the syndrome in lung transplant recipients with GERD.To test the hypothesis that prevention of GERD with early fundoplication would prevent bronchiolitis obliterans syndrome and improve survival, Dr. Canter and colleagues did a retrospective analysis of 458 patients who underwent lung transplantation between April 1992 and July 2003. In 336 patients who survived a minimum of three months, there were sufficient spirometry data to allow the researchers to determine actuarial freedom from the syndrome. Patients were stratified in four groups: no history of reflux, history of reflux, history of reflux and early fundoplication (less than 90 days) and history of reflux and late fundoplication.They found incidence of ostoperative reflux was 69.9% in pH-confirmed subgroups. In 12 patients with early fundoplication, actuarial survival was 100% at one and three years, compared to those with reflux (83%) and no intervention (67%). Furthermore, those who underwent early fundoplication had improved freedom from bronchiolitis obliterans syndrome at one and three years (100% in both), compared to no fundoplication in patients with reflux at one and three years (91% and 56%, respectively)."After a median two years of followup, there has been no mortality in the early fundoplication group," said Dr. Canter. While these results are encouraging, he said his study is a single-centre retrospective experience with differences in study group demographics. A randomized control trial with longer followup is required, he said. Copyright 2003 The Medical Post. All rights reserved. March 09, 2004 Volume 40 Issue 10