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 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.

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.

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.

scholarly journals Twelve-month effects of everolimus on renal and lung function in lung transplantation: differences in chronic lung allograft dysfunction phenotypes

2021 ◽  
Vol 12 ◽  
pp. 204062232199344
Author(s):  
Filippo Patrucco ◽  
Elias Allara ◽  
Massimo Boffini ◽  
Mauro Rinaldi ◽  
Cristina Costa ◽  
...  
Keyword(s):  
Renal Function ◽  
Lung Function ◽  
Lung Transplant ◽  
Bronchiolitis Obliterans Syndrome ◽  
Forced Expiratory Volume ◽  
Chronic Lung Allograft Dysfunction ◽  
Allograft Dysfunction ◽  
Transplant Patients ◽  
Restrictive Allograft Syndrome ◽  
Trend Data

Background: Chronic lung allograft dysfunction (CLAD), a complication affecting the survival of lung transplanted patients, includes two clinical phenotypes: bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). Everolimus is used in CLAD because of its antiproliferative mechanism. In lung transplant patients treated with everolimus, the clinical course of renal and lung function has not yet been assessed systematically in CLAD, BOS and RAS patients for more than 6 months. Methods: We retrospectively evaluated the 12-month follow-up of renal and lung function of lung-transplanted patients switched to everolimus and evaluated the reduction in immunosuppressant dosage (ISD) and mortality. Subgroups were based on indication for everolimus treatment: CLAD and non-CLAD patients, BOS and RAS among CLAD patients. Results: We included 26 patients, 17 with CLAD (10 BOS, seven RAS). After 1 year from the everolimus switch, we observed renal function improvement (serum creatinine −17%, estimated glomerular filtration rate +24%) and stable pulmonary function [forced expiratory volume in the first second (FEV1) −0.5%, forced vital capacity (FVC) +0.05%]. RAS patients had progressive functional loss, whereas BOS patients had FEV1 improvement and FVC stability. All-cause mortality was higher in the CLAD versus non-CLAD group (41% versus 11%), without differences between BOS and RAS patients ( p > 0.05). All patients had significant and persistent ISD reduction. Conclusion: Lung transplant patients treated with everolimus had improvements in renal function and reduced ISD. We observed sustained improvements in lung function for CLAD related to BOS subgroup results, whereas RAS confirmed the 1-year worsening functional trend. Data seem to suggest one more piece of the puzzle in CLAD phenotyping.

scholarly journals Intragraft donor-specific anti-HLA antibodies in phenotypes of chronic lung allograft dysfunction

2019 ◽  
Vol 54 (5) ◽  
pp. 1900847 ◽  
Author(s):  
Annelore Sacreas ◽  
Jean-Luc Taupin ◽  
Marie-Paule Emonds ◽  
Liesbeth Daniëls ◽  
Dirk E. Van Raemdonck ◽  
...  
Keyword(s):  
Human Leukocyte ◽  
Hla Class I ◽  
Bronchiolitis Obliterans Syndrome ◽  
Clinical Findings ◽  
Micro Computed Tomography ◽  
Serum Samples ◽  
Chronic Lung Allograft Dysfunction ◽  
Leukocyte Antigen ◽  
Allograft Dysfunction ◽  
Restrictive Allograft Syndrome

IntroductionCirculating anti-human leukocyte antigen (HLA) serum donor-specific antibodies (sDSAs) increase the risk of chronic lung allograft dysfunction (CLAD) and mortality. Discrepancies between serological and pathological/clinical findings are common. Therefore, we aimed to assess the presence of tissue-bound graft DSAs (gDSAs) in CLAD explant tissue compared with sDSAs.MethodsTissue cores, obtained from explant lungs of unused donors (n=10) and patients with bronchiolitis obliterans syndrome (BOS; n=18) and restrictive allograft syndrome (RAS; n=18), were scanned with micro-computed tomography before elution of antibodies. Total IgG levels were measured via ELISA. Anti-HLA class I and II IgG gDSAs were identified using Luminex single antigen beads and compared with DSAs found in serum samples.ResultsOverall, mean fluorescence intensity was higher in RAS eluates compared with BOS and controls (p<0.0001). In BOS, two patients were sDSA+/gDSA+ and two patients were sDSA−/gDSA+. In RAS, four patients were sDSA+/gDSA+, one patient was sDSA+/gDSA− and five patients were sDSA−/gDSA+. Serum and graft results combined, DSAs were more prevalent in RAS compared with BOS (56% versus 22%; p=0.04). There was spatial variability in gDSA detection in one BOS patient and three RAS patients, who were all sDSA−. Total graft IgG levels were higher in RAS than BOS (p<0.0001) and in gDSA+versus gDSA− (p=0.0008), but not in sDSA+versus sDSA− (p=0.33). In RAS, total IgG levels correlated with fibrosis (r= −0.39; p=0.02).ConclusionsThis study underlines the potential of gDSA assessment as complementary information to sDSA findings. The relevance and applications of gDSAs need further investigation.

Role of Lung Transplantation in the Treatment of Bronchogenic Carcinomas for Patients With End-Stage Pulmonary Disease

2004 ◽  
Vol 22 (21) ◽  
pp. 4351-4356 ◽  
Author(s):  
Marc de Perrot ◽  
Susan Chernenko ◽  
Thomas K. Waddell ◽  
Yaron Shargall ◽  
Andrew F. Pierre ◽  
...  
Keyword(s):  
Lung Transplantation ◽  
Bronchogenic Carcinoma ◽  
Stage I ◽  
Bronchioloalveolar Carcinoma ◽  
Actuarial Survival ◽  
Term Survival ◽  
Primary Indication ◽  
End Stage

Purpose To determine the role of lung transplantation in the treatment of patients presenting with bronchogenic carcinoma and end-stage lung disease. Methods An international survey was conducted to determine the outcome of patients with bronchogenic carcinoma in the explanted lung at the time of transplantation. A group of 69 patients was collected from 33 centers. Results Twenty-six patients underwent 29 lung transplantations for advanced multifocal bronchioloalveolar carcinoma (BAC) as the primary indication for transplantation, and 13 developed a recurrence, with an overall 5-year actuarial survival of 39%. Incidental bronchogenic carcinomas classified as stage I (n = 22), II (n = 12), and III (n = 2), or as incidental multifocal BAC (n = 7), were found in the explanted lung of the remaining 43 patients. The 5-year actuarial survival was 51% in patients with stage I carcinomas, and was significantly better than for patients with stage II and III carcinomas (survival of 14%) or with incidental multifocal BAC (survival of 23%). Time from transplantation to recurrence and from recurrence to death was significantly longer in patients with multifocal BAC than in patients with other types of bronchogenic carcinoma. In addition, the site of recurrence was limited to the transplanted lung in 88% of the patients with multifocal BAC, whereas it was always widespread in patients with other types of bronchogenic carcinoma. Conclusion This study demonstrates that long-term survival can be achieved after lung transplantation in patients with stage I bronchogenic carcinoma or with advanced multifocal BAC.

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