Hepatitis E Virus Infection in Lung Transplant Recipients: A Case Series.

BACKGROUND: Hepatitis E virus (HEV) is one of the common causes of acute and chronic viral hepatitis with a global distribution. Genotypes 1 and 2 only affect humans and produce acute hepatitis epidemics in endemic regions (Asia, Africa). In nonendemic areas (America, Europe), genotypes 3 and 4 are considered a zoonosis and cause sporadic acute hepatitis. HEV has been described in solid organ transplant recipients; however, data on lung transplant patients are limited. OBJECTIVE: To present the first 3 cases of HEV infection in lung transplant recipients in our unit. CASE PRESENTATION: We report 3 cases of HEV infection in post-transplant patients presenting with symptoms and alterations in liver enzymes. All patients have no history of travel outside Spain prior to observing abnormalities in the liver function. Diagnoses were made with in-home polymerase chain reaction and enzyme-linked immunosorbent assay (IgG/IgM). The first patient was not treated and died of progressive hepatic disease, with postmortem diagnosis of HEV infection complications. The other 2 patients were treated with ribavirin after the diagnosis of HEV infection. Ribavirin was discontinued in 1 patient because of anemia necessitating red blood cell transfusions. CONCLUSIONS: HEV should be considered in the differential diagnosis of patients with abnormal liver enzymes after transplant. Early detection and treatment have implications in the prevention of liver failure and mortality. Large prospective seroprevalence studies of HEV in lung transplant patients are warranted to recognize the epidemiology of this infection in lung transplant recipients.

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.

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.

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.

Cáncer de pulmón y trasplante / Lung cancer and transplant

Resumen. El trasplante pulmonar constituye hoy en día una alternativa eficaz para muchos pacientes con enfermedades respiratorias en sus fases más avanzadas. La indicación actual más frecuente de trasplante pulmonar es el enfisema y, por lo tanto, son pacientes que de base presentan más riesgo que la población general de desarrollar una neoplasia pulmonar. Además, se trata de pacientes que reciben inmunosupresión, lo que condiciona, por diversos motivos, el comportamiento de este tipo de tumores. Por último, en algunos centros se ha indicado el trasplante pulmonar en casos seleccionados con adenocarcinoma bronquioalveolar. El objetivo de este trabajo es revisar nuestra experiencia y la evidencia disponible en cuanto a trasplante pulmonar y cáncer de pulmón (AU)

Abstract. Lung transplantation is a therapeutic alternative to patients with end stage pulmonary disease. Emphysema represents the most frequent indication for lung transplantation, these are patients with a higher risk to develop lung cancer than the normal population. Moreover, lung transplant recipients must receive immunosuppressive drugs, which maymodify the clinical course of these tumors. Finally, there have been reports concerning lung transplantation in selected cases of bronchioalveolar carcinoma. The aim of this work is to revise our experience and the scientific evidence regarding lung transplantation and lung cancer (AU)

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.

Conversion from cyclosporine to tacrolimus stabilizes the course of lung function in lung transplant recipients with bronchiolitis obliterans syndrome.

Bronchiolitis obliterans syndrome (BOS) continues to be the main factor limiting the long-term survival of lung transplant recipients. The objective of this study was to prospectively assess the impact of conversion from cyclosporine (CsA) to tacrolimus on lung function in patients who developed BOS while receiving CsA-based immunosuppressive therapy. A total of 79 patients with BOS were included in the study. Sixty percent of patients had stage II or III BOS according to the International Society for Heart and Lung Transplantation criteria. Mean time from transplantation was 30.4 +/- 21.9 months and all patients were on CsA therapy at enrollment in the study, with mean trough levels of 232.75 +/- 98.26 ng/mL. After conversion, tacrolimus trough levels were 11.0 +/- 3.6 ng/mL at 3 months and 9.0 +/- 3.4 ng/mL at 12 months. Sixteen deaths occurred during the first year postconversion, 56% of which were due to respiratory failure. Comparison of forced expiratory volume in 1 second (FEV(1)) preconversion versus postconversion showed a change in the slope of the FEV(1)-time curve. The slope of the preconversion curve was -0.44 versus a zero slope, whereas the slope of the postconversion curve was 0.005, with a statistically significant difference between both slopes. This change in slopes, which was also seen in FEV(1%), suggests that lung function loss closed after conversion from CsA to tacrolimus supporting this therapeutic strategy in lung transplant recipients with BOS treated with CsA.

