Voriconazole and squamous cell carcinoma after lung transplantation: A multicenter study.

This study evaluated the independent contribution of voriconazole to the development of squamous cell carcinoma (SCC) in lung transplant recipients, by attempting to account for important confounding factors, particularly immunosuppression. This international, multicenter, retrospective, cohort study included adult patients who underwent lung transplantation during 2005-2008. Cox regression analysis was used to assess the effects of voriconazole and other azoles, analyzed as time-dependent variables, on the risk of developing biopsy-confirmed SCC. Nine hundred lung transplant recipients were included. Median follow-up time from transplantation to end of follow-up was 3.51 years. In a Cox regression model, exposure to voriconazole alone (adjusted hazard ratio 2.39, 95% confidence interval 1.31-4.37) and exposure to voriconazole and other azole(s) (adjusted hazard ratio 3.45, 95% confidence interval 1.07-11.06) were associated with SCC compared with those unexposed after controlling for important confounders including immunosuppressants. Exposure to voriconazole was associated with increased risk of SCC of the skin in lung transplant recipients. Residual confounding could not be ruled out because of the use of proxy variables to control for some confounders. Benefits of voriconazole use when prescribed to lung transplant recipients should be carefully weighed versus the potential risk of SCC. EU PAS registration number: EUPAS5269.

Epidemiology and Risk Factors for Cancer After Lung Transplantation.

Cancer is the third most common cause of death among lung transplant (LT) recipients who survive for more than 1 year. The purpose of this study was to analyze the incidence and risk factors for cancer after LT in a Spanish cohort. The epidemiology and risk factors for cancer were retrospectively analyzed in LT recipients from 2 cities in Spain, Madrid and Barcelona. Of the 1353 LT patients initially included in the study, 125 (9.2%) developed cancer after a mean of 3.7 years. This frequency was 5-fold higher than in the general population. The most prevalent tumors were skin cancer (32%), lymphoproliferative disease (18%), and lung cancer (16.5%). In 4 patients, lung cancer was diagnosed on the day of the operation. The risk of cancer increased with age >55 year (hazard ratio [HR] 2.89 [1.64-5.09]; P < .001), in men (HR 2.8 [1.4-5.6]; P = .004), and in heavy smokers (>20 pack-years) (HR 2.94 [1.64-5.27]; P < .001). Other factors such as sun exposure were not found to be risk factors. In conclusion, prevalence of cancer is high in LT recipients in a Mediterranean country. Skin tumors, lymphoproliferative disease, and lung cancer are the most prevalent cancers. Age, male sex, and smoking were the main risk factors for cancer in this population.

Prevalence and Diagnosis of Chronic Kidney Disease in Maintenance Lung Transplant Patients: ICEBERG Study.

BACKGROUND: Chronic renal dysfunction (CRD) after lung transplantation (LT) is a common and noteworthy complication associated with increased morbidity and mortality rates. The study objectives were to determine the prevalence of CRD according to different diagnostic criteria and describe its therapeutic management. METHODS: This observational, multicenter, retrospective study included LT patients with ≥ 2 years of evolution. CRD was defined according to 2 different methods: (1) by the physician's subjective clinical criteria and (2) by analytical criteria (estimated glomerular filtration rate [eGFR] by Modification of Diet in Renal Disease of ≤ 59 mL/min). RESULTS: We included 113 patients; 65.5% were men and the mean age at transplant was 49.1 (12.6) years. At 6 months after transplant, approximately half of patients had CRD according to analytical criteria, and, at 2 years after transplantation, the prevalence rose to 80%. Although clinical prevalence and analytical prevalence were similar (68.8% and 78.6%), a weak concordance was observed (Kappa index: 0.6). Among patients who were not classified as having CRD according to clinical criteria, 40.0% (14/35) were diagnosed with CRD according to analytical criteria. None of the patients underwent renal biopsy, and 5.1% of patients required dialysis. In 77.0% of patients with clinical CRD diagnosis, the immunosuppressive regimen was modified: reduction of isolated calcineurin inhibitors (CNIs) (35.0%), CNIs decreased with mycophenolic acid change (23.3%), and CNIs lowering with mammalian target of rapamycin introduction (6.7%). In a multivariate logistic regression model, the independent factors associated with CRD were an older recipient age, low body mass index (BMI) at transplant, treatment with cyclosporine/azathioprine, and low eGFR at the first month after transplant. CONCLUSIONS: We found a high incidence of CRD at the first year after transplantation, which increased subsequently. Moreover, CRD was considerably underestimated by physicians' subjective clinical criteria. End points related to CRD development were older age, low BMI, azathioprine use, and low eGFR during the first month after transplant. The latter finding provides an opportunity to implement prevention strategies.

