RESUMEN
Respiratory tract infection with pneumoviruses (PVs) and paramyxoviruses (PMVs) are increasingly associated with chronic lung allograft dysfunction (CLAD) in lung transplant recipients (LTRs). Ribavirin may be a treatment option but its effectiveness is unclear, especially with respect to infection severity. We retrospectively analyzed 10 years of PV/PMV infections in LTRs. The main end points were forced expiratory volume in 1 second (FEV1 ) at 3 and 6 months postinfection, expressed as a percentage of pre-infection FEV1 and incidence of new or progressed CLAD 6 months postinfection. A total of 139 infections were included: 88 severe infections (63%) (defined as >10% FEV1 loss at infection) and 51 mild infections (37%) (≤10% FEV1 loss). Overall postinfection CLAD incidence was 20%. Associations were estimated on postinfection FEV1 for ribavirin vs no ribavirin (+13.2% [95% CI: 7.79; 18.67]) and severe vs mild infection (-11.1% [95% CI: -14.76; -7.37]). Factors associated with CLAD incidence at 6 months were ribavirin treatment (odds ratio (OR [95% CI]) 0.24 [0.10; 0.59]), severe infection (OR [95% CI] 4.63 [1.66; 12.88]), and mycophenolate mofetil use (OR [95% CI] 0.38 [0.14; 0.97]). These data provide valuable information about the outcomes of lung transplant recipients with these infections and suggests possible associations of ribavirin use and infection severity with long-term outcomes. Well-designed prospective trials are needed to confirm these findings.
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Trasplante de Pulmón , Metapneumovirus , Infecciones por Virus Sincitial Respiratorio , Infecciones del Sistema Respiratorio , Antivirales/uso terapéutico , Humanos , Pulmón , Trasplante de Pulmón/efectos adversos , Estudios Prospectivos , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones por Virus Sincitial Respiratorio/etiología , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/etiología , Estudios Retrospectivos , Ribavirina/uso terapéutico , Receptores de TrasplantesRESUMEN
OBJECTIVE: To establish the incidence of massive transfusion and overall transfusion requirements during lung transplantation, changes over time, and association with outcome in relation to patient complexity. DESIGN: Retrospective cohort study. SETTING: University hospital. PARTICIPANTS: All 514 adult patients who underwent transplantation from 1990 until 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient records and transfusion data, divided into 5-year intervals, were analyzed. The incidence of massive transfusion (>10 units of red blood cells [RBCs] in 24 h) was 27% and did not change over time, whereas the median (interquartile range) transfusion requirement in the whole cohort decreased from 8 (5-12) to 3 (0-10) RBCs (p < 0.001). In patients transplanted from the intensive care unit, the incidence of massive transfusion increased over time from 25% to 54% (pâ¯=â¯0.04) and median transfusion requirements from 4.5 (3-8.5) units to 14.5 (5-26) units of RBCs (pâ¯=â¯0.03). Multivariable analysis showed that circulatory support, pulmonary hypertension, re-transplantation, cystic fibrosis, Eisenmenger syndrome, bilateral transplantation, and low body mass index were associated with massive transfusion. Patients with massive transfusion had more primary graft dysfunction grade III at 0, 24, 48, and 72 hours (p < 0.001), higher 30-day mortality (13% v 4%; p < 0.001), and lower 5-year survival (hazard ratio 3.67 [95% confidence interval 1.72-7.85]; p < 0.001). CONCLUSION: The incidence of massive transfusion did not change over time, whereas transfusion requirements in the whole cohort decreased. In patients transplanted from the intensive care unit, massive transfusion and transfusion requirements increased. Massive transfusion was associated with poor outcome.
