Lung transplantation

The supply of donor organs remains extremely limited, and improved methods of maintaining the lungs of potential donors to allow for transplantation must be developed. Currently the upper limit of donor lung ischemic even with our "best" preservation techniques is approximately 4 to 6 hours. Improved methods for preservation will increase the supply of suitable lungs and will considerably simplify the logistics of transplantation just as has occurred with liver transplantation. Efficient use of donor organs remains of paramount importance. We recently performed two single-lung transplants utilizing lungs from one donor. Likewise, there is no reason why a lung could not be sent to another center for transplantation if the harvesting group uses only one lung. Sufficient progress has been achieved to date to warrant continued application of lung transplantation for end-stage pulmonary disease. With increasing experience, one can anticipate refinement of techniques and broader application of these procedures. Single lung transplantation, initially restricted to patients with end-stage pulmonary fibrosis, has now been successfully applied to patients with emphysema, pulmonary hypertension, and other conditions. Although transplantation currently can offer real benefit only to a limited number of persons, it serves to create hope for many others. An additional benefit may prove to be the interest and attention that transplantation focuses on patients with end-stage lung disease and on the pathophysiology of chronic respiratory failure. Knowledge gained may ultimately result in the prevention of many of the disorders for which lung transplantation currently offers the only hope.     

Lung transplantation

Lung transplantation is an effective life-saving therapy for the treatment of a variety of end-stage lung diseases. However, the application of lung transplantation is hindered by multiple factors such as the shortage of organ donors, early graft failure, infection, and chronic graft dysfunction. A novel strategy for donor lung preservation--ex-vivo lung perfusion (EVLP)--that keeps the organ at physiological protective conditions, has shown great promise to increase lung utilization by reassessing, treating, and repairing injured donor lungs prior to transplantation. Infections are a major cause of early morbidity and mortality after lung transplantation. Because of the potential association of infections such as respiratory viral infections and gram-negative bacterial infections with bronchiolitis obliterans syndrome, prompt attention to these pathogens is critical. Despite marked improvements in early survival, long-term outcome after lung transplantation is still threatened by bronchiolitis obliterans syndrome. The program of lung transplantation in Czech Republic was started in University Hospital Motol in Prague in 1997. Nowadays in Czech Republic is performed about 20 transplants every year with results comparable to other advanced centers. Until September 2011, 175 transplants were carried out in Czech Republic.     

Lung transplantation

Over the past 20 years, many advances in surgical methods, transplantation immunology, donor organ procurement and preservation techniques, and postsurgical care regimens have influenced greatly the field of lung transplantation. The single remaining obstacle to widespread clinical success is donor lung availability. Improved methods of ex vivo lung preservation, organ donor maintenance, and donor lung retrieval after the completion of cardiac donation should help to ameliorate this problem.     

Lung transplantation. Lung preservation

Over the past decade, improvements in the technique of lung preservation have led to significant reduction in the incidence of ischemia-reperfusion-induced lung injury after lung transplantation. The challenge remains to improve the number of donor lungs available for transplantation. While the number of patients on the waiting list is constantly increasing, only 10% to 30% of donor lungs are currently being used for transplantation. Hence, the development of new strategies to assess, repair, and improve the quality of the lungs could have a tremendous impact on the number of transplants performed. In addition, an improved understanding of the mechanisms involved in lung preservation might help elucidate the potential link between acute lung injury and chronic graft dysfunction. In the future, genetic analysis using novel technologies such as microarray analysis will help researchers determine which genes control the injury seen in the transplantation process. Hopefully, this information will provide new insights into the mechanisms of injury and reveal potential new strategies and targets for therapies to improve lung preservation.     

Lung transplantation 1977

Many problems in the areas of donor lung procurement, bronchial anastomotic complications, and allograft rejection must be solved before widespread success in therapeutic lung transplantation becomes a reality. However, none of these problems is insurmountable. Considerable progress has already been made toward solving many of them, and the existence of promising new avenues of investigation appears to bode well for the solution of others. Thus, despite the disappointing human experience to date and despite the large number of complex problems that must be overcome, the prospects are good that increasing success with human lung transplantation will be achieved in the future.

