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1.
J Immunol ; 213(6): 898-905, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39072690

RESUMO

Lung transplant remains the primary therapeutic option for patients with end-stage lung disease, but long-term survival rates remain suboptimal compared with other solid organ transplants. Acute cellular rejection (ACR) is a significant challenge in lung transplant recipients, with T cell-mediated mechanisms playing a major role. IL-10 is known for its immunoregulatory function, although its specific role in lung allograft rejection remains unclear. Using the mouse orthotopic lung transplant model, we investigated the role of IL-10 in regulating alloeffector T cell responses. Unexpectedly, we found that IL-10 was not required for early costimulation blockade-induced allograft acceptance. However, IL-10 deficiency or blockade resulted in increased CD4+ T cell numbers, proliferation, graft infiltration, and alloeffector responses. In the absence of IL-10, CD4+ T cell responses predominated over CD8 responses during ACR in contrast to wild-type mice. Type 1 immunity (IFN-γ) responses along with elevated CD4+NKG7+ and CD4+CD107a+ responses predominated during ACR, highlighting a critical regulatory role for IL-10 in modulating CD4+ T cell alloimmune responses. We further demonstrated increased colocalization of NKG7 and CD107a in CD4+ T cells from IL-10-deficient allografts, suggesting coordination in cytotoxic activity. Together, our findings highlight a critical role for IL-10 in regulation of cytotoxic CD4+NKG7+ T cells, an effector population that needs further investigation to elucidate their role in lung allograft rejection.


Assuntos
Aloenxertos , Rejeição de Enxerto , Interleucina-10 , Transplante de Pulmão , Animais , Camundongos , Aloenxertos/imunologia , Linfócitos T CD4-Positivos/imunologia , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Interferon gama/imunologia , Interferon gama/metabolismo , Interleucina-10/imunologia , Interleucina-10/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Linfócitos T Citotóxicos/imunologia
3.
J Immunol ; 209(9): 1788-1795, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36113884

RESUMO

Chronic lung allograft dysfunction is the major barrier to long-term survival in lung transplant recipients. Evidence supports type 1 alloimmunity as the predominant response in acute/chronic lung rejection, but the immunoregulatory mechanisms remain incompletely understood. We studied the combinatorial F-box E3 ligase system: F-box protein 3 (FBXO3; proinflammatory) and F-box and leucine-rich repeat protein 2 (FBXL2; anti-inflammatory and regulates TNFR-associated factor [TRAF] protein). Using the mouse orthotopic lung transplant model, we evaluated allografts from BALB/c → C57BL/6 (acute rejection; day 10) and found significant induction of FBXO3 and diminished FBXL2 protein along with elevated T-bet, IFN-γ, and TRAF proteins 1-5 compared with isografts. In the acute model, treatment with costimulation blockade (MR1/CTLA4-Ig) resulted in attenuated FBXO3, preserved FBXL2, and substantially reduced T-bet, IFN-γ, and TRAFs 1-5, consistent with a key role for type 1 alloimmunity. Immunohistochemistry revealed significant changes in the FBXO3/FBXL2 balance in airway epithelia and infiltrating mononuclear cells during rejection compared with isografts or costimulation blockade-treated allografts. In the chronic lung rejection model, DBA/2J/C57BL/6F1 > DBA/2J (day 28), we observed persistently elevated FBXO3/FBXL2 balance and T-bet/IFN-γ protein and similar findings from lung transplant recipient lungs with chronic lung allograft dysfunction versus controls. We hypothesized that FBXL2 regulated T-bet and found FBXL2 was sufficient to polyubiquitinate T-bet and coimmunoprecipitated with T-bet on pulldown experiments and vice versa in Jurkat cells. Transfection with FBXL2 diminished T-bet protein in a dose-dependent manner in mouse lung epithelial cells. In testing type 1 cytokines, TNF-α was found to negatively regulate FBXL2 protein and mRNA levels. Together, our findings show the combinatorial E3 ligase FBXO3/FBXL2 system plays a role in the regulation of T-bet through FBXL2, with negative cross-regulation of TNF-α on FBXL2 during lung allograft rejection.


