Building a Lung Transplant Program

Twenty-five years have passed since the first lung transplant was performed at the Instituto do Coração (INCOR) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. On October 16, 1990, a 26-year-old woman with severe pulmonary fibrosis and secondary pulmonary hypertension underwent a single left lung transplant but only survived for 12 days, dying due to sepsis and diffuse alveolar damage. This occurred several months after the first and second (1) lung transplants in Brazil and seven years after the first in the world, which had been performed by Dr. Cooper in Toronto (2). Over a five-year period, nine more cases were performed, with the longest post-operative survival being 4 years. Despite the dedication of all the personnel involved with the program at that time, seven patients were never discharged due to acute respiratory failure and infection. At present, primary graft dysfunction remains a complication of transplant procedures, but in 1995, it seemed an almost insurmountable barrier. Despite the strong desire to continue performing this procedure, the group was not adequately prepared to continue in this field and the program was discontinued. In parallel, pulmonologists and surgeons sought training at other lung transplant centers and research in the field was initiated at our laboratory in the Medical School. Because bronchial healing remained a problem in clinical cases, it was chosen as a starting point for research. Using animal models of bronchial anastomosis and lung transplant as well as an established methodology for the evaluation of airway mucous clearance, the effect of immunosuppressive drugs was tested. Cyclosporin (3-5), Prednisone (6,7), Micophenolate (8) and combined therapies, including Tacrolimus (9,10), were tested and all drugs had a negative impact on mucous clearance. On August 9 2000, a single right lung transplant was performed on a 32-year-old male with silicosis. The postoperative period was uneventful and the patient is still alive fifteen years later. The main problems concerning intraoperative care, post-operative care and immunosuppression seemed to be solved. However, in the following three years we performed ten more procedures, of which only two patients survived for more than one year. Although only two patients of this period are still alive, the low survival rate indicated that there was still something lacking. At that time, the current knowledge and infrastructure were considered sufficient, but it was clear that unless a dedicated team was established, we could not proceed in this field. In 2003, a multi-professional and multi-disciplinary team was formed that included pulmonologists, surgeons, infectologists, nurses, physiotherapists, nutritionists, social workers and psychologists. We established a routine of morning rounds in ICU and on the wards; assessment meetings; scientific meetings and journal clubs. Based on candidate selection criteria established by the International Society for Heart and Lung Transplantation, patients considered for LTx were assessed and visited by all members of the lung transplant team. Inclusion on a waiting list was possible only upon the agreement of all members of the staff. Since then, almost 250 procedures have been performed, including some landmark procedures: the first bilateral procedure in 2003, the first pediatric transplant in 2006, the first split transplant in 2011 and the first transplant using the ex vivo lung perfusion (EVLP) technique in 2012. However, some problems persisted. Initially, simple preoperative monitoring and patient positioning were problematic and each transplant presented individualized challenges, illustrating the difficulties inherent in establishing routines in the operating room. However, over time, the program has achieved consistently satisfactory results and survival in line with international rates (Figure 1). For diseases such as cystic fibrosis, the survival to the end of the first year is over 90%, even higher than the ISHLT Resistries (11). Approximately 35 procedures are performed annually in the State of São Paulo a modest number compared to the number of patients on the waiting list, which impacts on the mortality rate of patients on the list. The main reason for the low number of transplants performed is the low success rate of lungs obtained from multiorgan donors. It is estimated that only 5% of available lungs are used, a very low frequency compared to the average rate of 15% reported by the UNOS (12). The main reason for the low utilization is the quality of the available lungs, which are rejected more than 50% of the time due to infection or inadequate management resulting in loss of lung function (13). Improving the quality of available donor lungs seemed to be the best solution for increasing the number of transplants. Thus, the first report on the reconditioning of initially rejected donor lungs by ex vivo perfusion (14) presented a solution for this problem. In 2007 we began preparations for EVLP via training courses and experimental studies with lungs rejected for transplantation. We initially sought to establish our methodology (15,16), then tested lung preservation solutions (17) and static or continuous topical preservation methodologies (18). This prepared us to perform the first lung transplantation using EVLP in Brazil in 2012. Three years after the procedure, the first patient is doing well. However, the cost and quality of using EVLP DOI: 10.6061/clinics/2015(12)02 Copyright & 2015 CLINICS – This is an Open Access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/ 4.0/) which permits unrestricted use, distribution, and reproduction in any medium or format, provided the original work is properly cited.