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Rationale: Primary graft dysfunction (PGD) is the leading cause of early morbidity and mortality after lung transplantation. Prior studies implicated proxy-defined donor smoking as a risk factor for PGD and mortality. Objectives: We aimed to more accurately assess the impact of donor smoke exposure on PGD and mortality using quantitative smoke exposure biomarkers. Methods: We performed a multicenter prospective cohort study of lung transplant recipients enrolled in the Lung Transplant Outcomes Group cohort between 2012 and 2018. PGD was defined as grade 3 at 48 or 72 hours after lung reperfusion. Donor smoking was defined using accepted thresholds of urinary biomarkers of nicotine exposure (cotinine) and tobacco-specific nitrosamine (4-[methylnitrosamino]-1-[3-pyridyl]-1-butanol [NNAL]) in addition to clinical history. The donor smoking-PGD association was assessed using logistic regression, and survival analysis was performed using inverse probability of exposure weighting according to smoking category. Measurements and Main Results: Active donor smoking prevalence varied by definition, with 34-43% based on urinary cotinine, 28% by urinary NNAL, and 37% by clinical documentation. The standardized risk of PGD associated with active donor smoking was higher across all definitions, with an absolute risk increase of 11.5% (95% confidence interval [CI], 3.8% to 19.2%) by urinary cotinine, 5.7% (95% CI, -3.4% to 14.9%) by urinary NNAL, and 6.5% (95% CI, -2.8% to 15.8%) defined clinically. Donor smoking was not associated with differential post-lung transplant survival using any definition. Conclusions: Donor smoking associates with a modest increase in PGD risk but not with increased recipient mortality. Use of lungs from smokers is likely safe and may increase lung donor availability. Clinical trial registered with www.clinicaltrials.gov (NCT00552357).
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Trasplante de Pulmón , Disfunción Primaria del Injerto , Fumar , Donantes de Tejidos , Humanos , Biomarcadores , Cotinina , Trasplante de Pulmón/efectos adversos , Disfunción Primaria del Injerto/epidemiología , Estudios Prospectivos , Fumar/efectos adversosRESUMEN
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
BACKGROUND: Gastroparesis is common after lung transplantation and is associated with worse transplant outcomes, including the development of chronic lung allograft dysfunction (CLAD). This study sought to identify the prevalence, risk factors, and outcomes associated with a new diagnosis of gastroparesis after lung transplantation. METHODS: This was a single-center retrospective study of patients who underwent lung transplantation in 2008-2018. The primary outcome was a new diagnosis of gastroparesis within 3 years of transplant. Secondary outcomes included a new diagnosis of gastroesophageal reflux and the association between gastroparesis and both post-transplant survival and CLAD-free survival. Multivariable logistic regression was used to compare diagnosis of gastroparesis and gastroesophageal reflux, while multivariable Cox proportional hazards models were used to analyze gastroparesis and post-transplant outcomes. RESULTS: Of 616 patients with no prior history of gastroparesis, 107 (17.4%) were diagnosed with delayed gastric emptying within 3 years of transplant. On multivariable logistic regression, black race (OR 2.16, 95% CI 1.18-3.98, p = 0.013) was significantly associated with a new diagnosis of gastroparesis. Age, sex, history of diabetes, connective tissue disease, type of transplant, diagnosis group, renal function, and body mass index were not predictive of gastroparesis post-transplant. Gastroparesis was significantly associated with CLAD (HR 1.76, 95% CI 1.20-2.59, p = 0.004), but not with overall mortality (HR 1.16, p = 0.43). CONCLUSION: While gastroparesis is common after lung transplantation, it remains difficult to predict which patients will develop these complications post-transplant. Black patients were more likely to be diagnosed with gastroparesis after adjusting for relevant confounders. Gastroparesis is associated with increased risk of CLAD, and further studies are needed to assess whether early detection and treatment can reduce the incidence of CLAD.
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Reflujo Gastroesofágico , Gastroparesia , Trasplante de Pulmón , Reflujo Gastroesofágico/diagnóstico , Reflujo Gastroesofágico/epidemiología , Reflujo Gastroesofágico/etiología , Gastroparesia/diagnóstico , Gastroparesia/epidemiología , Gastroparesia/etiología , Humanos , Trasplante de Pulmón/efectos adversos , Estudios Retrospectivos , Factores de RiesgoRESUMEN
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.
