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1.
Eur Respir J ; 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39209471

RESUMO

Despite the progress made in medical therapies for treating pulmonary hypertension (PH), a subset of patients remain susceptible to developing a maladaptive right ventricular phenotype. The effective management of end-stage PH presents substantial challenges, necessitating a multidisciplinary approach and early identification of patients prone to acute decompensation. Identifying potential transplant candidates and assessing the feasibility of such a procedure are pivotal tasks that should be undertaken early in the treatment algorithm. Inclusion on the transplant list is contingent upon a comprehensive risk assessment, also considering the specific type of PH and various factors affecting waiting times, all of which should inform the decision-making process. While bilateral lung transplantation is the preferred option, it demands expert intra- and post-operative management to mitigate the heightened risks of pulmonary oedema and primary graft dysfunction in PH patients.Despite the availability of risk assessment tools, the occurrence of acute PH decompensation episodes can be unpredictable, potentially leading to refractory right ventricular failure even with optimal medical intervention, necessitating the use of rescue therapies. Advancements in right ventricular assist techniques and adjustments to graft allocation protocols for the most critically ill patients have significantly enhanced the survival in intensive care, affording the opportunity to endure while awaiting an urgent transplant. Given the breadth of therapeutic options available, specialised centres capable of delivering comprehensive care have become indispensable for optimising patient outcomes. These centres are instrumental in providing holistic support and management tailored to the complex needs of PH patients, ultimately enhancing their chances of a successful transplant and improved long-term prognosis.

2.
Transpl Int ; 31(1): 45-55, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28833662

RESUMO

Alpha-1-antitrypsin deficiency (AATD) is grouped with chronic obstructive pulmonary disease (COPD); however, this may not be appropriate. This study assessed whether AATD confers a different prognosis than COPD following lung transplantation. We employed the United Network for Organ Sharing (UNOS) database, grouping patients by diagnoses of AATD or COPD. Kaplan-Meier methods and Cox modeling were performed to determine the association of diagnosis and overall survival. Of 9569 patients, 1394 (14.6%) had a diagnosis of AATD. Patients with AATD who received a single-lung transplant had reduced 1-year survival [adjusted hazard ratio (AHR): 1.68, 95% CI: 1.26, 2.23]. Among patients who received a bilateral lung transplant, there was no significant difference in survival by diagnosis (AHR for AATD as compared to COPD: 0.96, 95% CI: 0.82, 1.12). After the implementation of the lung allocation score (LAS), there was no significant difference in survival among patients who received a single (AHR: 1.15, 95% CI: 0.69, 1.95) or bilateral (AHR: 0.99, 95% CI: 0.73, 1.34) lung transplant by diagnosis. Lung transplantation is increasingly employed in the care of the patient with COPD. Although recipients undergoing LTX for AATD are at increased risk of both acute rejection and airway dehiscence post-transplant, in the post-LAS era, survival rates are similar for recipients with AATD in comparison with COPD.


Assuntos
Transplante de Pulmão/mortalidade , Doença Pulmonar Obstrutiva Crônica/genética , Deficiência de alfa 1-Antitripsina/cirurgia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/cirurgia , Análise de Sobrevida , Estados Unidos/epidemiologia , Deficiência de alfa 1-Antitripsina/complicações , Deficiência de alfa 1-Antitripsina/mortalidade
3.
Clin Transplant ; 31(7)2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28470765

RESUMO

PURPOSE: Early research suggests prolonged ischemic time in older donor lungs is associated with decreased survival following lung transplantation. The purpose of this study was to determine whether this association holds in the post-lung allocation score era. METHODS: We analyzed the United Network for Organ Sharing database 2005-2013 for adult recipients of cadaveric lung transplants. Cox proportional hazards modeling was utilized to determine the association of donor age, ischemic time, and the interaction of donor age and ischemic time with transplant-free survival. RESULTS: Eleven thousand eight hundred thirty-five patients met criteria. Median donor age was 32 years, and median ischemic time was 4.9 hours. Cox modeling demonstrated that donor age 50-60 (adjusted hazard ratio (HR): 1.11) and ≥60 (adjusted HR: 1.42) were associated with reduced overall survival. Neither ischemic time nor interaction of ischemic time and donor age were significantly associated with overall survival. Subanalysis demonstrated that this finding held true for patients undergoing either single or bilateral lung transplantation. CONCLUSIONS: Prolonged ischemic time is not associated with decreased overall survival in patients undergoing lung transplantation regardless of the donor's age. However, donor age >50 is independently associated with decreased survival. The lack of an association between ischemic time and survival should encourage broader geographic allocation of pulmonary allografts.


