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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.

La hipertension arterial pulmonar (HAP) se caracteriza por alteraciones vasculares en los pulmones que provocan una obstruccion de la microcirculacion pulmonar. Este proceso se conoce como remodelacion vascular pulmonar, que conlleva una progresiva elevacion de las resistencias vasculares pulmonares e insuficiencia ventricular derecha como evento final. Se han reconocido diversos mecanismos fisiopatologicos, tales como la produccion alterada de vasodilatadores y vasoconstrictores, alteraciones de los canales ionicos celulares y de los mecanismos angiogenos, la sobreexpresion del sistema transportador de serotonina y un aumento de la matriz extracelular. Ante la evidencia de esta gran complejidad, no es extrano que los farmacos existentes no puedan revertir las lesiones vasculares de la enfermedad. Del mismo modo que en el tratamiento de otras muchas enfermedades se combinan distintos farmacos, los pacientes con HAP podrian beneficiarse teoricamente de un tratamiento que combinara varios de los medicamentos conocidos. El objetivo de un tratamiento combinado ha de ser el incremento de la eficacia, con elevada seguridad y minimas interacciones medicamentosas. Los escasos estudios realizados hasta hoy sobre el tratamiento combinado en la HAP han utilizado como objetivo principal la capacidad de esfuerzo de los pacientes y la hemodinamica pulmonar, tal como se habia hecho en los estudios previos de los distintos farmacos de forma individual. Con los datos disponibles de estos estudios, quedan por responder las preguntas mas importantes: de las posibles combinaciones, ?cual es la mas eficaz?, ?algunos subgrupos de pacientes con HAP pueden responder a una combinacion determinada?, y ?cuales

OBJECTIVES Our aim was to assess the impact of positive cultures for non-Aspergillus molds on the risk of progression to invasive fungal infection (IFI), and the effect of prophylactic nebulized liposomal amphotericin B (n-LAB) on these pathogens. METHODS This was an observational study (2003-2013) including lung transplant recipients (LTR) receiving lifetime n-LAB prophylaxis, in whom non-Aspergillus molds were isolated on respiratory culture before and after transplantation (minimum 1-year follow-up). RESULTS We studied 412 patients, with a mean postoperative follow-up of 2.56 years (interquartile range 1.01-4.65). Pre- and post-transplantation respiratory samples were frequently positive for non-Aspergillus molds (11.9% and 16.9% of LTR respectively). Post transplantation, 10 (2.42%) patients developed non-Aspergillus mold infection (4 Scedosporium species, 4 Purpureocillium species, 1 Penicillium species, and 1 Scopulariopsis species); 5 (1.21%) had IFI, with 60% IFI-related mortality. Non-Aspergillus molds with intrinsic amphotericin B (AB) resistance were more commonly isolated in bronchoscopy samples than AB-variably sensitive or AB-sensitive molds (54.5% vs. 25%, P = 0.04) and were associated with a higher risk of infection (56.3% vs. 1.3%%, P < 0.01). CONCLUSIONS In LTR undergoing n-LAB prophylaxis, pre- and post-transplantation isolation of non-Aspergillus molds is frequent, but IFI incidence (1.21%) is low. Purpureocillium is an emerging mold. AB-resistant non-Aspergillus species were found more often in bronchoscopy samples and were associated with a higher risk of infection.

Objetivo El tratamiento con bosentan mejora la capacidad de ejercicio de los pacientes con hipertension pulmonar. Son muy escasos los estudios que evaluan este tratamiento a largo plazo, que es el objetivo propuesto en el presente trabajo. Pacientes y metodos Un grupo de 22 pacientes –18 mujeres y 4 varones, con una edad media de 45,5 anos (rango: 19-77 anos)– con hipertension pulmonar en clase functional III recibieron tratamiento con bosentan entre abril de 2002 y junio de 2005. La hipertension pulmonar era idiopatica en 10 casos y estaba asociada a cardiopatia corregida (n = 4), esclerodermia (n = 4), embolia periferica (n = 3) e hipertension portal (n = 1) en los restantes. Se estudiaron los datos clinicos y hemodinamicos y los cambios que habian experimentado desde el inicio del tratamiento hasta el fin del estudio. Resultados El seguimiento medio de los pacientes fue de 15,7 meses (rango: 12,6-31,8). La clase funcional mejoro o se estabilizo a los 3 meses de tratamiento en 21 (95%) y al ano en 14 (64%). La distancia recorrida en la prueba de la marcha de 6 min se incremento a los 3 meses de tratamiento una media de 64,5 m, mejoria que se mantuvo a los 6, 12 y 18 meses. El tratamiento se interrumpio en 4 pacientes (18%): por muerte en 2 casos, por empeoramiento en uno y por in-tolerancia a la medicacion en otro. En otros 4 pacientes (18%) se objetivo falta de eficacia. Ningun paciente presento hepatotoxicidad remarcable. Conclusiones Los resultados del presente estudio apoyan la idea de que el tratamiento con bosentan se asocia a una mejoria clinica y de la capacidad de ejercicio a largo plazo en aproximadamente dos terceras partes de los pacientes con hipertension pulmonar.

