scholarly journals Lung Transplantation: The State of the Airways

2016 ◽  
Vol 140 (3) ◽  
pp. 241-244 ◽  
Author(s):  
Aliya N. Husain ◽  
Edward R. Garrity
Keyword(s):  
Lung Transplantation ◽  
Bronchiolitis Obliterans ◽  
Review Literature ◽  
Definitive Treatment ◽  
Term Survival ◽  
Chronic Lung Allograft Dysfunction ◽  
Allograft Dysfunction ◽  
Restrictive Allograft Syndrome ◽  
Lung Transplants ◽  
End Stage

Context Lung transplantation has become a viable option for definitive treatment of several end-stage lung diseases for which there are no other options available. However, long-term survival continues to be limited by chronic lung allograft dysfunction, which primarily affects the airways. Objective —To highlight the complications occurring mainly in the airways of the lung transplant recipient from the early to late posttransplant periods. Data Sources Review literature focusing on the airways in patients with lung transplants and clinical experience of the authors. Conclusions Postsurgical complications and infections of the airways have decreased because of better techniques and management. Acute cellular rejection of the airways can be distinguished from infection pathologically and on cultures. Separating small from large airways need not be an issue because both are risk factors for bronchiolitis obliterans. Grading of airway rejection needs to be standardized. Chronic lung allograft dysfunction consists of both bronchiolitis obliterans and restrictive allograft syndrome, neither of which can be treated very effectively at present.

Chronic Lung Allograft Dysfunction: Evolving Concepts and Therapies

2018 ◽  
Vol 39 (02) ◽  
pp. 155-171 ◽  
Author(s):  
Ariss DerHovanessian ◽  
W. Wallace ◽  
Joseph Lynch ◽  
John Belperio ◽  
S. Weigt
Keyword(s):  
Lung Transplantation ◽  
Therapeutic Option ◽  
Bronchiolitis Obliterans Syndrome ◽  
Term Survival ◽  
Chronic Lung Allograft Dysfunction ◽  
Allograft Dysfunction ◽  
Restrictive Allograft Syndrome ◽  
Technical Advances ◽  
End Stage

AbstractLung transplantation has become an established therapeutic option for a variety of end-stage lung diseases. Technical advances in graft procurement, implantation, perioperative care, immunosuppression, and posttransplant medical management have led to significant improvements in 1-year survival, but outcomes after the first year have improved minimally over the last two decades. The main limitation to better long-term survival after lung transplantation is chronic lung allograft dysfunction (CLAD). CLAD also impairs quality of life and increases the costs of medical care. Our understanding of CLAD manifestations, risk factors, and mechanisms is rapidly evolving. Recognition of different CLAD phenotypes (e.g., bronchiolitis obliterans syndrome and restrictive allograft syndrome) and the unique pathogenic mechanisms will be important for developing novel therapies. In addition to alloimmune-mediated rejection, we now recognize the importance of alloimmune-independent mechanisms of injury to the allograft. CLAD is the consequence of dysregulated repair of allograft injury. Unfortunately, currently available therapies for CLAD are usually not effective. However, the advances in knowledge, reviewed in this manuscript, should lead to novel strategies for CLAD prevention and treatment, as well as improvement in long-term outcomes after lung transplantation. We provide an overview of the evolving terminology related to CLAD, its varying clinical phenotypes and their diagnosis, natural history, pathogenesis, and potential treatments.

scholarly journals Antifibrotic drugs in lung transplantation and chronic lung allograft dysfunction: a review

2021 ◽  
Vol 30 (160) ◽  
pp. 210050
Author(s):  
Saskia Bos ◽  
Laurens J. De Sadeleer ◽  
Arno Vanstapel ◽  
Hanne Beeckmans ◽  
Annelore Sacreas ◽  
...  
Keyword(s):  
Lung Transplantation ◽  
Lung Diseases ◽  
Case Reports ◽  
Randomised Trial ◽  
Lung Function Decline ◽  
Impaired Wound Healing ◽  
Chronic Lung Allograft Dysfunction ◽  
Antifibrotic Therapy ◽  
Allograft Dysfunction ◽  
Restrictive Allograft Syndrome

This review aims to provide an overview of pre-transplant antifibrotic therapy on peri-transplant outcomes and to address the possible role of antifibrotics in lung transplant recipients with chronic lung allograft dysfunction.Lung transplantation is an established treatment modality for patients with various end-stage lung diseases, of which idiopathic pulmonary fibrosis and other progressive fibrosing interstitial lung diseases are growing indications. Theoretically, widespread use of antifibrotics prior to lung transplantation may increase the risk of bronchial anastomotic complications and impaired wound healing.Long-term graft and patient survival are still hampered by development of chronic lung allograft dysfunction, on which antifibrotics may have a beneficial impact.Antifibrotics until the moment of lung transplantation proved to be safe, without increasing peri-transplant complications. Currently, best practice is to continue antifibrotics until time of transplantation. In a large multicentre randomised trial, pirfenidone did not appear to have a beneficial effect on lung function decline in established bronchiolitis obliterans syndrome. The results of antifibrotic therapy in restrictive allograft syndrome are eagerly awaited, but nonrandomised data from small case reports/series are promising.

scholarly journals Lung Transplantation: CT Assessment of Chronic Lung Allograft Dysfunction (CLAD)

