RESUMEN
BK virus DNAemia (BKPyV) and nephropathy are common after kidney transplant; however, there are limited data on BK infections in nonrenal solid organ transplant recipients. We examined the frequency, clinical and pathologic features, and kidney and lung outcomes of BKPyV and BK virus native kidney nephropathy (BKVN) in lung transplant recipients at our center. Among 878 recipients transplanted from 2003 to 2019, 56 (6%) developed BKPyV at a median of 30.1 months after transplant (range, 0.6-213) and 11 (1.3%) developed BKVN at a median of 46 months after transplant (range, 9-213). The incidence of end-stage kidney disease was significantly higher in patients with peak viral load ≥10 000 copies/mL (39% vs 8%, P < .001). All cases of BKVN were in patients with peak viral load of ≥10 000 copies/mL, and 55% of these patients developed end-stage kidney disease. Despite the reduction of immunosuppression to treat BKVN, only 1 patient developed acute rejection, and lung function was stable >1 year. BKPyV and nephropathy are more common after lung transplantation than previously reported. Routine screening for BKPyV should be considered in all lung transplant recipients.
Asunto(s)
Virus BK , Enfermedades Renales , Fallo Renal Crónico , Trasplante de Pulmón , Nefritis Intersticial , Infecciones por Polyomavirus , Poliomavirus , Infecciones Tumorales por Virus , Humanos , Enfermedades Renales/etiología , Enfermedades Renales/cirugía , Enfermedades Renales/epidemiología , Riñón/patología , Nefritis Intersticial/complicaciones , Trasplante de Pulmón/efectos adversos , Infecciones por Polyomavirus/etiología , Infecciones por Polyomavirus/diagnóstico , Receptores de Trasplantes , Fallo Renal Crónico/complicaciones , Infecciones Tumorales por Virus/complicacionesRESUMEN
Heterogeneous frailty pathobiology might explain the inconsistent associations observed between frailty and lung transplant outcomes. A Subphenotype analysis could refine frailty measurement. In a 3-center pilot cohort study, we measured frailty by the Short Physical Performance Battery, body composition, and serum biomarkers reflecting causes of frailty. We applied latent class modeling for these baseline data. Next, we tested class construct validity with disability, waitlist delisting/death, and early postoperative complications. Among 422 lung transplant candidates, 2 class model fit the best (P = .01). Compared with Subphenotype 1 (n = 333), Subphenotype 2 (n = 89) was characterized by systemic and innate inflammation (higher IL-6, CRP, PTX3, TNF-R1, and IL-1RA); mitochondrial stress (higher GDF-15 and FGF-21); sarcopenia; malnutrition; and lower hemoglobin and walk distance. Subphenotype 2 had a worse disability and higher risk of waitlist delisting or death (hazards ratio: 4.0; 95% confidence interval: 1.8-9.1). Of the total cohort, 257 underwent transplant (Subphenotype 1: 196; Subphenotype 2: 61). Subphenotype 2 had a higher need for take back to the operating room (48% vs 28%; P = .005) and longer posttransplant hospital length of stay (21 days [interquartile range: 14-33] vs 18 days [14-28]; P = .04). Subphenotype 2 trended toward fewer ventilator-free days, needing more postoperative extracorporeal membrane oxygenation and dialysis, and higher need for discharge to rehabilitation facilities (P ≤ .20). In this early phase study, we identified biological frailty Subphenotypes in lung transplant candidates. A hyperinflammatory, sarcopenic Subphenotype seems to be associated with worse clinical outcomes.