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There are limited data describing COVID-19 in lung transplant recipients. We performed a single center, retrospective case series study of lung transplant patients followed by the Columbia Lung Transplant program who tested positive for SARS-CoV-2 between March 19 and May 19, 2020. Thirty-two lung transplant patients developed mild (16%), moderate (44%), or severe (41%) COVID-19. The median age of patients was 65 years, and the median time from lung transplant was 5.6 years. Symptoms included cough (66%), dyspnea (50%), fever (47%), and gastrointestinal upset (44%). Patients received hydroxychloroquine (84%), azithromycin (75%), augmented steroids (44%), tocilizumab (19%), and remdesivir (9%). Eleven patients (34%) died at a median time of 14 days from admission. Complications during admission included: acute kidney injury (63%), transaminitis (31%), shock (31%), acute respiratory distress syndrome (25%), neurological events (25%), arrhythmias (22%), and venous thromboembolism (9%). Compared to patients with moderate COVID-19, patients with severe COVID-19 had higher peak white blood cell counts (15.8 vs 7 × 103 /uL, P = .019), C-reactive protein (198 vs. 107 mg/L, P = .010) and D-dimer (8.6 vs. 2.1 ug/mL, P = .004) levels, and lower nadir lymphocyte counts (0.09 vs. 0.4 × 103 /uL, P = .006). COVID-19 is associated with severe illness and a high mortality rate in lung transplant recipients.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , COVID-19/epidemiología , Rechazo de Injerto/prevención & control , Trasplante de Pulmón , Pandemias , SARS-CoV-2 , Receptores de Trasplantes , Adulto , Anciano , Antivirales/uso terapéutico , Femenino , Rechazo de Injerto/epidemiología , Humanos , Terapia de Inmunosupresión/métodos , Incidencia , Masculino , Persona de Mediana Edad , Ciudad de Nueva York/epidemiología , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Tratamiento Farmacológico de COVID-19RESUMEN
Solid organ transplant recipients may be at a high risk for SARS-CoV-2 infection and poor associated outcomes. We herein report our initial experience with solid organ transplant recipients with SARS-CoV-2 infection at two centers during the first 3 weeks of the outbreak in New York City. Baseline characteristics, clinical presentation, antiviral and immunosuppressive management were compared between patients with mild/moderate and severe disease (defined as ICU admission, intubation or death). Ninety patients were analyzed with a median age of 57 years. Forty-six were kidney recipients, 17 lung, 13 liver, 9 heart, and 5 dual-organ transplants. The most common presenting symptoms were fever (70%), cough (59%), and dyspnea (43%). Twenty-two (24%) had mild, 41 (46%) moderate, and 27 (30%) severe disease. Among the 68 hospitalized patients, 12% required non-rebreather and 35% required intubation. 91% received hydroxychloroquine, 66% azithromycin, 3% remdesivir, 21% tocilizumab, and 24% bolus steroids. Sixteen patients died (18% overall, 24% of hospitalized, 52% of ICU) and 37 (54%) were discharged. In this initial cohort, transplant recipients with COVID-19 appear to have more severe outcomes, although testing limitations likely led to undercounting of mild/asymptomatic cases. As this outbreak unfolds, COVID-19 has the potential to severely impact solid organ transplant recipients.