The purpose of this study was to evaluate the incidence and etiology of bacterial and fungal infection or contamination in lung allograft donors and to assess donor-to-host transmission of these infections. Recipients who survived more than 24 h and their respective donors were evaluated. The overall incidence of donor infection was 52% (103 out of 197 donors). Types of donor infection included isolated contamination of preservation fluids (n = 30, 29.1%), graft colonization (n = 65, 63.1%) and bacteremia (n = 8, 7.8%). Donor-to-host transmission of bacterial or fungal infection occurred in 15 lung allograft recipients, 7.6% of lung transplants performed. Among these cases, 2 were due to donor bacteremia and 13 to colonization of the graft. Twenty-five percent of donors with bacteremia and 14.1% of colonized grafts were responsible for transmitting infection. Excluding the five cases without an effective prophylactic regimen, prophylaxis failure occurred in 11 out of 197 procedures (5.58%). Donor-to-host transmission of infection is a frequent event after lung transplantation. Fatal consequences can be avoided with an appropriate prophylactic antibiotic regimen that must be modified according to the microorganisms isolated from cultures of samples obtained from donors, grafts, preservation fluids and recipients.

Background. Post-lung transplant infection is one of the leading causes of morbidity and mortality. The cause and incidence are similar in many series; however, infections such as Mycobacterium tuberculosis are influenced by the epidemiologic situation. The authors present a prospective and observational study to define the incidence, clinical presentation, and course of tuberculosis in a cohort of lung transplant patients at a single center in Spain. Methods. Between 1990 and 2002, cutaneous delayed-type hypersensitivity testing and pathologic and microbiologic study of explanted lungs were conducted in 187 lung transplant patients. Serial bronchoscopies with transbronchial biopsy and bronchioalveolar lavage were performed during follow-up. The diagnosis of tuberculosis was established only when M. tuberculosis was identified in any sample or when histopathologic study was conclusive. Results. Forty-eight patients were classified as anergic (25.6%) and 61 (32.6%) were classified as having a positive tuberculin skin test. Of the 109 patients, 95 received latent tuberculosis infection prophylaxis. Tuberculosis was diagnosed in 12 patients (6.41%); in six of them, diagnosis was determined from the explanted lungs. The remainder were diagnosed during follow-up. Fever and dyspnea were the most common symptoms. Chest radiographic findings presented an alveolar pattern. All patients responded well to antituberculous therapy; no deaths were attributable to tuberculosis. Conclusions. In the authors' experience, tuberculosis is not rare in lung transplant patients and can be managed successfully with antituberculous therapy without rifampin. A systematic protocol for diagnosing tuberculosis of the explanted lung is useful for reducing tuberculous complications of the implanted lung.

Background Lung transplant recipients may have pleural complications. However, the influence of these complications on the prognosis is not well known. Methods We analyzed pleural complications and clinical and radiologic data from 100 patients who underwent lung transplantation in a general hospital in a 9-year period. Pre-operative evaluation, surgical protocol, immunosuppressive regimen, and follow-up were carried out systematically. Chest computerized tomography (CT) was performed at 3 and 12 months after transplantation. Results All patients had early post-operative pleural effusion ipsilateral to the graft, which required drainage for a mean of 19.3 days (range, 5–52 days). Thirty-four patients had 43 acute pleural complications: 15 hemothoraxes, 10 persistent air leaks, 8 pneumothoraxes, 7 transient air leaks, and 3 empyemas. Multivariate analysis showed hemothorax and persistent air leak were associated with increased post-operative mortality (p = 0.024, p = 0.011, respectively). Post-operative mortality was not associated with any pre-transplant variable. Chest CT findings at 3 months revealed ≥1 pleural alteration in 58 of 70 patients (83%): 34 post-operative residual ipsilateral pleural effusions; 36 pleural thickenings; and 3 residual pneumothoraxes, 1 with a coexisting bronchial dehiscence. Chest CT at 12 months showed pleural alterations in 50 of 58 patients (86%): pleural thickening in 48, calcification in 4, and residual pleural effusion in 4. Conclusions Pleural complications are common in lung transplant recipients. Hemothorax and persistent air leak are associated with increased post-operative mortality. Chest CT showed pleural alterations in most patients 12 months after transplantation.