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Fragilidad , Trasplante de Pulmón , Humanos , Fragilidad/complicaciones , Proyectos Piloto , Estudios de Cohortes , BiomarcadoresRESUMEN
Cryptococcus neoformans infective endocarditis is rarely reported. In this report, we present a case of infective endocarditis secondary to Cryptococcus neoformans in a lung-transplant recipient and review the relevant literature. A 65-year-old man was hospitalized with hypoxemic respiratory failure and underwent left-sided single lung transplantation. In the setting of worsening hypoxemia, blood cultures were drawn, which grew C. neoformans. Lumbar puncture was performed, and CSF PCR was also positive for Cryptococcus. Further exposure history revealed that he had raised chickens while living in Peru. Transesophageal echocardiography showed an aortic valve vegetation, and he was diagnosed with cryptococcal infective endocarditis. He received liposomal amphotericin B and flucytosine for two weeks and was later transitioned to fluconazole. This case highlights the need for thorough social history prior to lung transplantation, as pulmonary colonization with C. neoformans may result in infective endocarditis after immunosuppression.
RESUMEN
Extracorporeal membrane oxygenation (ECMO) is becoming a key tool for bridge to heart, lung, or heart-lung transplantation, and ambulatory ECMO support offers many advantages to prepare the patients. We here present a case of successful en bloc heart and lung transplantation after long-term ambulatory support with a minimally invasive central venoarterial ECMO approach as bridge to transplant.
Asunto(s)
Cardiomiopatías/terapia , Oxigenación por Membrana Extracorpórea , Trasplante de Corazón-Pulmón , Neumonía/terapia , Cardiomiopatías/cirugía , Humanos , Masculino , Persona de Mediana Edad , Neumonía/cirugía , Resultado del TratamientoRESUMEN
Skin cancer is the most common malignancy affecting solid organ transplant recipients (SOTR), and SOTR experience increased skin cancer-associated morbidity and mortality. There are no formal multidisciplinary guidelines for skin cancer screening after transplant, and current practices are widely variable. We conducted three rounds of Delphi method surveys with a panel of 84 U.S. dermatologists and transplant physicians to establish skin cancer screening recommendations for SOTR. The transplant team should risk stratify SOTR for screening, and dermatologists should perform skin cancer screening by full-body skin examination. SOTR with a history of skin cancer should continue regular follow-up with dermatology for skin cancer surveillance. High-risk transplant patients include thoracic organ recipients, SOTR age 50 and above, and male SOTR. High-risk Caucasian patients should be screened within 2 years after transplant, all Caucasian, Asian, Hispanic, and high-risk African American patients should be screened within 5 years after transplant. No consensus was reached regarding screening for low-risk African American SOTR. We propose a standardized approach to skin cancer screening in SOTR based on multidisciplinary expert consensus. These guidelines prioritize and emphasize the need for screening for SOTR at greatest risk for skin cancer.
Asunto(s)
Técnica Delphi , Detección Precoz del Cáncer/métodos , Trasplante de Órganos/efectos adversos , Neoplasias Cutáneas/diagnóstico , Consenso , Femenino , Guías como Asunto , Humanos , Masculino , Medición de Riesgo , Neoplasias Cutáneas/epidemiología , Receptores de Trasplantes , Estados UnidosRESUMEN
Despite the Final Rule mandate for equitable organ allocation in the United States, geographic disparities exist in donor lung allocation, with the majority of donor lungs being allocated locally to lower-priority candidates. We conducted a retrospective cohort study of 19 622 lung transplant candidates waitlisted between 2006 and 2015. We used multivariable adjusted competing risk survival models to examine the relationship between local lung availability and waitlist outcomes. The primary outcome was a composite of death and removal from the waitlist for clinical deterioration. Waitlist candidates in the lowest quartile of local lung availability had an 84% increased risk of death or removal compared with candidates in the highest (subdistribution hazard ratio [SHR]: 1.84, 95% confidence interval [CI]: 1.51-2.24, P < .001). The transplantation rate was 57% lower in the lowest quartile compared with the highest (SHR: 0.43, 95% CI: 0.39-0.47). The adjusted death or removal rate decreased by 11% with a 50% increase in local lung availability (SHR: 0.89, 95% CI: 0.85-0.93, P < .001) and the adjusted transplantation rate increased by 19% (SHR: 1.19, 95% CI: 1.17-1.22, P < .001). There are geographically disparate waitlist outcomes in the current lung allocation system. Candidates listed in areas of low local lung availability have worse waitlist outcomes.
