RESUMO
Background: Many children undergo allogeneic hematopoietic stem cell transplantation (HSCT) for the treatment of malignant and nonmalignant conditions. Unfortunately, pulmonary complications occur frequently post-HSCT, with bronchiolitis obliterans syndrome (BOS) being the most common noninfectious pulmonary complication. Current international guidelines contain conflicting recommendations regarding post-HSCT surveillance for BOS, and a recent NIH workshop highlighted the need for a standardized approach to post-HSCT monitoring. As such, this guideline provides an evidence-based approach to detection of post-HSCT BOS in children. Methods: A multinational, multidisciplinary panel of experts identified six questions regarding surveillance for, and evaluation of, post-HSCT BOS in children. A systematic review of the literature was undertaken to answer each question. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to rate the quality of evidence and the strength of recommendations. Results: The panel members considered the strength of each recommendation and evaluated the benefits and risks of applying the intervention. In formulating the recommendations, the panel considered patient and caregiver values, the cost of care, and feasibility. Recommendations addressing the role of screening pulmonary function testing and diagnostic tests in children with suspected post-HSCT BOS were made. Following a Delphi process, new diagnostic criteria for pediatric post-HSCT BOS were also proposed. Conclusions: This document provides an evidence-based approach to the detection of post-HSCT BOS in children while also highlighting considerations for the implementation of each recommendation. Further, the document describes important areas for future research.
Assuntos
Bronquiolite Obliterante , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Bronquiolite Obliterante/diagnóstico , Bronquiolite Obliterante/etiologia , Bronquiolite Obliterante/terapia , Criança , Estados Unidos , Testes de Função Respiratória , Pré-Escolar , Síndrome de Bronquiolite ObliteranteRESUMO
We conducted a randomized, placebo-controlled, double-blind study of pediatric lung transplant recipients, hypothesizing that rituximab plus rabbit anti-thymocyte globulin induction would reduce de novo donor-specific human leukocyte antigen antibodies (DSA) development and improve outcomes. We serially obtained clinical data, blood, and respiratory samples for at least one year posttransplant. We analyzed peripheral blood lymphocytes by flow cytometry, serum for antibody development, and respiratory samples for viral infections using multiplex PCR. Of 45 subjects enrolled, 34 were transplanted and 27 randomized to rituximab (n = 15) or placebo (n = 12). No rituximab-treated subjects versus five placebo-treated subjects developed de novo DSA with mean fluorescence intensity >2000. There was no difference between treatment groups in time to the primary composite outcome endpoint (death, bronchiolitis obliterans syndrome [BOS] grade 0-p, obliterative bronchiolitis or listing for retransplant). A post-hoc analysis substituting more stringent chronic lung allograft dysfunction criteria for BOS 0-p showed no difference in outcome (p = .118). The incidence of adverse events including infection and rejection episodes was no different between treatment groups. Although the study was underpowered, we conclude that rituximab induction may have prevented early DSA development in pediatric lung transplant recipients without adverse effects and may improve outcomes (Clinical Trials: NCT02266888).
Assuntos
Bronquiolite Obliterante , Transplante de Pulmão , Bronquiolite Obliterante/tratamento farmacológico , Bronquiolite Obliterante/etiologia , Criança , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/prevenção & controle , Humanos , Pulmão , Transplante de Pulmão/efeitos adversos , Rituximab , TransplantadosRESUMO
BACKGROUND: Neuroblastoma is the most common extracranial solid tumor in children. Those with high-risk disease are treated with multimodal therapy, including high-dose chemotherapy, stem cell transplant, radiation, and immunotherapy that have led to multiple long-term complications in survivors. In the late 1990s, consolidation therapy involved myeloablative conditioning including total body irradiation (TBI) with autologous stem cell rescue. Recognizing the significant long-term toxicities of exposure to TBI, more contemporary treatment protocols have removed this from conditioning regimens. This study examines an expanded cohort of 48 high-risk neuroblastoma patients to identify differences in the late effect profiles for those treated with TBI and those treated without TBI. PROCEDURE: Data on the study cohort were collected from clinic charts, provider documentation in the electronic medical record of visits to survivorship clinic, including all subspecialists, and ancillary reports of laboratory and diagnostic tests done as part of risk-based screening at each visit. RESULTS: All 48 survivors of BMT for high-risk neuroblastoma had numerous late effects of therapy, with 73% having between five and 10 late effects. TBI impacted some late effects significantly, including growth hormone deficiency (GHD), bone outcomes, and cataracts. CONCLUSION: Although high-risk neuroblastoma survivors treated with TBI have significant late effects, those treated without TBI also continue to have significant morbidity related to high-dose chemotherapy and local radiation. A multidisciplinary care team assists in providing comprehensive care to those survivors who are at highest risk for significant late effects.