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.

Development and validation of a specific questionnaire for evaluating the impact of gastrointestinal symptoms on the health-related quality of life of transplant patients.

BACKGROUND: Transplant patients receiving immunosuppressant treatment suffer gastrointestinal symptoms (GIS) limiting their health-related quality of life (HRQOL) and causing dose redíuctions and discontinuations. METHODS: This observational, multicenter, cross-sectional study aims to develop and validate a questionnaire for detecting and quantifying the impact of GIS on the HRQOL of patients with functioning organ transplants. We developed a pilot version of the questionnaire SIGIT-QOL (Impact of Gastrointestinal Symptoms on Quality Of Life) and then evaluated the feasibility, validity, and reliability. We consecutively recruited 274 solid organ transplant patients from 20 hospitals. Sociodemographic and clinical data were collected. Patients completed the SIGIT-QOL and Gastrointestinal Quality of Life Index-GIQLI- questionnaires. RESULTS: Mean age was 52.7 (SD, 7.59) and 181 were male; 43.4% showed an episode of GIS since transplantation (3-12 months before). Of all patients, 95.3% completed the SIGIT-QOL. Mean time of completion was 6.49 minutes. Exploratory factorial analysis identified a 1-dimensional structure (42% of total variance). Internal consistency was high (Cronbach's alpha, 0.889). A significant association was found between the SGITI-QOL and the presence of GIS (P < .01). Finally, correlation coefficients between SIGIT-QOL and GIQLI were moderate-high except for Social Function. CONCLUSION: The brief SIGIT-QOL questionnaire can detect and quantify the GIS and their impact on the HRQOL of solid organ transplant patients.

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.

El test de seis minutos de marcha como predictor de mortalidad en lista de espera para trasplante pulmonar / The six-minute walking test as predictor of mortality on the waiting list for lung transplant

Introducción. La mortalidad en lista de espera de trasplante pulmonar hace necesario identificar los criterios de priorización. Objetivos. Analizar la utilidad del test de 6 minutos de marcha (T6MM), para predecir la mortalidad en lista de espera. Pacientes y métodos. Estudio prospectivo de los pacientes valorados para trasplante entre 1998 y 2007. Las variables analizadas son metros recorridos y saturación de oxígeno (SaO2) mínima durante el T6MM, edad, sexo, diagnóstico y mortalidad en lista. Resultados. Se incluyó a 453 pacientes, el 64,2% varones (49,7±14,8 años). La distancia recorrida fue 322±92 m y la SaO2 mínima, 84,1%±7,6%. Murieron 18 pacientes en lista (4%; intervalo de confianza [IC] del 95%, 2,2%-5,8%). Los pacientes que sobrevivieron caminaron significativamente más que los que fallecieron (321±90 frente a 262±115 m; p = 0,001). De forma similar, cifras de SaO2 < 85% se asociaron al 6,5% de mortalidad, frente al 1% con valores superiores (p = 0,006). Los pacientes con fibrosis quística presentaron una mortalidad mayor que con otros diagnósticos (el 10,4 frente al 3,2%; p = 0,043). El análisis multivariable confirmó la relación de los tres factores de riesgo con la mortalidad. La odds ratio (OR) de muerte en lista para la FQ fue de 5,6 (IC del 95%, 1,7-18,9); SaO2 < 85%, OR = 5,7 (IC del 95%, 1,3-25,1), y para los que caminaron menos de 200 m, OR = 7,3 (IC del 95%, 2,5-21). Conclusiones. Los pacientes con FQ tienen mayor riesgo de mortalidad en lista de espera. Los pacientes que caminan menos de 200 m y/o presentan SaO2 mínima < 85% durante el T6MM tienen alto riesgo de mortalidad en lista, por lo que se debería valorar su priorización(AU)