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Transfusión Sanguínea/mortalidad , Transfusión Sanguínea/tendencias , Trasplante de Pulmón/mortalidad , Trasplante de Pulmón/tendencias , Adulto , Estudios de Cohortes , Femenino , Humanos , Incidencia , Trasplante de Pulmón/efectos adversos , Masculino , Persona de Mediana Edad , Mortalidad/tendencias , Estudios Retrospectivos , Factores de TiempoRESUMEN
Air pollution from road traffic is a serious health risk, especially for susceptible individuals. Single-centre studies showed an association with chronic lung allograft dysfunction (CLAD) and survival after lung transplantation, but there are no large studies.13 lung transplant centres in 10 European countries created a cohort of 5707 patients. For each patient, we quantified residential particulate matter with aerodynamic diameter ≤10â µm (PM10) by land use regression models, and the traffic exposure by quantifying total road length within buffer zones around the home addresses of patients and distance to a major road or freeway.After correction for macrolide use, we found associations between air pollution variables and CLAD/mortality. Given the important interaction with macrolides, we stratified according to macrolide use. No associations were observed in 2151 patients taking macrolides. However, in 3556 patients not taking macrolides, mortality was associated with PM10 (hazard ratio 1.081, 95% CI 1.000-1.167); similarly, CLAD and mortality were associated with road lengths in buffers of 200-1000 and 100-500â m, respectively (hazard ratio 1.085- 1.130). Sensitivity analyses for various possible confounders confirmed the robustness of these associations.Long-term residential air pollution and traffic exposure were associated with CLAD and survival after lung transplantation, but only in patients not taking macrolides.
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Contaminación del Aire/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Trasplante de Pulmón/mortalidad , Disfunción Primaria del Injerto/fisiopatología , Adulto , Contaminantes Atmosféricos/análisis , Estudios de Cohortes , Europa (Continente)/epidemiología , Femenino , Supervivencia de Injerto , Humanos , Macrólidos/uso terapéutico , Masculino , Persona de Mediana Edad , Material Particulado/análisis , Modelos de Riesgos Proporcionales , Análisis de RegresiónRESUMEN
OBJECTIVES: To conduct an exploration of the hospital costs of extracorporeal life support therapy. Extracorporeal life support seems an efficient therapy for acute, potentially reversible cardiac or respiratory failure, when conventional therapy has been inadequate, or as bridge to transplant, but unfortunately, no evidence in randomized controlled trials is delivered yet. DESIGN: Single-center retrospective exploratory cohort cost study. The study is performed from a hospital perspective with a time horizon of patients' complete hospital admission in which they received extracorporeal life support. SETTING: ICU of a university teaching hospital in The Netherlands. PATIENTS: All 67 consecutive adult patients who were admitted to the ICU of the University Medical Center Groningen in the period 2010-2013 and received extracorporeal life support treatment. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The bottom-up microcosting method was used except when stated otherwise. Medical costs were estimated by multiplying every registered healthcare consumption with unit prices. Unit prices were largely based on Dutch reference prices. For each patient, the personnel costs and material costs were assessed in detail. The costs of extracorporeal life support were differentiated in costs of procedures and costs of daily surcharge of therapy. Procedure-related costs were subdivided in costs of devices and disposables, costs of additional human resources, and surgery hours. The mean total hospital costs were 106.263 ( 83.841 to 126.266) per patient ($145,580). On average, 52% of the total costs arose from hospital nursing days and 11% of direct procedure-related extracorporeal life support costs. Surgery and diagnostics represented a vast amount of the remaining costs. CONCLUSIONS: This large and detailed economic evaluation of hospital costs of extracorporeal life support therapy in the Netherlands showed that mean total hospital cost of extracorporeal life support treatment is 106.263 per patient. The majority of the costs are composed of nursing days.
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Oxigenación por Membrana Extracorpórea/economía , Costos de Hospital/estadística & datos numéricos , Adulto , Anciano , Cuidados Críticos , Femenino , Humanos , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Países Bajos , Insuficiencia Respiratoria/economía , Insuficiencia Respiratoria/terapia , Estudios RetrospectivosRESUMEN
Combined lung-liver transplantation is a logistically challenging procedure hampered by shortage of organ donors. We describe the case of a young patient with end-stage lung disease due to of cystic fibrosis and liver cirrhosis who needed combined lung-liver transplantation. The long waiting for this caused an interesting clinical dilemma. We decided to change our policy in this situation by listing him only for the lung transplantation and to apply for a high urgent liver transplantation if the liver failed after the lung transplantation. This strategy enabled us to use lungs treated with ex vivo lung perfusion (EVLP) from an unsuitable donor after circulatory death. After conditioning for 4 h via EVLP, the pO2 was 59.7 kPa. The lungs were transplanted successfully. He developed an acute-on-chronic liver failure for which he received a successful liver transplantation 19 days after the lung transplantation.