Asunto(s)
Geografía , Trasplante de Pulmón , Donantes de Tejidos , Listas de Espera , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Frailty is associated with increased mortality among lung transplant candidates. We sought to determine the association between frailty, as measured by the Short Physical Performance Battery (SPPB), and mortality after lung transplantation. In a multicenter prospective cohort study of adults who underwent lung transplantation, preoperative frailty was assessed with the SPPB (n = 318) and, in a secondary analysis, the Fried Frailty Phenotype (FFP; n = 299). We tested the association between preoperative frailty and mortality following lung transplantation with propensity score-adjusted Cox models. We calculated postestimation marginalized standardized risks for 1-year mortality by frailty status using multivariate logistic regression. SPPB frailty was associated with an increased risk of both 1- and 4-year mortality (adjusted hazard ratio [aHR]: 7.5; 95% confidence interval [CI]: 1.6-36.0 and aHR 3.8; 95%CI: 1.8-8.0, respectively). Each 1-point worsening in SPPB was associated with a 20% increased risk of death (aHR: 1.20; 95%CI: 1.08-1.33). Frail subjects had an absolute increased risk of death within the first year after transplantation of 12.2% (95%CI: 3.1%-21%). In secondary analyses, FFP frailty was associated with increased risk of death within the first postoperative year (aHR: 3.8; 95%CI: 1.1-13.2) but not over longer follow-up. Preoperative frailty is associated with an increased risk of death after lung transplantation.
Asunto(s)
Fragilidad/mortalidad , Enfermedades Pulmonares/mortalidad , Trasplante de Pulmón/mortalidad , Complicaciones Posoperatorias , Calidad de Vida , Índice de Severidad de la Enfermedad , Anciano , Femenino , Estudios de Seguimiento , Fragilidad/diagnóstico , Humanos , Enfermedades Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Fenotipo , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
RATIONALE: Anecdotally, short lung transplant candidates suffer from long waiting times and higher rates of death on the waiting list compared with taller candidates. OBJECTIVES: To examine the relationship between lung transplant candidate height and waiting list outcomes. METHODS: We conducted a retrospective cohort study of 13,346 adults placed on the lung transplant waiting list in the United States between 2005 and 2011. Multivariable-adjusted competing risk survival models were used to examine associations between candidate height and outcomes of interest. The primary outcome was the time until lung transplantation censored at 1 year. MEASUREMENTS AND MAIN RESULTS: The unadjusted rate of lung transplantation was 94.5 per 100 person-years among candidates of short stature (<162 cm) and 202.0 per 100 person-years among candidates of average stature (170-176.5 cm). After controlling for potential confounders, short stature was associated with a 34% (95% confidence interval [CI], 29-39%) lower rate of transplantation compared with average stature. Short stature was also associated with a 62% (95% CI, 24-96%) higher rate of death or removal because of clinical deterioration and a 42% (95% CI, 10-85%) higher rate of respiratory failure while awaiting lung transplantation. CONCLUSIONS: Short stature is associated with a lower rate of lung transplantation and higher rates of death and respiratory failure while awaiting transplantation. Efforts to ameliorate this disparity could include earlier referral and listing of shorter candidates, surgical downsizing of substantially oversized allografts for shorter candidates, and/or changes to allocation policy that account for candidate height.