Assuntos
Proteínas F-Box , Animais , Camundongos , Abatacepte , Aloenxertos , Citocinas/metabolismo , Modelos Animais de Doenças , Proteínas F-Box/genética , Proteínas F-Box/metabolismo , Rejeição de Enxerto , Pulmão/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , RNA Mensageiro , Peptídeos e Proteínas Associados a Receptores de Fatores de Necrose Tumoral/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
4.
J Exp Med ; 219(4)2022 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-35285873

RESUMO

Acute cellular rejection is common after lung transplantation and is associated with an increased risk of early chronic rejection. We present combined single-cell RNA and TCR sequencing on recipient-derived T cells obtained from the bronchoalveolar lavage of three lung transplant recipients with rejection and compare them with T cells obtained from the same patients after treatment of rejection with high-dose systemic glucocorticoids. At the time of rejection, we found an oligoclonal expansion of cytotoxic CD8+ T cells that all persisted as tissue resident memory T cells after successful treatment. Persisting CD8+ allograft-resident T cells have reduced gene expression for cytotoxic mediators after therapy with glucocorticoids but accumulate around airways. This clonal expansion is discordant with circulating T cell clonal expansion at the time of rejection, suggesting in situ expansion. We thus highlight the accumulation of cytotoxic, recipient-derived tissue resident memory T cells within the lung allograft that persist despite the administration of high-dose systemic glucocorticoids. The long-term clinical consequences of this persistence have yet to be characterized.


Assuntos
Glucocorticoides , Transplante de Pulmão , Linfócitos T CD8-Positivos/metabolismo , Glucocorticoides/metabolismo , Rejeição de Enxerto/genética , Rejeição de Enxerto/metabolismo , Humanos , Células T de Memória
5.
Chest ; 160(5): 1624-1633, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33878342

RESUMO

BACKGROUND: Pseudomonas aeruginosa (PA) is a common cause of respiratory infection and morbidity. Pseudomonas elastase is an important virulence factor regulated by the lasR gene. Whether PA elastase activity is associated with worse clinical outcomes in ICU patients is unknown. RESEARCH QUESTION: Is there an association between PA elastase activity and worse host outcomes in a cohort of ICU patients? METHODS: PA respiratory isolates from 238 unique ICU patients from two tertiary-care centers within the University of Pittsburgh Medical Center health system were prospectively collected and screened for total protease and elastase activity, biofilm production, antimicrobial resistance, and polymicrobial status. The association between pathogen characteristics and 30-day and 90-day mortality was calculated using logistic regression. For subgroup analysis, two patterns of early (≤72 h) and late sample (>72 h) collection from the index ICU admission were distinguished using a finite mixture model. Lung inflammation and injury was evaluated in a mouse model using a PA high elastase vs low elastase producer. RESULTS: PA elastase activity was common in ICU respiratory isolates representing 75% of samples and was associated with increased 30-day mortality (adjusted OR [95% CI]: 1.39 [1.05-1.83]). Subgroup analysis demonstrated that elastase activity was a risk factor for 30- and 90-day mortality in the early sample group, whereas antimicrobial resistance was a risk factor for 90-day mortality in the late sample group. Whole genome sequencing of high and low elastase producers showed that predicted loss-of-function lasR genotypes were less common among high elastase producers. Mice infected with a high elastase producer showed increased lung bacterial burden and inflammatory profile compared with mice infected with a low elastase producer. INTERPRETATION: Elastase activity is associated with 30-day ICU mortality. A high elastase producing clinical isolate confers increased lung tissue inflammation compared with a low elastase producer in vivo.


Assuntos
Proteínas de Bactérias/metabolismo , Estado Terminal , Unidades de Terapia Intensiva/estatística & dados numéricos , Pulmão , Metaloendopeptidases/metabolismo , Mortalidade , Pneumonia Bacteriana , Infecções por Pseudomonas , Pseudomonas aeruginosa , Animais , Correlação de Dados , Estado Terminal/mortalidade , Estado Terminal/terapia , Demografia , Modelos Animais de Doenças , Feminino , Humanos , Pulmão/imunologia , Pulmão/microbiologia , Masculino , Camundongos , Pessoa de Meia-Idade , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/mortalidade , Infecções por Pseudomonas/etiologia , Infecções por Pseudomonas/mortalidade , Pseudomonas aeruginosa/enzimologia , Pseudomonas aeruginosa/isolamento & purificação , Pseudomonas aeruginosa/patogenicidade , Respiração Artificial/estatística & dados numéricos , Estados Unidos/epidemiologia , Fatores de Virulência
6.
Transplantation ; 104(3): 640-651, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31335759