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Enfermedad Hepática en Estado Terminal/cirugía , Trasplante de Hígado/métodos , Enfermedades Pulmonares/cirugía , Trasplante de Pulmón/métodos , Adulto , Fibrosis Quística/cirugía , Edema/patología , Femenino , Humanos , Cirrosis Hepática/cirugía , Pulmón/patología , Masculino , Perfusión/métodos , Donantes de Tejidos , Resultado del Tratamiento , Adulto JovenRESUMEN
INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal fibrosing lung disease with a median survival of approximately 3 years after diagnosis. The only medical option to improve survival in IPF is lung transplantation (LTX). The purpose of this study was to evaluate trajectory data of IPF patients listed for LTX and to investigate the survival after LTX. METHODS AND RESULTS: Data were retrospectively collected from September 1989 until July 2011 of all IPF patients registered for LTX in the Netherlands. Patients were included after revision of the diagnosis based on the criteria set by the ATS/ERS/JRS/ALAT. Trajectory data, clinical data at time of screening, and donor data were collected. In total, 98 IPF patients were listed for LTX. During the waiting list period, 30 % of the patients died. Mean pulmonary artery pressure, 6-min walking distance, and the use of supplemental oxygen were significant predictors of mortality on the waiting list. Fifty-two patients received LTX with a median overall survival after transplantation of 10 years. CONCLUSIONS: This study demonstrated a 10-year survival time after LTX in IPF. Furthermore, our study demonstrated a significantly better survival after bilateral LTX in IPF compared to single LTX although bilateral LTX patients were significantly younger.
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Fibrosis Pulmonar Idiopática/cirugía , Trasplante de Pulmón , Estudios de Cohortes , Prueba de Esfuerzo , Femenino , Humanos , Hipertensión Pulmonar/epidemiología , Fibrosis Pulmonar Idiopática/epidemiología , Fibrosis Pulmonar Idiopática/mortalidad , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Terapia por Inhalación de Oxígeno/estadística & datos numéricos , Presión Esfenoidal Pulmonar , Estudios Retrospectivos , Tasa de Supervivencia , Listas de Espera/mortalidadRESUMEN
Ex vivo lung perfusion (EVLP) is a technique for reconditioning and evaluating lungs. However, the use of EVLP for logistical reasons is still under discussion. In this retrospective study, all EVLPs performed between July 2012 and October 2019 were analyzed for ventilation and perfusion data. After transplantation, primary graft dysfunction (PGD), lung function, chronic lung allograft dysfunction (CLAD)-free survival, and overall survival were analyzed. Fifty EVLPs were performed: seventeen logistic EVLPs led to 15 lung transplantations (LT) and two rejections (LR), and 33 medical EVLPs resulted in 26 lung transplantations (MT) and seven rejections (MR). Pre-EVLP PaO2 was lower for MT than LT (p < 0.05). Dynamic lung compliance remained stable in MT and LT but decreased in MR and LR. Plateau airway pressure started at a higher level in MR (p < 0.05 MT vs. MR at T60) and increased further in LR. After transplantation, there were no differences between MT and LT in PGD, lung function, CLAD-free survival, and overall survival. In addition, the LT group was compared with a cohort group receiving standard donor lungs without EVLP (LTx). There were no significant differences between LT and LTx for PGD, CLAD-free survival, and overall survival. FVC was significantly lower in LT than in LTx after 1 year (p = 0.005). We found that LT lungs appear to perform better than MT lungs on EVLP. In turn, the outcome in the LT group was comparable with the LTx group. Overall, lung transplantation after EVLP for logistic reasons is safe and makes transplantation timing controllable.
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BACKGROUND: Evaluating and bridging patients to lung transplantation (LTx) on the intensive care unit (ICU) remains controversial, especially without a previous waitlist status. Long term outcome data after LTx from ICU remains scarce. We compared long-term survival and development of chronic lung allograft dysfunction (CLAD) in elective and LTx from ICU, with or without previous waitlist status. METHODS: Patients transplanted between 2004 and 2018 in 2 large academic Dutch institutes were included. Long-term survival and development of CLAD was compared in patients who received an elective LTx (ELTx), those bridged and transplanted from the ICU with a previous listing status (BTT), and in patients urgently evaluated and bridged on ICU (EBTT). RESULTS: A total of 582 patients underwent a LTx, 70 (12%) from ICU, 39 BTT and 31 EBTT. Patients transplanted from ICU were younger than ELTx (46 vs 51 years) and were bridged with mechanical ventilation (n = 42 (60%)), extra corporeal membrane oxygenation (n = 28 (40%)), or both (n = 21/28). Bridging success was 48% in the BTT group and 72% in the EBTT group. Patients bridged to LTx on ICU had similar 1 and 5 year survival (86.8% and 78.4%) compared to elective LTx (86.8% and 71.9%). This was not different between the BTT and EBTT group. 5 year CLAD free survival was not different in patients transplanted from ICU vs ELTx. CONCLUSION: Patients bridged to LTx on the ICU with and without prior listing status had excellent short and long-term patient and graft outcomes, and was similar to patients electively transplanted.