Asunto(s)
Estatura , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Disparidades en Atención de Salud/estadística & datos numéricos , Trasplante de Pulmón/estadística & datos numéricos , Listas de Espera , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Estados UnidosRESUMEN
RATIONALE: Frailty is associated with morbidity and mortality in abdominal organ transplantation but has not been examined in lung transplantation. OBJECTIVES: To examine the construct and predictive validity of frailty phenotypes in lung transplant candidates. METHODS: In a multicenter prospective cohort, we measured frailty with the Fried Frailty Phenotype (FFP) and Short Physical Performance Battery (SPPB). We evaluated construct validity through comparisons with conceptually related factors. In a nested case-control study of frail and nonfrail subjects, we measured serum IL-6, tumor necrosis factor receptor 1, insulin-like growth factor I, and leptin. We estimated the association between frailty and disability using the Lung Transplant Valued Life Activities disability scale. We estimated the association between frailty and risk of delisting or death before transplant using multivariate logistic and Cox models, respectively. MEASUREMENTS AND MAIN RESULTS: Of 395 subjects, 354 completed FFP assessments and 262 completed SPPB assessments; 28% were frail by FFP (95% confidence interval [CI], 24-33%) and 10% based on the SPPB (95% CI, 7-14%). By either measure, frailty correlated more strongly with exercise capacity and grip strength than with lung function. Frail subjects tended to have higher plasma IL-6 and tumor necrosis factor receptor 1 and lower insulin-like growth factor I and leptin. Frailty by either measure was associated with greater disability. After adjusting for age, sex, diagnosis, and transplant center, both FFP and SPPB were associated with increased risk of delisting or death before lung transplant. For every 1-point worsening in score, hazard ratios were 1.30 (95% CI, 1.01-1.67) for FFP and 1.53 (95% CI, 1.19-1.59) for SPPB. CONCLUSIONS: Frailty is prevalent among lung transplant candidates and is independently associated with greater disability and an increased risk of delisting or death.
Asunto(s)
Personas con Discapacidad/estadística & datos numéricos , Evaluación Geriátrica/métodos , Evaluación Geriátrica/estadística & datos numéricos , Trasplante de Pulmón , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Actividades Cotidianas , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Anciano Frágil , Humanos , Factor I del Crecimiento Similar a la Insulina , Interleucina-6/sangre , Leptina/sangre , Masculino , Persona de Mediana Edad , Fenotipo , Complicaciones Posoperatorias/sangre , Prevalencia , Estudios Prospectivos , Receptores del Factor de Necrosis Tumoral/sangre , Reproducibilidad de los Resultados , Estados Unidos/epidemiologíaRESUMEN
RATIONALE: Obesity and underweight are contraindications to lung transplantation based on their associations with mortality in studies performed before implementation of the lung allocation score (LAS)-based organ allocation system in the United States Objectives: To determine the associations of body mass index (BMI) and plasma leptin levels with survival after lung transplantation. METHODS: We used multivariable-adjusted regression models to examine associations between BMI and 1-year mortality in 9,073 adults who underwent lung transplantation in the United States between May 2005 and June 2011, and plasma leptin and mortality in 599 Lung Transplant Outcomes Group study participants. We measured body fat and skeletal muscle mass using whole-body dual X-ray absorptiometry in 142 adult lung transplant candidates. MEASUREMENTS AND MAIN RESULTS: Adjusted mortality rates were similar among normal weight (BMI 18.5-24.9 kg/m(2)), overweight (BMI 25.0-29.9), and class I obese (BMI 30-34.9) transplant recipients. Underweight (BMI < 18.5) was associated with a 35% increased rate of death (95% confidence interval, 10-66%). Class II-III obesity (BMI ≥ 35 kg/m(2)) was associated with a nearly twofold increase in mortality (hazard ratio, 1.9; 95% confidence interval, 1.3-2.8). Higher leptin levels were associated with increased mortality after transplant surgery performed without cardiopulmonary bypass (P for interaction = 0.03). A BMI greater than or equal to 30 kg/m(2) was 26% sensitive and 97% specific for total body fat-defined obesity. CONCLUSIONS: A BMI of 30.0-34.9 kg/m(2) is not associated with 1-year mortality after lung transplantation in the LAS era, perhaps because of its low sensitivity for obesity. The association between leptin and mortality suggests the need to validate alternative methods to measure obesity in candidates for lung transplantation. A BMI greater than or equal to 30 kg/m(2) may no longer contraindicate lung transplantation.