Assuntos
Neuroblastoma , Irradiação Corporal Total , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Progressão da Doença , Humanos , Neuroblastoma/complicações , Transplante de Células-Tronco/efeitos adversos , Sobreviventes , Irradiação Corporal Total/efeitos adversosRESUMO
BACKGROUND: Long-term survival after lung transplantation (LTx) is limited by chronic lung allograft dysfunction (CLAD). METHODS: We report an analysis of cytokine profiles in bronchoalveolar lavage samples collected during a prospective multicenter non-interventional trial primarily designed to determine the impact of community-acquired respiratory viral infections (CARV) in outcomes after pediatric LTx. In this analysis, we identify potential biomarkers of auto-inflammation and auto-immunity associated with survival and risk of bronchiolitis obliterans (BOS) after LTx with cytokine analysis of bronchoalveolar lavage fluid (BALF) from 61 pediatric recipients. RESULTS: Higher IL-23 (p = .048) and IL-31 (p = .035) levels were associated with the risk of BOS, and lower levels of epithelial growth factor (EGF) (p = .041) and eotaxin (EOX) (p = .017) were associated with BOS. Analysis using conditional inference trees to evaluate cytokines at each visit associated with survival identified soluble CD30 (p < .001), pro-inflammatory cytokine IL-23 (p = .02), and sTNFRI (p = .01) below cutoff levels as associated with BOS-free survival. CONCLUSIONS: Our results indicate that post-LTx survival in children may be linked to activation of alternate pathways of the immune system that affect airway remodeling in addition to activation of "classical" pathways that have been described in adult LTx recipients. These may indicate pathways to target for intervention.
Assuntos
Bronquiolite Obliterante , Transplante de Pulmão , Adulto , Bronquiolite Obliterante/diagnóstico , Bronquiolite Obliterante/etiologia , Criança , Citocinas/metabolismo , Humanos , Inflamação , Interleucina-23 , Estudos ProspectivosRESUMO
Autologous hematopoietic stem cell transplant (ASCT) may be curative therapy for pediatric patients with relapsed/refractory Hodgkin lymphoma (HL). Therapy for HL may involve pulmonary toxic modalities. Little information exists regarding pulmonary function in these patients post-ASCT. A retrospective chart review was performed for patients undergoing ASCT from February 2012 to December 2019. Lung disease was defined as a z -score ≤-1.7 in forced expiratory volume in the first second (FEV 1 ), forced vital capacity (FVC), total lung capacity (TLC), or diffusing capacity of lung for carbon monoxide. Descriptive and limited statistical analyses were performed. Twenty-eight patients were included. Median age at diagnosis was 15 (2 to 19) and was 17 (4 to 21) at ASCT. Twenty-three received radiation before ASCT. Fourteen received brentuximab before, and 9 after, transplant. Nineteen met criteria for lung disease post-ASCT. Sixteen had lung disease before ASCT. Longitudinal trends for pulmonary function testing parameters did not reach statistical significance, however, FEV 1 , FVC, and TLC trended towards worsening immediately post-transplant. There was no statistically significant change in FEV 1 , FVC, or TLC at 2 years as compared with pretransplant data, suggesting no substantial difference from baseline. Diffusing capacity of lung for carbon monoxide showed statistically significant improvement at the 2 year timepoint ( P =0.03). This data reinforces the importance of close follow-up for these patients. Large cohort studies are necessary to identify risk factors so that possible mitigative strategies or alternate regimens could be used.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin , Pneumopatias , Protocolos de Quimioterapia Combinada Antineoplásica , Monóxido de Carbono/uso terapêutico , Criança , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença de Hodgkin/patologia , Humanos , Pulmão/patologia , Pneumopatias/etiologia , Estudos Retrospectivos , Transplante AutólogoRESUMO
