scholarly journals Lung Transplantation, Pulmonary Endothelial Inflammation, and Ex-Situ Lung Perfusion: A Review

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1417
Author(s):  
Keir A. Forgie ◽  
Nicholas Fialka ◽  
Darren H. Freed ◽  
Jayan Nagendran

Lung transplantation (LTx) is the gold standard treatment for end-stage lung disease; however, waitlist mortality remains high due to a shortage of suitable donor lungs. Organ quality can be compromised by lung ischemic reperfusion injury (LIRI). LIRI causes pulmonary endothelial inflammation and may lead to primary graft dysfunction (PGD). PGD is a significant cause of morbidity and mortality post-LTx. Research into preservation strategies that decrease the risk of LIRI and PGD is needed, and ex-situ lung perfusion (ESLP) is the foremost technological advancement in this field. This review addresses three major topics in the field of LTx: first, we review the clinical manifestation of LIRI post-LTx; second, we discuss the pathophysiology of LIRI that leads to pulmonary endothelial inflammation and PGD; and third, we present the role of ESLP as a therapeutic vehicle to mitigate this physiologic insult, increase the rates of donor organ utilization, and improve patient outcomes.

2004 ◽  
Vol 286 (6) ◽  
pp. L1129-L1139 ◽  
Author(s):  
Tina L. Sumpter ◽  
David S. Wilkes

Lung transplantation is the only definitive treatment modality for many forms of end-stage lung disease. However, the lung is rejected more often than any other type of solid organ allograft due to chronic rejection known as bronchiolitis obliterans (BO). Indeed, BO is the primary reason why the 5- and 7-yr survival rates are worse for the lung than for any other transplanted organ. Alloimmunity to donor antigens is established as the primary mechanism that mediates rejection responses. However, newer immunosuppressive regimens designed to abrogate alloimmune activation have not improved survival. Therefore, these data suggest that other antigens, unrelated to donor transplantation antigens, are involved in rejection. Utilizing human and rodent studies of lung transplantation, our laboratory has documented that a native collagen, type V collagen [col(V)], is a target of the rejection response. Col(V) is highly conserved; therefore, these data indicate that transplant rejection involves both alloimmune and autoimmune responses. The role of col(V) in lung transplant rejection is described in this review article. In addition, the potential role of regulatory T cells that are crucial to modulating autoimmunity and alloimmunity is also discussed.


2020 ◽  
pp. 977-986
Author(s):  
Daniel Mansour ◽  
Sophia Roberts ◽  
Madonna Lee ◽  
Bassam Shukrallah ◽  
Bryan A. Whitson

Author(s):  
S. V. Gautier ◽  
O. M. Tsirulnikova ◽  
I. V. Pashkov ◽  
N. V. Grudinin ◽  
D. O. Oleshkevich ◽  
...  

Respiratory diseases, together with infectious complications and hereditary lung diseases, rank third in international mortality statistics. Today, lung transplantation is a recognized method of treating end-stage lung diseases. However, the number of transplant surgeries performed is not much. This is down to the high requirements on the condition of a potential lung donor and directly on the quality of the donor lung. This has significantly limited the number of optimal donors. Rehabilitation of donor lungs to optimal gas exchange indicators can be achieved and objectively assessed in the course of ex vivo lung perfusion (EVLP). The EVLP procedure is widespread in leading transplantation centers in Europe and North America. It allows to significantly expand the pool of donor lungs, thereby serving a greater number of patients in need of lung transplantation. The possibility of EVLP procedure using publicly available perfusion equipment was demonstrated. The optimized protocol fully demonstrated its reliability and efficiency. The developed perfusion solution had no statistically significant differences in comparison with the Steen SolutionTM, which in the future will serve as an alternative for EVLP procedure.


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Max T. Buchko ◽  
Nasim Boroumand ◽  
Jeffrey C. Cheng ◽  
Alim Hirji ◽  
Kieran Halloran ◽  
...  