Asunto(s)
Composición Corporal , Índice de Masa Corporal , Trasplante de Pulmón/mortalidad , Estudios de Cohortes , Estudios Transversales , Femenino , Humanos , Leptina/sangre , Enfermedades Pulmonares/sangre , Enfermedades Pulmonares/complicaciones , Enfermedades Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Obesidad/sangre , Obesidad/complicaciones , Estudios Retrospectivos , Sarcopenia/sangre , Sarcopenia/complicaciones , Tasa de Supervivencia , Estados UnidosRESUMEN
Many patients with severe COVID-19 have been affected by acute respiratory distress syndrome, which has been associated with increased mortality, and up to 31% of these survivors had persistent interstitial lung abnormalities with impaired lung function and quality of life even after 6 to 24 months after initial disease. Lung transplantation quickly emerged as a viable therapy for select patients with respiratory failure due to COVID-19 by mid-2020. In this report, we identified 477 patients who underwent lung transplantation for COVID-19 in the U.S. between March 2020 and December 2022. The number of patients waitlisted and undergoing lung transplantation for COVID-19 increased steadily in the early part of the pandemic with a peak of 97 patients waitlisted between October and December 2021, before steadily decreasing since. Notably, the procedure is now increasingly being done for survivors of COVID-19 with pulmonary fibrosis, rather than for refractory ARDS patients. The 1-year post-transplant mortality was 13.7%.
Asunto(s)
COVID-19 , Trasplante de Pulmón , Síndrome de Dificultad Respiratoria , Insuficiencia Respiratoria , Humanos , COVID-19/complicaciones , Calidad de Vida , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/cirugíaRESUMEN
A third of patients with idiopathic pulmonary fibrosis (IPF) develop pulmonary hypertension (PH-IPF), which is associated with increased mortality. Whether an altered gene expression profile in the pulmonary vasculature precedes the clinical onset of PH-IPF is unknown. We compared gene expression in the pulmonary vasculature of IPF patients with and without PH with controls. Pulmonary arterioles were isolated using laser capture microdissection from 16 IPF patients: eight with PH (PH-IPF) and eight with no PH (NPH-IPF), and seven controls. Probe was prepared from extracted RNA, and hybridised to Affymetrix Hu133 2.0 Plus genechips. Biometric Research Branch array tools and Ingenuity Pathway Analysis software were used for analysis of the microarray data. Univariate analysis revealed 255 genes that distinguished IPF arterioles from controls (p<0.001). Mediators of vascular smooth muscle and endothelial cell proliferation, Wnt signalling and apoptosis were differentially expressed in IPF arterioles. Unsupervised and supervised clustering analyses revealed similar gene expression in PH-IPF and NPH-IPF arterioles. The pulmonary arteriolar gene expression profile is similar in IPF patients with and without coexistent PH. Pathways involved in vascular proliferation and aberrant apoptosis, which may contribute to pulmonary vascular remodelling, are activated in IPF patients.
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Arteriolas/metabolismo , Perfilación de la Expresión Génica , Hipertensión Pulmonar/metabolismo , Fibrosis Pulmonar Idiopática/metabolismo , Pulmón/metabolismo , Adulto , Anciano , Estudios de Casos y Controles , Proliferación Celular , Análisis por Conglomerados , Femenino , Regulación de la Expresión Génica , Humanos , Inmunohistoquímica , Captura por Microdisección con Láser , Pulmón/patología , Enfermedades Pulmonares Intersticiales/metabolismo , Masculino , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , TranscriptomaRESUMEN
According to the Scientific Registry of Transplant Recipients, both transplant volume and survival among lung transplant recipients are improving over time. However, the outcomes of lung transplantation remain challenged by multiple thoracic and extrathoracic complications. With improving lung transplant survival, patients experience prolonged exposure to chronic immunosuppressive agents that can lead to multiple infectious and noninfectious complications. This article focuses on most common noninfectious complications with significant clinical impact.