Introduction. Lung transplant waiting list mortality makes it necessary to prioritize the criteria. Objective. To analyze the role of the six-minute walking test (6MWT) as a predictor of waiting list mortality. Patients and methods. We conducted a prospective study of patients considered for lung transplantation between 1998 and 2007. The variables analyzed were: distance walked in metros and minimum oxygen saturation (SaO2) during 6MWT, age, gender, underlying disease and waiting list mortality. Results. A total of 453 patients were included, 64.2% males, mean age 49.7±14.8years. Mean distance walked was 322±93 m and minimum SaO2 84.1%±7.6%. Eighteen patients on the waiting list died (4%) (95%CI, 2.2-5.8). Those patients in the survival group walked significantly farther than those who had died (321±90 vs. 262±115 m; P=.001). Similarly, 6.5% of patients with SaO2 <85% died compared to 1% with higher values (P=.006). Cystic fibrosis patients had higher mortality than other diagnosis (10.4% vs. 3.2; P=.043). Multivariate analysis confirmed the independent relation between mortality and the three risk factors. The odds ratio (OR) for cystic fibrosis waiting list mortality was 5.6 (95%CI, 1.7-18.9); for SaO2 <85%, 5.7 (95%CI, 1.3-25.1), and 7.3 (95%CI, 2.5-21) for less than 200 m walk. Conclusions. Cystic fibrosis patients have a higher risk of waiting list mortality. Patients who walk less than 200 m and/or have a SaO2 <85% during the 6MWT have a higher risk of waiting list mortality so that their prioritization should be considered(AU)

Aspergillus endocarditis in lung transplant recipients: case report and literature review.

We present a case of endocarditis caused by Aspergillus in a lung transplant (LT) patient and review 6 previously reported cases. All cases were caused by Aspergillus fumigatus. Five patients (71%) were transplanted due to cystic fibrosis. None of the patients had any previously known valvular heart disease. The time that elapsed between LT surgery and the diagnosis of Aspergillus endocarditis was 8±6 months. Large peripheral emboli were observed in 6 patients (85%); blood cultures were negative in all. Transthoracic echocardiography did not detect the presence of vegetations in 3 patients (43%); the vegetations measured >1.5 cm in all cases. Five patients (71%) died from disseminated disease. Both survivors underwent combined therapy with antifungal drugs and surgical treatment.

Cutaneous aspergillosis in a lung transplant recipient.

Organ transplant recipients are at increased risk for Aspergillus infections. Cutaneous aspergillosis (CA) occurs less frequently and is poorly characterized. The case of a lung transplant recipient with CA is presented. Six months after transplantation, 3 painful skin nodules appeared, with 1 each in the right calf, left arm, and upper back. Exudate from the leg nodule yielded Aspergillus fumigatus. Computed tomography of the chest showed bilateral hilar lymphadenopathy, but <1 cm in size. The case could be the result of Aspergillus dissemination from a hypothetical asymptomatic pulmonary infection. The lack of lung radiological signs could be related to prophylactic treatment with inhaled liposomal amphotericin B, which could have prevented clinically evident Aspergillus lung infection. The patient was treated with voriconazole, which was maintained for 3 months. The patient recovered completely.