RESUMO

BACKGROUND: In a randomized controlled trial, lung transplant recipients (LTRs) using a mobile health intervention, Pocket Personal Assistant for Tracking Health (Pocket PATH), showed better adherence to the medical regimen than LTRs receiving usual care during the first year posttransplant. We examined whether these effects were maintained beyond the end of the trial and evaluated other potential risk factors for long-term nonadherence. METHODS: Adherence in 8 areas was evaluated at follow-up in separate LTR and family caregiver (collateral) assessments. Pocket PATH and usual care groups' nonadherence rates were compared; multivariable regression analyses then examined and controlled for other patient characteristics' associations with nonadherence. RESULTS: One hundred five LTRs (75% of survivors) were assessed (M = 3.9 years posttransplant, SD = 0.8). Nonadherence rates in the past month were 23%-81% for self-care and lifestyle requirements (diet, exercise, blood pressure monitoring, spirometry), 13%-23% for immunosuppressants and other medications, and 4% for tobacco use, with 31% clinic appointment nonadherence in the past year. In multivariable analysis, the Pocket PATH group showed lower risk of nonadherence to lifestyle requirements (diet/exercise) than the usual care group (P < 0.05). Younger age and factors during the first year posttransplant (acute graft rejection, chronically elevated anxiety, less time rehospitalized, nonadherence at the final randomized controlled trial assessment) were each associated with nonadherence in at least 1 area at follow-up (P < 0.05). CONCLUSIONS: Pocket PATH did not have sustained impact on most areas of the regimen, although we identified other risk factors for long-term nonadherence. Future work should explore strategies to facilitate sustained effects of mobile health interventions.


Assuntos
Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Transplante de Pulmão/efeitos adversos , Adesão à Medicação/estatística & dados numéricos , Aplicativos Móveis , Adulto , Fatores Etários , Idoso , Feminino , Seguimentos , Rejeição de Enxerto/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Sistemas de Alerta/instrumentação , Smartphone , Telemedicina/instrumentação , Telemedicina/métodos , Transplantados/estatística & dados numéricos
7.
J Thorac Cardiovasc Surg ; 159(3): 1142-1150, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31839224

RESUMO

BACKGROUND: Deep vein thrombosis (DVT) remains a common complication following lung transplantation despite universal routine DVT screening. Moreover, many of the previously reported risk factors are incompletely defined. We sought to explore the influence of DVT screening and to more definitively assess predisposing risk factors. METHODS: A single-institution, retrospective, cohort study of 1141 patients undergoing lung transplantation from January 1, 2005, to December 31, 2014, was performed evaluating for the rate of DVT. Patients were given prophylactic subcutaneous heparin postoperatively. DVT events were noted if they occurred before 90 days after transplant. We compared DVT rates before and after 2008 when universal screening was implemented. We also evaluated the timing of DVT event and location (above the knee vs below the knee). DVTs were treated with standard anticoagulation therapy or an inferior cava filter when patients were unable to tolerate anticoagulation treatment. Univariable and multivariable models were used to identify risk factors for occurrence. A propensity match was performed to match groups across the eras, and a Cox regression was performed to identify differences in 1-year survival trajectory between cohorts. RESULTS: The rates of DVT before and after routine screening were 8.8% (36 DVT out of 412 transplants) and 17.3% (126 out of 729 transplants), respectively. These 2 rates were significantly different (P < .01); moreover, the observed DVT incidence per year was not significantly different across the 6 years after universal DVT screening was implemented (P > .90 for all comparisons). Observed DVT incidence at day 0 and day 14 were 3.8% and 3.8%, respectively, for the cohort before DVT protocols were established. Observed DVT incidence for the cohort after protocols were established at the same time points was 8.7% and 3.7%, respectively. Univariable analysis revealed that significant factors associated with a DVT include hypercholesterolemia (odds ratio [OR], 6.90; 95% confidence interval [CI], 1.82-26.13; P < .01), the number of days in the intensive care unit (OR, 1.03; 95% CI, 1.00-1.01; P < .01), and the length of stay in the hospital (OR, 1.01; 95% CI, 1.01-1.02; P < .01), whereas having quit smoking (vs never smoked) was associated with a decrease in DVT development (OR, 0.50; 95% CI, 0.33-0.75; P < .01). Multivariable analysis revealed 2 significant variables: hypercholesterolemia (OR, 8.13; 95% CI, 1.22-54.37; P = .03) and length of stay (OR, 1.03; 95% CI, 1.01-1.05; P < .01). There was a trend for better 1-year survival in the post-2008 era (Exp[ß], 1.49; P = .09). CONCLUSIONS: The rate of DVT diagnosis significantly increased after universal DVT screening was implemented. Furthermore, those patients undergoing lung transplantation with extended length of stay and hypercholesterolemia were prone to increased rates of DVT. There was a trend toward better 1-year survival in DVT-screened patients, suggesting DVT screening may result in beneficial outcomes.