Assuntos
Isquemia/mortalidade , Transplante de Pulmão/mortalidade , Pulmão/irrigação sanguínea , Doadores de Tecidos , Obtenção de Tecidos e Órgãos , Adolescente , Adulto , Fatores Etários , Idoso , Cadáver , Criança , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Adulto Jovem
4.
Transpl Int ; 29(2): 253-61, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26820489

RESUMO

Repetitive gastric fluid aspirations have been shown to lead to obliterans bronchiolitis (OB), but the component or components of gastric fluid that are responsible are unknown. This study investigates the role of particulates and, separately, soluble material in gastric fluid during the development of OB. Whole gastric fluid (WGF) was collected from male Fischer 344 (F344) rats and separated by centrifugation into particle reduced gastric fluid (PRGF) and particulate components resuspended in normal saline (PNS). Orthotopic left lung transplants from male Wistar-Kyoto rats into F344 rats were performed using a modification of the nonsuture external cuff technique with prolonged cold ischemia. Rats were subjected to weekly aspiration of 0.5 ml/kg of WGF (n = 9), PRGF (n = 10), PNS (n = 9), or normal saline (control, NS; n = 9) for 8 weeks following transplantation. Lung allografts treated with WGF, PRGF, or PNS developed a significantly greater percentage of OB-like lesions compared with the control. No statistical difference was observed when comparing the fibrosis grades or the percentage of OB lesions of WGF, PRGF, and PNS groups, suggesting that both soluble and insoluble components of gastric fluid can promote the development of aspiration-induced OB and fibrosis in lung allografts.


Assuntos
Bronquiolite Obliterante/etiologia , Mucosa Gástrica/metabolismo , Transplante de Pulmão/efeitos adversos , Aspiração Respiratória/complicações , Animais , Pulmão/patologia , Complacência Pulmonar , Masculino , Fibrose Pulmonar/etiologia , Ratos , Ratos Endogâmicos F344 , Ratos Endogâmicos WKY , Transplante Homólogo
5.
Exp Lung Res ; 42(1): 37-43, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26873328

RESUMO

PURPOSE: In the clinical setting, there is no reliable tool for diagnosing gastric aspiration. A potential way of diagnosing gastric fluid aspiration entails bronchoalveolar lavage (BAL) with subsequent examination of the BAL fluid for gastric fluid components that are exogenous to the lungs. The objective of this study was to determine the longevity of the gastric fluid components bile and trypsin in the lung, in order to provide an estimate of the time frame in which assessment of these components in the BAL might effectively be used as a measure of aspiration. MATERIALS AND METHODS: Human gastric fluid (0.5 mg/kg) was infused in the right lung of intubated male Fischer 344 rats (n = 30). Animals were sacrificed at specified times following the experimentally induced aspiration, and bronchoalveolar lavage fluid (BALF) was collected. Bile concentrations were analyzed by an enzyme-linked chromatogenic method, and the concentration of trypsin was quantified using an ELISA. Data were analyzed using non-linear regression and a one-phase decay equation. RESULTS: In this experimental model, the half-life of bile was 9.3 hours (r(2) = 0.81), and the half-life of trypsin was 9.0 hours (r(2) = 0.68). CONCLUSIONS: The half-lives of bile and trypsin in the rodent aspiration model suggest that the ability to detect aspiration may be limited to a few days post-aspiration. If studies using rats are any indication, it may be most effective to collect BAL samples within the first 24 hours of suspected aspiration events in order to detect aspiration.


Assuntos
Bile/metabolismo , Líquidos Corporais/metabolismo , Tripsina/metabolismo , Animais , Lavagem Broncoalveolar/métodos , Líquido da Lavagem Broncoalveolar , Humanos , Pulmão , Masculino , Paracentese/métodos , Ratos , Ratos Endogâmicos F344
6.
Am J Respir Crit Care Med ; 192(7): 843-52, 2015 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-26067395