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Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/epidemiología , Trasplante de Órganos/efectos adversos , Neumonía Viral/complicaciones , Neumonía Viral/epidemiología , Receptores de Trasplantes , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Adulto , Anciano , Alanina/análogos & derivados , Alanina/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antivirales/uso terapéutico , Azitromicina/uso terapéutico , Betacoronavirus , COVID-19 , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/mortalidad , Cuidados Críticos , Femenino , Hospitalización , Humanos , Hidroxicloroquina/uso terapéutico , Terapia de Inmunosupresión , Inmunosupresores/uso terapéutico , Unidades de Cuidados Intensivos , Intubación , Masculino , Persona de Mediana Edad , Ciudad de Nueva York/epidemiología , Pandemias , Neumonía Viral/mortalidad , Respiración Artificial , SARS-CoV-2 , Esteroides/uso terapéutico , Resultado del Tratamiento , Estados Unidos , Tratamiento Farmacológico de COVID-19RESUMEN
CT measurement of body composition may improve lung transplant candidate selection. We assessed whether skeletal muscle adipose deposition on abdominal and thigh CT scans was associated with 6 min walk distance (6MWD) and wait-list survival in lung transplant candidates. Each ½-SD decrease in abdominal muscle attenuation (indicating greater lipid content) was associated with 14 m decrease in 6MWD (95% CI -20 to -8) and 20% increased risk of death or delisting (95% CI 10% to 40%). Each ½-standard deviation decrease in thigh muscle attenuation was associated with 15 m decrease in 6MWD (95% CI -21 to -10). CT imaging may improve candidate risk stratification.
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Adiposidad , Enfermedades Pulmonares/cirugía , Trasplante de Pulmón , Músculo Esquelético/diagnóstico por imagen , Pared Abdominal/diagnóstico por imagen , Anciano , Estudios de Cohortes , Femenino , Humanos , Enfermedades Pulmonares/mortalidad , Enfermedades Pulmonares/fisiopatología , Masculino , Persona de Mediana Edad , Músculo Esquelético/fisiopatología , Medición de Riesgo , Tasa de Supervivencia , Muslo/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Listas de Espera/mortalidad , Prueba de PasoRESUMEN
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.
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Geografía , Trasplante de Pulmón , Donantes de Tejidos , Listas de Espera , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
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%.
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COVID-19 , Trasplante de Pulmón , Síndrome de Dificultad Respiratoria , Insuficiencia Respiratoria , Humanos , COVID-19/complicaciones , Calidad de Vida , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/cirugíaRESUMEN
Obesity at the time of lung transplant is associated with decreased survival. How providers manage obesity after lung transplantation is unknown. We performed an international survey of lung transplant providers to assess beliefs and practices regarding post-transplant obesity management. Eighty-one providers initiated the survey and 73 (90%) completed the full survey. Respondents were primarily North American-based pulmonary physicians. Nearly all providers believe treating obesity improves quality of life (99%) and survival (95%) after lung transplantation, but that only 41% of patients attempting weight loss are successful. While respondents nearly always recommend diet (96%), exercise (92%), and dietician consultation (89%), they less frequently recommend prescription weight loss medications (29%) or bariatric surgery (11%). Lung transplant providers are motivated to treat obesity in transplant recipients. However, there is a gap between general obesity treatment guidelines and lung transplant practice. Additional training, education, and trials in this population could address this gap.
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BACKGROUND: Primary graft dysfunction (PGD) is the leading cause of early morbidity and mortality after lung transplantation. Accurate prediction of PGD risk could inform donor approaches and perioperative care planning. We sought to develop a clinically useful, generalizable PGD prediction model to aid in transplant decision-making. METHODS: We derived a predictive model in a prospective cohort study of subjects from 2012 to 2018, followed by a single-center external validation. We used regularized (lasso) logistic regression to evaluate the predictive ability of clinically available PGD predictors and developed a user interface for clinical application. Using decision curve analysis, we quantified the net benefit of the model across a range of PGD risk thresholds and assessed model calibration and discrimination. RESULTS: The PGD predictive model included distance from donor hospital to recipient transplant center, recipient age, predicted total lung capacity, lung allocation score (LAS), body mass index, pulmonary artery mean pressure, sex, and indication for transplant; donor age, sex, mechanism of death, and donor smoking status; and interaction terms for LAS and donor distance. The interface allows for real-time assessment of PGD risk for any donor/recipient combination. The model offers decision-making net benefit in the PGD risk range of 10% to 75% in the derivation centers and 2% to 10% in the validation cohort, a range incorporating the incidence in that cohort. CONCLUSION: We developed a clinically useful PGD predictive algorithm across a range of PGD risk thresholds to support transplant decision-making, posttransplant care, and enrich samples for PGD treatment trials.