Diagnostics ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 817
Author(s):  
Anne-Laure Brun ◽  
Marie-Laure Chabi ◽  
Clément Picard ◽  
François Mellot ◽  
Philippe A. Grenier
Keyword(s):  
Lung Transplantation ◽  
Functional Decline ◽  
Bronchiolitis Obliterans Syndrome ◽  
The Other ◽  
Imaging Features ◽  
Chronic Lung Allograft Dysfunction ◽  
Allograft Dysfunction ◽  
Restrictive Allograft Syndrome ◽  
Mixed Phenotype

Chronic lung allograft rejection remains one of the major causes of morbi-mortality after lung transplantation. The term Chronic Lung Allograft Dysfunction (CLAD) has been proposed to describe the different processes that lead to a significant and persistent deterioration in lung function without identifiable causes. The two main phenotypes of CLAD are Bronchiolitis Obliterans Syndrome (BOS) and Restrictive Allograft Syndrome (RAS), each of them characterized by particular functional and imaging features. These entities can be associated (mixed phenotype) or switched from one to the other. If CLAD remains a clinical diagnosis based on spirometry, computed tomography (CT) scan plays an important role in the diagnosis and follow-up of CLAD patients, to exclude identifiable causes of functional decline when CLAD is first suspected, to detect early abnormalities that can precede the diagnosis of CLAD (particularly RAS), to differentiate between the obstructive and restrictive phenotypes, and to detect exacerbations and evolution from one phenotype to the other. Recognition of early signs of rejection is crucial for better understanding of physiopathologic pathways and optimal management of patients.

scholarly journals Disease progression in patients with the restrictive and mixed phenotype of Chronic Lung Allograft dysfunction—A retrospective analysis in five European centers to assess the feasibility of a therapeutic trial

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260881
Author(s):  
Jens Gottlieb ◽  
Geert M. Verleden ◽  
Michael Perchl ◽  
Christina Valtin ◽  
Alexander Vallee ◽  
...  
Keyword(s):  
Disease Progression ◽  
Retrospective Analysis ◽  
Missing Values ◽  
Graft Function ◽  
Therapeutic Trial ◽  
Term Survival ◽  
Chronic Lung Allograft Dysfunction ◽  
Allograft Dysfunction ◽  
Restrictive Allograft Syndrome ◽  
Mixed Phenotype

Background Chronic Lung Allograft Dysfunction (CLAD) is a major obstacle for long term survival after lung transplantation (LTx). Besides Bronchiolitis Obliterans Syndrome, two other phenotypes of CLAD, restrictive allograft syndrome (RAS) and mixed phenotype, have been described. Trials to test in these conditions are desperately needed and analyzing natural outcome to plan such trials is essential. Methods We performed a retrospective analysis of functional outcome in bilateral LTx recipients with RAS and mixed phenotype, transplanted between 2009 and 2018 in five large European centers with follow- up spirometry up to 12 months after diagnosis. Based on these data, sample size and power calculations for randomized therapeutic trial was estimated using two imputation methods for missing values. Results Seventy patients were included (39 RAS and 31 mixed phenotype), median 3.1 years after LTx when CLAD was diagnosed. Eight, 13 and 25 patients died within 6, 9 and 12 months after diagnosis and a two patients underwent re-transplantation within 12 months leading to a graft survival of 89, 79 and 61% six, nine and 12 months after diagnosis, respectively. Observed FEV1 decline was 451 ml at 6 months and stabilized at 9 and 12 months, while FVC showed continuous decline. Using two methods of imputation, a progressive further decline after 6 months for FEV1 was noted. Conclusion The poor outcome of these two specific CLAD phenotypes suggests the urgent need for future therapeutic randomized trials. The number of missing values in a potential trial seems to be high and most frequently attributed to death. Survival may be used as an endpoint in clinical trials in these distinct phenotypes and imputation techniques are relevant if graft function is used as a surrogate of disease progression in future trials.

Advances in Human Lung Transplantation

2020 ◽  
Vol 72 (1) ◽  
Author(s):  
Aparna C. Swaminathan ◽  
Jamie L. Todd ◽  
Scott M. Palmer
Keyword(s):  
Lung Transplantation ◽  
Bronchiolitis Obliterans Syndrome ◽  
Annual Review ◽  
Publication Date ◽  
Term Survival ◽  
Restrictive Allograft Syndrome ◽  
Lung Transplants ◽  
Lung Transplant Recipients

Lung transplantation improves survival and quality of life in patients with advanced pulmonary disease. Over the past several decades, the volume of lung transplants has grown substantially, with increasing transplantation of older and acutely ill individuals facilitated by improved utilization and preservation of available donor organs. Other advances include improvements in the diagnosis and mechanistic understanding of frequent post-transplant complications, such as primary graft dysfunction, acute rejection, and chronic lung allograft dysfunction (CLAD). CLAD occurs as a result of the host immune response to the allograft and is the principal factor limiting long-term survival after lung transplantation. Two distinct clinical phenotypes of CLAD have emerged, bronchiolitis obliterans syndrome and restrictive allograft syndrome, and this distinction has enabled further understanding of underlying immune mechanisms. Building on these advances, ongoing studies are exploring novel approaches to diagnose, prevent, and treat CLAD. Such studies are necessary to improve long-term outcomes for lung transplant recipients. Expected final online publication date for the Annual Review of Medicine, Volume 72 is January 27, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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