Advances in Lung Transplantation

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (1 December 2021) | Viewed by 23474

Special Issue Editors


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Guest Editor
1. Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
2. Thoracic Surgery and Lung Transplantation Unit, Fondazione IRCCS Ca’ Granda - Ospedale Maggiore Policlinico of Milan, Via F. Sforza, 35 20122 Milan, Italy
Interests: lung transplantation; donation after circulatory death (DCD); video-assisted thoracic surgery (VATS); robotic-assisted thoracic surgery (RATS); diaphragm dysfunction
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
1. Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
2. Thoracic Surgery and Lung Transplantation Unit, Fondazione IRCCS Ca’ Granda - Ospedale Maggiore Policlinico of Milan, Via F. Sforza, 35 20122 Milan, Italy
Interests: lung transplantation; non-small-cell lung cancer; mediastinum; thymic malignancies; video-assisted thoracic surgery (VATS); robotic-assisted thoracic surgery (RATS)
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Nowadays, lung transplantation is a clinical reality for the treatment of benign end-stage respiratory diseases. Candidates' selection and correct timing, evaluation and management of potential donors, therapy and post-transplant monitoring are certainly the most relevant aspects of this complicated path. Although great progress has been made in the overall approach, the results can still be improved, especially in terms of mortality and survival rates. The most relevant aspect is the incomplete understanding of the physiopathological mechanisms underlying the different phases of the donation–transplant process, from lung damage in the donor to chronic rejection in the recipient. In addition, the lack of harmony and contact between basic and clinical research has a great impact in an area where, on the contrary, the two aspects should closely interact. This Special Issue aims to address the current and more challenging topics in the lung transplant scenario, facilitating a moment of dynamic debate between clinicians and researchers, and providing the necessary tools to merge the experiences.

This Special Issue aims to address the most current and challenging topics in the lung transplant scenario, facilitating a moment of dynamic debate between clinicians and physicians, providing the tools necessary to merge the experiences.

We look forward to your contribution.

Dr. Alessandro Palleschi
Dr. Davide Tosi
Guest Editors

Manuscript Submission Information

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Keywords

  • The history of lung transplantation
  • Recipients: referral and listing
  • DBD donors
  • DCD donors
  • Living donors
  • Bridge to transplant
  • Machine perfusion
  • Intraoperative extracorporeal support
  • Primary graft dysfunction
  • Post-transplant prophylaxis
  • Post-transplant surveillance
  • Acute rejection
  • Chronic rejection
  • Post-transplant tumours
  • Bronchial complications
  • Retransplant
  • Combined transplant
  • Animal models for the study of lung transplantation
  • The artificial lung

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Published Papers (7 papers)