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Trasplante de Pulmón , Disfunción Primaria del Injerto , Humanos , Factores de Riesgo , Medición de Riesgo , Disfunción Primaria del Injerto/diagnóstico , Disfunción Primaria del Injerto/epidemiología , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
BACKGROUND: Blood group O candidates have lower lung transplantation rates despite having the most common blood group. We postulated that waitlist outcomes among these candidates and those with other blood types vary with disease severity and lung allocation score (LAS). METHODS: We performed a retrospective cohort study of 32,772 waitlist candidates using the United Network of Organ Sharing registry from May 2005 to 2020. After identifying an interaction between blood group and LAS, we evaluated the association between blood group and waitlist outcomes within LAS quartiles using unadjusted and adjusted competing risk models. RESULTS: In the lowest LAS quartile, blood group O had a 20% reduced transplantation rate (SHR: 0.80, 95%CI: 0.75-0.85) and higher waitlist death/removal (1.33, 95%CI: 1.15-1.55) compared with group A. Blood group AB had a 52% higher transplantation rate (SHR: 1.52, 95%CI: 1.34-1.73) in the lowest LAS quartile compared with group A. In the highest LAS quartile, there was no difference in transplantation rates between groups O and A. In contrast, group B had a 19% reduced transplantation rate (SHR, 0.81 95%CI: 0.73-0.89) and AB had a 28% reduced transplantation rate (SHR: 0.72, 95%CI: 0.61-0.86) in the highest LAS quartile. Additionally, groups B and AB had increased risk of waitlist death/removal in the highest LAS quartile compared with A (SHR: 1.27, 95%CI: 1.08-1.48; SHR: 1.31, 95%CI: 1.00-1.72). CONCLUSIONS: Waitlist outcomes among ABO blood groups vary depending on illness severity, which is represented by LAS. Blood group O has lower transplantation rates at low LAS while groups B and AB have lower transplantation rates at high LAS.
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Sistema del Grupo Sanguíneo ABO , Enfermedades Pulmonares , Trasplante de Pulmón , Gravedad del Paciente , Obtención de Tejidos y Órganos , Listas de Espera , Humanos , Pulmón , Trasplante de Pulmón/estadística & datos numéricos , Estudios Retrospectivos , Obtención de Tejidos y Órganos/estadística & datos numéricos , Sistema de Registros/estadística & datos numéricos , Estados Unidos/epidemiología , Enfermedades Pulmonares/epidemiología , Enfermedades Pulmonares/cirugíaRESUMEN
BACKGROUND: Pulmonary function tests (PFT) are a frequent component of heart transplant evaluation. In cardiac surgery abnormal PFTs, especially reduced DLCO, have been associated with poor outcomes. We sought to evaluate the impact of pretransplant PFTs on post-transplant pulmonary outcomes and patient survival. METHODS: Among the 652 adult heart transplant recipients between January 1, 2010 and July 31, 2021, 462 had PFTs and constituted the patient cohort. Obstructive ventilatory defects (OVD), restrictive ventilatory defects (RVD), and reduced DLCO were defined according to established criteria. The primary outcome was the combined endpoint of a post-transplant pulmonary complication defined as reintubation, postoperative pneumonia, prolonged intubation, or tracheostomy. Secondary outcomes included 90-day all-cause mortality, length of stay, and the odds of individual pulmonary complications. Kaplan-Meier survival analysis, multivariable Cox proportional-hazards regression, and multivariable logistic regression were performed to compare outcomes between the groups. RESULTS: Patients with severe OVD (OR 1.48, 95% CI 1.18-5.23, p = 0.02) or severely reduced DLCO (OR 1.95, 95% CI 1.19-3.20, p = 0.008) had increased odds of post-transplant pulmonary complications. Following multivariable adjustment, severe OVD (aOR 2.67, 95% CI 1.15-6.19, p = 0.02) and severely reduced DLCO (aOR 1.79, 95% CI 1.05-3.04) remained strongly associated with post-transplant pulmonary complications. Patients with any degree of extrinsic RVD, moderate or less OVD, or moderately reduced DLCO or less did not have increased odds of post-transplant pulmonary complications. Ninety-day post-transplant survival was significantly reduced for both severe OVD (97.2% vs 86.5%, p = 0.04) and severely reduced DLCO (97.3% vs 90.4%, p = 0.004). Post-transplant ICU and hospital length of stay were nominally longer for both groups as well. CONCLUSIONS: Severe OVD or severely reduced DLCO on preheart transplant PFTs were associated with increased odds of post-transplant pulmonary complications and early mortality.