Fundamento La hipertension pulmonar primaria es una enfermedad poco conocida y de tratamientocomplejo. Pacientes y me;todo Estudio retrospectivo de 44 pacientes con hipertension pulmonar primariaestudiados entre 1992 y 2000 en un solo centro. Resultados En el momento del diagnostico, 6 pacientes (13%) se encontraban en clasefuncional I de la NYHA, 11 (25%) en clase II, 25 (57%) en clase III y 2 (4,5%) en clase IV. Lamedia de la presion sistolica en arteria pulmonar medida por eco-Doppler fue de 92 (limites,43–154) mmHg. El cateterismo derecho basal demostro que la media (DE) de la presion en arteriapulmonar fue de 58 (18) mmHg, las resistencias pulmonares totales basales fueron de1.679 (1.071) din/cm 2 y el indice cardiaco fue de 2,2 (1) l/min/m 2 . Cinco pacientes (11%)mejoraron con anticoagulacion y antagonistas del calcio. Desde 1998, 11 pacientes fueron tratadoscon epoprostenol intravenoso continuo; de ellos, tres (27%) presentaron mejoria clinicasignificativa. La supervivencia a los 5 anos del diagnostico fue del 56%. Siete (70%) de los 10pacientes tratados mediante trasplante pulmonar estan vivos al cierre del estudio (seguimientomedio, 34 meses; limites, 3–62 meses). Conclusiones La hipertension pulmonar es una enfermedad con mal pronostico, si bien el tratamientocon prostaglandinas y el trasplante pulmonar ofrecen resultados esperanzadores.

Background The optimal length of cytomegalovirus (CMV) prophylaxis in lung transplantation according to CMV serostatus is not well established. Methods We have performed a prospective, observational, multicenter study to determine the incidence of CMV infection and disease in 92 CMV-seropositive lung transplant recipients (LTR), their related outcomes and risk factors, and the impact of prophylaxis length. Results At 18 months post transplantation, 37 patients (40%) developed CMV infection (23 [25%]) or disease (14 [15.2%]). Overall mortality was higher in patients with CMV disease (64.3% vs 10.2%; P

Venous thromboembolism (VTE) is a major complication after solid organ transplantation (SOT), with an incidence that ranges from 2 to 34%. Besides genetic risk factors such as inherited thrombophilia, other specific risk factors for VTE in SOT recipients include impairment of fibrinolysis produced by corticosteroids, in vitro procoagulant effects of calcineurin inhibitors, endothelial damage due to cytomegalovirus infection, and specific surgical factors. Prevention strategies have not been systematically studied. Therefore, it is mandatory for the international scientific community to conduct large, multicenter, randomized clinical trials to define strategies for the prevention of VTE in SOT recipients.

COPD and emphysema due to alpha-1 antitrypsin deficiency (AATD) are the first and fourth indications for lung transplantation worldwide, respectively. Despite this, there is little information regarding the health status of these patients at the time of transplantation.Patients who received a lung transplant in the Hospital Vall d'Hebron between July 1993 and August 2013 were identified and data from the evaluation prior to the transplant were collected.A total of 217 patients who received a lung transplant for COPD and 19 in whom the indication was AATD were included. These patients were severely impaired at the time of the evaluation for lung transplantation, although the trend in recent years has been to evaluate patients at earlier stages of the disease. Baseline characteristics were similar in both groups except that patients with AATD were younger [43 (7.7) vs. 53.6 (6.1) years old, P.001], with less exposure to tobacco [23.9 (15) vs. 50 (29) packs-year, P002] and lower PCO2 [41.7 (7.6) vs. 47.9 (9.7) mmHg, P.004].The number of patients receiving a lung transplant for COPD has progressively increased and the tendency is to perform the evaluation in earlier stages of the disease. Patients receiving transplants for COPD and AATD had similar characteristics at the time of the evaluation, although AATD patients were younger and had less exposure to tobacco and lower PCO2.