Remote interventions are increasingly used in transplant medicine but have rarely been rigorously evaluated. We investigated a remote intervention targeting immunosuppressant management in pediatric lung transplant recipients. Patients were recruited from a larger multisite trial if they had a Medication Level Variability Index (MLVI) ≥2.0, indicating worrisome tacrolimus level fluctuation. The manualized intervention included three weekly phone calls and regular follow-up calls. A comparison group included patients who met enrollment criteria after the subprotocol ended. Outcomes were defined before the intent-to-treat analysis. Feasibility was defined as ≥50% of participants completing the weekly calls. MLVI was compared pre- and 180 days postenrollment and between intervention and comparison groups. Of 18 eligible patients, 15 enrolled. Seven additional patients served as the comparison. Seventy-five percent of participants completed ≥3 weekly calls; average time on protocol was 257.7 days. Average intervention group MLVI was significantly lower (indicating improved blood level stability) at 180 days postenrollment (2.9 ± 1.29) compared with pre-enrollment (4.6 ± 2.10), p = .02. At 180 days, MLVI decreased by 1.6 points in the intervention group but increased by 0.6 in the comparison group (p = .054). Participants successfully engaged in a long-term remote intervention, and their medication blood levels stabilized. NCT02266888.
Assuntos
Transplante de Fígado , Transplante de Órgãos , Criança , Humanos , Imunossupressores/uso terapêutico , Tacrolimo , TransplantadosRESUMO
The increasing global prevalence of SARS-CoV-2 and the resulting COVID-19 disease pandemic pose significant concerns for clinical management of solid organ transplant recipients (SOTR). Wearable devices that can measure physiologic changes in biometrics including heart rate, heart rate variability, body temperature, respiratory, activity (such as steps taken per day) and sleep patterns, and blood oxygen saturation show utility for the early detection of infection before clinical presentation of symptoms. Recent algorithms developed using preliminary wearable datasets show that SARS-CoV-2 is detectable before clinical symptoms in >80% of adults. Early detection of SARS-CoV-2, influenza, and other pathogens in SOTR, and their household members, could facilitate early interventions such as self-isolation and early clinical management of relevant infection(s). Ongoing studies testing the utility of wearable devices such as smartwatches for early detection of SARS-CoV-2 and other infections in the general population are reviewed here, along with the practical challenges to implementing these processes at scale in pediatric and adult SOTR, and their household members. The resources and logistics, including transplant-specific analyses pipelines to account for confounders such as polypharmacy and comorbidities, required in studies of pediatric and adult SOTR for the robust early detection of SARS-CoV-2, and other infections are also reviewed.
