Francisco Santos

Airway complications after lung transplantation: a review of 151 anastomoses

OBJECTIVE To analyze the incidence, treatment and follow up of airway complications after lung transplantation. METHODS From October 1993 to April 2000, 104 lung transplants were performed in 101 patients. One hundred and fifty one bronchial anastomoses at risk were included in the study (29 single lung and 61 sequential double lung). Donor lungs were flushed both antegradely and retrogradely with Eurocollins. In the recipients, either a single or a sequential bilateral lung transplantation was performed when indicated. The bronchial anastomosis was telescoped and covered with peribronchial tissue in all cases. Postoperative fiberoptic bronchoscopic examinations were dictated by clinical grounds. Recipient variables were recorded and analyzed to assess possible differences between both complicated and non-complicated groups. RESULTS Eight bronchial anastomotic complications (5.3%) occurred in six patients (6.8%). All complicated cases developed in sequential bilateral lung recipients (P=0.08): stenosis (n=5), granulation tissue (n=2), and bronchial dehiscence (n=1). Treatment consisted of lobectomy and subsequent completion pneumonectomy in one patient, rigid bronchoscopy dilation in two, balloon bronchodilation in two, laser debridement and stenting in one, and conservative therapy in two cases. One patient with severe sepsis and bronchial dehiscence died on day +30. The rest of the patients remain well so far. Airway complications were related to longer intubation periods (P<0.01). Other perioperative donor and recipient factors including the incidence of infections and acute rejection episodes, and actuarial survival, did not differ between groups. CONCLUSION In our experience, the incidence of airway complications after lung transplantation is 5.3%. The careful surgical technique and organ preservation, the close surveillance of rejection and infection, and early postoperative extubation might play a role in reducing this incidence. Either surgical therapy or bronchoscopic dilation and stenting methods may contribute to resolve these complications.

GESITRA-SEIMC/REIPI recommendations for the management of cytomegalovirus infection in solid-organ transplant patients

Cytomegalovirus infection remains a major complication of solid organ transplantation. In 2005 the Spanish Transplantation Infection Study Group (GESITRA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) developed consensus guidelines for the prevention and treatment of CMV infection in solid organ transplant recipients. Since then, numerous publications have clarified or questioned the aspects covered in the previous document. These aspects include the situations and populations who must receive prophylaxis and its duration, the selection of the best diagnosis and monitoring technique and the best therapeutic strategy. For these reasons, we have developed new consensus guidelines to include the latest recommendations on post-transplant CMV management based on new evidence available.

Registro Español de Trasplante Pulmonar: primer informe de resultados (2006-2010)

The Spanish Lung Transplant Registry (SLTR) began its activities in 2006 with the participation of all the lung transplantation (LT) groups with active programs in Spain. This report presents for the first time an overall description and results of the patients who received lung transplants in Spain from 2006 to 2010. LT activity has grown progressively, and in this time period 951 adults and 31 children underwent lung transplantation. The mean age of the recipients was 48.2, while the mean age among the lung donors was 41.7. In adult LT, the most frequent cause for lung transplantation was emphysema/COPD, followed by idiopathic pulmonary fibrosis, both representing more than 60% the total number of indications. The probability for survival after adult LT to one and three years was 72% and 60%, respectively, although in patients who survived until the third month post-transplantation, these survival rates reached 89.7% and 75.2%. The factors that most clearly influenced patient survival were the age of the recipient and the diagnosis that indicated the transplantation. Among the pediatric transplantations, cystic fibrosis was the main cause for transplantation (68%), with a one-year survival of 80% and a three-year survival of 70%. In adult as well as pediatric transplantations, the most frequent cause of death was infection. These data confirm the consolidated situation of LT in Spain as a therapeutic option for advanced chronic respiratory disease, both in children as well as in adults.

A multicenter study of valganciclovir prophylaxis up to day 120 in CMV-seropositive lung transplant recipients.

