Graft dysfunction and rejection of lung transplant, a review on diagnosis and management

Sun, Haishuang; Deng, Meifeng; Chen, Wenhui; Liu, Min; Dai, Hehua; Wang, Chen

doi:10.1111/crj.13471

Cited by 14 publications

(18 citation statements)

References 58 publications

(112 reference statements)

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“…Unfortunately, the short- and long-term outcomes of LTxs are still less favorable than other solid organ transplants, the main faults being organ shortage and the fact that more than 80% of potential organ donors are not suitable or used for transplantation [ 2 , 3 , 4 , 5 , 6 ]. Moreover, other factors, such as postoperative graft dysfunction (PGD), infections, and rejection may also contribute to post-transplant mortality [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stromal/Stem Cells and Their Products as a Therapeutic Tool to Advance Lung Transplantation

Miceli

Bertani

2022

Cells

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Lung transplantation (LTx) has become the gold standard treatment for end-stage respiratory failure. Recently, extended lung donor criteria have been applied to decrease the mortality rate of patients on the waiting list. Moreover, ex vivo lung perfusion (EVLP) has been used to improve the number/quality of previously unacceptable lungs. Despite the above-mentioned progress, the morbidity/mortality of LTx remains high compared to other solid organ transplants. Lungs are particularly susceptible to ischemia-reperfusion injury, which can lead to graft dysfunction. Therefore, the success of LTx is related to the quality/function of the graft, and EVLP represents an opportunity to protect/regenerate the lungs before transplantation. Increasing evidence supports the use of mesenchymal stromal/stem cells (MSCs) as a therapeutic strategy to improve EVLP. The therapeutic properties of MSC are partially mediated by secreted factors. Hence, the strategy of lung perfusion with MSCs and/or their products pave the way for a new innovative approach that further increases the potential for the use of EVLP. This article provides an overview of experimental, preclinical and clinical studies supporting the application of MSCs to improve EVLP, the ultimate goal being efficient organ reconditioning in order to expand the donor lung pool and to improve transplant outcomes.

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Section: Introductionmentioning

confidence: 99%

Mesenchymal Stromal/Stem Cells and Their Products as a Therapeutic Tool to Advance Lung Transplantation

Miceli

Bertani

2022

Cells

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“…ABO-identical matching of transplanted organs with recipients prevents erythrocyte destruction by donor lymphocytes, which is a major cause of hyperacute rejection and earlier onset of CLAD [119]. Hyperacute rejection can occur within minutes of transplantation up to 24 hours postoperatively and is an antibody mediated reaction that can range in severity leading to significant alveolar injury and subsequent death [120]. Due to these concerns, historically ABO-identical matches in solid organ transplants have been preferred.…”

Section: Detection Of Rejectionmentioning

confidence: 99%

“…The most common complication in the early postoperative period is primary graft dysfunction (PGD), responsible for nearly 50% of early (30-day) deaths [123,124]. PGD is characterized by noncardiogenic pulmonary edema caused by ischemic pulmonary vascular injury and increased pulmonary vascular permeability resulting in diffuse alveolar damage and hyaline membrane formation [120]. It often occurs within the first 72 hours following transplant becoming most severe by post-op day 4 or 5, presenting as progressive dyspnea and decline in lung function [120].…”

Section: Detection Of Rejectionmentioning

confidence: 99%

“…PGD is characterized by noncardiogenic pulmonary edema caused by ischemic pulmonary vascular injury and increased pulmonary vascular permeability resulting in diffuse alveolar damage and hyaline membrane formation [120]. It often occurs within the first 72 hours following transplant becoming most severe by post-op day 4 or 5, presenting as progressive dyspnea and decline in lung function [120]. PGD can be classified based on presence of radiographic pulmonary infiltrates and a decline PaO 2 /FiO 2 (P/F ratio) ranging from grade 0-3, of which grade 3 being the most severe with a P/F ratio <200 and presence of infiltrates consistent with pulmonary edema [125].…”

Section: Detection Of Rejectionmentioning

confidence: 99%

“…Several risk factors for PGD have been reported as described by the ISHLT working group on PGD, as recipient comorbidities, prior thoracic surgery, underlying disease, and surgical complications [123]. The main treatment modality for PGD remains supportive therapy and ECMO-BTT techniques [67,120,124].…”

Section: Detection Of Rejectionmentioning

confidence: 99%

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A Breath of Fresh Air - Lung Transplantation Has Come of Age