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.

Pneumonia after lung transplantation in the RESITRA Cohort: a multicenter prospective study.

The aim of the present study is to evaluate the epidemiology, etiology and prognosis of pneumonia in lung transplant (LT) recipients. This is a prospective, multicenter study of a consecutive cohort of LT recipients in Spain. From September 2003 to November 2005, 85 episodes of pneumonia in 236 LT recipients were included (incidence 72 episodes per 100 LT/year). Bacterial pneumonia (82.7%) was more frequent than fungal (14%) and viral pneumonia (10.4%). The most frequent microorganisms in each etiological group were Pseudomonas aeruginosa (n = 14, 24.6%), CMV (n = 6, 10.4%) and Aspergillus spp. (n = 5, 8.8%). Incidence of Aspergillus spp. and CMV pneumonia is lower than previously reported, probably due to the spread of universal prophylaxis. Pneumonia caused by viruses appeared significantly later than pneumonia due to gram-negative bacilli, fungi and those without known etiology (p < 0.01, p = 0.03 and p = 0.02, respectively). The routine use of ganciclovir has changed the natural history of CMV infection, so that pneumonia appears later, once prophylaxis is suspended. The probability of survival during the first year of follow-up was significantly higher in the multivariate analysis in LT recipients who did not have a pneumonia episode compared with those that had at least one episode (p < 0.01).

[Lung transplant therapy for suppurative diseases]. / Trasplante pulmonar en enfermedades supurativas.

OBJECTIVE: Lung transplantation is a valid therapeutic approach for patients with bronchiectasis. The objective of the present study was to evaluate our experience with bronchiectasis patients and compare the results in patients with cystic fibrosis to results in those with bronchiectasis caused by other processes. PATIENTS AND METHOD: We carried out a retrospective study of bronchiectasis patients treated by lung transplantation in order to analyze demographic, functional and microbiological characteristics before and after transplantation, and survival. RESULTS: From 1991 to 2002 lung transplants were performed on 171 patients, 44 of whom had suppurative lung disease (27 had cystic fibrosis and 17 had bronchiectasis caused by other processes). There were no significant differences in the demographic variables between the 2 groups. At transplantation, lung function variables showed severe bronchial obstruction (mean [SD] forced expiratory volume in 1 second of 808 [342] mL and forced vital capacity of 1,390 [611] mL) and respiratory insufficiency (PaO2 at 52 [10] mm Hg and PaCO2 at 48 [9] mm Hg). Only PaO2 was significantly lower in patients with bronchiectasis from causes other than cystic fibrosis. Airway colonization was present in 91% of the patients; Pseudomonas spp germs were detected in 64% of the cases and were multiresistant in 9%. In the early postoperative period germs were isolated in 59% of the cases, half of which involved the same germ as had been isolated before transplantation. One year after lung transplantation, 34% of the patients continued to have bronchial colonization. Survival at 1 year was 79% and at 5 years, 49%, with no significant difference between the patients with cystic fibrosis and those with other suppurative diseases, nor between the patients with and without Pseudomonas colonization. Only 2 patients had died of bacterial pneumonia at 1 month after transplantation. CONCLUSIONS: Although airway colonization in patients with suppurative diseases complicates postoperative management, the results in terms of survival are good.

Trasplante pulmonar en enfermedades supurativas / Lung transplant therapy for suppurative diseases