Assuntos
Transplante de Pulmão/efeitos adversos , Programas de Rastreamento/métodos , Ultrassonografia Doppler Dupla , Trombose Venosa/diagnóstico por imagem , Adulto , Idoso , Anticoagulantes/administração & dosagem , Esquema de Medicação , Feminino , Heparina/administração & dosagem , Humanos , Hipercolesterolemia/epidemiologia , Incidência , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pennsylvania/epidemiologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Filtros de Veia Cava , Trombose Venosa/epidemiologia , Trombose Venosa/prevenção & controle
9.
Int Forum Allergy Rhinol ; 9(7): 759-765, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31162888

RESUMO

BACKGROUND: Chronic rhinosinusitis (CRS) is a significant manifestation of cystic fibrosis (CF) with wide-ranging symptom and disease severity. The goal of the study was to determine clinical variables that correlate with outcome measures of disease severity. METHODS: A prospective, longitudinal, observational study of 33 adults with symptomatic CRS treated in a CF-focused otolaryngology clinic was performed. Symptom severity, the presence of rhinosinusitis exacerbations, and endoscopic appearance were assessed, and regression analysis was used to determine clinical predictors of disease outcome. RESULTS: Thirty-three adults with CF-CRS were included in the study and followed for a mean of 15 months. Rhinosinusitis exacerbations occurred in 61% of participants during the study, and female sex increased the odds of presenting with an exacerbation visit. Sinus disease exacerbations were associated with an odds ratio of 2.07 for presenting with a pulmonary exacerbation at the next visit. CF-related diabetes was found to be associated with worse symptoms and endoscopic appearance. Infection with Staphylococcus aureus predicted worsening of symptoms, whereas infections with Pseudomonas aeruginosa improved over time. Allergic rhinitis was associated with worse endoscopic appearance, and nasal steroid use was associated with improved endoscopic appearance. CONCLUSION: Sex, CF-related diabetes, sinonasal infection status, allergic rhinitis, and nasal steroid use may all modulate severity of CF-CRS in adults. Sinusitis exacerbation may be a precursor to pulmonary exacerbation.


Assuntos
Fibrose Cística , Rinite , Sinusite , Adulto , Antibacterianos/uso terapêutico , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/fisiopatologia , Infecções Bacterianas/terapia , Doença Crônica , Fibrose Cística/diagnóstico , Fibrose Cística/fisiopatologia , Fibrose Cística/terapia , Endoscopia , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Lavagem Nasal , Rinite/diagnóstico , Rinite/fisiopatologia , Rinite/terapia , Índice de Gravidade de Doença , Fatores Sexuais , Sinusite/diagnóstico , Sinusite/fisiopatologia , Sinusite/terapia , Esteroides/uso terapêutico
10.
Blood Adv ; 3(3): 432-445, 2019 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-30733303

RESUMO

Thrombocytopenia is associated with worse outcomes in patients with acute respiratory distress syndrome, which is most commonly caused by infection and marked by alveolar-capillary barrier disruption. However, the mechanisms by which platelets protect the lung alveolar-capillary barrier during infectious injury remain unclear. We found that natively thrombocytopenic Mpl -/- mice deficient in the thrombopoietin receptor sustain severe lung injury marked by alveolar barrier disruption and hemorrhagic pneumonia with early mortality following acute intrapulmonary Pseudomonas aeruginosa (PA) infection; barrier disruption was attenuated by platelet reconstitution. Although PA infection was associated with a brisk neutrophil influx, depletion of airspace neutrophils failed to substantially mitigate PA-triggered alveolar barrier disruption in Mpl -/- mice. Rather, PA cell-free supernatant was sufficient to induce lung epithelial cell apoptosis in vitro and in vivo and alveolar barrier disruption in both platelet-depleted mice and Mpl -/- mice in vivo. Cell-free supernatant from PA with genetic deletion of the type 2 secretion system, but not the type 3 secretion system, mitigated lung epithelial cell death in vitro and lung injury in Mpl -/- mice. Moreover, platelet releasates reduced poly (ADP ribose) polymerase cleavage and lung injury in Mpl -/- mice, and boiling of platelet releasates, but not apyrase treatment, abrogated PA supernatant-induced lung epithelial cell cytotoxicity in vitro. These findings indicate that while neutrophil airspace influx does not potentiate infectious lung injury in the thrombocytopenic host, platelets and their factors protect against severe pulmonary complications from pathogen-secreted virulence factors that promote host cell death even in the absence of overt infection.