RESUMO

RATIONALE: The use of 6-minute-walk distance (6MWD) as an indicator of exercise capacity to predict postoperative survival in lung transplantation has not previously been well studied. OBJECTIVES: To evaluate the association between 6MWD and postoperative survival following lung transplantation. METHODS: Adult, first time, lung-only transplantations per the United Network for Organ Sharing database from May 2005 to December 2011 were analyzed. Kaplan-Meier methods and Cox proportional hazards modeling were used to determine the association between preoperative 6MWD and post-transplant survival after adjusting for potential confounders. A receiver operating characteristic curve was used to determine the 6MWD value that provided maximal separation in 1-year mortality. A subanalysis was performed to assess the association between 6MWD and post-transplant survival by disease category. MEASUREMENTS AND MAIN RESULTS: A total of 9,526 patients were included for analysis. The median 6MWD was 787 ft (25th-75th percentiles = 450-1,082 ft). Increasing 6MWD was associated with significantly lower overall hazard of death (P < 0.001). Continuous increase in walk distance through 1,200-1,400 ft conferred an incremental survival advantage. Although 6MWD strongly correlated with survival, the impact of a single dichotomous value to predict outcomes was limited. All disease categories demonstrated significantly longer survival with increasing 6MWD (P ≤ 0.009) except pulmonary vascular disease (P = 0.74); however, the low volume in this category (n = 312; 3.3%) may limit the ability to detect an association. CONCLUSIONS: 6MWD is significantly associated with post-transplant survival and is best incorporated into transplant evaluations on a continuous basis given limited ability of a single, dichotomous value to predict outcomes.


Assuntos
Teste de Esforço , Transplante de Pulmão/mortalidade , Adulto , Tolerância ao Exercício , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos , Adulto Jovem
7.
Am J Respir Crit Care Med ; 188(4): 466-73, 2013 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-23777361

RESUMO

RATIONALE: Patients who progress to brain death after resuscitation from cardiac arrest have been hypothesized to represent an underused source of potential organ donors; however, there is a paucity of data regarding the viability of lung allografts after a period of cardiac arrest in the donor. OBJECTIVES: To analyze postoperative complications and survival after lung transplant from brain-dead donors resuscitated after cardiac arrest. METHODS: The United Network for Organ Sharing database records donors with cardiac arrest occurring after brain death. Adult recipients of lung allografts from these arrest/resuscitation donors between 2005 and 2011 were compared with nonarrest donors. Propensity score matching was used to reduce the effect of confounding. Postoperative complications and overall survival were assessed using McNemar's test for correlated binary proportions and Kaplan-Meier methods. MEASUREMENTS AND MAIN RESULTS: A total of 479 lung transplant recipients from arrest/resuscitation donors were 1:1 propensity matched from a cohort of 9,076 control subjects. Baseline characteristics in the 1:1-matched cohort were balanced. There was no significant difference in perioperative mortality, airway dehiscence, dialysis requirement, postoperative length of stay (P ≥ 0.38 for all), or overall survival (P = 0.52). A subanalysis of the donor arrest group demonstrated similar survival when stratified by resuscitation time quartile (P = 0.38). CONCLUSIONS: There is no evidence of inferior outcomes after lung transplant from brain-dead donors who have had a period of cardiac arrest provided that good lung function is preserved and the donor is otherwise deemed acceptable for transplantation. Potential expansion of the donor pool to include cardiac arrest as the cause of brain death requires further study.


Assuntos
Morte Encefálica , Reanimação Cardiopulmonar , Parada Cardíaca/mortalidade , Transplante de Pulmão , Doadores de Tecidos , Adulto , Feminino , Humanos , Masculino , Pontuação de Propensão , Transplante Homólogo , Adulto Jovem
8.
J Surg Res ; 181(1): e31-8, 2013 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-22765998

RESUMO

BACKGROUND: Chronic aspiration of gastric fluid potentially plays a central role in the pathogenesis of obliterative bronchiolitis, which is often associated with chronic pulmonary allograft failure. It remains unknown whether pharmaceutical-induced increases in gastric pH might effectively prevent any putative pulmonary injury associated with chronic aspiration. MATERIALS AND METHODS: To test the hypothesis that neutralization of gastric fluid would affect the development of aspiration-associated obliterative bronchiolitis, an established rat lung transplant model (WKY-to-F344) was utilized. Pulmonary allograft recipients were subjected to eight weekly aspirations of gastric fluid at pH 2.5 (low-pH), gastric fluid at pH 7.4 (neutralized-pH), or saline as a control. RESULTS: Histologic analysis revealed that the fraction of airways affected with lesions consistent with obliterative bronchiolitis was 0.55 ± 0.08 (mean ± SEM) in rats receiving aspiration with low-pH gastric fluid, 0.49 ± 0.07 in animals receiving neutralized-pH gastric fluid, and 0.07 ± 0.05 in rats receiving normal saline only. The difference between groups receiving gastric fluid, regardless of pH, was significantly different from the saline control (P < 0.0001), whereas the difference between the groups receiving low-pH gastric fluid and neutralized-pH gastric fluid was not significant (P = 0.75). CONCLUSIONS: Effective management of gastroesophageal reflux disease in lung transplant recipients should probably include more than neutralization of gastric fluid.