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Oxigenación por Membrana Extracorpórea , Trasplante de Pulmón , Oxigenación por Membrana Extracorpórea/efectos adversos , Humanos , Unidades de Cuidados Intensivos , Pulmón , Trasplante de Pulmón/efectos adversos , Estudios RetrospectivosRESUMEN
The aim of this study was to design and validate a lung donor score that reflects experts' perceived risk of allograft failure. All lung donors reported to Eurotransplant from 1999 to 2007 [N=6080] were used to create a lung donor score. Based on observed discard rates and using multivariate regression, points were assigned for six preprocurement donor variables. Donors reported in 2008 were used to validate the score [N=751]. All the six factors significantly predicted discard; as an example, the following donor with points: age 55-59years: 2; compromised history: 4; smoking: 2; shadow on chest X-ray: 2; purulent secretion during bronchoscopy: 2; and Pao(2) /Fio(2) ratio below 300mmHg: 3. Discard rates for donors with a lung donor score of 6 points (class 1) was 18%, while 36% and 54% of the donors with a score of 7-8 (class 2) and 9+(class 3) were discarded (P<0.001), respectively. In addition, the donor lung score was significantly associated with 1-year survival: class 1: 91%; class 2: 80%; and class 3: 72% (P=0.017). The lung donor score accurately reflects the likelihood of organ acceptance and predicts patient mortality, and its application at time of donor reporting may facilitate donor risk assessment and patient selection.
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Trasplante de Pulmón/normas , Pulmón/fisiopatología , Donantes de Tejidos , Obtención de Tejidos y Órganos/normas , Adulto , Factores de Edad , Cadáver , Europa (Continente)/epidemiología , Rechazo de Injerto/epidemiología , Humanos , Persona de Mediana Edad , Oxígeno/sangre , Presión Parcial , Selección de Paciente , FumarRESUMEN
BACKGROUND: Obesity-related diseases have been shown to affect post-lung transplantation survival. An estimated 30% of lung transplant recipients develop overweight. OBJECTIVE: The aim of this study was to examine the possible determinants of large increases in weight after lung transplantation. The contribution of physical activity, food intake, and resting energy expenditure was examined in lung transplant recipients. METHODS: In this cross-sectional study 21 overweight lung transplant recipients (11 men, mean age 57 ± 7 years; BMI 30 ± 3) and 21 normal-weight lung transplant recipients (11 men, mean age 56 ± 5 years; BMI 22 ± 3) were matched for disease, gender, age, prescribed medication, and time since lung transplantation. Physical activity was measured by a pedometer and a questionnaire; resting energy expenditure was measured by the ventilated-hood technique, and daily food intake by a dietician. Additionally, fat-free mass, lower-body strength, and fatigue were measured. RESULTS: The overweight lung transplant recipients had a significantly lower number of steps per day (4,686 ± 3,266 vs. 7,524 ± 3,448 steps/day, p = 0.01) and a lower fat-free mass (64 ± 9 vs. 75 ± 6%, p < 0.05) compared to normal-weight recipients. Obese subjects had a lower percentage of predicted resting energy expenditure level compared to normal-weight recipients (90 ± 14 vs. 100 ± 14% predicted, p = 0.04). CONCLUSION: Our data suggest that overweight in lung transplant recipients is associated with a lower fat-free mass and lower levels of physical activity and resting energy expenditure compared to normal-weight recipients.