Objetivo: El trasplante pulmonar es una opción terapéutica válida para pacientes con bronquiectasias. El objetivo de nuestro trabajo ha sido analizar nuestra experiencia en estos pacientes y comparar los resultados entre los pacientes con fibrosis quística y bronquiectasias de otra etiología. Pacientes y método: Se ha realizado un estudio retrospectivo de los pacientes trasplantados por bronquiectasias para analizar las características demográficas, funcionales y aspectos microbiológicos antes y después del trasplante, así como la supervivencia. Resultados: Entre 1991 y 2002 trasplantamos a 171 pacientes, de los cuales 44 presentaban enfermedad pulmonar supurativa (27 fibrosis quística y 17 bronquiectasias de otras etiologías). No había diferencias significativas en las variables demográficas entre ambos grupos. En el momento del trasplante la función pulmonar mostraba grave obstrucción bronquial (volumen espiratorio forzado en el primer segundo: 808 ± 342 ml; capacidad vital forzada: 1.390 ± 611 ml) e insuficiencia respiratoria (presión arterial de oxígeno: 52 ± 10 mmHg; presión arterial de anhídrido carbónico: 48 ± 9 mmHg). Sólo la presión arterial de oxígeno fue significativamente inferior en los pacientes con bronquiectasias de etiología diferente de la fibrosis quística. El 91% de los pacientes presentaba colonización de la vía aérea; el germen más frecuente fue Pseudomona spp. (64%), que en un 9% de los casos fue multirresistente. En el postoperatorio inmediato se aislaron gérmenes en el 59% de los casos; la mitad de ellos eran los mismos que se habían aislado antes del trasplante. Un año después del trasplante pulmonar, un 34% de los pacientes seguían mostrando colonización bronquial. La supervivencia al año fue del 79% y a los 5 años del 49%, sin diferencias significativas entre los pacientes con fibrosis quística y el resto de las enfermedades supurativas, ni entre los pacientes con o sin colonización por Pseudomonas spp. Sólo 2 pacientes fallecieron por neumonía bacteriana en el primer mes del trasplante pulmonar. Conclusiones: A pesar de que la colonización de la vía aérea de los pacientes con enfermedad supurativa complica el manejo tras el trasplante pulmonar, los resultados en términos de supervivencia son buenos

Objective: Lung transplantation is a valid therapeutic approach for patients with bronchiectasis. The objective of the present study was to evaluate our experience with bronchiectasis patients and compare the results in patients with cystic fibrosis to results in those with bronchiectasis caused by other processes. Patients and method: We carried out a retrospective study of bronchiectasis patients treated by lung transplantation in order to analyze demographic, functional and microbiological characteristics before and after transplantation, and survival. Results: From 1991 to 2002 lung transplants were performed on 171 patients, 44 of whom had suppurative lung disease (27 had cystic fibrosis and 17 had bronchiectasis caused by other processes). There were no significant differences in the demographic variables between the 2 groups. At transplantation, lung function variables showed severe bronchial obstruction (mean [SD] forced expiratory volume in 1 second of 808 [342] mL and forced vital capacity of 1,390 [611] mL) and respiratory insufficiency (PaO2 at 52 [10] mm Hg and PaCO2 at 48 [9] mm Hg). Only PaO2 was significantly lower in patients with bronchiectasis from causes other than cystic fibrosis. Airway colonization was present in 91% of the patients; Pseudomonas spp germs were detected in 64% of the cases and were multiresistant in 9%. In the early postoperative period germs were isolated in 59% of the cases, half of which involved the same germ as had been isolated before transplantation. One year after lung transplantation, 34% of the patients continued to have bronchial colonization. Survival at 1 year was 79% and at 5 years, 49%, with no significant difference between the patients with cystic fibrosis and those with other suppurative diseases, nor between the patients with and without Pseudomonas colonization. Only 2 patients had died of bacterial pneumonia at 1 month after transplantation. Conclusions: Although airway colonization in patients with suppurative diseases complicates postoperative management, the results in terms of survival are good

Urgent lung transplantation in Spain.