Background Tacrolimus twice-daily (TAC BID) is widely used in lung transplantation (LT), but there are little data on the use of tacrolimus once-daily (TAC QD) in this population. The objective of this study was to compare the pharmacokinetics (PK) of TAC BID and TAC QD in stable, adult LT patients. Methods Phase II, open-label, single-center, single-arm, prospective pilot PK study. Nineteen LT recipients with more than 6 months of postoperative follow-up and on TAC BID-based therapy were converted to TAC QD on a 1:1 (mg/mg) basis. Patients had been stable during the previous 3 months, and cystic fibrosis patients were excluded. One 24-hr PK profile was obtained on day -14 while patients were under TAC BID. A second PK profile was obtained 14 to 28 days after switching (day 0) to the same dose of TAC QD. Pre- and post-switch 24-hr PK profiles were compared. Results Mean AUC0-24 hr was 279.8 ng mL/hr for TAC BID and 278.7 ng mL/hr for TAC QD (P=0.92). AUC0-12 hr of TAC BID was higher than the AUC12-24 hr. There was a good correlation between AUC0-24 hr and C24 for both QD (r=0.96) and BID (r=0.94) formulations. There were no differences in the adverse events occurring with the two formulations. Conclusions Tacrolimus bioavailability in steady state is similar in BID and QD formulations after conversion in stable LT recipients, excluding those with cystic fibrosis. Thus, our results indicate TAC BID can be safely switched to the more convenient QD formulation in this population.

Background Aspergillus infection remains a major cause of morbidity and mortality after lung transplantation. Therefore, some strategies have been attempted, one of which is nebulized amphotericin B (nAB); however, the efficacy of this prophylaxis has not been shown clearly. The aim is to study whether nAB can protect against Aspergillus infection in lung transplant recipients. Patients and methods A study of risk factors was conducted in 55 consecutive lung allograft recipients. Twenty-three potential risk factors were analyzed. In 44 (80%) patients, nAB was indicated as prophylaxis. Multivariate analysis using logistic regression was performed. Results Eighteen of the 55 patients (33%) developed infection due to Aspergillus spp. Multivariate analysis showed nAB to be a preventive factor (odds ratio: 0.13; 95% confidence interval [CI] 0.02–0.69; p < 0.05) and cytomegalovirus (CMV) disease was an independent risk factor for developing Aspergillus infection (odds ratio: 5.1; 95% CI 1.35–19.17; p < 0.05). Only 1 patient required withdrawal of the prophylaxis owing to bronchospasm. nAB was well-tolerated in the remaining patients with only a few, mild, easily controlled side effects. Conclusions The present results show that nAB prophylaxis may be efficient and safe in preventing Aspergillus infection in lung-transplanted patients, and CMV disease increases the probability of Aspergillus infection.

Mycophenolate mofetil (MMF) in combination with cyclosporine (CsA) or Tacrolimus (TAC) has been show to be a potent immunosuppressive agent. The authors assessed the mycophenolic acid (MPA) plasma levels achieved in clinical practice and evaluated the effect of concomitant administration of CsA and TAC . One hundred forty transplant patients (kidney: 120 and lung: 20) received a triple immunosuppression regimen of CsA or TAC, prednisone and MMF. Twenty-two renal transplant patients received double therapy with MMF and prednisone. There was no correlation between MMF dose and MPA trough concentrations (r = -0.0657). The medians (range) of the MPA dose-to-concentration ratio (D/C) in the CsA and TAC groups were 0.90 (0.11-8.33) and 0.56 (0.11-14.3), respectively (p0.0001). According to the post transplant period (1-3, 4-6 and6 months), D/C values were significantly lower in patients receiving MMF and TAC than those receiving MMF and CsA in all three periods. MPA levels in patients treated with MMF and CsA were significantly lower than those obtained in double therapy. The D/C ratio in CsA-treated patients, increased significantly (p = 0.0005) when CsA level increased. There was no relationship between D/C ratio and TAC blood concentrations. These results suggest that CsA exerts an influence on MPA trough levels, although further work is required to characterize the mechanism of interaction.