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Neumonía , Insuficiencia Respiratoria , Adulto , Humanos , Pulmón , Espirometría , Pruebas de Función Respiratoria , Estudios RetrospectivosRESUMEN
Rationale: Low and high body mass index (BMI) are associated with increased mortality after lung transplantation. Why extremes of BMI might increase risk of death is unknown. Objectives: To estimate the association of extremes of BMI with causes of death after transplantation. Methods: We performed a retrospective study of the United Network for Organ Sharing database, including 26,721 adults who underwent lung transplantation in the United States between May 4, 2005, and December 2, 2020. We mapped 76 reported causes of death into 16 distinct groups. We estimated cause-specific hazards for death from each cause using Cox models. Results: Relative to a subject with a BMI of 24 kg/m2, a subject with a BMI of 16 kg/m2 had 38% (hazard ratio [HR], 1.38; 95% confidence interval [95% CI], 0.99-1.90), 82% (HR, 1.82; 95% CI, 1.34-2.46), and 62% (HR, 1.62; 95% CI, 1.18-2.22) increased hazards of death from acute respiratory failure, chronic lung allograft dysfunction (CLAD), and infection, respectively, and a subject with a BMI of 36 kg/m2 had 44% (HR, 1.44; 95% CI, 0.97-2.12), 42% (HR, 1.42; 95% CI, 0.93-2.15), and 185% (HR, 2.85; 95% CI, 1.28-6.33) increased hazards of death from acute respiratory failure, CLAD, and primary graft dysfunction, respectively. Conclusions: Low BMI is associated with increased risk of death from infection, acute respiratory failure, and CLAD after lung transplantation, whereas high BMI is associated with increased risk of death from primary graft dysfunction, acute respiratory failure, and CLAD.
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Trasplante de Pulmón , Disfunción Primaria del Injerto , Insuficiencia Respiratoria , Adulto , Humanos , Estados Unidos/epidemiología , Causas de Muerte , Índice de Masa Corporal , Estudios Retrospectivos , Factores de Riesgo , Disfunción Primaria del Injerto/etiología , Trasplante de Pulmón/efectos adversos , Modelos de Riesgos Proporcionales , Insuficiencia Respiratoria/etiologíaRESUMEN
BACKGROUND: Most idiopathic pulmonary fibrosis (IPF) lung transplant recipients (IPF-LTRs) have short telomere (ST) length. Inherited mutations in telomere-related genes are associated with the development of T cell immunodeficiency. Despite this, IPF-LTRs with telomere-related rare variants are not protected from acute cellular rejection (ACR). We set out to determine the impact of both age and telomere length on the circulating T cell compartment and ACR burden of IPF-LTRs. METHODS: We identified 106 IPF-LTRs who had telomere length testing using flowFISH (57 with short telomeres and 49 with long telomeres) as well as a subset from both cohorts who had cryopreserved PBMC at least 1 time point, 6 months posttransplantation. Circulating T cells from before transplantation and at 6 and 12 months posttransplantation were analyzed using multiparameter flow cytometry to study phenotype and functional capacity, and bulk T cell receptor sequencing was performed to study repertoire diversity. Linear regression was used to study the relationship of age and telomere length on early (within 1 year) and late (between 1 and 2 years) ACR. RESULTS: IPF-LTRs with ST were found to have premature "aging" of their circulating T cell compartment, with age-agnostic elevations in posttransplant terminal differentiation of CD8+ T cells, increased granzyme B positivity of both CD8+ and CD4+ T cells, upregulation of the exhaustion marker, CD57, and chemotactic protein CCR5, and enhanced T cell receptor clonal expansion. Additionally, we found a significant decline in early ACR burden with increasing age, but only in the ST cohort. CONCLUSIONS: IPF-LTRs with ST have premature "aging" of their circulating T cell compartment posttransplantation and a clear age-related decline in ACR burden.
