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1.
Thorax ; 69(2): 123-9, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24431095

RESUMO

BACKGROUND: Pulmonary hypertension (PH)-targeted therapy in the setting of pulmonary fibrosis (PF) is controversial; the main clinical concern is worsening of systemic hypoxaemia. We sought to determine the effects of gentle initiation and chronic administration of parenteral treprostinil on right heart function in patients with PF associated with an advanced PH phenotype. METHODS: Open-label, prospective analysis of patients with PF-PH referred for lung transplantation (LT). Advanced PH was defined as mean pulmonary artery pressure (mPAP) ≥35 mm Hg. We compared haemodynamics, Doppler echocardiography (DE), oxygenation, dyspnoea and quality of life indices, and 6 min walk distance (6MWD) before and 12 weeks after parenteral treprostinil. RESULTS: 15 patients were recruited in the study. After therapy, there were significant improvements in right heart haemodynamics (right atrial pressure (9.5 ± 3.4 vs 6.0 ± 3.7); mPAP (47 ± 8 vs 38.9 ± 13.4); CI (2.3 ± 0.5 vs 2.7 ± 0.6); pulmonary vascular resistance (698 ± 278 vs 496 ± 229); transpulmonary gradient (34.7 ± 8.7 vs 28.5 ± 10.3); mvO2 (65 ± 7.2 vs 70.9 ± 7.4); and stroke volume index (29.2 ± 6.7 vs 33 ± 7.3)) and DE parameters reflecting right heart function (right ventricular (RV) end diastolic area (36.4 ± 5.2 vs 30.9 ± 8.2 cm(2)), left ventricular eccentricity index (1.7 ± 0.6 vs 1.3 ± 0.5), tricuspid annular planar systolic excursion (1.6 ± 0.5 vs 1.9 ± 0.2 cm)). These changes occurred without significant alteration in systemic oxygenation, heart rate, or mean systemic arterial pressure. In addition, improvements were seen in 6MWD (171 ± 93 vs 230 ± 114), 36-Item Short Form Health Survey Mental Component Summary aggregate (38 ± 11 vs 44.2 ± 10.7), University of California, San Diego Shortness of Breath Questionnaire (87 ± 17.1 vs 73.1 ± 21), and brain natriuretic peptide (558 ± 859 vs 228 ± 340). CONCLUSIONS: PH-targeted therapy may improve right heart haemodynamics and echocardiographic function without affecting systemic oxygen saturation in an advanced PH phenotype associated with RV dysfunction in the setting of PF.


Assuntos
Anti-Hipertensivos/uso terapêutico , Epoprostenol/análogos & derivados , Hipertensão Pulmonar/tratamento farmacológico , Fibrose Pulmonar/complicações , Disfunção Ventricular Direita/tratamento farmacológico , Idoso , Dispneia/tratamento farmacológico , Dispneia/etiologia , Dispneia/fisiopatologia , Ecocardiografia Doppler , Epoprostenol/uso terapêutico , Teste de Esforço/métodos , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio/efeitos dos fármacos , Fenótipo , Projetos Piloto , Estudos Prospectivos , Qualidade de Vida , Resultado do Tratamento , Disfunção Ventricular Direita/diagnóstico por imagem , Disfunção Ventricular Direita/etiologia , Disfunção Ventricular Direita/fisiopatologia
2.
Curr Opin Organ Transplant ; 19(3): 303-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24759186

RESUMO

PURPOSE OF REVIEW: The determination of antibody-mediated rejection (AMR) in the pulmonary allograft remains a diagnostic challenge. Herein, we review the pathologic findings from recent studies, including the International Society of Heart and Lung Transplantation (ISHLT) summary statement on pulmonary AMR and preliminary data from the Banff allograft pathology study on AMR in lung transplant patients. RECENT FINDINGS: Some pathologic findings, including acute lung injury and neutrophilic capillary infiltration, are likely to be associated with pulmonary AMR but do not appear to be specific pathologic markers. The ISHLT statement on pulmonary AMR lists numerous pathologic findings that may be associated with donor-specific antibodies (DSAs). Other recent studies, including the Banff study on pulmonary AMR, have found correlations between clinical AMR, defined in part by the presence of DSAs, and nonspecific acute lung injury and capillary neutrophils with or without C4d deposition. SUMMARY: At this time, the diagnosis of lung transplant AMR requires multidisciplinary coordination and is ultimately determined by the managing clinician. In the full clinical context, including knowledge of serologic data for the presence or absence of DSAs, pathologic interpretation may provide valuable information that can guide therapy and support the clinical diagnosis.