Assuntos
Transplante de Pulmão/efeitos adversos , Aspiração Respiratória de Conteúdos Gástricos/etiologia , Animais , Determinação da Acidez Gástrica , Refluxo Gastroesofágico/etiologia , Concentração de Íons de Hidrogênio , Pulmão/patologia , Complacência Pulmonar , Masculino , Ratos , Ratos Endogâmicos F344 , Ratos Endogâmicos WKY , Transplante Homólogo
9.
Ann Thorac Surg ; 115(4): 1024-1032, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36216086

RESUMO

BACKGROUND: Aspiration has been associated with graft dysfunction after lung transplantation, leading some to advocate for selective use of fundoplication despite minimal data supporting this practice. METHODS: We performed a multicenter retrospective study at 4 academic lung transplant centers to determine the association of gastroesophageal reflux disease and fundoplication with bronchiolitis obliterans syndrome and survival using Cox multivariable regression. RESULTS: Of 542 patients, 136 (25.1%) underwent fundoplication; 99 (18%) were found to have reflux disease without undergoing fundoplication. Blanking the first year after transplantation, fundoplication was not associated with a benefit regarding freedom from bronchiolitis obliterans syndrome (hazard ratio [HR], 0.93; 95% CI, 0.58-1.49) or death (HR, 0.97; 95% CI, 0.47-1.99) compared with reflux disease without fundoplication. However, a time-dependent adjusted analysis found a slight decrease in mortality (HR, 0.59; 95% CI, 0.28-1.23; P = .157), bronchiolitis obliterans syndrome (HR, 0.68; 95% CI, 0.42-1.11; P = .126), and combined bronchiolitis obliterans syndrome or death (HR, 0.66; 95% CI, 0.42-1.04; P = .073) in the fundoplication group compared with the gastroesophageal reflux disease group. CONCLUSIONS: Although a statistically significant benefit from fundoplication was not determined because of limited sample size, follow-up, and potential for selection bias, a randomized, prospective study is still warranted.


Assuntos
Síndrome de Bronquiolite Obliterante , Bronquiolite Obliterante , Refluxo Gastroesofágico , Transplante de Pulmão , Humanos , Estudos Retrospectivos , Estudos Prospectivos , Bronquiolite Obliterante/epidemiologia , Bronquiolite Obliterante/etiologia , Refluxo Gastroesofágico/cirurgia , Transplante de Pulmão/efeitos adversos
10.
Inflamm Res ; 61(8): 863-73, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22565668

RESUMO

OBJECTIVE AND DESIGN: The hypothesis that aspiration of gastric fluid drives the anti-ovalbumin response toward a Th2 reaction even in animals not prone to Th2 responses was evaluated. SUBJECTS: Forty-eight male C57BL/6 mice were used. METHODS: Mice were sensitized and challenged with ovalbumin starting 5 weeks prior to the initiation of weekly aspirations of either gastric fluid or normal saline as a control. Weekly aspiration continued during the course of exposure to ovalbumin. TREATMENT: Aspiration consisted of 50 µl of gastric fluid with 50 µl of 0.9 % normal saline used as a control. Antigen exposure consisted of sensitization to ovalbumin via intraperitoneal injection on days 0 and 14 and challenge on day 21 with aerosolized antigen for 30 min. RESULTS: No evidence of a shift toward a Th2 response as a result of gastric fluid aspiration was seen in the Th1-prone strain utilized, although a profound down-regulation of a broad array of T cell-associated cytokines and chemokines and up-regulation of macrophage-associated markers was observed as a result of aspiration. CONCLUSIONS: These data provide support for the hypothesis that the clinical association between asthma and gastroesophageal reflux disease (GERD) does not involve an exacerbation of asthma by GERD-associated aspiration of gastric fluid, but may cause immune reactions unrelated to the asthma pathology.


Assuntos
Asma/imunologia , Suco Gástrico , Aspiração Respiratória , Imunidade Adaptativa , Animais , Antígenos/imunologia , Asma/patologia , Citocinas/imunologia , Modelos Animais de Doenças , Refluxo Gastroesofágico/imunologia , Células Gigantes/patologia , Imunidade Inata , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ovalbumina/imunologia
11.
Clin Transplant ; 26(1): 97-104, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-21395692

RESUMO

Caregivers for patients undergoing solid organ transplantation play an essential role in the process of transplantation. However, little is known about stress and coping among these caregivers. Six hundred and twenty-one primary caregivers of potential candidates for lung (n = 317), liver (n = 147), heart (n = 115), and/or kidney (n = 42) transplantation completed a psychometric test battery at the time of the candidate's initial pre-transplant psychosocial evaluation. Caregivers were generally well adjusted, with only 17% exhibiting clinical symptoms of depression (Beck Depression Inventory-II score >13) and 13% reporting clinical levels of anxiety (State Trait Anxiety Inventory score >48). Greater caregiver burden and negative coping styles were associated with higher levels of depression. Greater objective burden and avoidant coping were associated with higher levels of anxiety. Caregivers evidenced a high degree of socially desirable (i.e., defensive) responding, which may reflect a deliberate effort to minimize fears or worries so as to not jeopardize patients' listing status.