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Trasplante de Pulmón , Obesidad/etiología , Obesidad/fisiopatología , Sobrepeso/etiología , Sobrepeso/fisiopatología , Complicaciones Posoperatorias , Índice de Masa Corporal , Estudios Transversales , Ingestión de Alimentos , Metabolismo Energético , Fatiga/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Actividad Motora , Fuerza MuscularAsunto(s)
Heparina/uso terapéutico , Trasplante de Pulmón/efectos adversos , Tromboembolia Venosa/prevención & control , Adulto , Anciano , Anticoagulantes/administración & dosificación , Anticoagulantes/uso terapéutico , Quimioprevención/métodos , Comorbilidad , Femenino , Heparina/administración & dosificación , Humanos , Trasplante de Pulmón/métodos , Masculino , Persona de Mediana Edad , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiologíaRESUMEN
OBJECTIVES: Efforts to evaluate the health of solid organ transplant recipients are hampered by the lack of adequate patient-reported outcome measures (PROMs) targeting this group. We developed the Transplant ePROM (TXP), which is based on a novel measurement model and administered through a mobile application to fill this gap. The main objective of this article is to elucidate how we derived the weights for different items, and to report initial empirical results. STUDY DESIGN AND SETTING: The nine health items in the TXP were fatigue, skin, worry, self-reliance, activities, weight, sexuality, stooling, and memory. Via an online survey solid organ recipient participating in the TransplantLines Biobank and Cohort study (NCT03272841) were asked to describe and then compare their own health state with six other health states. Coefficients for item levels were obtained using a conditional logit model. RESULTS: A total of 232 solid organ transplant recipients (mean age: 54 years) participated. The majority (106) were kidney recipients, followed by lung, liver, and heart recipients. Fatigue was the most frequent complaint (54%). The strongest negative coefficients were found for activities and worry, followed by self-reliance and memory. CONCLUSION: A set of coefficients and values were developed for TXP. The TXP score approximated an optimal health state for the majority of respondents and recipients of different organs reported comparable health states.
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Medición de Resultados Informados por el Paciente , Satisfacción del Paciente/estadística & datos numéricos , Calidad de Vida/psicología , Receptores de Trasplantes/psicología , Receptores de Trasplantes/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Países Bajos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
OBJECTIVES: Patient-reported outcome measures (PROMs) are widely applied to assess perceived health status. To date, no transplant-specific PROM is available for generating a single, standardized score regarding the health status of transplant recipients. The objective of this study is to generate health items for a new patient-centered PROM for organ recipients: the Transplant PROM (TXP). STUDY DESIGN AND SETTING: A five-phase, mixed-method approach was applied to identify and select the health items: scoping literature review, expert meetings, focus-group meetings with organ recipients, a special judgmental task within an online survey, and expert meetings for final selection of health items. RESULTS: Based on a previously published scoping literature review, a first round of expert meetings, and a total of four focus-group meetings with kidney, lung, and liver transplant recipients (N = 18), a list of 83 relevant health items relating to post-transplant life was selected. In an online survey, 183 transplant recipients selected the 10 most important health items from this list. After evaluating the frequency of selected health items and combining items that assess closely related or similar concepts in the second round of expert meetings, nine health items were chosen to be included in TXP: fatigue, skin, worry/anxiety, self-reliance, activities, weight, sexuality, stooling, and memory/concentration. CONCLUSION: The nine TXP health items reflect the most prominent issues transplant recipients experience. The TXP can be administered by means of a mobile phone app.
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Teléfono Celular/instrumentación , Participación del Paciente/psicología , Atención Dirigida al Paciente/métodos , Receptores de Trasplantes/psicología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Grupos Focales , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Participación del Paciente/estadística & datos numéricos , Medición de Resultados Informados por el Paciente , Atención Dirigida al Paciente/normas , Calidad de Vida/psicología , Encuestas y Cuestionarios , Receptores de Trasplantes/estadística & datos numéricosRESUMEN
OBJECTIVES: Despite progress in lung transplantation (LTx) techniques, a shortage of donor lungs persists worldwide. Ex vivo lung perfusion (EVLP) is a technique that evaluates, optimizes and enables transplantation of the lungs that would otherwise have been discarded. Herein, we present our centre's first EVLP experiences between July 2012 and June 2016, when we performed 149 LTxs. METHODS: It was a single-centre, retrospective analysis of a prospectively collected database. The EVLP group (n = 9) consisted of recipients who initially received discarded donor lungs that were reconditioned using EVLP. The non-EVLP (N-EVLP) group (n = 18) consisted of data-matched patients receiving conventional quality lungs in the conventional way. Both groups were compared on primary graft dysfunction (PGD) grades 0-3, pulmonary function, chronic lung allograft dysfunction and survival. RESULTS: In the EVLP group, 33% (3/9) developed PGD1 at 72 h post-LTx. In the N-EVLP group, 11% (2/18) developed PGD1, 6% (1/18) PGD2 and 11% (2/18) PGD3 at 72 h post-LTx. At 3 and 24 months post-LTx, forced expiratory volume in 1 s as percentage of predicted was similar in the EVLP (78% and 92%) and N-EVLP groups (69% and 89%). Forced vital capacity as a percentage of predicted was comparable in the EVLP (77% and 93%) and N-EVLP groups (68% and 101%). Chronic lung allograft dysfunction was diagnosed in 1 N-EVLP patient at 2 years post-LTx. Three-year survival was 78% (7/9) (the EVLP group) vs 83% (15/18) (the N-EVLP group). CONCLUSIONS: These results are in line with the existing literature suggesting that transplantation of the previously discarded lungs recovered by EVLP leads to equal outcomes compared to conventional LTx methods.
