Quimerismo donante-receptor como origen del desarrollo de bronquiolitis obliterante en un modelo experimental de retrasplante de tráquea en ratas / Donor-receiver chimerism as the ori gin of obliterative bronchiolitis in an experimental model for trachea re transplant in rats

OBJETIVOS: 1. Desarrollar un modelo de bronquiolitis obli-terante en ratas (BO), mediante trasplante heterotópico de tráquea; 2. Eliminar el componente de rechazo alogénico me-diante el reimplante del injerto en un animal isogénico; y 3. Estudiar la respuesta inflamatoria persistente que podría auto-perpetuar la lesión.MÉTODOS: Se utilizaron ratas de las razas Lewis (LW), Wistar (W) y Brown Norway (BN). Se realizaron trasplantes singéni-cos (LW-LW, n=14; W-W, n=6; y BN-BN, n=6) y alogénicos AB (LW-W, n=6; BN-LW, n=6; y W-LW, n=6), alojando el injerto en el tejido celular subcutáneo cervical. Tras 15 días, se explantó el injerto e implantó en una tercera rata singéni-ca o alogénica por otros 15 días, estableciendo un modelo de retrasplante A-B-A y A-B-B. Los injertos se procesaron para realizar estudios histológicos e inmunohistoquímicos. El ori-gen de las células epiteliales se analizó mediante PCR.RESULTADOS: El retrasplante de tráquea, tanto en el diseño A-B-B como A-B-A, dió lugar a la aparición de una rápida respuesta inflamatoria compatible con un proceso de BO, en aquellos animales que habían desarrollado rechazo por tras-plante alogénico previo. En trasplantes ♀-♂-♀, se detectaron células con el cromosoma Y en tráqueas del 2º receptor ♀.CONCLUSIONES: En el modelo de retrasplante de tráquea en ratas, junto a los hallazgos típicos de BO se produce una res-puesta inflamatoria leve-moderada compatible con un recha-zo celular MHC incompatible. Células procedentes del primer receptor se integrarían en la tráquea del segundo trasplante, produciéndose un quimerismo donante receptor, que sería el responsable, en último término, del desarrollo de BO

OBJECTIVES: 1. Develop an obliterative bronchiolitis (OB) model in rats, by means of heterotopic trachea transplant; 2. Eliminate the allogenic rejection component by re-implanting a graft in an isogenic animal; and 3. Study the persistent in-flammatory response that could self-perpetuate the injury. METHODS: The following rat breeds were used: Lewis (LW), Wistar (W) and Brown Norway (BN). Syngenic (LW-LW, n=14; W-W, n=6; and BN-BN, n=6) and allogenic AB (LW-W, n=6; BN-LW, n=6; and W-LW, n=6) transplants were performed, housing the graft in the cervical subcutaneous ce-llular tissue. After 15 days, the graft was removed and implan-ted into a third syngenic or allogenic rat for another 15 days, to establish a re-transplant model A-B-A and A-B-B. The grafts were processed to carry out histological and immunohistoche-mical studies. The origin of the epithelial cells was analyzed using PCR. RESULTS: The tracheal re-transplant, both in the A-B-B and A-B-A design, gave rise to the appearance of a rapid inflam-matory response compatible with OB process, in those ani-mals that rejected the transplant due to previous allogenic transplant. In ♀ -♂ -♀ transplants, cells were detected with the Y chromosome in trachea of the 2nd ♀ receiver. CONCLUSIONS: In the trachea re-transplant model in rats, together with typical OB discoveries, a compatible slight-moderate inflammatory response takes place with an MHC incompatible cellular rejection. Cells from the first receiver became integrated into the trachea of the second transplant, producing a donor-receiver chimerism that would, in the final location, be responsible for the development of OB. Key words: Lung transplant, chronic rejection, obliterative bronchiolitis, chronic dysfunction of the lung graft

Bone mineral density in patients with chronic obstructive pulmonary disease who are candidates for lung transplant.

UNLABELLED: INTRODUCTIóN: After cystic fibrosis, lung transplantation (LT) patients with prior chronic obstructive pulmonary disease (COPD) are most susceptible to loss of bone mineral density (BMD). OBJECTIVES: To determine the prevalence of BMD loss among COPD patients being evaluated as LT candidates, seeking to identify, their risk profile. PATIENTS AND METHODS: This cross-sectional study included COPD patients who were LT candidates evaluated from January 2007 to December 2009. To identify patients at risk of fracture, BMD at the femoral neck and lumbar spine was assessed by bone densitometry. For categorization, we followed the World Health Organization criteria. To evaluate the risk profile, we recorded data on age, sex, smoking, lung function forced expiratory volume in 1 second, distance covered in the 6-minute walk test, body mass index, and degree of dyspnea. We recorded individual data as well as grouped them the multidimensional BODE (Body mass index Obstruction Dyspnea Exercise capacity) index. RESULTS: The study cohort consisted of 64 patients (51 men and 13 women). The overall prevalence of low BMD in any of the explored territories was 84.4%, affecting 88.2% of men and 69.2% of women. Osteoporosis was identified in 56.2% of patients, reaching a serious degree in 11/64 (17.2%). No significant differences were observed in any evaluated parameter when patients were separated into those with normal versus pathological BMD. When patients with osteopenia and osteoporosis were compared, we observed that the former showed a lower exercise capacity (P=.023) and a higher BODE index (P=.002). CONCLUSIONS: The prevalence of a low BMD level was increased among male patients with a worse BODE index, especially due to a reduced exercise capacity.