Assuntos
Adaptação Psicológica , Cuidadores/psicologia , Transplante de Órgãos/psicologia , Estresse Psicológico/etiologia , Listas de Espera , Ansiedade/etiologia , Depressão/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica
12.
Curr Opin Organ Transplant ; 17(5): 474-8, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22941322

RESUMO

PURPOSE OF REVIEW: Chronic allograft failure remains the leading cause of late mortality following lung transplantation. Considerable evidence demonstrates a relationship between gastroesophageal reflux disease (GERD) induced allograft injury and bronchiolitis obliterans syndrome; however, the mechanism of injury, identification of at-risk patients, and treatment options remain to be elucidated. RECENT FINDINGS: The recent findings in this area help delineate the inflammatory pathways associated with GERD-induced lung injury. They also demonstrate that clinically useful markers of aspiration-induced injury may be available via studying bronchoalveolar fluid or even induced sputum. Simple acid neutralization is not adequate to protect these patients from aspiration injury. In fact, there are no convincing data to indicate that medical therapies provide adequate treatment. In contradistinction, surgical fundoplication is associated with decreased levels of inflammatory cytokines and markers of aspiration in bronchoalveolar fluid, as well as improvements in pulmonary function in these patients. SUMMARY: Recent findings support ubiquitous testing for GERD or aspiration in patients with end-stage lung disease both pretransplant and posttransplant and demonstrate that fundoplication can safely and effectively protect these patients from the on-going injury of GERD-induced pulmonary injury.


Assuntos
Refluxo Gastroesofágico/etiologia , Transplante de Pulmão/efeitos adversos , Refluxo Gastroesofágico/cirurgia , Humanos
13.
Crit Care Med ; 39(12): 2593-8, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21765353

RESUMO

OBJECTIVE: Extracorporeal membrane oxygenation as a bridge to lung transplantation has traditionally been associated with substantial morbidity and mortality. A major contributor to these complications may be weakness and overall deconditioning secondary to pretransplant critical illness and immobility. In an attempt to address this issue, we developed a collaborative program to allow for active rehabilitation and physical therapy for patients requiring life support with extracorporeal membrane oxygenation before lung transplantation. DESIGN: An interdisciplinary team responded to an acute need to develop a mechanism for active rehabilitation and physical therapy for patients awaiting lung transplantation while being managed with extracorporeal membrane oxygenation. We describe a series of three patients who benefited from this new approach. SETTING: A quaternary care pediatric intensive care unit in a children's hospital set within an 800-bed university academic hospital with an active lung transplantation program for adolescent and adult patients. PATIENTS, INTERVENTIONS, AND MAIN RESULTS: Three patients (ages 16, 20, and 24 yrs) with end-stage respiratory failure were rehabilitated while on extracorporeal membrane oxygenation awaiting lung transplantation. These patients were involved in active rehabilitation and physical therapy and, ultimately, were ambulatory on extracorporeal membrane oxygenation before successful transplantation. Following lung transplantation, the patients were liberated from mechanical ventilation, weaned to room air, transitioned out of the intensive care unit, and ambulatory less than 1 wk posttransplant. CONCLUSIONS: A comprehensive, multidisciplinary system can be developed to safely allow for active rehabilitation, physical therapy, and ambulation of patients being managed with extracorporeal membrane oxygenation. Such programs may lead to a decreased threshold for the utilization of extracorporeal membrane oxygenation before transplant and have the potential to improve conditioning, decrease resource utilization, and lead to better outcomes in patients who require extracorporeal membrane oxygenation before lung transplantation.


Assuntos
Oxigenação por Membrana Extracorpórea/reabilitação , Transplante de Pulmão , Modalidades de Fisioterapia , Adolescente , Deambulação Precoce/métodos , Feminino , Humanos , Unidades de Terapia Intensiva Pediátrica , Transplante de Pulmão/métodos , Equipe de Assistência ao Paciente , Cuidados Pré-Operatórios/métodos , Adulto Jovem
14.
Xenotransplantation ; 18(1): 6-13, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21342283