[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

Is gammaglobulin anti-CMV warranted in lung transplantation?

UNLABELLED: The usefulness of anti-CMV hyperimmune gammaglobulin (IgG-CMV, Cytotec) in lung transplant patients (LTx) is controversial. The objective of this study was to analyze the effectiveness of IgG-CMV in our LTx receptors. PATIENTS AND METHODS: A retrospective study of LTx recipients treated with IgG-CMV as prophylaxis or as treatment for invasive disease. We used IgG-CMV associated with IV ganciclovir (GCV) as treatment for invasive disease. High-risk patients (CMV-negative recipients from CMV-positive donors; CMV-/+) were also with IgG-CMV prophylaxis during the first year. Other prophylactic uses of IgG-CMV were as an alternative to GCV in patients with related GCV toxicity, and as preemptive therapy in cases of persistent positive viral load (antigenemia > or = 1 cell and/or a PCR > or = 400) although oral GCV administration. RESULTS: Between January 2000 and August 2003, 14 of the 74 lung transplant recipients (19%) received IgG-CMV as treatment for invasive disease (4 cases: 2 gastritis, 1 esophagitis, 1 hepatitis) and/or as prophylaxis (14 cases). All patients treated for invasive disease evolved favorably. No therapeutic failure were observed in CMV-/+ patients during treatment. Three of the six patients treated with IgG-CMV developed positive antigenemia despite treatment. The four patients treated for persistent antigenemia while receiving oral GCV achieved neutralization during the first month of treatment. CONCLUSION: IgG-CMV associated with Gancyclovir is effective as treatment for invasive disease and as pre-emptive therapy in patients with persistent positive viral load. In CMV-/+ recipients, IgG-CMV prevents pneumonitis and delays the development of invasive disease after the first year.

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.

[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.

Sarcoidosis pulmonar y síndromeantifosfolipídico / Pulmonary sarcoidosis and antiphospholipid syndrome

La sarcoidosis pulmonar es una enfermedad granulomatosa de etiología desconocida que puede cursar con un cuadro clínico de disnea, tos, dolor torácico y alteraciones radiológicas características. Presentamos el primer caso descrito en toda la bibliografía revisada en PubMed, entre los años 1990 y 2002, en revistas de lenguas inglesa y española, de sarcoidosis pulmonar asociada a síndrome antifosfolipídico primario, en un paciente de 35 años, que cursó con trombosis venosa y desarrolló posteriormente sarcoidosis pulmonar que, a pesar de presentar factores considerados de buen pronóstico, evolucionó de forma poco favorable. Concluimos que la asociación de ambas entidades clínicas es poco frecuente y que la presencia de un síndrome antifosfolipídico asociado podría condicionar una mayor morbimortalidad (AU)

Phenylephrine in treating maternal hypotension due to spinal anaesthesia for caesarean delivery: effects on neonatal catecholamine concentrations, acid base status and Apgar scores.