BACKGROUND: Lung donors are scarce and lung transplantation resources are limited. Because urgent lung transplantation (ULT) is assumed to yield poor results, its use is controversial. We assessed the outcome of patients who received ULT seeking to determine effectiveness and risk factors. PATIENTS AND METHOD: We collected data from every ULT performed in Spain during 5 years (1998-2002). The survival of patients was studied using Kaplan-Meier, Cox regression, and chi-square statistical analyses. We compared outcomes and perioperative mortality (over 30 days) for ULT procedures, analyzing the influence of certain variables (age, type of transplant, diagnosis, indication, and time on waiting list). RESULTS: Among 109 patients proposed for the procedure, 73 ULT were performed during the period. The most frequent indications were pulmonary fibrosis (19 cases) and cystic fibrosis (19 cases), showing the worst and the better survival rates, respectively. The bad prognosis, determined mainly by per operative mortality rate (35.62%), was significantly affected by age (worse for patients older than 40 years) and type of LT (single worse than double; P < .05). A longer time waiting for ULT also showed a worse prognosis (P < .005). CONCLUSIONS: Long-term survival after ULT shows that the procedure is effective and efficient for a select group of patients, despite the high per operative risk. ULT should be reserved for younger patients. It also requires performance in a short period (just a few days), initially rejecting a single lung transplant, provided that the patient is adequately monitored.

Consecuencias fisiopatológicas de la cirugía de reducción de volumen en pacientes con enfisema / Pathophysiological consequences of lung volume reduction surgery in patients with emphysema

No disponible

Rapamycin in lung transplantation: preliminary results.

INTRODUCTION: Rapamycin is a potent immunosuppressive agent with a different mechanism of action and different adverse effects from those of calcineurin inhibitors (CNIs). OBJECTIVE: To analyze our experience with rapamycin in patients undergoing lung transplantation and heart-lung transplantation in our center. PATIENTS AND METHODS: Patients were treated with rapamycin when showing chronic rejection and/or toxicity associated with the CNI after lung transplantation or heartlung transplantation. Patients with chronic rejection were administered rapamycin in combination with CNIs, whereas the CNIs were eliminated in patients with toxicity. RESULTS: Since October 2001, 7 patients (4 women), of mean age 45+/-15 years, received treatment with rapamycin (heart-lung transplantation, 2 cases; lung transplantation, 5 cases). The indications were chronic rejection in 4 patients and CMIs toxicity in 3 patients (kidney failure in 2 cases and optic neuropathy in 1 case). Pulmonary function stabilization was observed in 3 of 4 patients receiving rapamycin for chronic rejection. In the 3 patients with CNIs toxicity elimination of these drugs did not result in pulmonary functional deterioration. Patients with kidney failure showed an improvement in creatinine levels; visual acuity improved in the patient with optic neuropathy. We observed 2 infectious complications (pneumococcal pneumonia and pulmonary aspergillosis), which resolved with treatment. CONCLUSION: Rapamycin is an alternative for lung-transplant recipients who develop chronic rejection and/or CNIs toxicity.

[Prognostic factors of early morbidity and mortality after lung transplantation]. / Factores pronósticos de morbimortalidad en el postoperatorio inmediato del transplante pulmonar.

OBJECTIVES: Despite years of experience with lung transplantation, the rate of perioperative mortality remains high. The objective of this study was to look at our experience in the early postoperative period following lung transplantation in an effort to identify possible pre-, intra- and postoperative risk factors associated with mortality. PATIENTS AND METHODS: A retrospective study of 68 consecutive patients receiving lung transplants over a period of 56 months. The conditions that led to transplantation were obstructive disease (40%), interstitial disease (33%) and suppurative disease (27%). Pre-, intra- and postoperative characteristics of donors and recipients were analyzed for their relation to morbidity and mortality. Statistical studies were done using SPSS 10.0 software. A p-value less than.05 was considered significant. Univariate analysis identified variables associated with the incidence of mortality in the postoperative recovery unit, and the variables with statistically significant associations were entered into multivariate analysis, using a logistic regression model to calculate odds ratio (OR) and 95% confidence intervals (CI). RESULTS: No donor variables correlated with mortality. Patients with suppurative lung disease had a lower mortality rate (0% vs 30%; P = 0.04). Mortality was related to ischemic time longer than 300 minutes (OR = 2) and the use of extracorporeal circulation (OR = 4). A PaO2/FiO2 ratio less than 150 during the first 24 hours following transplantation (OR = 5) and reoperation due to bleeding (OR = 12) were the variables showing the highest correlations with mortality during the early postoperative period. CONCLUSIONS: The mortality rate during the early postoperative period in our series was 22%. The survival rate was better in patients with suppurative lung disease. Bleeding that required reoperation and early graft dysfunction (defined in part by a PaO2/FiO2 ratio less than 150 during the first 24 hours) were the variables that best predicted death in the early postoperative period following lung transplantation.