RESUMO

BACKGROUND: After substantial progress on many fronts, one of the remaining barriers still opposing the clinical application of xenotransplantation is a disseminated intravascular coagulopathy (DIC) that is observed in the pre-clinical model of porcine-to-primate transplantation. The onset of DIC is particularly rapid in recipients of pulmonary xenografts, usually occurring within the first days or even hours of reperfusion. METHODS: In this study, we describe the results of two porcine-to-baboon transplants utilizing porcine lungs depleted of macrophages, deficient in the α-1,3-galactosyltransferase gene, and with the expression of human decay-accelerating factor, a complement regulatory protein. RESULTS: In both cases, evidence of DIC was observed within 48 h of reperfusion, with thrombocytopenia and increases in levels of thrombin-antithrombin complex evident in both cases. Depletion of fibrinogen was observed in one graft, whereas elevation of D-dimer levels was observed in the other. One graft, which showed focal lymphocytic infiltrates pre-operatively, failed within 3 h. CONCLUSIONS: The results indicate that further efforts to address the coagulopathy associated with pulmonary xenotransplantation are needed. Further, evidence suggests that resident porcine immune cells can play an important role in the coagulopathy associated with xenotransplantation.


Assuntos
Transtornos da Coagulação Sanguínea/imunologia , Galactosiltransferases/genética , Transplante de Pulmão/imunologia , Transplante Heterólogo/imunologia , Animais , Antitrombinas/metabolismo , Antígenos CD55/genética , Antígenos CD55/imunologia , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Galactosiltransferases/metabolismo , Técnicas de Silenciamento de Genes , Sobrevivência de Enxerto , Humanos , Papio/imunologia , Suínos/imunologia , Trombina/metabolismo , Transplante Heterólogo/patologia
15.
JMIR Res Protoc ; 10(5): e25397, 2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-33848258

RESUMO

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare sequela of acute pulmonary embolism that is treatable when recognized. Awareness of this disease has increased with recent advancements in therapeutic options, but delays in diagnosis remain common, and diagnostic and treatment guidelines are often not followed. Data gathered from international registries have improved our understanding of CTEPH, but these data may not be applicable to the US population owing to differences in demographics and medical practice patterns. OBJECTIVE: The US CTEPH Registry (US-CTEPH-R) was developed to provide essential information to better understand the demographics, risk factors, evaluation, and treatment of CTEPH in the United States, as well as the short- and long-term outcomes of surgical and nonsurgical therapies in the modern treatment era. METHODS: Thirty sites throughout the United States enrolled 750 subjects in this prospective, longitudinal, observational registry of patients newly diagnosed with CTEPH. Enrollment criteria included a mean pulmonary artery pressure ≥25 mmHg by right heart catheterization and radiologic confirmation of CTEPH by a multidisciplinary adjudication committee. Following enrollment, subjects were followed biannually until the conclusion of the study. Quality of life surveys were administered at enrollment and biannually, and all other testing was at the discretion of the treating clinician. Details regarding surgical therapy, balloon pulmonary angioplasty, and medical therapy were collected at enrollment and at follow-up, as well as information related to health care utilization and survival. RESULTS: Data from this registry will improve understanding of the demographics, risk factors, and treatment patterns of patients with CTEPH, and the longitudinal impact of therapies on quality of life, health care utilization, and survival. CONCLUSIONS: This manuscript details the methodology and design of the first large, prospective, longitudinal registry of patients with CTEPH in the United States. TRIAL REGISTRATION: ClinicalTrials.gov NCT02429284; https://www.clinicaltrials.gov/ct2/show/NCT02429284. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/25397.

16.
Open Forum Infect Dis ; 8(10): ofab170, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34642634

RESUMO

It has been established that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses angiotensin-converting enzyme 2 (ACE2), a membrane-bound regulatory peptide, for host cell entry. Renin-angiotensin-aldosterone system (RAAS) inhibitors have been reported to increase ACE2 in type 2 pneumocyte pulmonary tissue. Controversy exists for the continuation of ACE inhibitors, angiotensin II receptor blockers, and mineralocorticoid receptor antagonists in the current pandemic. ACE2 serves as a regulatory enzyme in maintaining homeostasis between proinflammatory angiotensin II and anti-inflammatory angiotensin 1,7 peptides. Derangements in these peptides are associated with cardiovascular disease and are implicated in the progression of acute respiratory distress syndrome. Augmentation of the ACE2/Ang 1,7 axis represents a critical target in the supportive management of coronavirus disease 2019-associated lung disease. Observational data describing the use of RAAS inhibitors in the setting of SARS-CoV-2 have not borne signals of harm to date. However, equipoise persists, requiring an analysis of novel agents including recombinant human-ACE2 and existing RAAS inhibitors while balancing ongoing controversies associated with increased coronavirus infectivity and virulence.