The incidence of tuberculous disease (TD) is higher in lung-transplant patients than in the general population. During a 7-year period, we included 61 patients who underwent lung transplantation in a prospective isoniazid prophylaxis protocol. Isoniazid was prescribed to infected and anergic patients not previously treated when added to the waiting list. Six of 61 patients (10%) developed tuberculosis. We observed no differences in tuberculous disease incidence between infected–anergic and non-infected patients. In our tuberculous-endemic area, isoniazid prophylaxis is safe and offers protection from TD to infected and anergic patients who must be enrolled in a lung transplantation program.

Fundamento Descripcion y seguimiento de las pacientes diagnosticadas de linfangioleiomiomatosis en un hospital con programa de trasplante pulmonar. Pacientes y metodo Se efectuo un estudio retrospectivo de 15 mujeres (edad media en el momento del diagnostico, 43; rango, 36-52 anos) diagnosticadas en el Hospital Vall d'Hebron de linfangioleiomiomatosis (9 pacientes) o remitidas de otros hospitales (6 pacientes) para evaluacion preoperatoria de trasplante pulmonar. Resultados La disnea aparecio en todos los casos y fue el sintoma mas constante. Tambien fueron muy frecuentes los problemas pleurales en fases tempranas de la evolucion de la enfermedad (l2 de 15 pacientes). Por ello, se efectuo una pleurodesis quimica en 7 pacientes y una pleurectomia en dos (una bilateral). La tomografia computarizada (TC) toracica puso de manifiesto imagenes quisticas muy caracteristicas, y la TC abdominal demostro la presencia de angiomiolipomas asociados en un caso. En 2 pacientes no se llego al diagnostico de linfangioleiomiomatosis hasta estudiar el pulmon explantado. El diagnostico previo en estas 2 pacientes fue de enfisema y hemosiderosis pulmonar. La supervivencia actuarial desde el inicio de los sintomas fue del 82 y del 49% a los 5 y 10 anos, respectivamente. Seis de las 8 pacientes en las que se realizo un trasplante pulmonar consiguieron una supervivencia postoperatoria prolongada. Conclusiones Aunque podrian existir algunos casos con diagnosticos alternativos, la linfangio-leiomiomatosis parece que es poco frecuente en nuestro ambito. El trasplante pulmonar es util en fases avanzadas de la enfermedad, y en nuestros pacientes ha mejorado de forma prolongada la insuficiencia respiratoria en la mitad de los casos.

The contamination of nebulizer may be the origin of respiratory infections. The aim of this study was to determine the incidence of contamination in nebulizers used to nebulize amphotericin B in lung transplant (LT) patients and the relationship with bacterial isolation in sputum culture. A prospective, cross-sectional study was conducted with 41 LT patients who were administered amphotericin B with a jet nebulizer. Samples were taken from the nebulizers (prior to nebulization). Sputum culture was carried out and patients were asked whether or not they followed a cleaning and disinfection protocol (washing and brushing with soap and water followed by subsequent disinfection with the Milton method after each nebulization). Contamination was defined as such when potentially pathogenic bacteria were isolated in the nebulizer. Seventeen of the 41 nebulizers (41.4%) were contaminated. In 7 of the 17 cases (41.1%) contamination was polymicrobial. The most common microorganism was Pseudomonas aeruginosa. Fourteen of the 41 patients (34.1%) presented positive sputum cultures, most common was P aeruginosa. In 10 patients (24.3%) pathogenic bacteria was isolated both in the nebulizer and in the sputum. In four of these patients (9.7%) the species was the same. The cleaning and disinfection protocol was carried out by 16 of the 41 patients (39.0%). In 2 of the 16 patients (12.5%) who were following the protocol the nebulizer was contaminated, compared to 15 of 25 patients (60.0%) whose nebulizer was not contaminated (P < .05). Two of the 16 patients (12.%) who were following the protocol presented positive sputum culture compared to 12 of 25 (48.0%) who did not (P < .05). In conclusion, the contamination of the nebulizing systems is frequent when no strict cleaning and disinfection protocol is followed. Patients who did not follow the protocol presented a greater isolation of pathogenic bacteria in the sputum.