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Résumé Avant que la transplantation pulmonaire ne devienne une réalité dans l'arsenal thérapeutique plusieurs problèmes restent à résoudre, en particulier quant aux phénomènes de rejet, aux complications reliés a l'anastomose bronchique et au procurement d'organe. Aucun de ces problèmes cependant n'est insurmontable; des progrès considérables ont déjà été accomplis et les travaux faits au laboratoire permettent de prévoir des solutions pour la plupart d'entre eux. Donc, en dépit des résultats décevants obtenus à date et malgré la multitude et la complexité des problèmes rencontrés, la transplantation pulmonaire chez l'homme devrait s'accompagner de succès croissants.

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Supported in part by grants from the United States Public Health Service (HL17417 and HL16476) and from the Manning Foundation.     

Lung transplantation]

In the past 10 years, three different types of lung transplantation were introduced into clinical practice, the combined transplantation of the heart and both lungs (HLTx), unilateral single lung transplantation (SLTx), and bilateral sequential lung transplantation (DLTx). At present, the indications for the various procedures have not been ultimately defined. Through 1991, a total of about 1,100 HLTx, 460 SLTx, and 160 DLTx was performed worldwide. One- und 3-year survival rates amount to 75-60% resp. in HLTx, to 80-70% resp. in SLTx, and to 70-60% resp. in DLTx. In our own experience with 24 HLTx, 32 SLTx, and 18 DLTx patients, global survival rates at one and 3 years are 85 and 80%, resp. The vast majority of surviving patients is able to lead a near normal life both physically and socially.     

Lung and heart-lung transplantation

This report is a brief summary on current events related to lung and heart-lung transplantation. Eleven patients have undergone transplantation of the heart and both lungs at Stanford University. The ages ranged from 22–45, the average age being about 36 years, and included were four females and seven males. The diagnosis was primary pulmonary hypertension in three and Eisenmenger syndrome-congenital heart disease with pulmonary hypertension-in eight. Eight patients are living and well, two to more than 24 months after transplantation of the heart and both lungs. All these patients were discharged and are fully rehabilitated, which is an important consideration. There have been three operative deaths, one was secondary to two previous operations that made our operation much too long, another was secondary to the use of intravenous cyclosporine, and the third was related to the poor maintenance of the donor lung. Three of the eleven patients were catheterized following the transplant from six months to a year after transplantation, and the pulmonary artery pressure and pulmonary vascular resistance were absolutely normal in all three of these individuals. Of course the plan is to go ahead with further catheter studies at yearly intervals in all of the patients. The last patient underwent transplantation in January, 1983. I think no matter how effective or how ingenious the medical staff is with artificial organs, it will be a long time before these early results of transplantation of the heart and both lungs can be matched by any types of artificial organ implants. Supported in part by a grant (HL 13108) from the National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, and from the Dr. Ralph and Marian Falk Foundation for Medical Research Gist of a Lecture given at the Japan Surgical Society, April 7, 1983.     

Lung transplantation. Xenotransplantation

The continued and growing success of lung allotransplantation has intensified the worldwide shortage of donor organs. Yet, xenotransplantation remains a daunting challenge. Additional molecular incompatibilities and unforeseen complications will continue to be discovered. Progress has been made, notably on the generation of alpha-Gal double knockout pigs. Progressive increases in organ survival times have been seen for most organs after significant investments of time and money. The lung continues to be an organ with the lowest supply of cadaveric donors and the least potential for expanded living donation or mechanical alternatives. As such, the impetus for xenotransplantation is strong. The lung appears to be exquisitely sensitive to xenograft rejection and resistant to strategies that have been moderately successful in other organs. A complex program involving genetically modified donor organs, recipient preparation for antibody removal or tolerance promotion, and multitargeted drug therapy will likely be required for successful clinical application.     