Assuntos
COVID-19 , Transplante de Órgãos , Dispositivos Eletrônicos Vestíveis , Adulto , Criança , Humanos , Pandemias , SARS-CoV-2RESUMO
The importance of preoperative cardiac function in pediatric lung transplantation is unknown. We hypothesized that worse preoperative right ventricular (RV) systolic and worse left ventricular (LV) diastolic function would be associated with a higher risk of primary graft dysfunction grade 3 (PGD 3) between 48 and 72 hours. We performed a single center, retrospective pilot study of children (<18 years) who had echocardiograms <1 year prior to lung transplantation between 2006 and 2019. Conventional and strain echocardiography parameters were measured, and PGD was graded. Area under the receiver operating characteristic (AUROC) curves and logistic regression were performed. Forty-one patients were included; 14 (34%) developed PGD 3 and were more likely to have pulmonary hypertension (PH) as the indication for transplant (P = .005). PGD 3 patients had worse RV global longitudinal strain (P = .01), RV free wall strain (FWS) (P = .003), RV fractional area change (P = .005), E/e' (P = .01) and lateral e' velocity (P = .004) but not tricuspid annular plane systolic excursion (P = .61). RV FWS (AUROC 0.79, 95% CI 0.62-0.95) and lateral e' velocity (AUROC 0.87, 95% CI 0.68-1.00) best discriminated PGD 3 development and showed the strongest association with PGD 3 (RV FWS OR 3.87 [95% CI 1.59-9.43], P = .003; lateral e' velocity OR 0.10 [95% CI 0.01-0.70], P = .02). These associations remained when separately adjusting for age, weight, primary PH diagnosis, ischemic time, and bypass time. In this pilot study, worse preoperative RV systolic and worse LV diastolic function were associated with PGD 3 and may be modifiable recipient risk factors in pediatric lung transplantation.
Assuntos
Ecocardiografia , Transplante de Pulmão , Disfunção Primária do Enxerto/etiologia , Disfunção Ventricular/diagnóstico por imagem , Adolescente , Área Sob a Curva , Criança , Pré-Escolar , Feminino , Humanos , Modelos Logísticos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Projetos Piloto , Período Pré-Operatório , Disfunção Primária do Enxerto/diagnóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Disfunção Ventricular/complicaçõesRESUMO
Stent angioplasty of patent ductus arteriosus has been shown to be a viable alternative to operative shunt placement in cyanotic neonates. With broader implementation of this strategy, novel complications are bound to arise. We present a series of cases evaluated for ductal stent angioplasty in which a dilated and torturous ductus arteriosus compressed the left mainstem bronchus. After reviewing our recent experience with ductal stenting and isolated Blalock-Taussig shunts, our best estimate of the incidence of bronchial compression by the dilated ductus is 4.6% (3/64, 95% confidence interval 1.0-12.9%). Awareness of the airway and other nonvascular contents of the thorax is an important consideration prior to ductal stenting.
Assuntos
Obstrução das Vias Respiratórias/etiologia , Brônquios , Permeabilidade do Canal Arterial/complicações , Obstrução das Vias Respiratórias/diagnóstico por imagem , Obstrução das Vias Respiratórias/fisiopatologia , Angioplastia/efeitos adversos , Angioplastia/instrumentação , Procedimento de Blalock-Taussig , Brônquios/diagnóstico por imagem , Brônquios/fisiopatologia , Tomada de Decisão Clínica , Permeabilidade do Canal Arterial/diagnóstico por imagem , Permeabilidade do Canal Arterial/fisiopatologia , Permeabilidade do Canal Arterial/terapia , Feminino , Humanos , Recém-Nascido , Cuidados Paliativos , Fatores de Risco , Stents , Resultado do TratamentoRESUMO
BACKGROUND: Infection with rhinovirus (HRV) occurs following pediatric lung transplantation. Prospective studies documenting frequencies, persistence, and progression of HRV in this at-risk population are lacking. METHODS: In the Clinical Trials in Organ Transplant in Children prospective observational study, we followed 61 lung transplant recipients for 2 years. We quantified molecular subtypes of HRV in serially collected nasopharyngeal (NP) and bronchoalveolar lavage (BAL) samples and correlated them with clinical characteristics. RESULTS: We identified 135 community-acquired respiratory infections (CARV) from 397 BAL and 480 NP samples. We detected 93 HRV events in 42 (68.8%) patients, 22 of which (23.4%) were symptomatic. HRV events were contiguous with different genotypes identified in 23 cases, but symptoms were not preferentially associated with any particular species. Nine (9.7%) HRV events persisted over multiple successive samples for a median of 36 days (range 18-408 days). Three persistent HRV were symptomatic. When we serially measured forced expiratory volume in one second (FEV1) in 23 subjects with events, we did not observe significant decreases in lung function over 12 months post-HRV. CONCLUSION: In conjunction with our previous reports, our prospectively collected data indicate that molecularly heterogeneous HRV infections occur commonly following pediatric lung transplantation, but these infections do not negatively impact clinical outcomes.