17.
Chest ; 160(5): 1822-1831, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34090871

RESUMO

BACKGROUND: The United States Chronic Thromboembolic Pulmonary Hypertension Registry (US-CTEPH-R) was designed to characterize the demographic characteristics, evaluation, clinical course, and outcomes of surgical and nonsurgical therapies for patients with chronic thromboembolic pulmonary hypertension. RESEARCH QUESTION: What are the differences in baseline characteristics and 1-year outcomes between operated and nonoperated subjects? STUDY DESIGN AND METHODS: This study describes a multicenter, prospective, longitudinal, observational registry of patients newly diagnosed (< 6 months) with CTEPH. Inclusion criteria required a mean pulmonary artery pressure ≥ 25 mm Hg documented by right heart catheterization and radiologic confirmation of CTEPH. Between 2015 and 2018, a total of 750 patients were enrolled and followed up biannually until 2019. RESULTS: Most patients with CTEPH (87.9%) reported a history of acute pulmonary embolism. CTEPH diagnosis delays were frequent (median, 10 months), and most patients reported World Health Organization functional class 3 status at enrollment with a median mean pulmonary artery pressure of 44 mm Hg. The registry cohort was subdivided into Operable patients undergoing pulmonary thromboendarterectomy (PTE) surgery (n = 566), Operable patients who did not undergo surgery (n = 88), and those who were Inoperable (n = 96). Inoperable patients were older than Operated patients; less likely to be obese; have a DVT history, non-type O blood group, or thrombophilia; and more likely to have COPD or a history of cancer. PTE resulted in a median pulmonary vascular resistance decline from 6.9 to 2.6 Wood units (P < .001) with a 3.9% in-hospital mortality. At 1-year follow-up, Operated patients were less likely treated with oxygen, diuretics, or pulmonary hypertension-targeted therapy compared with Inoperable patients. A larger percentage of Operated patients were World Health Organization functional class 1 or 2 at 1 year (82.9%) compared with the Inoperable (48.2%) and Operable/No Surgery (56%) groups (P < .001). INTERPRETATION: Differences exist in the clinical characteristics between patients who exhibited operable CTEPH and those who were inoperable, with the most favorable 1-year outcomes in those who underwent PTE surgery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02429284; URL: www.clinicaltrials.gov.


Assuntos
Tratamento Conservador , Endarterectomia , Hipertensão Pulmonar , Embolia Pulmonar , Anti-Hipertensivos/uso terapêutico , Tratamento Conservador/métodos , Tratamento Conservador/estatística & dados numéricos , Endarterectomia/efeitos adversos , Endarterectomia/métodos , Endarterectomia/estatística & dados numéricos , Feminino , Estado Funcional , Humanos , Hipertensão Pulmonar/epidemiologia , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/terapia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Oxigenoterapia/métodos , Oxigenoterapia/estatística & dados numéricos , Embolia Pulmonar/complicações , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/cirurgia , Pressão Propulsora Pulmonar , Sistema de Registros , Medição de Risco , Fatores de Risco , Estados Unidos/epidemiologia , Resistência Vascular
18.
J Clin Microbiol ; 48(11): 4083-8, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20720025

RESUMO

The Fungitell assay for (1,3)ß-D-glucan (BG) detection in serum has been evaluated in patients with invasive fungal infections (IFIs) and healthy controls and for the early diagnosis of IFI in cancer patients. We evaluated the BG assay for the detection of IFI in lung transplant recipients. Serial serum samples were prospectively collected from patients undergoing lung transplants at Duke Hospital. Fungal infections were classified according to revised European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. A receiver operator characteristic (ROC) curve was generated; possible causes for false-positive and false-negative tests were investigated by linear regression analysis. Seven hundred fifty-six serum specimens from 59 subjects without IFI and 41 specimens from 14 patients with proven or probable IFI were tested. The area under the ROC curve was 0.69. Based on a 60-pg/ml positive cutoff, per-patient sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 64%, 9%, 14%, and 50%, respectively; per-test estimates were 71%, 59%, 9%, and 97%, respectively. The majority (92%) of patients not diagnosed with an IFI had at least one BG level of ≥60 pg/ml, and 90% had at least one BG level of ≥80 pg/ml. Respiratory colonization with mold and hemodialysis significantly affected mean BG levels. In conclusion, the accuracy of the BG test is marginal and its utility as a tool for the early diagnosis of IFI is questionable in the lung transplant population. Although the NPV of the BG test is high, the low PPV limits its utility as a screening tool for early diagnosis of IFI.