Background Accepted treatment for severe pulmonary arterial hypertension (PAH) includes intravenous epoprostenol and lung transplantation (LT). Inhaled iloprost plus oral sildenafil (Ilo-Sil) is an alternative strategy that may also delay the need for LT. Patients and Methods This was a long-term descriptive study in eight patients with PAH functional class (FC) IV with right heart failure, four of them potential candidates for LT, who were treated with Ilo-Sil as an alternative to epoprostenol. Results At the start of the study, patients (seven women; mean age, 43.8 [range, 34–66] years) were in FC IV and unable to perform the 6-minute walk test. Mean cardiac index was 1.9 (range, 1.4–2.1) L/min/m 2 . Treatment with Ilo-Sil provoked a rapid and sustained improvement; mean walking distance at 3 months was 322 ± 90 m and no patient remained in FC IV. Survival at 1 and 5 years was 100% and 75%, respectively. Of the four potential LT candidates, one underwent transplantation after 6.8 years and one died after 1.2 years. Conclusions These results suggest that therapy with Ilo-Sil represents an acceptable alternative in patients with severe and unstable PAH.

Lung transplant recipients, more than other organ transplant recipients, are at particular risk for cytomegalovirus (CMV) infection and disease. CMV prevention avoids the indirect effects of this virus, such as opportunistic fungal infections and obliterative bronchiolitis, the latter being the major limiting factor in the long-term success of lung-transplantation. CMV prevention strategies have significantly reduced CMV disease and CMV-related mortality. Two major strategies are commonly used for CMV prevention: universal prophylaxis and preemptive therapy. In lung transplant recipients, the efficacy and safety of preemptive treatment have not been studied and therefore, cannot be recommended. Universal prophylaxis is the best strategy for preventing CMV disease in lung transplant recipients. There is no consensus on the optimal duration of prophylaxis, but the recently published GESITRA-SEIMC/REIPI 2011 Guidelines for the management of CMV infection in solid-organ transplant patients recommend 6 months posttransplantation. In D+/R- recipients, this period can be prolonged to 12 months if there are difficulties in monitoring at 6 months posttransplantation. The future of prevention will probably depend on immunoguided strategies.

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. (C) 2011 Elsevier Espana, S.L. All rights reserved.

Mycophenolate mofetil is a highly effective immunosuppressant drug used in the prophylaxis of organ rejection in combination with cyclosporine or tacrolimus and corticosteroids. The present study is a retrospective data analysis of the routinely estimated mycophenolic acid plasma trough levels in 60 transplant patients (kidney, n = 49; lung, n = 11) receiving mycophenolate mofetil in combination with prednisone and cyclosporine (n = 45) or tacrolimus (n = 15). Coadministration of cyclosporine instead of tacrolimus resulted in a significant increase of median (range) of the ratio of dose-to-concentration 0.92 (0.11-8.33) (n=167) versus 0.38 (0.11-14.28) (n = 66); P < 0.0001. No correlation was seen between mycophenolate mofetil dose and mycophenolic acid trough concentrations. The dose-to-concentration in cyclosporine-treated patients increased significantly (P

Lung transplant patients have an increased risk of pulmonary embolism which is often associated with hypercoagulability disorders. We present a case of sudden death resulting from pulmonary intravascular platelet thromboembolism following a single-lung transplant.

Pulmonary hypertension is a serious disease that, in its terminal phase, requires lung transplantation.A retrospective study was undertaken of 15 patients with pulmonary hypertension who underwent lung transplantation between 1994 and 2004. Clinical data recorded before the procedure and during follow-up were reviewed.Pulmonary hypertension was reported as idiopathic in 8 patients (53%) and related to consumption of toxic oil in 2. The remaining causes were documented as chronic peripheral pulmonary embolism, histiocytosis X, venoocclusive disease, scleroderma, and simple corrected congenital heart defect in 1 patient each. The mean values of the hemodynamic variables were 100, 50, and 67 mm Hg for systolic, diastolic, and mean pulmonary artery pressure, respectively; 2.63 L/min for cardiac output; and 20.9 Wood units for total pulmonary resistance. The mean time between diagnosis of pulmonary hypertension and lung transplantation was 5.9 years (range, 0.4-20 y). Seven patients were in functional class III and 8 in functional class IV. The mean 6-minute walk distance was 204 m (range, 0-360 m). Four patients (26%) died during the during the perioperative period and 9 (60%), 7 (46%), and 6 (40%) were still alive at 1, 3, and 5 years, respectively.Double-lung transplantation is a therapeutic option that, in certain cases, has similar outcomes to those achieved with the most aggressive medical treatment for pulmonary hypertension.