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Trasplante de Corazón , Trasplante de Pulmón , Humanos , Trasplante de Corazón/efectos adversos , Trasplante de Pulmón/efectos adversos , Inmunosupresores , Factores de Tiempo , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/terapiaRESUMEN
BACKGROUND: Existing measures of frailty developed in community dwelling older adults may misclassify frailty in lung transplant candidates. We aimed to develop a novel frailty scale for lung transplantation with improved performance characteristics. METHODS: We measured the short physical performance battery (SPPB), fried frailty phenotype (FFP), Body Composition, and serum Biomarkers representative of putative frailty mechanisms. We applied a 4-step established approach (identify frailty domain variable bivariate associations with the outcome of waitlist delisting or death; build models sequentially incorporating variables from each frailty domain cluster; retain variables that improved model performance ability by c-statistic or AIC) to develop 3 candidate "Lung Transplant Frailty Scale (LT-FS)" measures: 1 incorporating readily available clinical data; 1 adding muscle mass, and 1 adding muscle mass and research-grade Biomarkers. We compared construct and predictive validity of LT-FS models to the SPPB and FFP by ANOVA, ANCOVA, and Cox proportional-hazard modeling. RESULTS: In 342 lung transplant candidates, LT-FS models exhibited superior construct and predictive validity compared to the SPPB and FFP. The addition of muscle mass and Biomarkers improved model performance. Frailty by all measures was associated with waitlist disability, poorer HRQL, and waitlist delisting/death. LT-FS models exhibited stronger associations with waitlist delisting/death than SPPB or FFP (C-statistic range: 0.73-0.78 vs. 0.57 and 0.55 for SPPB and FFP, respectively). Compared to SPPB and FFP, LT-FS models were generally more strongly associated with delisting/death and improved delisting/death net reclassification, with greater improvements with increasing LT-FS model complexity (range: 0.11-0.34). For example, LT-FS-Body Composition hazard ratio for delisting/death: 6.0 (95%CI: 2.5, 14.2), SPPB HR: 2.5 (95%CI: 1.1, 5.8), FFP HR: 4.3 (95%CI: 1.8, 10.1). Pre-transplant LT-FS frailty, but not SPPB or FFP, was associated with mortality after transplant. CONCLUSIONS: The LT-FS is a disease-specific physical frailty measure with face and construct validity that has superior predictive validity over established measures.
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Fragilidad , Trasplante de Pulmón , Humanos , Fragilidad/diagnóstico , Estudios Prospectivos , Biomarcadores , FenotipoRESUMEN
RATIONALE: Idiopathic pulmonary fibrosis is often initially misdiagnosed. Delays in accessing subspecialty care could lead to worse outcomes among those with idiopathic pulmonary fibrosis. OBJECTIVES: To examine the association between delayed access to subspecialty care and survival time in idiopathic pulmonary fibrosis. METHODS: We performed a prospective cohort study of 129 adults who met American Thoracic Society criteria for idiopathic pulmonary fibrosis evaluated at a tertiary care center. Delay was defined as the time from the onset of dyspnea to the date of initial evaluation at a tertiary care center. We used competing risk survival methods to examine survival time and time to transplantation. MEASUREMENTS AND MAIN RESULTS: The mean age was 63 years and 76% were men. The median delay was 2.2 years (interquartile range 1.03.8 yr), and the median follow-up time was 1.1 years. Age and lung function at the time of evaluation did not vary by delay. A longer delay was associated with an increased risk of death independent of age, sex, forced vital capacity, third-party payer, and educational attainment (adjusted hazard ratio per doubling of delay was 1.3, 95% confidence interval 1.03 to 1.6). Longer delay was not associated with a lower likelihood of undergoing lung transplantation. CONCLUSIONS: Delayed access to a tertiary care center is associated with a higher mortality rate in idiopathic pulmonary fibrosis independent of disease severity. Early referral to a specialty center should be considered for those with known or suspected interstitial lung disease.