Assuntos
Hospedeiro Imunocomprometido , Transplante de Pulmão , Micologia/métodos , Micoses/diagnóstico , beta-Glucanas/sangue , Adulto , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Proteoglicanas , Sensibilidade e Especificidade , Soro/química
19.
Surg Endosc ; 24(5): 1066-74, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-19915914

RESUMO

BACKGROUND: A large number of studies point toward chronic aspiration associated with gastroesophageal reflux disease (GERD) as an important factor involved in the development of asthma, the incidence of which has increased dramatically in industrially developed countries. Recent work suggests that medical intervention aimed at acid blockade is not sufficient to relieve the effects of chronic aspiration on asthma pathology, leaving surgical treatment of the disease as one of the few remaining options. This study examined the effect of chronic aspiration on the airway-associated immune response to allergens using a model of experimentally induced airway hypersensitivity in Balb/c mice. METHODS: The mice received aspiration of gastric fluid on days 1, 8, 15, 22, 29, 36, 43, and 50 and were sensitized to ovalbumin by intraperitoneal (IP) injection on days 33 and 47, challenged with aerosolized ovalbumin on day 54, and killed on day 56. Control mice received sham gastric fluid aspirations, sham induction of airway hypersensitivity, or both. RESULTS: Chronic aspiration of 50 microl murine gastric fluid once per week for 8 weeks had a profound effect on the immune system in the lung, with upregulation of the macrophage/monocyte-associated cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-12 (IL-12) and profound downregulation of a broad array of T-cell-associated cytokines including interleukins 2, 4, 5, 6, 10, 13, and 23, as well as interferon-gamma. The aspiration-induced depression of IL-5 production in particular was found only in mice with airway hypersensitivity and not in control mice without airway hypersensitivity. CONCLUSIONS: The results indicate that chronic aspiration of gastric fluid has a profound effect on the nature of the allergic response to aerosolized allergens, suggesting that the aspiration may be an important factor affecting the pathogenesis of asthma.


Assuntos
Asma/imunologia , Ácido Gástrico/metabolismo , Refluxo Gastroesofágico/complicações , Imunidade Celular , Pulmão/imunologia , Macrófagos Alveolares/imunologia , Linfócitos T/imunologia , Animais , Asma/etiologia , Modelos Animais de Doenças , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Seguimentos , Refluxo Gastroesofágico/metabolismo , Interleucina-12/imunologia , Interleucina-5/biossíntese , Pulmão/metabolismo , Macrófagos Alveolares/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fator de Necrose Tumoral alfa/imunologia
20.
J Heart Lung Transplant ; 39(9): 954-961, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32475748

RESUMO

BACKGROUND: Ex vivo lung perfusion (EVLP) allows for a reassessment of lung grafts initially deemed unsuitable for transplantation, increasing the available donor pool; however, this requires a pre- and post-EVLP period of cold ischemic time (CIT). Paucity of data exists on how the sequence of cold normothermic-cold preservations affect outcomes. METHODS: A total of 110 patients were retrospectively analyzed. Duration of 3 preservation phases was measured: cold pre-EVLP, EVLP, and cold post-EVLP. The donor and recipient clinical data were collected. Primary graft dysfunction (PGD) and survival were monitored. Risk of mortality or PGD was calculated using Cox proportional hazards and logistic regression models to adjust for baseline characteristics. RESULTS: Using the highest quartile, patients were stratified into extended vs non-extended pre-EVLP (<264 vs ≥264 minutes) and post-EVLP (<287 vs ≥287 minutes) CIT. The rates of 1-year mortality (8.4% vs 29.6%, p = 0.013), PGD 2-3 (20.5% vs 52%, p = 0.002), and PGD 3 (8.4% vs 29.6%, p = 0.005) at 72 hours were increased in the extended post-EVLP CIT group. After adjusting for baseline risk factors, the extended group remained an independent predictor of PGD ≥2 (odd ratio: 6.18, 95% CI: 1.88-20.3, p = 0.003) and PGD 3 (odd ratio: 20.4, 95% CI: 2.56-161.9, p = 0.004) at 72 hours and 1-year mortality (hazard ratio: 17.9, 95% CI: 3.36-95.3, p = 0.001). Cold pre-EVLP was not a significant predictor of primary outcomes. CONCLUSIONS: Extended cold post-EVLP preservation is associated with a risk for PGD and 1-year mortality. Pre-EVLP CIT does not increase mortality or high-grade PGD. These findings from a multicenter trial should caution on the implementation of extended cold preservation after EVLP.


Assuntos
Transplante de Pulmão/efeitos adversos , Preservação de Órgãos/métodos , Perfusão/métodos , Disfunção Primária do Enxerto/prevenção & controle , Doadores de Tecidos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Disfunção Primária do Enxerto/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologia , Adulto Jovem
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