Assuntos
Infecções Comunitárias Adquiridas , Transplante de Pulmão , Infecções por Picornaviridae , Infecções Respiratórias , Criança , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/virologia , Feminino , Humanos , Masculino , Infecções por Picornaviridae/epidemiologia , Estudos Prospectivos , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , RhinovirusRESUMO
Based on reports in adult lung transplant recipients, we hypothesized that community-acquired respiratory viral infections (CARVs) would be a risk factor for poor outcome after pediatric lung transplant. We followed 61 pediatric lung transplant recipients for 2+ years or until they met a composite primary endpoint including bronchiolitis obliterans syndrome/obliterative bronchiolitis, retransplant, or death. Blood, bronchoalveolar lavage, and nasopharyngeal specimens were obtained with standard of care visits. Nasopharyngeal specimens were obtained from recipients with respiratory viral symptoms. Respiratory specimens were interrogated for respiratory viruses by using multiplex polymerase chain reaction. Donor-specific HLA antibodies, self-antigens, and ELISPOT reactivity were also evaluated. Survival was 84% (1 year) and 68% (3 years). Bronchiolitis obliterans syndrome incidence was 20% (1 year) and 38% (3 years). The primary endpoint was met in 46% of patients. CARV was detected in 156 patient visits (74% enterovirus/rhinovirus). We did not find a relationship between CARV recovery from respiratory specimens and the primary endpoint (hazard ratio 0.64 [95% confidence interval: 0.25-1.59], P = .335) or between CARV and the development of alloimmune or autoimmune humoral or cellular responses. These findings raise the possibility that the immunologic impact of CARV following pediatric lung transplant is different than that observed in adults.
Assuntos
Bronquiolite Obliterante/cirurgia , Infecções Comunitárias Adquiridas/virologia , Rejeição de Enxerto/virologia , Sobrevivência de Enxerto/imunologia , Transplante de Pulmão/efeitos adversos , Infecções Respiratórias/virologia , Viroses/virologia , Adolescente , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/imunologia , Feminino , Seguimentos , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/imunologia , Humanos , Incidência , Lactente , Estudos Longitudinais , Masculino , Prognóstico , Estudos Prospectivos , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/imunologia , Fatores de Risco , Transplantados , Viroses/epidemiologia , Viroses/imunologia , Vírus/isolamento & purificaçãoRESUMO
INTRODUCTION: Totally implantable venous access devices (TIVADs) are the preferred devices for patients with advanced lung disease who require long-term venous access. The primary purpose of this study was to describe the natural history of TIVADs left in place at the time of transplant. METHODS: This multicenter retrospective cohort study evaluated pediatric and adult lung transplant recipients from 5/5/2005 to 12/31/17 with pretransplant TIVAD. Incident rates (IR) for infectious and mechanical complications were calculated. Poisson regression models were used to identify TIVAD characteristics associated with complications. RESULTS: Of 1253 transplant recipients, 82 (6.5%) had pretransplant TIVAD. Five (6.1%) TIVADs were removed at transplantation. Fifty-five (67.1%) TIVADs were eventually removed, most commonly because they were no longer required (50.9%) or because of infection (25.5%). Overall incident rates (IR) of infectious or mechanical complications were 0.33 and 0.14, respectively. The IR of infection was highest within one year of transplant, particularly during the index hospitalization (IR = 1.67). Youngest tertile (<22 years) had the lowest incident rate ratio of TIVAD infections (IRR = 0.22). CONCLUSION: Although TIVAD complication rates in lung transplant recipients are similar to non-transplant and other immunocompromised patients, TIVAD removal at transplant or within the first post-transplant year may minimize the risk of TIVAD infections.