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Diagnóstico Tardío/mortalidad , Accesibilidad a los Servicios de Salud , Disparidades en Atención de Salud , Fibrosis Pulmonar Idiopática/mortalidad , Adulto , Anciano , Femenino , Humanos , Fibrosis Pulmonar Idiopática/diagnóstico , Masculino , Persona de Mediana Edad , Ciudad de Nueva York/epidemiología , Estudios Prospectivos , Derivación y Consulta , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
RATIONALE: Lung transplantation has evolved into a life-saving therapy for select patients with end-stage lung diseases. However, long-term survival remains limited because of chronic rejection. Sirolimus is beneficial in preventing cardiac rejection and may decrease rejection after lung transplantation. OBJECTIVES: To determine the potential benefit versus risk of sirolimus in lung transplantation. METHODS: We conducted a multicenter randomized, open label controlled trial comparing sirolimus (SIR) with azathioprine (AZA) in a tacrolimus-based immunosuppressive regimen in lung transplantation. The primary end point was the incidence of acute rejection at 1 year after transplantation between the two study groups. MEASUREMENTS AND MAIN RESULTS: One hundred eighty-one patients were randomized to be included in this study. At 1 year after transplantation, there was no significant difference in the incidence of grade A acute rejection between the two study groups. Similarly, the incidence of chronic rejection and graft survival was no different between the two study groups. Cytomegalovirus infection was decreased in the SIR arm compared with the AZA arm (relative risk, 0.67 [95% confidence interval, 0.55, 0.82]; P < 0.01). There was a higher rate of adverse events leading to early discontinuation of SIR (64%) compared with AZA (49%) during the course of this study. CONCLUSIONS: Sirolimus, an mTOR inhibitor, did not decrease the incidence of acute rejection at 1 year compared with azathioprine in lung transplantation. These results differ from previous results in cardiac and renal transplantation and emphasize the need for multicenter randomized controlled trials in lung transplantation. Clinical trial registered with www.clinicaltrials.gov (NCT 00321906).
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Azatioprina/uso terapéutico , Inmunosupresores/uso terapéutico , Trasplante de Pulmón , Sirolimus/uso terapéutico , Tacrolimus/uso terapéutico , Azatioprina/efectos adversos , Bronquiolitis Obliterante/etiología , Quimioterapia Combinada , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/prevención & control , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Sirolimus/efectos adversos , Factores de TiempoRESUMEN
RATIONALE: Obesity has been linked to acute lung injury and is a risk factor for early mortality after lung transplantation. OBJECTIVES: To examine the associations of obesity and plasma adipokines with the risk of primary graft dysfunction after lung transplantation. METHODS: We performed a prospective cohort study of 512 adult lung transplant recipients with chronic obstructive pulmonary disease or interstitial lung disease enrolled in the Lung Transplant Outcomes Group Study. In a nested case-control study, we measured plasma leptin, adiponectin, and resistin before lung transplantation and 6 and 24 hours after lung transplantation in 40 cases of primary graft dysfunction and 80 control subjects. Generalized linear mixed models and logistic regression were used to estimate risk ratios and odds ratios. MEASUREMENTS AND MAIN RESULTS: Grade 3 primary graft dysfunction developed within 72 hours of transplantation in 29% participants. Obesity was associated with a twofold increased risk of primary graft dysfunction (adjusted risk ratio 2.1; 95% confidence interval, 1.7-2.6). The risk of primary graft dysfunction increased by 40% (confidence interval, 3050%) for each 5 kg/m(2) increase in body mass index after accounting for center, diagnosis, cardiopulmonary bypass, and transplant procedure. Higher plasma leptin levels were associated with a greater risk of primary graft dysfunction (sex-adjusted P = 0.02). The associations of both obesity and leptin with primary graft dysfunction tended to be stronger among those who did not undergo cardiopulmonary bypass. CONCLUSIONS: Obesity is an independent risk factor for primary graft dysfunction after lung transplantation.