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Research

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16 pages, 3745 KiB  
Article
Quantitative CT Correlates with Local Inflammation in Lung of Patients with Subtypes of Chronic Lung Allograft Dysfunction
by Sundaresh Ram, Stijn E. Verleden, Alexander J. Bell, Benjamin A. Hoff, Wassim W. Labaki, Susan Murray, Bart M. Vanaudenaerde, Robin Vos, Geert M. Verleden, Ella A. Kazerooni, Stefanie Galbán, Charles R. Hatt, Meilan K. Han, Vibha N. Lama and Craig J. Galbán
Cells 2022, 11(4), 699; https://doi.org/10.3390/cells11040699 - 16 Feb 2022
Cited by 3 | Viewed by 2620
Abstract
Chronic rejection of lung allografts has two major subtypes, bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS), which present radiologically either as air trapping with small airways disease or with persistent pleuroparenchymal opacities. Parametric response mapping (PRM), a computed tomography (CT) methodology, [...] Read more.
Chronic rejection of lung allografts has two major subtypes, bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS), which present radiologically either as air trapping with small airways disease or with persistent pleuroparenchymal opacities. Parametric response mapping (PRM), a computed tomography (CT) methodology, has been demonstrated as an objective readout of BOS and RAS and bears prognostic importance, but has yet to be correlated to biological measures. Using a topological technique, we evaluate the distribution and arrangement of PRM-derived classifications of pulmonary abnormalities from lung transplant recipients undergoing redo-transplantation for end-stage BOS (N = 6) or RAS (N = 6). Topological metrics were determined from each PRM classification and compared to structural and biological markers determined from microCT and histopathology of lung core samples. Whole-lung measurements of PRM-defined functional small airways disease (fSAD), which serves as a readout of BOS, were significantly elevated in BOS versus RAS patients (p = 0.01). At the core-level, PRM-defined parenchymal disease, a potential readout of RAS, was found to correlate to neutrophil and collagen I levels (p < 0.05). We demonstrate the relationship of structural and biological markers to the CT-based distribution and arrangement of PRM-derived readouts of BOS and RAS. Full article
(This article belongs to the Special Issue Advances in Lung Transplantation)
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15 pages, 3484 KiB  
Article
Ex Vivo Lung Perfusion with K(ATP) Channel Modulators Antagonize Ischemia Reperfusion Injury
by Stephan Arni, Tatsuo Maeyashiki, Tsogyal Latshang, Isabelle Opitz and Ilhan Inci
Cells 2021, 10(9), 2296; https://doi.org/10.3390/cells10092296 - 3 Sep 2021
Cited by 8 | Viewed by 2185
Abstract
Ex vivo lung perfusion (EVLP) has been implemented to increase the number of donor lungs available for transplantation. The use of K(ATP) channel modulators during EVLP experiments may protect against lung ischemia-reperfusion injury and may inhibit the formation of reactive oxygen species. In [...] Read more.
Ex vivo lung perfusion (EVLP) has been implemented to increase the number of donor lungs available for transplantation. The use of K(ATP) channel modulators during EVLP experiments may protect against lung ischemia-reperfusion injury and may inhibit the formation of reactive oxygen species. In a rat model of donation after circulatory death with 2 h warm ischemic time, we evaluated rat lungs for a 4-hour time in EVLP containing either mitochondrial-specific or plasma membrane and/or sarcolemmal-specific forms of K(ATP) channel modulators. Lung physiological data were recorded, and metabolic parameters were assessed. When compared to the control group, in the EVLP performed with diazoxide or 5-hydroxydecanoic acid (5-HD) we recorded significantly lower pulmonary vascular resistance and only in the diazoxide group recorded significant lung weight loss. In the perfusate of the 5-HD group, interleukin-1β and interleukin-1α were significantly lower when compared to the control group. Perfusate levels of calcium ions were significantly higher in both 5-HD and cromakalim groups, whereas the levels of calcium, potassium, chlorine and lactate were reduced in the diazoxide group, although not significantly when compared to the control. The use of a diazoxide mitochondrial-specific K(ATP) channel opener during EVLP improved lung physiological and metabolic parameters and reduced edema. Full article
(This article belongs to the Special Issue Advances in Lung Transplantation)
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12 pages, 1194 KiB  
Article
Perfluorocarbon-Based Oxygen Carriers and Subnormothermic Lung Machine Perfusion Decrease Production of Pro-Inflammatory Mediators
by Stephan Arni, Citak Necati, Tatsuo Maeyashiki, Isabelle Opitz and Ilhan Inci
Cells 2021, 10(9), 2249; https://doi.org/10.3390/cells10092249 - 30 Aug 2021
Cited by 8 | Viewed by 2531
Abstract
The quality of marginal donor lungs is clinically assessed with normothermic machine perfusion. Although subnormothermic temperature and perfluorocarbon-based oxygen carriers (PFCOC) have proven favourable for other organ transplants, their beneficial use for ex vivo lung perfusion (EVLP) still requires further investigation. In a [...] Read more.
The quality of marginal donor lungs is clinically assessed with normothermic machine perfusion. Although subnormothermic temperature and perfluorocarbon-based oxygen carriers (PFCOC) have proven favourable for other organ transplants, their beneficial use for ex vivo lung perfusion (EVLP) still requires further investigation. In a rat model, we evaluated on a 4 h EVLP time the effects of PFCOC with either 28 °C or 37 °C perfusion temperatures. During EVLP at 28 °C with PFCOC, we recorded significantly lower lung pulmonary vascular resistance (PVR), higher dynamic compliance (Cdyn), significantly lower potassium and lactate levels, higher lung tissue ATP content, and significantly lower myeloperoxidase tissue activity when compared to the 37 °C EVLP with PFCOC. In the subnormothermic EVLP with or without PFCOC, the pro-inflammatory mediator TNFα, the cytokines IL-6 and IL-7, the chemokines MIP-3α, MIP-1α, MCP-1, GRO/KC as well as GM-CSF, G-CSF and the anti-inflammatory cytokines IL-4 and IL-10 were significantly lower. The 28 °C EVLP improved both Cdyn and PVR and decreased pro-inflammatory cytokines and pCO2 levels compared to the 37 °C EVLP. In addition, the 28 °C EVLP with PFCOC produced a significantly lower level of myeloperoxidase activity in lung tissue. Subnormothermic EVLP with PFCOC significantly improves lung donor physiology and ameliorates lung tissue biochemical and inflammatory parameters. Full article
(This article belongs to the Special Issue Advances in Lung Transplantation)
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Review