Seventy‐six cytomegalovirus (CMV)‐seropositive lung transplant recipients receiving valganciclovir (900 mg/day) for CMV prophylaxis were compared with a group of 87 patients receiving oral ganciclovir (3000 mg/day). Prophylaxis was administered to day 120 post‐transplantation and follow‐up was 1 year. In addition, a study was conducted on risk factors for CMV infection/disease. CMV disease incidence was 7.9% and 16.1% for valganciclovir and oral ganciclovir, respectively (p = 0.11). Patients receiving valganciclovir had fewer viral syndromes (2.6% vs. 11.5%, p < 0.05), a similar rate of tissue‐invasive disease (5.2% vs. 4.6%, p = ns), longer time‐to‐onset of CMV infection/disease (197.5 vs. 155.2 days, p < 0.05), and a lower probability of infection/disease while on prophylaxis (1.3% vs. 12.6%, p < 0.01). Nonetheless, leukopenia incidence was higher with valganciclovir (15.8% vs. 2.3%, p < 0.01), as was the need for treatment withdrawal due to adverse effects (11.8% vs. 1.1%, p < 0.01). CMV infection was similar in both groups (32.9% vs. 34.5%). Induction therapy with basiliximab and glucocorticosteroid treatment were independent risk factors for developing CMV infection/disease. In conclusion, valganciclovir prophylaxis results in a low incidence of CMV disease in lung transplant recipients and appears more effective than oral ganciclovir. Despite the comparatively higher incidence of adverse events with valganciclovir, the drug can be considered safe for prophylaxis.

Extended recipients but not extended donors are associated with poor outcomes following lung transplantation

OBJECTIVES Extended donors (EDs) are safely used to increase the donor pool in lung transplantation (LT), but their influence in critically ill patients (extended recipients [ERs]) remains controversial. We compared LT outcomes matching optimal donors (ODs) or EDs with optimal recipients (ORs) or ERs. METHODS Three hundred and sixty-five LTs were reviewed. ED criteria: age >55, PaO2/FiO2 < 350 mmHg, pulmonary infiltrates/purulent secretions and ischaemic times >6 h (single LT [SLT]) and >9 h (double LT [DLT]). ER criteria: pulmonary fibrosis or pulmonary hypertension, pretransplant intubation, age >60 years and bypass >2 h. Four groups were created: Group 1 (OD/OR), Group 2 (OD/ER), Group 3 (ED/OR) and Group 4 (ED/ER). Thirty-day mortality, primary graft dysfunction (PGD), onset of bronchiolitis obliterans syndrome (BOS), long-term survival and other transplant outcomes were compared between OD and ED, OR and ER and among the four groups of study. RESULTS There were 151 SLTs and 214 DLTs. Donors: OD (n = 229) vs ED (n = 136); PGD 8 vs 10% (P = 0.43); 30-day mortality 19 vs 20% (P = 0.53) and survival (1, 5, 10 and 15 years) 67, 47, 34, 26 vs 69, 53, 46 and 29% (P = 0.33). Recipients: OR (n = 182) vs ER (n = 183); PGD 7 vs 10% (P = 0.10); 30-day mortality 15 vs 23% (P = 0.04) and survival (1, 5, 10 and 15 years): 73, 57, 46, 30 vs 61, 42, 29 and 23% (P = 0.002). Four donor/recipient (D/R) groups: Group 1 (n = 122), Group 2 (n = 106), Group 3 (n = 61), Group 4 (n = 76); PGD 10, 6, 3 and 16% (P = 0.05); 30-day mortality 13, 26, 19 and 20%, respectively (P = 0.13); survival (1, 5, 10 and 15 years) 74, 55, 44 and 35% (Group 1), 55, 39, 22 and 16% (Group 2), 70, 59, 48 and 26% (Group 3) and 68, 47, 37 and 22% (Group 4) (P = 0.004). No differences in the onset of BOS were observed among the four study groups. CONCLUSIONS LT in critically ill recipients is associated with poor early and long-term outcomes, irrespective of the quality of the donor and length of ischaemic times.

Age-Dependent Association between Low Frequency of CD27/CD28 Expression on pp65 CD8+ T Cells and Cytomegalovirus Replication after Transplantation

ABSTRACT In this cross-sectional study of 42 solid organ transplant recipients, the association of human cytomegalovirus (HCMV) replication and age with the phenotype of the HCMV-specific CD8+ T cells was analyzed by using the CMV pp65 HLA-A*0201 pentamer. A correlation between the proportion of CD28− HCMV-specific CD8+ T cells and age was observed in patients without HCMV replication (r = 0.50; P = 0.02) but not in patients with HCMV replication (r = −0.05; P = 0.83), a finding which differs from that observed for total CD8+ T cells. Within the group of patients younger than 50 years of age, patients with HCVM replication after transplantation had higher percentages of CD28− HCMV-specific CD8+ T cells (85.6 compared with 58.7% for patients without HCMV replication; P = 0.004) and CD27− HCMV-specific CD8+ T cells (90.7 compared with 68.8% for patients without HCMV replication; P = 0.03). However, in patients older than age 50 years, a high frequency of these two subpopulations was observed in patients both with and without previous HCMV replication (for CD28− HCMV-specific CD8+ T cells, 84.4 and 80.9%, respectively [P = 0.39]; for CD27− HCMV-specific CD8+ T cells 86.6 and 81.5%, respectively [P = 0.16]). In conclusion, the present study shows that in the group of recipients younger than age 50 years, HCMV replication after transplantation is associated with a high percentage of CD27− and CD28− HCMV-specific CD8+ T cells. These results suggest that the increased percentage of CD27− or CD28− HCMV-specific subsets can be considered a biomarker of HCMV replication in solid organ transplant recipients younger than age 50 years but not in older patients. Further studies are necessary to define the significance of these changes in HCMV-associated clinical complications posttransplantation.