AbstractLung transplantation remains the best treatment option for end-stage lung disease; however, is limited by a shortage of donor grafts. Ex situ lung perfusion, also known as ex vivo lung perfusion, has been shown to allow for the safe evaluation and reconditioning of extended criteria donor lungs, increasing donor utilization. Negative pressure ventilation ex situ lung perfusion has been shown, preclinically, to result in less ventilator-induced lung injury than positive pressure ventilation. Here we demonstrate that, in a single-arm interventional study (ClinicalTrials.gov number NCT03293043) of 12 extended criteria donor human lungs, negative pressure ventilation ex situ lung perfusion allows for preservation and evaluation of donor lungs with all grafts and patients surviving to 30 days and recovered to discharge from hospital. This trial also demonstrates that ex situ lung perfusion is safe and feasible with no patients demonstrating primary graft dysfunction scores grade 3 at 72 h or requiring post-operative extracorporeal membrane oxygenation.


2004 ◽  
Vol 22 (21) ◽  
pp. 4351-4356 ◽  
Author(s):  
Marc de Perrot ◽  
Susan Chernenko ◽  
Thomas K. Waddell ◽  
Yaron Shargall ◽  
Andrew F. Pierre ◽  
...  

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.


2021 ◽  
Vol 22 (10) ◽  
pp. 5233
Author(s):  
Christina Bogensperger ◽  
Julia Hofmann ◽  
Franka Messner ◽  
Thomas Resch ◽  
Andras Meszaros ◽  
...  

Transplantation represents the treatment of choice for many end-stage diseases but is limited by the shortage of healthy donor organs. Ex situ normothermic machine perfusion (NMP) has the potential to extend the donor pool by facilitating the use of marginal quality organs such as those from donors after cardiac death (DCD) and extended criteria donors (ECD). NMP provides a platform for organ quality assessment but also offers the opportunity to treat and eventually regenerate organs during the perfusion process prior to transplantation. Due to their anti-inflammatory, immunomodulatory and regenerative capacity, mesenchymal stem cells (MSCs) are considered as an interesting tool in this model system. Only a limited number of studies have reported on the use of MSCs during ex situ machine perfusion so far with a focus on feasibility and safety aspects. At this point, no clinical benefits have been conclusively demonstrated, and studies with controlled transplantation set-ups are urgently warranted to elucidate favorable effects of MSCs in order to improve organs during ex situ machine perfusion.


2013 ◽  
Vol 1 (2) ◽  
pp. 48-56 ◽  
Author(s):  
Stephen A Esper

ABSTRACT Lung transplantation is the only option for patients with end-stage lung disease. Chronic obstructive lung disease, idiopathic pulmonary fibrosis, cystic fibrosis and primary pulmonary hypertension are few common indications for lung transplantation. Patients with end-stage lung disease may have pre-existing cardiovascular compromise related to pulmonary hypertension and other cardiovascular lesions, such as coronary artery disease or valvular heart disease. Preoperative evaluation and optimization of hemodynamics is expected to improve outcomes from lung transplantation. Intraoperative hemodynamic instability is common during lung transplantation and requires highest level of cardiovascular monitoring. After transplantation, vascular anastomosis should be evaluated for flow patterns to rule out obstruction from stenosis or thrombosis. Postoperative complications are common and include bleeding, cardiac failure and hypoxemia from right to left shunt. Primary graft dysfunction may necessitate mechanical cardiorespiratory support. Transesophageal echocardiography plays a central role in preoperative evaluation, intraoperative hemodynamic management, evaluation of pulmonary vascular anastomosis, diagnosis of postoperative complications and also in the critical care management of mechanical cardiorespiratory support. How to cite this article Subramaniam K, Esper SA. Role of Transesophageal Echocardiography in Perioperative Patient Management of Lung Transplantation Surgery. J Perioper Echocardiogr 2013;1(2):48-56.


2008 ◽  
Vol 27 (3) ◽  
pp. 272-275 ◽  
Author(s):  
Benjamin D. Fox ◽  
Ilanit Ben Nachum ◽  
Hanna Bernstine ◽  
Anat Amital ◽  
Ilana Bakal ◽  
...  

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