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Trasplante de Pulmón , Pulmón , Reperfusión/métodos , Trasplantes , Adulto , Anciano , Femenino , Humanos , Pulmón/fisiología , Pulmón/cirugía , Trasplante de Pulmón/efectos adversos , Trasplante de Pulmón/métodos , Trasplante de Pulmón/mortalidad , Masculino , Persona de Mediana Edad , Países Bajos , Disfunción Primaria del Injerto/fisiopatología , Estudios Retrospectivos , Trasplantes/fisiología , Trasplantes/trasplanteRESUMEN
RATIONALE: Acute allograft rejection is one of the major complications after lung transplantation, and adequate and early recognition is important. Till now, the reference standard to detect acute rejection is the histopathological grading of transbronchial biopsies (TBBs). Acute rejection is characterised by high levels of activated T lymphocytes. Interleukin-2 (IL-2) binds specifically to high-affinity IL-2 receptors expressed on the cell membrane of activated T lymphocytes. The aim of this proof-of-concept study was to evaluate if non-invasive imaging with 99mTc-HYNIC-IL-2 is able to detect acute rejection after lung transplantation. METHODS: 99mTc-HYNIC-IL-2 scintigraphy (static, SPECT/CT of the lungs) was performed shortly before routine transbronchial biopsy (pathology as reference standard). Scans were scored as likely or unlikely for rejection, and semiquantitative analysis (target-to-background ratio) was performed. RESULTS: Thirteen patients were included of which 3 showed acute rejection at transbronchial biopsy; in 2 of these patients (scored as graded 2-3 at pathology), the scan was scored likely for rejection, and in 1 patient (scored grade 1 at pathology), the scan was scored unlikely. No correlation was found between biopsy results and semiquantitative analysis. CONCLUSION: 99mTc-HYNIC-IL-2 scintigraphy proved to be a good technique to detect grade 2 and 3 acute rejection in a small sample population of patients after lung transplantation. Larger studies are necessary to really show the added value of this non-invasive specific imaging technique over transbronchial biopsy. Alternatively, imaging with the PET tracer 18F-IL-2 may be useful for this purpose.
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BACKGROUND: Chronic immunosuppression after solid-organ transplantation is a risk factor for cutaneous squamous cell carcinoma (cSCC) development. Certain immunosuppressant drugs, namely azathioprine and calcineurin inhibitors, increase this risk more than others. We investigated incidence of cSCC in a Dutch lung transplant recipient (LTR) cohort and analyzed associated risk factors. METHODS: All LTRs with post-transplant survival of >30 days were included. Data included indication for lung transplantation and duration of medication use. Skin cancer data were extracted from the Dutch nationwide registry of histopathology (PALGA). Uni- and multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression analyses. RESULTS: Five hundred forty-four patients were included with a median survival of 11.05 years. Fifty-two (9.6%) LTRs developed at least one cSCC, with a cumulative incidence of 3.9% and 15.3% after 5 and 10 years, respectively. Multivariate analyses showed that the sequential use of azathioprine and mycophenolate mofetil (MMF), both at for least 1 year, was associated with a lower risk of developing cSCC (hazard ratio [HR] 0.24; 95% confidence interval [CI] 0.10 to 0.56) compared with azathioprine use only. Furthermore, age at transplantation (HR 3.42; 95% CI 1.33 to 8.79), male gender (HR 1.75; 95% CI 1.00 to 3.05), previous skin cancer (HR 4.75; 95% CI 1.14 to 19.76), and history of smoking (HR 3.30; 95% CI 1.69 to 6.44) were associated with increased risk of developing cSCC in univariate analyses. CONCLUSIONS: Apart from known risk factors, we found that switching from azathioprine to MMF is associated with reduced incidence of cSCC in LTR, prompting a discussion of whether switching azathioprine to MMF should be considered in high-risk patients.