Lung transplantation for bronchiolitis obliterans after allogenic bone marrow transplantation.

INTRODUCTION: Bronchiolitis obliterans (BO) occurring after allogeneic bone marrow transplant (ABMT) may be an expression of lung damage of multifactorial origins. At present, it is not a usual condition for lung transplant (LT), accounting for <1% of all indications in the international registry. We sought, to describe the clinical features and outcomes of patients undergoing LT for BO after ABMT in our group. PATIENTS AND METHODS: We undertook a cross-sectional study of patients with an indication for LT due to BO after ABMT from the beginning of our program. We recorded the type of transplant, patient age, clinical course, functional outcome, and survival. RESULTS: Among 313 LT, 13 cases (4.2%) were due to BO, including 3 after ABMT (0.96%). ABMT was indicated after bone marrow aplasia in 2 cases and acute myeloid leukemia in the other patient. The patients were 2 men (both 35 years old) and 1 woman, aged 25 years. All subjects received double elective LT at 24, 20, and 9 years post ABMT. At the time of LT, all displayed severe obstructive ventilatory defects with a forced expiratory volume in 1 second (FEV1)<30% and partial respiratory insufficiency. The initial immunosuppression was cyclosporine, mycophenolate mofetil, and steroids in all cases. Two of the subjects required changes in the immunosuppressive regimen: 1 due to chronic graft rejection with subsequent functional recovery and the other due to hematologic and neurologic toxicity. After 96, 37, and 9 months, all the patients were alive with baseline dyspnea of functional class 0 and a FEV1 of about 68%. CONCLUSION: LT is an effective therapy in terms of lung function and survival for patients with respiratory failure secondary to the development of BO after ABMT.

Analisis secuencial y cronológico de la actividad de donación y trasplante pulmonar en Andalucía desde 1993 hasta 2007 / Sequential and chronological analysis of the activity of pulmonary donation and transplant in Andalusia between 1993 and 2007

Objetivo: la escasez de donantes pulmonares válidos es el principal factor que limita el desarrollo de un programa de trasplante pulmonar (TxP). Nuestra experiencia inicial analizando 280 donantes, demostró que solo el 54,7% eran válidos para trasplante. El presente trabajo pretende reexaminar el problema, analizando la evolución de las tasas de validez pulmonar con los años, identificando qué factores son susceptibles de mejorar para incrementar el número de donantes pulmonares, y determinando si el empleo de donantes subóptimos influye en los resultados del TxP a corto y largo plazo. Métodos: se revisaron todos los donantes ofertados a nuestra unidad desde octubre 1993 hasta diciembre 2007. La evaluación del donante pulmonar se dividió en tres fases: fase 1 (análisis de PaO2/FiO2, radiografía de tórax y hallazgos fibrobroncoscópicos); fase 2 (inspeccióny palpación pulmonar en campo operatorio); fase 3 (evaluación pulmonar después de la extracción donante). Se analizaron variables del donante y del receptor y se compararon entre dos periodos: donantes A (entre 1993 y 2001) y donantes B (entre 2002 y 2007). Se realizó un análisis adicional en un subgrupo de donantes con criterios de “subóptimo” (..) (AU)

Objective: The shortage of donors is a major problem limiting lung transplant programmes (LTx). Our early experience analysing 280 donors demonstrated that only 54.7% were (..) (AU)

Combined lung and liver transplantation-University Hospital Reina Sofia experience: two case reports.

OBJECTIVE: To analyze the results of combined lung and liver transplantation. METHODS: We performed two combined lung and liver transplantations for patients with cystic fibrosis with chronic respiratory failure accompanied by advanced liver disease. In each case, all thoracic and abdominal organs were obtained from a single donor by means of standard harvest techniques. In the recipient, a two-stage procedure was adopted with completion of the bilateral lung transplantation before the liver operation. Immunosuppression consisted of three-drug therapy used for isolated lung transplantation. RESULTS: The patients were both boys of 13 and 15 years old. Episodes of acute pulmonary rejection were successfully treated with intravenous steroids. Neither lung disorder was associated with a liver rejection episode. Airway complications that occurred in both cases were managed endoscopically. CONCLUSION: Combined transplantation of lung and liver is a feasible and therapeutically effective procedure for patients with cystic fibrosis complicated by advanced liver disease. Herein we have described our experience in two of the only three cases of combined liver and lung transplantation performed in Spain to date. Patient and graft survivals were comparable to isolated liver or isolated bilateral lung transplantations.