Assuntos
Cateterismo Venoso Central/efeitos adversos , Cateteres de Demora/efeitos adversos , Transplante de Pulmão/efeitos adversos , Complicações Pós-Operatórias , Adolescente , Adulto , Criança , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Adulto JovemRESUMO
Anelloviruses are DNA viruses ubiquitously present in human blood. Due to their elevated levels in immunosuppressed patients, anellovirus levels have been proposed as a marker of immune status. We hypothesized that low anellovirus levels, reflecting relative immunocompetence, would be associated with adverse outcomes in pediatric lung transplantation. We assayed blood samples from 57 patients in a multicenter study for alpha- and betatorquevirus, two anellovirus genera. The primary short-term outcome of interest was acute rejection, and longer-term outcomes were analyzed individually and as "composite" (death, chronic rejection, or retransplant within 2 years). Patients with low alphatorquevirus levels at 2 weeks post-transplantation were more likely to develop acute rejection within 3 months after transplant (P = .013). Low betatorquevirus levels at 6 weeks and 6 months after transplant were associated with death (P = .047) and the composite outcome (P = .017), respectively. There was an association between low anellovirus levels and adverse outcomes in pediatric lung transplantation. Alphatorquevirus levels were associated with short-term outcomes (ie, acute rejection), while betatorquevirus levels were associated with longer-term outcomes (ie, death, or composite outcome within 2 years). These observations suggest that anelloviruses may serve as useful biomarkers of immune status and predictors of adverse outcomes.
Assuntos
Anelloviridae/isolamento & purificação , Rejeição de Enxerto/virologia , Transplante de Pulmão , Carga Viral , Adolescente , Anelloviridae/imunologia , Biomarcadores , Criança , Pré-Escolar , Feminino , Seguimentos , Rejeição de Enxerto/imunologia , Humanos , Tolerância Imunológica , Terapia de Imunossupressão , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Transplante de Pulmão/mortalidade , Masculino , Avaliação de Resultados em Cuidados de Saúde , Reoperação/estatística & dados numéricos , Estudos RetrospectivosRESUMO
BACKGROUND: Plastic bronchitis is a potentially fatal disorder occurring in children with single-ventricle physiology, and other diseases, as well, such as asthma. In this study, we report findings of abnormal pulmonary lymphatic flow, demonstrated by MRI lymphatic imaging, in patients with plastic bronchitis and percutaneous lymphatic intervention as a treatment for these patients. METHODS AND RESULTS: This is a retrospective case series of 18 patients with surgically corrected congenital heart disease and plastic bronchitis who presented for lymphatic imaging and intervention. Lymphatic imaging included heavy T2-weighted MRI and dynamic contrast-enhanced magnetic resonance lymphangiogram. All patients underwent bilateral intranodal lymphangiogram, and most patients underwent percutaneous lymphatic intervention. In 16 of 18 patients, MRI or lymphangiogram or both demonstrated retrograde lymphatic flow from the thoracic duct toward lung parenchyma. Intranodal lymphangiogram and thoracic duct catheterization was successful in all patients. Seventeen of 18 patients underwent either lymphatic embolization procedures or thoracic duct stenting with covered stents to exclude retrograde flow into the lungs. One of the 2 patients who did not have retrograde lymphatic flow did not undergo a lymphatic interventional procedure. A total of 15 of 17(88%) patients who underwent an intervention had significant symptomatic improvement at a median follow-up of 315 days (range, 45-770 days). The most common complication observed was nonspecific transient abdominal pain and transient hypotension. CONCLUSIONS: In this study, we demonstrated abnormal pulmonary lymphatic perfusion in most patients with plastic bronchitis. Interruption of the lymphatic flow resulted in significant improvement of symptoms in these patients and, in some cases, at least temporary resolution of cast formation.
