Post-Transplant Obliterative Bronchiolitis and Other Late Lung Sequelae in Human Heart-Lung Transplantation

Burke, Conor M.; Theodore, James; Dawkins, Keith D.; Yousem, Samuel A.; Blank, Norman; Billingham, Margaret E.; Kessel, Antonius Van; Jamieson, Stuart W.; Oyer, Philip E.; Baldwin, John C.; Stinson, Edward B.; Shumway, Norman E.; Robin, Eugene D.

doi:10.1378/chest.86.6.824

Cited by 386 publications

(132 citation statements)

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“…9 In analogous clinical observations, O'Connell et al 44 reported that a large number of donor leukocytes in bronchoalveolar lavage specimens from human lung recipients was associated with the absence in the allograft of bronchiolitis obliterans, the hallmark lesion of CR in pulmonary allografts. 45 Although a high proportion of donor leukocytes in the heart grafts correlated with the CR-free state, it did not predict the extent to which donor-specific nonreactivity had developed. The presence of a large percentage of donor leukocytes in the cell suspensions prepared from CR-free heart allografts in group 4 was clearly dependent on a once-weekly maintenance dose of TAC.…”

Section: Discussionmentioning

confidence: 88%

Donor and recipient leukocytes in organ allografts of recipients with variable donor-specific tolerance: With particular reference to chronic rejection

et al. 2000

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We have attributed organ engraftment to clonal exhaustion-deletion of host-versus-graft and graft-versus-host reactions that are reciprocally induced and governed by migratory donor and recipient leukocytes. The so-called donor passenger leukocytes that migrate from the allograft into the recipients have been thoroughly studied (chimerism), but not the donor leukocytes that remain in, or return to, the transplanted organ. Therefore, using flow cytometry we determined the percentage and lineages of donor leukocytes in cell suspensions prepared from Lewis (LEW) cardiac allografts to 100 days posttransplantation. The LEW hearts were transplanted to naïve untreated Brown Norway (BN) recipients (group 2), to naïve BN recipients treated with a 28-day or continuous course of tacrolimus (TAC) (groups 3 and 4), and to drug-free BN recipients pretolerized by earlier bone marrow cell (BMC) or orthotopic LEW liver transplantation (groups 5 and 6). The findings in the heart cell suspensions were correlated with the results from parallel histopathologic-immunocytochemical studies and other studies of the grafts and of host tissues. Although the LEW heart allografts were rejected in 9.6 days by the unmodified recipients of group 2, all beat for 100 days in the recipients of groups 3 through 6. Nevertheless, all of the long-surviving cardiac allografts (but not the isografts in group 1) were the targets of an immune reaction at 5 days, reflected by dramatic increases in the ratio of leukocytes to nonleukocyte nucleated cells from normal values of 1:5-1:6 to 1:1-5:1 and by manifold other evidence of a major inflammatory event. The acute changes returned to baseline by 100 days in the chronic rejection (CR) free hearts of groups 4 and 6, but not in the CR-afflicted hearts of short-course TAC group 3 or the less-severely damaged hearts of the BMC-prime group 5.The freedom from CR in groups 4 and 6 was associated with a large donor contribution to the intracardiac leukocyte population at 5 days (28.6% and 22% in the respective groups) and at 100 days (30.5% in group 4 and 8.4% in group 6) compared with 2% and 1.2% at 100 days in the CR-blighted allografts of the partially tolerant animals of groups 3 and 5. Whether large or small, the donor leukocyte fraction always included a subset of class II leukocytes that had histopathologic features of dendritic cells. These class II ؉ cells were of mixed myeloid (CD11-b/c ؉ ) and lymphoid lineages; their migration was markedly inhibited by TAC and accelerated by donor-specific priming and TAC discontinuance. Although a large donor leukocyte population and a normal leukocyte/nonleukocyte cell ratio were associated with freedom from CR, these findings and the lineage profile of the intracardiac leukocytes were not associated with tolerance in the animals of groups 3 and 4 under active TAC treatment. The findings in this study, singly and in their entirety, are compatible with our previously proposed leukocyte migration-localization paradigm of organ allograft acceptance and tolerance. (Liver ...