Factores pronósticos de morbimortalidad en el postoperatorio inmediato del trasplante pulmonar / Prognostic factors of morbidity and mortality in the early postoperative period following lung transplantation

OBJETIVOS: A pesar de la experiencia acumulada, la mortalidad perioperatoria del trasplante pulmonar (TP) continúa siendo elevada. El objetivo de este estudio es revisar nuestra experiencia en el postoperatorio inmediato del TP tratando de identificar las posibles variables pre, intra y postoperatorias asociadas a riesgo de mortalidad. PACIENTES Y MÉTODOS: Estudio retrospectivo de 68 pacientes sometidos de forma consecutiva a TP, durante un período de 56 meses. Las enfermedades que motivaron el TP fueron obstructiva (40 por ciento), intersticial (33 por ciento) y supurativa (27 por ciento). Se analizaron las variables relativas a los donantes y a los receptores (pre, intra y postoperatorias) relacionadas con la morbimortalidad. El estudio estadístico se realizó con el paquete informático SPSS, versión 10.0. Un valor de p inferior a 0,05 se consideró significativo. Se realizó un análisis univariante para identificar las variables asociadas con la incidencia de mortalidad en la unidad de reanimación. Las variables que presentaron significación estadística se sometieron a análisis multivariante, mediante modelo de regresión logística, para calcular la odds ratio (OR) y su intervalo de confianza (IC) del 95 por ciento. RESULTADOS: Ninguna de las variables relativas al donante se relacionó con la mortalidad. Los pacientes con enfermedad supurativa presentaron menor mortalidad (el 0 frente al 30 por ciento; p = 0,04). El tiempo de isquemia superior a 300 min y la utilización de circulación extracorpórea presentaron OR de mortalidad de 2 y 4, respectivamente. La relación PaO2/FiO2 inferior a 150 en las primeras 24 h postrasplante (OR = 5) y la reintervención por hemorragia (OR = 12) fueron las variables con mayor relación con la mortalidad en el postoperatorio inmediato. CONCLUSIONES: La mortalidad durante el postoperatorio inmediato en nuestra serie fue del 22 por ciento. Los pacientes con enfermedad supurativa presentaron una mayor supervivencia. La hemorragia que obliga a la reintervención y la disfunción temprana del injerto (definida en parte por la relación PaO2/FiO2 < 150 en las primeras 24 h) fueron las variables analizadas con mayor valor predictivo de mortalidad en el postoperatorio inmediato del TP (AU)

[Pulmonary sarcoidosis and antiphospholipid syndrome]. / Sarcoidosis pulmonar y síndrome antifosfolipídico.

Pulmonary sarcoidosis is an idiopathic granulomatosis with a clinical picture involving dyspnea, coughing, chest pain and characteristic radiologic changes. A review of English and Spanish language publications (PubMed 1990 through 2002) suggests that our report of a case of pulmonary sarcoidosis associated with primary antiphospholipid syndrome is the first one in the literature for this period. The patient was a 35-year-old man with venous thrombosis who later developed pulmonary sarcoidosis. The clinical course was not favorable in spite of good prognostic factors. We conclude that the association of these two clinical conditions is rare and that the presence of antiphospholipid syndrome may lead to greater morbidity and mortality.