Assuntos
Bronquite Crônica/terapia , Procedimentos Cirúrgicos Cardíacos , Embolização Terapêutica/métodos , Vasos Linfáticos , Complicações Pós-Operatórias/terapia , Adolescente , Oclusão com Balão , Bronquite Crônica/etiologia , Broncoscopia , Cateterismo Cardíaco , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Criança , Pré-Escolar , Óleo Etiodado/administração & dosagem , Óleo Etiodado/uso terapêutico , Feminino , Técnica de Fontan , Derivação Cardíaca Direita/efeitos adversos , Cardiopatias Congênitas/cirurgia , Transplante de Coração , Humanos , Vasos Linfáticos/fisiopatologia , Linfografia , Imageamento por Ressonância Magnética , Masculino , Complicações Pós-Operatórias/etiologia , Estudos RetrospectivosRESUMO
BACKGROUND: Prospective studies to determine associated risk factors and related outcomes for pulmonary fungal infection (PFI) after pediatric lung transplant (PLT) are lacking. METHODS: NIH-sponsored Clinical Trials in Organ Transplantation in Children enrolled PLT candidates, collecting data prospectively for 2 years post-transplant. Demographics, signs/symptoms, radiology, pathology and microbiology were collected. Analyses evaluated for PFI-related risks and outcomes. RESULTS: In 59 PLT, pre-transplant fungal colonization occurred in 6 donors and 15 recipients. Cystic fibrosis (CF) was associated with pre-transplant colonization (P < .01). Twenty-five (42%) PLT had 26 post-transplant colonizations (median = 67 days, range = 0-750 days) with Candida (13), Aspergillus (4), mold (6) or yeast (3). Post-PLT colonization was not associated with CF, age, or pre-PLT colonization. Thirteen PFIs occurred in 10 (17%) patients, 3 proven (Candida species) and 10 probable (Candida [3], Aspergillus [3], Penicillium [3], and mold [1]). Pulmonary fungal infection was preceded by post-PLT colonization with the same organism in 4 of 13 PFI, but post-PLT colonization did not predict subsequent PFI (P = .87). Older age at transplant was a risk for PFI (P < .01). No mortality was attributed to PFI. Prophylaxis use was not associated with decreased post-PLT colonization (P = .60) or PFI (P = .48). CONCLUSION: In PLT, PFI and fungal colonization are common but without associated mortality. Post-PLT colonization did not predict PFI. Optimal prevention strategies require additional study.
Assuntos
Fibrose Cística/complicações , Rejeição de Enxerto/mortalidade , Pneumopatias Fúngicas/mortalidade , Transplante de Pulmão/efeitos adversos , Complicações Pós-Operatórias/mortalidade , Adolescente , Criança , Fibrose Cística/microbiologia , Fibrose Cística/cirurgia , Feminino , Seguimentos , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Estudos Longitudinais , Pneumopatias Fúngicas/etiologia , Masculino , Prognóstico , Estudos Prospectivos , Fatores de RiscoRESUMO
Transplant volume represents lung transplant (LTx) expertise and predicts outcomes, so we sought to determine outcomes related to center volumes in cystic fibrosis (CF). United Network for Organ Sharing data were queried for patients with CF in the United States (US) receiving bilateral LTx from 2005 to 2015. Multivariable Cox regression was used to model survival to 1 year and long-term (>1 year) survival, conditional on surviving at least 1 year. A total of 2025 patients and 67 centers were included in the analysis. The median annual LTx volumes were three in CF [interquartile range (IQR): 2, 6] and 17 in non-CF (IQR: 8, 33). Multivariable Cox regression in cases with complete data and surviving at least 1 year (n = 1510) demonstrated that greater annual CF LTx volume (HR per 10 LTx = 0.66; 95% CI: 0.49, 0.89; P = 0.006) but not greater non-CF LTx volume (HR = 1.00; 95% CI: 0.96, 1.05; P = 0.844) was associated with improved long-term survival in LTx recipients with CF. A Wald interaction test confirmed that CF LTx volume was more strongly associated with long-term outcomes than non-CF LTx volume (P = 0.012). In a US cohort, center volume was not associated with 1-year survival. CF-specific expertise predicted improved long-term outcomes of LTx for CF, whereas general LTx expertise was unassociated with CF patients' survival.