Keshavamurthy¹,

Russell²

2023

OBM Transplant

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A boundless spectrum of chronic lung diseases is said to effect over 500 million persons globally. Lung transplantation is a well-established therapeutic option for patients suffering from end-stage lung diseases, however waitlist mortality and primary graft failure remain major determinants as post-transplantation 5-year survival is just above 50 percent. Recent innovations in lung transplantation have been aimed at increasing organ availability, improving allograft quality, function, and longevity. Ex-vivo Lung Perfusion (EVLP) is an exciting modality responsible for multiple paths of lung allograft reconditioning as well as significantly extending preservation times. Mechanical circulatory support (MCS), specifically extracorporeal membrane oxygenation (ECMO) has consistently gained popularity not only for its use as a bridge to transplantation, but also its intraoperative role. In tandem, EVLP and ECMO have shown promising results in increasing the number of lung transplantations performed, therefore decreasing waitlist mortality. Primary graft dysfunction (PGD) and chronic lung allograft rejection (CLAD) continue to be the most feared predictors of poor outcomes. In this review we will highlight the historical progression of lung transplantation, its encumbrance, and the most recent advancements in promising techniques for long-term allograft protection and patient survival.

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Outcomes Following Lung Transplant for COVID-19–Related Complications in the US

et al. 2023

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ImportanceThe COVID-19 pandemic led to the use of lung transplant as a lifesaving therapy for patients with irreversible lung injury. Limited information is currently available regarding the outcomes associated with this treatment modality.ObjectiveTo describe the outcomes following lung transplant for COVID-19–related acute respiratory distress syndrome or pulmonary fibrosis.Design, Setting, and ParticipantsIn this cohort study, lung transplant recipient and donor characteristics and outcomes following lung transplant for COVID-19–related acute respiratory distress syndrome or pulmonary fibrosis were extracted from the US United Network for Organ Sharing database from March 2020 to August 2022 with a median (IQR) follow-up period of 186 (64-359) days in the acute respiratory distress syndrome group and 181 (40-350) days in the pulmonary fibrosis group. Overall survival was calculated using the Kaplan-Meier method. Cox proportional regression models were used to examine the association of certain variables with overall survival.ExposuresLung transplant following COVID-19–related acute respiratory distress syndrome or pulmonary fibrosis.Main Outcomes and MeasuresOverall survival and graft failure rates.ResultsAmong 385 included patients undergoing lung transplant, 195 had COVID-19–related acute respiratory distress syndrome (142 male [72.8%]; median [IQR] age, 46 [38-54] years; median [IQR] allocation score, 88.3 [80.5-91.1]) and 190 had COVID-19–related pulmonary fibrosis (150 male [78.9%]; median [IQR] age, 54 [45-62]; median [IQR] allocation score, 78.5 [47.7-88.3]). There were 16 instances of acute rejection (8.7%) in the acute respiratory distress syndrome group and 15 (8.6%) in the pulmonary fibrosis group. The 1-, 6-, and 12- month overall survival rates were 0.99 (95% CI, 0.96-0.99), 0.95 (95% CI, 0.91-0.98), and 0.88 (95% CI, 0.80-0.94) for the acute respiratory distress syndrome cohort and 0.96 (95% CI, 0.92-0.98), 0.92 (95% CI, 0.86-0.96), and 0.84 (95% CI, 0.74-0.90) for the pulmonary fibrosis cohort. Freedom from graft failure rates were 0.98 (95% CI, 0.96-0.99), 0.95 (95% CI, 0.90-0.97), and 0.88 (95% CI, 0.79-0.93) in the 1-, 6-, and 12-month follow-up periods in the acute respiratory distress cohort and 0.96 (95% CI, 0.92-0.98), 0.93 (95% CI, 0.87-0.96), and 0.85 (95% CI, 0.74-0.91) in the pulmonary fibrosis cohort, respectively. Receiving a graft from a donor with a heavy and prolonged history of smoking was associated with worse overall survival in the acute respiratory distress syndrome cohort, whereas the characteristics associated with worse overall survival in the pulmonary fibrosis cohort included female recipient, male donor, and high recipient body mass index.Conclusions and RelevanceIn this study, outcomes following lung transplant were similar in patients with irreversible respiratory failure due to COVID-19 and those with other pretransplant etiologies.

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Graft dysfunction and rejection of lung transplant, a review on diagnosis and management

Cited by 14 publications

References 58 publications

Mesenchymal Stromal/Stem Cells and Their Products as a Therapeutic Tool to Advance Lung Transplantation

Mesenchymal Stromal/Stem Cells and Their Products as a Therapeutic Tool to Advance Lung Transplantation

A Breath of Fresh Air - Lung Transplantation Has Come of Age

Outcomes Following Lung Transplant for COVID-19–Related Complications in the US

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