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Enfermedades Pulmonares Intersticiales/cirugía , Trasplante de Pulmón/efectos adversos , Obesidad/sangre , Obesidad/complicaciones , Disfunción Primaria del Injerto/sangre , Disfunción Primaria del Injerto/etiología , Enfermedad Pulmonar Obstructiva Crónica/cirugía , Adiponectina/sangre , Anciano , Biomarcadores/sangre , Índice de Masa Corporal , Estudios de Casos y Controles , Femenino , Humanos , Leptina/sangre , Modelos Lineales , Modelos Logísticos , Enfermedades Pulmonares Intersticiales/complicaciones , Trasplante de Pulmón/mortalidad , Masculino , Persona de Mediana Edad , Obesidad/mortalidad , Oportunidad Relativa , Sobrepeso/sangre , Sobrepeso/complicaciones , Disfunción Primaria del Injerto/mortalidad , Estudios Prospectivos , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Resistina/sangre , Factores de Riesgo , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Factores de Tiempo , Estados UnidosRESUMEN
Long-term exposure to immunosuppressive therapy may exacerbate pre-existing medical comorbidities or result in the development of new chronic medical conditions after lung transplantation. This article focuses on common nonallograft complications with the highest impact on short- and long-term outcomes after transplantation. These include diabetes mellitus, hypertension, dyslipidemia, kidney disease (acute and chronic), and malignancy. We discuss evidence-based strategies for the prevention, diagnosis, and management of these nonallograft complications in this article.
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Inmunosupresores , Trasplante de Pulmón , Humanos , Terapia de Inmunosupresión , Trasplante de Pulmón/efectos adversos , Complicaciones PosoperatoriasRESUMEN
Lung nodules or masses due to a variety of malignant or benign conditions such as opportunistic infections are observed after lung transplant. Malakoplakia is a rare complication in immunocompromised patients. Here we describe the clinical course and management of a lung transplant recipient with pulmonary malakoplakia and provide a review of the literature. To our knowledge, this is the first report of a case of pulmonary malakoplakia due to Escherichia coli infection in a lung allograft.
Asunto(s)
Infecciones por Escherichia coli , Trasplante de Pulmón , Malacoplasia , Humanos , Pulmón/diagnóstico por imagen , Trasplante de Pulmón/efectos adversos , Malacoplasia/diagnóstico , Malacoplasia/etiología , Receptores de TrasplantesRESUMEN
BACKGROUND: The primary lung allocation unit was expanded from the donation service area to a 250-mile radius in 2017. Prior to the change, geographic disparities in donor lung availability impacted waitlist outcomes. We sought to determine if the new allocation system improved these disparities. METHODS: We conducted a retrospective cohort study comparing the 2-year period before and after the change. Donor lung availability was defined as the ratio of donor lungs to waitlist candidates in the primary allocation unit. Transplant centers were divided into quartiles by donor lung availability. Multivariable competing risk models were used to determine the association between lung availability and waitlist outcomes. Multivariable Cox proportional hazards models compared post-transplant survival. RESULTS: Prior to the allocation change, the unadjusted transplant rate at centers in the lowest and highest quartiles was 132 and 607 transplants per 100 waitlist years. Candidates in the lowest quartile of donor lung availability had a 61% adjusted lower transplantation rate compared to candidates in highest quartile (sub-hazard ratio [sHR]: 0.39, 95% confidence interval [CI]: 0.34-0.44). After the allocation change, the disparity decreased resulting in an unadjusted transplant rate of 141 and 309 among centers in the lowest and highest quartiles. Candidates in the lowest quartile had a 38% adjusted lower transplantation rate compared to those in the highest (sHR: 0.62, 95% CI: 0.57-0.68). There was no significant difference in 1-year post-transplant survival. CONCLUSIONS: Although the expansion of the primary allocation unit improved disparities in waitlist outcomes without any change in post-transplant survival, there still remain significant differences due to geography.