Assuntos
Plaquetas/metabolismo , Lesão Pulmonar/etiologia , Trombocitopenia/complicações , Animais , Apoptose , Plaquetas/citologia , Morte Celular , Células Epiteliais , Lesão Pulmonar/sangue , Camundongos
12.
Transplant Direct ; 4(8): e372, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30255132

RESUMO

BACKGROUND: Immunosuppressive therapies have led to improved survival for lung transplant (LT) recipients but these therapies can lead to hypogammaglobulinemia (HGG) and potentially an increased risk of infection. Large prospective studies have not been performed to evaluate the impact of HGG on outcomes for LT recipients. METHODS: This is a single-center prospective observational study of LT recipients. Pretransplant and posttransplant IgG levels were measured and related to infection, rejection, antibiotic use, and immunosuppression use. RESULTS: One hundred thirty-three LT recipients were prospectively evaluated. Pretransplant IgG values were higher than IgG values at the time of transplant or any time thereafter (all P < 0.0001). Severe HGG (IgG < 400 mg/dL) was highest at the time of transplant (32.4%) while at 3, 6, 9, and 12 months posttransplant the prevalence of severe HGG was 7.4%, 7.5%, 8.9%, and 6.3%, respectively. Severe HGG was associated with 2 or more pneumonias (P = 0.0006) and increased number of antibiotic courses (P = 0.003) compared with the subjects without severe HGG. Pretransplant IgG level and less than 30% of pretransplant protective pneumococcal antibody levels were identified as pretransplant risk factors for severe HGG. In multivariate analysis, chronic obstructive pulmonary disease as the underlying disease and the use of basiliximab as the induction agent in conjunction with higher prednisone and mycophenolate dosing were most predictive of severe HGG (P = 0.005), whereas the combination of age, severe HGG and number of acute steroid courses were most predictive of total days of pneumonia (P = 0.0001). CONCLUSIONS: Our large prospective study identifies risk factors for severe HGG after LT and demonstrates that LT recipients with severe HGG are at increased risk for recurrent pneumonias and more antibiotic courses.

13.
J Thorac Cardiovasc Surg ; 152(3): 901-9, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27234020

RESUMO

OBJECTIVES: Atrial arrhythmia (AA) after lung transplantation (LTx) is a potentially morbid event often associated with increased length of hospital stay. Predictors of postsurgical AA, however, are incompletely understood. We characterized the incidence and predisposing risk factors for AA in patients undergoing LTx. METHODS: A retrospective analysis of prospectively collected data was conducted to identify LTx recipients between January 2008 and October 2013. Patients were divided into 2 groups on the basis of postoperative AA development. Univariable and multivariable analyses were performed to define differences between groups and identify factors associated with AA. Survival differences were assessed by the use of competing risks methodology. RESULTS: A total of 198 of 652 (30.4%) patients developed AA at a median onset of 5 days after transplant. Increasing age (hazard ratio [HR] 1.03 per additional year, P < .001) and previous coronary artery bypass grafting (HR 2.77, P = .002) were found to be independent risk factors. Counterintuitively, patients with a medical history of AA before LTx had a lower incidence of postoperative AA. Preoperative beta-blocker usage was not a significant predictor of postoperative AA. Postoperative AA was a significant predictor of long-term mortality (HR 1.63, P = .007) when we adjusted for other risk factors. CONCLUSIONS: AA is a common occurrence after LTx, occurring with greatest frequency in the first postoperative week, and results in a significant reduction in long-term survival. Increasing age and before coronary artery bypass grafting were identified as independent risk factors for AA development. Better understanding of these risk factors may improve identification of patients at heightened risk after transplantation.