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Azatioprina/administración & dosificación , Carcinoma de Células Escamosas/inducido químicamente , Carcinoma de Células Escamosas/epidemiología , Sustitución de Medicamentos/efectos adversos , Trasplante de Pulmón , Ácido Micofenólico/administración & dosificación , Complicaciones Posoperatorias/inducido químicamente , Complicaciones Posoperatorias/epidemiología , Neoplasias Cutáneas/inducido químicamente , Neoplasias Cutáneas/epidemiología , Adolescente , Adulto , Anciano , Azatioprina/efectos adversos , Niño , Femenino , Humanos , Inmunosupresores , Incidencia , Masculino , Persona de Mediana Edad , Ácido Micofenólico/efectos adversos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND Donor hypernatremia has been associated with reduced graft and recipient survival after heart, liver, kidney, and pancreas transplantation. However, it is unknown what effect donor hypernatremia has on graft and recipient outcomes after lung transplantation. The aim of this study was to investigate the relation of donor hypernatremia with the duration of postoperative mechanical ventilation, the incidence of severe primary graft dysfunction, and survival following lung transplantation. MATERIAL AND METHODS We analyzed all consecutive lung transplantations performed in adult patients at our center between 1995 and 2016. During the study period, donor hypernatremia was not considered a reason to reject lungs for transplantation. Donors were classified into 3 groups: normonatremia (sodium <145 mmol/L), moderate hypernatremia (sodium 145-154 mmol/L), or severe hypernatremia (sodium ≥155 mmol/L). Short-term outcome was defined by the duration of mechanical ventilation and incidence of primary graft dysfunction; long-term outcome was defined by 10-year mortality. RESULTS Donor hypernatremia was recorded in 275 (58%) of the 474 donors. There were no differences in baseline characteristics between the 3 study groups. The duration of mechanical ventilation was similar for all groups (8±25, 7±17, and 9±15 days respectively, P=0.204). Severe primary graft dysfunction was not different between the 3 groups (29%, 26%, 28%, P=0.724). Donor hypernatremia was not associated with (graft) survival, or after correction for potential confounders. CONCLUSIONS Donor hypernatremia was not associated with a worse outcome in lung transplant recipients. Thus, in contrast to solid organ transplantation, donor hypernatremia is not a contraindication for lung transplantation.
Asunto(s)
Selección de Donante , Hipernatremia/complicaciones , Trasplante de Pulmón/mortalidad , Disfunción Primaria del Injerto/etiología , Adulto , Femenino , Supervivencia de Injerto , Humanos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Disfunción Primaria del Injerto/mortalidad , Pronóstico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) is a serious complication after lung transplantation and its relation with Epstein-Barr virus (EBV) is well recognized. It has been postulated that preemptive reduction of immunosuppression guided by EBV-DNA load may lead to a significantly lower incidence of PTLD, because of the reconstitution of T-cell control. In this report, we describe the feasibility of this approach in terms of safety with regard to the risk of acute as well as chronic allograft rejection in 75 lung transplant recipients transplanted between 1990 and 2001 and followed for this study from June 1, 2001 until January 1, 2006. METHODS: From all patients visiting our outpatient clinic, EBV-DNA load was measured at least twice a year during the study period. In patients with positive results, measurements were repeated every two to four weeks. EBV reactivation was defined as two consecutive EBV-DNA load measurements with a rising trend; with the last measurement exceeding 10.000 copies/mL under stable immunosuppression. In such case, immunosuppression was reduced. RESULTS: EBV reactivation was observed in 26/75 patients (35%). One (1.5%) of these patients developed PTLD during the study period. Acute rejection, acceleration of chronic allograft rejection, or worse survival were not observed after reduction of immunosuppression. CONCLUSIONS: Preemptive reduction of immunosuppression after lung transplantation guided by EBV-DNA load appears to be a safe approach for the prevention of PTLD in lung transplant recipients late after transplantation.