Assuntos
Rejeição de Enxerto/patologia , Isoanticorpos/imunologia , Transplante de Pulmão , Aloenxertos , Autoanticorpos/sangue , Biomarcadores , Complemento C4b/imunologia , Rejeição de Enxerto/imunologia , Humanos , Fragmentos de Peptídeos/imunologia , Doadores de Tecidos
3.
J Heart Lung Transplant ; 32(3): 326-32, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23313559

RESUMO

BACKGROUND: Despite data indicating a positive correlation between donor-specific anti-HLA antibodies (DSAs) and early development of bronchiolitis obliterans syndrome (BOS) in lung allografts, the role of an antibody-mediated process in acute and chronic lung allograft rejection has not been elucidated. In this study we evaluated pathologic features of transplant lung biopsies in patients with and without DSAs. METHODS: Forty-one lung transplant biopsies from 41 patients at our institution were included in our study. The biopsy H&E slides were reviewed in a blinded fashion, and scored for presence of microvascular inflammation, acute rejection, bronchiolar inflammation and acute lung injury, as well as diffuse alveolar damage (DAD). Microvascular inflammation was graded by the presence of capillary neutrophils on a scale of 0 to 4(+). For immunohistochemical analysis, the pattern and intensity of staining for C4d and C3d deposition were evaluated in airways and alveolar capillaries. RESULTS: Histopathology suspicious for antibody-mediated rejection (AMR)-defined as≥2(+) neutrophilic infiltration and/or DAD-were more common in DSA-positive cases than controls (11 of 16 vs 6 of 25, p<0.01). Evidence of allograft dysfunction was significantly more common among patients with both DSA and suspicious histopathology compared with controls (5 of 10 vs 3 of 25, p = 0.03). The combination of DSAs and histopathology suspicious for AMR was associated with both BOS (p = 0.002) and mortality (p = 0.03). Immunohistochemistry for C3d and C4d showed no correlation with each other, DSAs or histopathology. CONCLUSIONS: Grade 2(+) neutrophilic infiltration is the histopathologic finding most closely related to DSAs with graft dysfunction and development of BOS in lung transplant recipients and may be a marker for AMR.


Assuntos
Anticorpos/imunologia , Antígenos HLA/imunologia , Transplante de Pulmão/imunologia , Transplante de Pulmão/patologia , Adulto , Idoso , Biópsia , Bronquiolite Obliterante/etiologia , Feminino , Sobrevivência de Enxerto , Humanos , Transplante de Pulmão/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Doadores de Tecidos , Transplante Homólogo , Adulto Jovem
4.
J Heart Lung Transplant ; 28(9): 964-7, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19716051

RESUMO

The available therapies and prognosis of idiopathic pulmonary fibrosis remain relatively poor, and concurrent pulmonary hypertension further increases the risk of death and complications after lung transplantation. Limited data exist for the treatment of pulmonary hypertension associated with idiopathic pulmonary fibrosis. We describe a case where intravenous treprostinil was used to bridge an elderly patient with idiopathic pulmonary fibrosis with severe pulmonary hypertension to successful single-lung transplantation.


Assuntos
Anti-Hipertensivos/uso terapêutico , Epoprostenol/análogos & derivados , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/cirurgia , Fibrose Pulmonar Idiopática/complicações , Fibrose Pulmonar Idiopática/cirurgia , Transplante de Pulmão/métodos , Idoso , Epoprostenol/uso terapêutico , Feminino , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/diagnóstico por imagem , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Piperazinas/uso terapêutico , Purinas/uso terapêutico , Citrato de Sildenafila , Espirometria , Sulfonas/uso terapêutico , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Vasodilatadores/uso terapêutico
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