Assuntos
Fibrose Cística/cirurgia , Hospitais/estatística & dados numéricos , Transplante de Pulmão , Adolescente , Adulto , Criança , Feminino , Humanos , Pulmão/cirurgia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Transplantes , Resultado do Tratamento , Estados Unidos , Adulto JovemRESUMO
Prediction of PTLD after pediatric lung transplant remains difficult. Use of EBV VL in WB has been poorly predictive, while measurement of VL in BAL fluid has been suggested to have enhanced utility. The NIH-sponsored Clinical Trials in Organ Transplantation in Children (CTOTC-03) prospectively obtained serial quantitative measurements of EBV PCR in both WB and BAL fluid after pediatric lung transplantation. Descriptive statistics, contingency analyses, and Kaplan-Meier analyses evaluated possible association between EBV and PTLD. Of 61 patients, 34 (56%) had an EBV+PCR (at least once in WB or BAL). EBV donor (D)+patients more often had a positive PCR (D+/recipient (R)-: 13/18; D+/R+: 14/23) compared to EBV D- patients (6/17). Several D-/R- (5/12) patients developed EBV, but none developed PTLD. All four PTLD patients were D+/R- with EBV+PCR. Neither the time to first EBV+PCR nor the CT for PCR positivity in BAL or WB was statistically different between those with and without PTLD. Having an EBV-seropositive donor was associated with increased risk of EBV+PCR in WB. EBV load in BAL was not predictive of PTLD.
Assuntos
Herpesvirus Humano 4/isolamento & purificação , Transplante de Pulmão , Transtornos Linfoproliferativos/virologia , Complicações Pós-Operatórias/virologia , Carga Viral , Adolescente , Líquido da Lavagem Broncoalveolar/virologia , Criança , Pré-Escolar , DNA Viral/análise , Feminino , Herpesvirus Humano 4/genética , Humanos , Lactente , Estimativa de Kaplan-Meier , Masculino , Reação em Cadeia da Polimerase , Estudos Prospectivos , Fatores de Risco , Adulto JovemRESUMO
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.
Assuntos
Estatura , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Disparidades em Assistência à Saúde/estatística & dados numéricos , Transplante de Pulmão/estatística & dados numéricos , Listas de Espera , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados UnidosRESUMO
Stenosis of the pulmonary arteries frequently occurs during staged palliation of hypoplastic left heart syndrome and variants, often necessitating stent angioplasty. A complication of stent angioplasty is compression of the ipsilateral mainstem bronchus. Following such a case, we re-evaluated our approach to PA stent angioplasty in these patients. The incident case is described. A retrospective observational study of children and adults with superior (SCPC) and/or total cavopulmonary connection (TCPC) undergoing left pulmonary artery (LPA) stent angioplasty between January 1, 2005 and January 5, 2014 and subsequent chest CT was performed to assess the incidence of bronchial compression. The current strategy of employing bronchoscopy to assess bronchial compression during angioplasty is described with short-term results. Sixty-five children and adults underwent LPA stent angioplasty. Other than the incident case, none had symptomatic bronchial compression. Of the total study population, 12 % had subsequent CT, of which one subject had moderate bronchial compression. To date, seven subjects have undergone angioplasty of LPA stenosis and bronchoscopy. In one case, stent angioplasty was not performed because of baseline bronchial compression, exacerbated during angioplasty. In the rest of cases, mild-moderate compression was seen during angioplasty. Following stent angioplasty, the resultant compression was not worse than that seen on test angioplasty. Bronchial compression is a rare complication of stent angioplasty of the pulmonary arteries in children and adults with SCPC/TCPC. Angioplasty of the region of interest with procedural bronchoscopy can help to identify patients at risk of this complication.