Background The main problem with using nebulized liposomal amphotericin (n-LAB) as prophylaxis for Aspergillus infection after lung transplantation is the lack of knowledge of its pharmacokinetics and its possible adverse effects. The aim of this study was to measure post-inhalation amphotericin B concentration in the respiratory tract and serum of lung transplant patients and assess the effects of n-LAB on respiratory function. Methods Thirty-two consecutive bronchoscopies were performed on 27 lung transplant patients at two hospitals. Amphotericin B concentration in the first and third aliquot of bronchoalveolar lavage material was measured in steady state. The first aliquot approximates most closely the true amphotericin B concentrations in the proximal airway, whereas the third aliquot provides an optimum sample from the distal airway. Results At 2 days, mean amphotericin B concentrations were 11.1 μg/ml (95% confidence interval [CI]: 16.5 to 5.7 μg/ml) and 9.0 μg/ml (95% CI: 14.3 to 3.8 μg/ml) in the first and third aliquot, respectively. Thereafter, concentrations declined progressively. At 14 days, concentrations were 3.0 μg/ml (95% CI: 4.4 to 1.5 μg/ml) in the first aliquot and 4.1 μg/ml (95% CI: 6.1 to 2.1 μg/ml) in the third aliquot ( p = not statistically significant). Traces of amphotericin B (0.1 μg/ml) were found in serum samples from only 1 of 27 patients. Mean value of forced expiratory volume in the first second (FEV 1 ) was similar before and after n-LAB. Conclusions Amphotericin B concentrations after n-LAB remained high for 14 days, at adequate concentrations for prophylaxis of Aspergillus infection. No significant systemic absorption of amphotericin B was detected and no effect was observed on respiratory function. This promising prophylactic regimen warrants assessment in future clinical studies.

Objective Treatment with bosentan improves exercise capacity in patients with pulmonary hypertension. Few studies have assessed treatment with this drug over long periods. The aim was therefore to assess long-term treatment with bosentan. Patients and methods A group of 22 functional class III patients—18 women and 4 men, mean age, 45.5 years (range, 19-77 years)—with pulmonary hypertension were treated with bosentan between April 2002 and June 2005. Pulmonary hypertension was idiopathic in 10 patients. In the remaining patients, etiologies were associated with compensated heart failure (n=4), scleroderma (n=4), peripheral embolism (n=3), and portal hypertension (n=1). Clinical and hemodynamic variables and their changes between baseline and the end of study were analyzed. Results The mean duration of follow-up of the patients was 15.7 months (range, 12.6-31.8 months). Functional class improved or stabilized after 3 months of treatment in 21 (95%) and after 1 year in 14 (64%). At 3 months, the distance covered in the 6-minute walk test increased by a mean of 64.5 m, an improvement that was maintained at 6, 12, and 18 months. Treatment was interrupted in 4 patients (18%). Reasons for discontinuation were death in 2 patients, deterioration in 1 patient, and intolerance of the medication in 1 patient. Treatment was ineffective for 4 patients (18%). No patient experienced notable liver toxicity. Conclusions The results of this study suggest that treatment with bosentan is associated with long-term improvement in clinical variables and exercise capacity in approximately two thirds of the patients with pulmonary hypertension.