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Section: Discussionmentioning

confidence: 88%

Donor and recipient leukocytes in organ allografts of recipients with variable donor-specific tolerance: With particular reference to chronic rejection

et al. 2000

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“…In the lung, this process is now termed chronic lung allograft dysfunction (CLAD) and is characterised by a permanent 20% decline in FEV 1 over the best achieved post-transplant. CLAD is associated with reduced quality of life and increased mortality following lung transplantation (1)(2)(3)(4)(5)(6). Acute rejection remains the most important risk factor (7).…”

Section: Introductionmentioning

confidence: 99%

Erratic tacrolimus exposure, assessed using the standard deviation of trough blood levels, predicts chronic lung allograft dysfunction and survival

Gallagher

Sarwar

Tse

et al. 2015

The Journal of Heart and Lung Transplantation

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“…confirmaram 19 casos pediátricos, após revisarem todos os casos de autópsia (n = 2.897) e biópsia pulmonar (n = 244) realizadas no Hospital Infantil Saint Christopher, na Filadélfia, durante um período de 25 anos 9 . No entanto, nas últimas décadas, surgiu um interesse crescente a respeito dessa doença em adultos (Figura 1), devido ao reconhecimento de novos fatores causais, principalmente transplante de órgãos [10][11][12][13][14][15][16] .Em crianças, na maioria das vezes, a BO é precedida por uma infecção das vias aéreas inferiores, principalmente causada por adenovírus [17][18][19][20][21] . Em contraste com o número crescente de referências bibliográficas sobre a BO em adultos, essa doença ainda não chamou a atenção dos pediatras.…”

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Bronchiolitis obliterans in children

Zhang¹,

Silva²

2000

J Pediatr (Rio J)

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Objective: To review the literature on general aspects of bronchiolitis obliterans, with emphasis on childhood postinfectious bronchiolitis obliterans.Methods: The most important publications on bronchiolitis obliterans were selected, using basically the Medline database (January of 1966 to September of 1999.Results: This review is organized as follows: introduction, general aspects of bronchiolitis obliterans (terminology, histopathology and classification), and postinfectious bronchiolitis obliterans (etiological agents, clinical and radiological aspects, diagnosis and investigation, and treatment).Comments: Bronchiolitis obliterans is a clinical syndrome wich is more common than previously believed in the pediatric population, thus deserving pediatricians' attention.J. pediatr. (Rio J.). 2000; 76(3): 185-192: bronchiolitis obliterans, organizing pneumonia. ResumoObjetivos: Apresentar uma revisão sobre os aspectos gerais da bronquiolite obliterante, com ênfase na bronquiolite obliterante pós-infecciosa em crianças.Métodos: Foram selecionadas as publicações mais relevantes sobre a bronquiolite obliterante, utilizando basicamente o banco de dados do Medline (janeiro de 1966 a setembro de 1999).Resultados: A presente revisão inclui os seguintes tópicos: introdução, aspectos gerais da bronquiolite obliterante (terminologia, histopatologia e classificação) e bronquiolite obliterante pós-infecciosa (agentes etiológicos, aspectos clínico-radiológicos, diagnóstico e investigação, e tratamento).Comentários: A bronquiolite obliterante é uma síndrome clíni-ca mais comum do que se imaginava na população pediátrica, merecendo atenção dos pediatras. J. pediatr. (Rio J. IntroduçãoBronquiolite obliterante (BO), no sentido clínico, refere-se a uma síndrome de obstrução crônica do fluxo aéreo associada a lesão inflamatória das pequenas vias aéreas 1 . Patologicamente, o termo BO tem sido usado para descrever dois tipos de lesão bronquiolar, ou seja, bronquiolite proliferativa e bronquiolite constritiva 1-3 . Embora a descrição inicial de BO tenha ocorrido já há um século 4 , os aspectos da sua epidemiologia, patogenia, tratamento efetivo e prognóstico permanecem desconhecidos ou duvidosos.A BO, tanto em adultos quanto em crianças, até recentemente, foi considerada uma doença rara [5][6][7] . Em 1941, LaDue descobriu só um caso em 42.038 autópsias realizadas na Universidade de Minnesota, num período de 42 anos 8 . Em 1988, Hardy e cols. confirmaram 19 casos pediátricos, após revisarem todos os casos de autópsia (n = 2.897) e biópsia pulmonar (n = 244) realizadas no Hospital Infantil Saint Christopher, na Filadélfia, durante um período de 25 anos 9 . No entanto, nas últimas décadas, surgiu um interesse crescente a respeito dessa doença em adultos (Figura 1), devido ao reconhecimento de novos fatores causais, principalmente transplante de órgãos [10][11][12][13][14][15][16] .Em crianças, na maioria das vezes, a BO é precedida por uma infecção das vias aéreas inferiores, principalmente causada por adenovírus [17][18][19][2...

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Post-Transplant Obliterative Bronchiolitis and Other Late Lung Sequelae in Human Heart-Lung Transplantation

Cited by 386 publications

References 5 publications

Donor and recipient leukocytes in organ allografts of recipients with variable donor-specific tolerance: With particular reference to chronic rejection

Donor and recipient leukocytes in organ allografts of recipients with variable donor-specific tolerance: With particular reference to chronic rejection

Erratic tacrolimus exposure, assessed using the standard deviation of trough blood levels, predicts chronic lung allograft dysfunction and survival

Bronchiolitis obliterans in children

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