Lung transplantation in children

OBJECTIVE: To report the authors' experience with pediatric lung transplantation (LTX) to provide an overview of patients selected for this procedure and their outcomes. SUMMARY BACKGROUND DATA: Pediatric LTX differs from adults in many ways, including recipient size, indications, posttransplant care, and rehabilitation. METHODS: Two hundred seven isolated lung transplants on 190 children under the age of 18 years were performed from 1990 to the present. This represents the single largest series of lung transplants in children in the world. Thirty-two patients were less than 1 year of age, 22 were 1 to 5 years of age, 32 were 5 to 10 years of age, and 121 were 10 to 18 years old. The groups by major diagnostic category were cystic fibrosis (n = 89), pulmonary vascular disease (n = 44), bronchiolitis obliterans (n = 21), pulmonary alveolar proteinosis (n = 12), pulmonary fibrosis (n = 15), and other (n = 26). The average age at the time of transplant was 9.5 +/- 5.9 years (range 36 days to 18 years). RESULTS: Survival by Kaplan-Meier analysis was 77% at 1 year, 62% at 3 years, and 55% at 5 years. There was no significant difference in survival according to primary diagnosis leading to LTX or age at LTX. There were 25 early (<60 days) and 61 late deaths. The most common cause of early deaths was graft failure (13/25, 52%). The most common causes of late death were bronchiolitis obliterans (35/61, 57%), infection (13/61, 21%), and posttransplant malignancies (11/61, 18%). No patient died of acute rejection. In those surviving greater than 3 months (mean follow-up 3.5 years, range 3 months to 11 years), the overall rate of occurrence of bronchiolitis obliterans was 46% (80/175) and the overall incidence of posttransplant malignancies was 24/175 (14%). Major risk factors for the development of bronchiolitis obliterans were age older than 3 years, more than two episodes of acute rejection, and organ ischemic time longer than 180 minutes. CONCLUSIONS: In children, LTX is a high-risk but viable treatment for end-stage pulmonary parenchymal and vascular disease. The major hurdle to overcome in long-term survival is bronchiolitis obliterans.     

Lung and heart-lung transplantation

This report is a brief summary on current events related to lung and heart-lung transplantation. Eleven patients have undergone transplantation of the heart and both lungs at Stanford University. The ages ranged from 22-45, the average age being about 36 years, and included were four females and seven males. The diagnosis was primary pulmonary hypertension in three and Eisenmenger syndrome--congenital heart disease with pulmonary hypertension--in eight. Eight patients are living and well, two to more than 24 months after transplantation of the heart and both lungs. All these patients were discharged and are fully rehabilitated, which is an important consideration. There have been three operative deaths, one was secondary to two previous operations that made our operation much too long, another was secondary to the use of intravenous cyclosporine, and the third was related to the poor maintenance of the donor lung. Three of the eleven patients were catheterized following the transplant from six months to a year after transplantation, and the pulmonary artery pressure and pulmonary vascular resistance were absolutely normal in all three of these individuals. Of course the plan is to go ahead with further catheter studies at yearly intervals in all of the patients. The last patient underwent transplantation in January, 1983. I think no matter how effective or how ingenious the medical staff is with artificial organs, it will be a long time before these early results of transplantation of the heart and both lungs can be matched by any types of artificial organ implants.     

Lung transplantation after hematopoietic stem cell transplantation

Whitson BA, Shelstad RC, Hertz MI, Kelly RF, D’Cunha J, Shumway SJ. Lung transplantation after hematopoietic stem cell transplantation.
Clin Transplant 2011 DOI: 10.1111/j.1399‐0012.2011.01482.x.
© 2011 John Wiley & Sons A/S. Abstract: Introduction: Pulmonary insufficiency following bone marrow transplant (BMT) is common and has significant associated mortality. Lung transplantation (LTX) is the only viable treatment for patients with end‐stage pulmonary disease, but LTX after BMT is an uncommon event given the medical candidacy of the potential recipients. We sought to evaluate the short‐ and long‐term outcomes of LTX in BMT recipients. Methods: We performed a retrospective evaluation of our institution’s longitudinal LTX and BMT databases. Demographic and outcomes variables were collected. Results: We identified 639 LTX from January 1, 1988, through December 31, 2009, and 5525 BMT from program inception, March 21, 1974, through December 31, 2009. From the cross‐referenced cohort, we identified four patients who had BMT followed by LTX. Our series was composed of two men and two women, with a mean age of 32.3 yr (range, 20–59 yr). Single LTX were performed in two recipients (50%). All patients had significant and expected morbidities related to their transplant immunosuppression. Three patients (75%) required cardiopulmonary bypass at the time of LTX. The two recipients who underwent bilateral LTX required open chest management and subsequent tracheostomy. All patients are still alive at follow‐up (range, 19–119 months, median 39.5). Conclusion: Our study demonstrates that LTX in the setting of BMT is a high‐risk operation with the potential for a tumultuous perioperative course. Despite this, good outcomes and survival are obtainable in carefully selected patients. Selection factors include clinically stable patients without active sepsis and preoperative optimization of nutrition in anticipation of a prolonged recovery. An experienced multidisciplinary team approach and a protocol‐driven management plan are paramount for successful outcomes in this challenging population.