Recommendations on the use of everolimus in lung transplantation

The antiproliferative effect of everolimus provides a therapeutic option in the immunosuppression therapy of lung transplantation, by reducing both the risk of acute rejection and the process of progressive fibrosis that determines chronic graft rejection. However, few data on the use of everolimus in lung transplantation have been published to date, and the specific indications of the drug, along with the most adequate time for its introduction or dosing, have not been defined yet. The aim of this article is to propose recommendations for the use of everolimus in lung transplant recipients, including indications, dosing schedules and the use of concomitant immunosuppression. This consensus document has been developed by experts of all the Spanish lung transplant groups from the review of the existing literature and the clinical experience.

Normativa para la selección de pacientes candidatos a trasplante pulmonar

The present guidelines have been prepared with the consensus of at least one representative of each of the hospitals with lung transplantation programs in Spain. In addition, prior to their publication, these guidelines have been reviewed by a group of prominent reviewers who are recognized for their professional experience in the field of lung transplantation. Within the following pages, the reader will find the selection criteria for lung transplantation candidates, when and how to remit a patient to a transplantation center and, lastly, when to add the patient to the waiting list. A level of evidence has been identified for the most relevant questions. Our intention is for this document to be a practical guide for pulmonologists who do not directly participate in lung transplantations but who should consider this treatment for their patients. Finally, these guidelines also propose an information form in order to compile in an organized manner the patient data of the potential candidate for lung transplantation, which are relevant in order to be able to make the best decisions possible.

A retrospective 12-month study of conversion to everolimus in lung transplant recipients.

BACKGROUND Everolimus has potent antifibrotic effects that may potentially affect the clinical course of bronchiolitis obliterans syndrome (BOS) or provide nephroprotective immunosuppressive regimens for lung transplantation. METHODS We retrospectively assessed the 12-month outcomes of the conversion to everolimus among lung recipients in six Spanish centers. RESULTS From March 2005 to December 2007, 65 lung recipients who were at a mean posttransplantation time of 10.2 ± 7.9 months were converted to everolimus, mainly because of BOS (64.6%) or renal insufficiency (RI; 12.3%). The initial dose of everolimus was 1.9 ± 0.6 mg/d and the mean blood trough levels were stable over time (6.4 ± 2.8 ng/mL at 12 months). Conversion to everolimus allowed us to eliminate the calcineurin inhibitor (CNI) in 21% of patients. Among the overall population, the forced expiratory volume at 1 second (FEV(1)) and renal function remained stable. Mean FEV(1) did not change among the 35 (81%) patients surviving BOS at 12 months: preconversion FEV(1): 1.449.5 ± 641.9 mL vs 12-month FEV(1): 1420.0 ± 734.6 mL (P = .866). There was a significant improvement in renal function among the RI patients with mean glomerular filtration rates of 42.2 ± 15.2 mL/min/1.73 m(2) (P = .043) at 6 and 44.4 ± 18.8 mL/min/1.73 m(2) at 12 months, (P = .063) and a decrease in the use of CNIs from 1% of RI patients preconversion to 57% at 6 and 75% at 12 months. With a mean of 8.1- months follow-up (range: 1-31.3) overall survival was 84.6% at 1 year and 50% at 22.3 months. Progressive BOS was the main cause of death. Reasons for everolimus discontinuation were patient death (n = 10), lack of efficacy (n = 4), gastrointestinal adverse events (n = 2), and edema (n = 2). CONCLUSIONS BOS and RI were the main indications for conversion to everolimus among lung recipients. Conversion to everolimus improved renal function among patients converted because of RI. The present results were inconclusive regarding effects of everolimus on BOS.

Risk factors, survival, and impact of prophylaxis length in cytomegalovirus-seropositive lung transplant recipients: A prospective, observational, multicenter study

The optimal length of cytomegalovirus (CMV) prophylaxis in lung transplantation according to CMV serostatus is not well established.