The most effective strategy for the prevention of cytomegalovirus (CMV) disease in lung transplantation has not been conclusively established. The aim of this study was to determine the efficacy of preemptive ganciclovir therapy for this purpose. Twenty-five consecutive adult patients positive for CMV before transplantation and surviving more than 30 days after the procedure were studied. Mean follow-up was 732.2 days (range, 210–1125). All patients received intravenous (IV) ganciclovir prophylaxis for the first 21 days and subsequently underwent frequent CMV antigenemia monitoring: weekly for the first 3 months, every 15 days between 3 and 6 months, and monthly thereafter. IV ganciclovir was given when antigenemia results were greater than 10 infected cells per 100,000 polymorphonuclears. The study group was compared with a historical group of 30 consecutive patients who had received IV ganciclovir prophylaxis and continued on oral ganciclovir up to day 120 posttransplantation. Eighteen of the 25 patients (72.0%) presented episodes of CMV infection. Six of the 25 patients (24.0%) had CMV disease, including 3 viral syndromes and 3 cases of pneumonitis. Four patients debuted with CMV disease, 1 of them with pneumonitis. CMV resistance to ganciclovir was observed in 2 patients. The incidence of infection was higher than in the historical group (72.0% vs 46.7%; P < .05), but there were no significant differences in the incidence of CMV disease (24.0% vs 40.0%; P = not significant [NS]). Mean time before onset of the first episode of disease was lower in the preemptive therapy group than in the comparison patients (82.8 days; range, 42–240 vs 175 days; range, 90–243; P < .05). In conclusion, preemptive therapy for CMV disease is as effective a prevention strategy as oral ganciclovir prophylaxis. However, the early appearance of CMV disease with preemptive therapy can make this approach inadvisable.

Background. A criticism of using nebulized amphotericin B (nAB) as prophylaxis against Aspergillus infection after lung transplantation is the lack of knowledge of its pharmacokinetics and distribution in the lung. The aim of this study was to ascertain the concentrations and distribution of nAB in the respiratory tract of patients receiving lung transplantations. Methods. In the drug-concentration study, 120 bronchoscopies were performed in 39 patients receiving lung transplantions after administration of 6 mg of nAB once daily for a minimum of 7 days. Mean nAB concentration in bronchial aspirated secretions (BAS) and bronchoalveolar lavage (BAL) was determined at 4, 12, 24, and 48 hours postnebulization. In the distribution study, 17 patients inhaled 6 mg of 99m technetium-labeled AB, and pulmonary distribution was measured using a gamma camera. Pulmonary perfusion was also measured. Both tests were quantitatively evaluated. Results. In the drug-concentration study, mean concentrations of 1.46 μg/mL in BAS and 15.75 μg/mL in BAL were reached at 4 hours. At 24 hours, concentrations were 0.37 μg/m and 11.02 μg/mL in BAS and BAL, respectively. In the distribution study, 99m technetium-labeled AB distribution was uniform in 12 of 13 allografts without bronchiolitis obliterans syndrome (BOS) and in 1 of 4 allografts with BOS. A close correlation was observed between regional drug distribution and regional perfusion (r=0.82, P

Primary pulmonary hypertension is a poorly understood disease with a difficult treatment.Retrospective study of a series of 44 patients suffering from pulmonary hypertension who were studied in our center between 1992 and 2000.At diagnosis, 6 (13%) patients were classified as having NYHA functional class I, 11 (25%) had class II, 25 (57%) had class III, and 2 had class IV. Mean pulmonary artery systolic pressure by echo-doppler was 92 (range: 43-154) mmHg. Basal right catheterization showed a mean (SD) pulmonary artery pressure of 58 (18) mmHg, total basal pulmonary resistances of 1679 (1,071) din/cm2 and cardiac index of 2.2 (1) 1/minute/m2. Five patients improved with anticoagulation and calcium channel blockers therapy. Since 1998, 11 patients had been treated with continuous endovenous epoprostenol, yet only 3 (27%) had significant clinical improvement. Survival at 5 years after diagnosis was 56%. At the end of study, 7 (70%) out of 10 patients who underwent pulmonary transplantation were alive (mean: 34, range: 3-62 months).Pulmonary hypertension is a disease with a poor prognosis. However, treatment with prostaglandins and pulmonary transplantation may lead to encouraging results.

The aim of this study was to determine whether cyclosporine levels predose (C0) and at two hours postdose (C2) were higher among patients presenting with cytomegalovirus (CMV) infection or disease. Between days 40 and 365 posttransplantation serial C0 and C2 levels were measured in 15 lung transplant recipients. Nine developed 13 episodes of CMV infection or disease. Both C0 and C2 levels were higher during CMV infection or disease episodes. Eleven of the 13 CMV episodes (84%) displayed C0220 ng/mL and none had C0200 ng/mL. For C2, 11 of 13 CMV episodes (84%) showed C21200 ng/mL and none had C21000 ng/mL. Among determinations that did not coincide with a CMV episode, 7 of 21 (33%) showed C0220 and 9 of 21 (42%) showed C21200, respectively (P.05). In conclusion, cyclosporine blood levels are higher among patients presenting with CMV infection or disease.