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Fibrosis Pulmonar Idiopática , Trasplante de Pulmón , Humanos , Lactante , Leucocitos Mononucleares , Linfocitos T CD8-positivos , Fibrosis Pulmonar Idiopática/genética , Fibrosis Pulmonar Idiopática/cirugía , Telómero , Receptores de Antígenos de Linfocitos T/genéticaRESUMEN
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
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.
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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: Despite therapeutic advances, people with cystic fibrosis (CF) develop progressive worsening and exacerbations of their lung disease, which can lead to acute respiratory failure. Historically, survival after mechanical ventilation (MV) has been poor. Outcomes related to use of extracorporeal membrane oxygenation (ECMO) have not been well described in CF. METHODS: We conducted a retrospective analysis of adult patients with CF admitted to the ICU for acute respiratory failure and requiring invasive MV with or without ECMO between July 1, 2006 and June 30, 2016. Separate analysis for the subgroup of MV patients who were eligible for transplant was conducted. RESULTS: Mortality for all patients with respiratory failure requiring advanced support was 37%. Ten of 28 (36%) MV patients, 10 of 26 (38%) ECMO+MV patients and 7 of the 21 (33%) transplant eligible MV patients died. Intensive care unit (ICU) length of stay (LOS) was 24.5±16.6 days for ECMO+MV; 12.9±9.0 days for MV (p=0.001), and 12.3 ±10 days for transplant eligible MV patients (p=0.005 for ECMO+MV comparison). Seven transplant eligible MV patients (33%) and 16 ECMO+MV patients (62%) underwent lung transplantation (p<0.001) during the hospital admission. One and 2-year survival for individuals who survived ICU admission was similar regardless of mode of support. Cox-proportional hazards model did not yield any variables that significantly influenced ICU mortality, 1-year or 2-year mortality. CONCLUSION: Survival for CF patients with acute respiratory failure requiring MV with or without ECMO has improved over time. ECMO may be an appropriate modality for respiratory support in patients with CF and acute respiratory failure who have greater risk of death from MV alone.
Asunto(s)
Fibrosis Quística , Oxigenación por Membrana Extracorpórea , Síndrome de Dificultad Respiratoria , Insuficiencia Respiratoria , Adulto , Fibrosis Quística/complicaciones , Fibrosis Quística/terapia , Oxigenación por Membrana Extracorpórea/efectos adversos , Humanos , Respiración Artificial , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/terapia , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Disparidades en Atención de Salud/estadística & datos numéricos , Trasplante de Pulmón/estadística & datos numéricos , Obtención de Tejidos y Órganos/provisión & distribución , Obtención de Tejidos y Órganos/normas , Anciano , Estudios de Cohortes , Femenino , Geografía , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Estados UnidosRESUMEN
BACKGROUND: There are 2 main aims of lung transplantation for people with end-stage lung disease: (1) to extend life and (2) to improve its quality. Much consideration is given to how to support the longevity and functioning of the allograft, though less robust studies have been done on the quality of the recipients' lives. With an interest in providing compassionate and holistic patient-centered care, it is vital that the treatment providers accurately understand their patients' lived experience. This study aimed to describe the health-related quality of life experiences of lung transplant recipients. An interest was held for where patients may struggle, thus informing where support might be needed to achieve the best possible outcomes. METHODS: This single-center study used a validated Lung Transplant Quality of Life questionnaire, which was sent in autumn of 2020 to all of the lung transplant recipients (n = 581) under the care of Columbia University Irving Medical Center (New York, NY). RESULTS: "Anxiety/Depression" had the highest concentration of struggle responses, followed closely by "Pulmonary Symptoms" and "Neuromuscular Symptoms." "Neuromuscular Problems" and "Sexual Problems" had the highest percentage of struggle responses. As the struggles increased, the overall quality of life rating dropped proportionately. There was no correlation between the overall quality of life and graft dysfunction, age, or time out from transplant date. All of the domains held an average rating of "Satisfactory," except "Treatment Burden," which was rated as "Favorable." Those ratings dropped for the cohort of patients who died during the study period. CONCLUSIONS: With the goal of providing comprehensive care at the forefront of transplant priorities, we found the newly developed questionnaire invaluable in targeting areas for quality improvements, mostly notably respecting recipient mental health.