Maternal and neonatal catecholamine concentrations, following the use of either phenylephrine or ephedrine to treat a drop in maternal blood pressure after spinal anaesthesia for caesarean delivery, were compared. Patients were randomly assigned to one of two groups: Group 1 patients (n = 20) were treated with ephedrine given as 5 mg intravenous bolus injections; Group 2 patients (n = 20) were treated with phenylephrine given as 40 micrograms intravenous bolus injections, for decreases in maternal systolic blood pressure to maintain maternal systolic blood pressure above 100 mmHg. Maternal vein (MV), umbilical vein (UV), and umbilical artery (UA) blood samples were taken at the time of delivery. Samples were analyzed for catecholamine concentrations and blood gas values. Noradrenaline concentrations in UA, UV and MV (at delivery) samples were significantly higher in group 1 compared to group 2; they were 6858 +/- 3689 vs 1674 +/- 944 pg.ml-1 (P < 0.0001), 1265 +/- 758 vs 395 +/- 470 pg.ml-1 (P < 0.001) and 239 +/- 165 vs 103 +/- 93 pg.ml-1 (P < 0.01), respectively. Comparing blood gas values between groups 1 and 2, statistically significant differences were observed in UA pH (7.28 +/- 0.01 and 7.32 +/- 0.01 pH units, P = 0.01), UA pCO2 (7.32 +/- 0.24 and 6.68 +/- 0.21 kPa, P = 0.03), UA base excess (2.2 +/- 0.4 and 0.9 +/- 0.4 mmol.1-1, P = 0.04) and UV base excess (2.0 +/- 0.3 and 0.7 +/- 0.3 mmol.1-1, P = 0.004). No significant differences in maternal characteristics, acid base values, incidence of nausea and vomiting, and Apgar scores were observed between groups. Phenylephrine appears to be as safe and effective as ephedrine in treatment of drop in blood pressure in healthy non-labouring parturients undergoing caesarean delivery. The use of phenylephrine was also associated with significantly lower noradrenaline concentrations in both mother and neonate.

Pulmonary oedema after lithotripsy in a patient with hypertrophic subaortic stenosis.

Pulmonary oedema in a patient with hypertrophic subaortic stenosis undergoing extracorporeal shock wave lithotripsy is described. This event occurred upon emergence from the bath. It is suggested that pulmonary oedema followed emergence because of a reduction in central venous pressures and a decrease in preload which led to transient dynamic obstruction. Treatment with beta adrenergic blockade reduced outflow tract obstruction. Anaesthetists should be aware of the haemodynamic consequences of immersion and emersion with extracorporeal shock wave lithotripsy.

Phenylephrine in the prevention of hypotension following spinal anesthesia for cesarean delivery.

STUDY OBJECTIVE: Phenylephrine and ephedrine were compared in the prevention of maternal hypotension following spinal anesthesia for elective cesarean delivery. DESIGN: Randomized, double-blind trial. SETTING: Obstetric suite at a university-affiliated hospital. PATIENTS: Sixty healthy patients electively scheduled for cesarean delivery under spinal anesthesia. INTERVENTIONS: Patients were randomly assigned to receive either ephedrine (n = 29) in 10 mg intravenous (IV) bolus injections or phenylephrine (n = 31) in 80 microgram IV bolus injections to maintain systolic blood pressure (SBP) above 100 mmHg. MEASUREMENTS AND MAIN RESULTS: Maternal venous, umbilical artery, and umbilical vein blood gases were measured, and neonatal Apgar scores and Early Neonatal Neurobehavior Scale scores were assessed. In the ephedrine group, umbilical artery pH was 7.28 +/- 0.01 (mean +/- SEM), umbilical artery partial pressure of carbon dioxide (PCO2) was 56.6 +/- 1.4 mmHg, and umbilical artery base deficit was 2.2 +/- 0.04 meq. In the phenylephrine group, umbilical artery pH was 7.32 +/- 0.01, umbilical artery PCO2 was 52.1 +/- 1.3 torr, and umbilical artery base deficit was 0.38 +/- 0.35 meq. There were significant differences between the groups in mean umbilical artery pH, PCO2, and base deficit, although all values obtained were within normal limits. There were no significant differences between the groups in the remaining acid-base values, neonatal Apgar scores, Early Neonatal Neurobehavior Scale scores, or frequency of maternal nausea and vomiting. CONCLUSIONS: Phenylephrine is as effective as ephedrine in the treatment of maternal hypotension, and when used in small incremental bolus injections, it appears to have no adverse neonatal effects in healthy, nonlaboring parturients.

Intraspinal opioids: implications for monitoring. Monitoring in the intensive care unit is essential.

Patients receiving intraspinal opiates should be monitored in the intensive care unit for at least 24 hours to prevent potentially lethal outcomes. These include respiratory depression caused by sequestration of the morphine in the cerebrospinal fluid and migration of epidural catheters in the subarachnoid or intravascular space. At this time, most hospitals are not equipped or staffed adequately to guarantee the safety of these patients outside the intensive care unit.