Assuntos
Fibrilação Atrial/epidemiologia , Flutter Atrial/epidemiologia , Transplante de Pulmão , Idoso , Feminino , Humanos , Incidência , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Pennsylvania/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento
14.
J Thorac Cardiovasc Surg ; 151(4): 1171-9, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26778374

RESUMO

OBJECTIVE: Lung transplantation is a life-saving procedure for patients who have end-stage lung disease. The frequency and severity of complications have not been fully characterized. We hypothesized that early in-hospital, postoperative complications decrease long-term survival. METHODS: We retrospectively identified in-hospital complications in lung transplant recipients, from the period January 2007 to October 2013. Complications were graded using the extended Accordion Severity Grading System (ASGS). Complications were categorized by event and organ system. Survival analysis was performed (P < .05) using a time-dependent model. RESULTS: Among 748 eligible patients, 3381 independent in-hospital, postoperative complications occurred in 92.78% of patients. Median follow-up was 5.4 years. Complications associated with significant decrease in 5-year survival were: renal (hazard ratio [HR] 2.58, 95% confidence interval [CI] 1.40-4.48); hepatic (HR 4.08, 95% CI 2.86-5.82); cardiac (HR 1.95, 95% CI 1.56-2.45). The maximum ASGS of ≥5 (18.5% vs 73.8%), and the weighted ASGS sum >10 (2.5% vs 73.8%), were found to be significant predictors of long-term survival. Multivariate analysis identified a weighted ASGS sum of >10, and renal, cardiac, and vascular complications as predictors of decreased long-term survival. CONCLUSIONS: Rigorous delineation of complications after lung transplantation showed that grade 5 ASGS in-hospital postoperative complications, and a weighted ASGS sum >10, were independent predictors of decreased long-term survival well beyond the initial perioperative period. These results may identify important targets for best practice guidelines and quality-of-care measures after lung transplantation.


Assuntos
Transplante de Pulmão/efeitos adversos , Complicações Pós-Operatórias/etiologia , Idoso , Comorbidade , Feminino , Humanos , Transplante de Pulmão/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pennsylvania , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/mortalidade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
15.
Transplantation ; 100(12): 2693-2698, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26760568

RESUMO

BACKGROUND: Adult lung transplant recipients with small chests have traditionally received lungs from pediatric donors, placing an additional strain on the already restricted pediatric donor pool. Performing lobar lung transplantation (LLT) can circumvent issues with donor-recipient size mismatch; however, LLT imparts additional risks. Here, we review our experience using LLT and standard lung transplantation using a pediatric donor (PDLT) for adults with small chests. METHODS: We retrospectively reviewed consecutive patients with end-stage lung disease and a height of 65 inches or less who underwent LLT (n = 15) or PDLT (n = 15) between 2006 and 2012 at our institution, a high-volume lung transplant center. RESULTS: Lobar lung transplantation recipients were older (54 ± 10 vs 48 ± 8 years) and had higher pulmonary pressure (57 ± 11 vs 52 ± 27 mmHg) and higher lung allocation scores (70 ± 9 vs 51 ± 8) than PDLT recipients (all P < 0.05). Mean waiting time was 62 days for PDLT and 9 days for LLT. Postoperatively, the incidence of severe primary graft dysfunction and the incidence of acute renal insufficiency were higher, and the mean intensive care unit stay was longer in the LLT group, but the incidence of bronchial anastomotic complications was higher in the PDLT group because of significant size discrepancy in the main bronchus (P < 0.05). Interestingly, long-term functional outcomes and survival rates were similar between the groups. CONCLUSIONS: Both LLT and PDLT are viable surgical options for adult patients with small chests. Because of the potential impact on posttransplant outcomes, the technical complexity of transplantation, decisions regarding the best surgical approach should be made by experienced surgeons.


Assuntos
Pneumopatias/cirurgia , Transplante de Pulmão/métodos , Adolescente , Adulto , Idoso , Algoritmos , Anastomose Cirúrgica , Tamanho Corporal , Brônquios/cirurgia , Criança , Seleção do Doador , Feminino , Sobrevivência de Enxerto , Humanos , Pulmão/anatomia & histologia , Pulmão/cirurgia , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Retrospectivos , Fatores de Tempo , Doadores de Tecidos , Resultado do Tratamento
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