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18 pages, 992 KiB  
Review
Mesenchymal Stromal/Stem Cells and Their Products as a Therapeutic Tool to Advance Lung Transplantation
by Vitale Miceli and Alessandro Bertani
Cells 2022, 11(5), 826; https://doi.org/10.3390/cells11050826 - 27 Feb 2022
Cited by 15 | Viewed by 2784
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Advances in Lung Transplantation)
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19 pages, 3107 KiB  
Review
A Focused Review on Primary Graft Dysfunction after Clinical Lung Transplantation: A Multilevel Syndrome
by Jan Van Slambrouck, Dirk Van Raemdonck, Robin Vos, Cedric Vanluyten, Arno Vanstapel, Elena Prisciandaro, Lynn Willems, Michaela Orlitová, Janne Kaes, Xin Jin, Yanina Jansen, Geert M. Verleden, Arne P. Neyrinck, Bart M. Vanaudenaerde and Laurens J. Ceulemans
Cells 2022, 11(4), 745; https://doi.org/10.3390/cells11040745 - 21 Feb 2022
Cited by 9 | Viewed by 4455
Abstract
Primary graft dysfunction (PGD) is the clinical syndrome of acute lung injury after lung transplantation (LTx). However, PGD is an umbrella term that encompasses the ongoing pathophysiological and -biological mechanisms occurring in the lung grafts. Therefore, we aim to provide a focused review [...] Read more.
Primary graft dysfunction (PGD) is the clinical syndrome of acute lung injury after lung transplantation (LTx). However, PGD is an umbrella term that encompasses the ongoing pathophysiological and -biological mechanisms occurring in the lung grafts. Therefore, we aim to provide a focused review on the clinical, physiological, radiological, histological and cellular level of PGD. PGD is graded based on hypoxemia and chest X-ray (CXR) infiltrates. High-grade PGD is associated with inferior outcome after LTx. Lung edema is the main characteristic of PGD and alters pulmonary compliance, gas exchange and circulation. A conventional CXR provides a rough estimate of lung edema, while a chest computed tomography (CT) results in a more in-depth analysis. Macroscopically, interstitial and alveolar edema can be distinguished below the visceral lung surface. On the histological level, PGD correlates to a pattern of diffuse alveolar damage (DAD). At the cellular level, ischemia-reperfusion injury (IRI) is the main trigger for the disruption of the endothelial-epithelial alveolar barrier and inflammatory cascade. The multilevel approach integrating all PGD-related aspects results in a better understanding of acute lung failure after LTx, providing novel insights for future therapies. Full article
(This article belongs to the Special Issue Advances in Lung Transplantation)
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12 pages, 1223 KiB  
Review
A Comprehensive Review on the Surgical Aspect of Lung Transplant Models in Mice and Rats
by Xin Jin, Janne Kaes, Jan Van Slambrouck, Ilhan Inci, Stephan Arni, Vincent Geudens, Tobias Heigl, Yanina Jansen, Marianne S. Carlon, Robin Vos, Dirk Van Raemdonck, Yi Zhang, Bart M. Vanaudenaerde and Laurens J. Ceulemans
Cells 2022, 11(3), 480; https://doi.org/10.3390/cells11030480 - 30 Jan 2022
Cited by 3 | Viewed by 3423
Abstract
Lung transplantation improves the outcome and quality of life of patients with end-stage pulmonary disease. However, the procedure is still hampered by the lack of suitable donors, the complexity of the surgery, and the risk of developing chronic lung allograft dysfunction. Over the [...] Read more.
Lung transplantation improves the outcome and quality of life of patients with end-stage pulmonary disease. However, the procedure is still hampered by the lack of suitable donors, the complexity of the surgery, and the risk of developing chronic lung allograft dysfunction. Over the past decades, translational experiments in animal models have led to a better understanding of physiology and immunopathology following the lung transplant procedure. Small animal models (e.g., rats and mice) are mostly used in experiments regarding immunology and pathobiology and are preferred over large animal models due to the ethical aspects, the cost–benefit balance, and the high throughput possibility. In this comprehensive review, we summarize the reported surgical techniques for lung transplantation in rodent models and the management of perioperative complications. Furthermore, we propose a guide to help identify the appropriate species for a given experiment and discuss recent experimental findings in small animal lung transplant models. Full article
(This article belongs to the Special Issue Advances in Lung Transplantation)
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17 pages, 593 KiB  
Review
Current Status and Future Perspectives on Machine Perfusion: A Treatment Platform to Restore and Regenerate Injured Lungs Using Cell and Cytokine Adsorption Therapy
by Anna Niroomand, Gabriel Hirdman, Franziska Olm and Sandra Lindstedt
Cells 2022, 11(1), 91; https://doi.org/10.3390/cells11010091 - 29 Dec 2021
Cited by 8 | Viewed by 3779
Abstract
Since its advent in the 1990′s, ex vivo lung perfusion (EVLP) has been studied and implemented as a tool to evaluate the quality of a donor organ prior to transplantation. It provides an invaluable window of opportunity for therapeutic intervention to render marginal [...] Read more.
Since its advent in the 1990′s, ex vivo lung perfusion (EVLP) has been studied and implemented as a tool to evaluate the quality of a donor organ prior to transplantation. It provides an invaluable window of opportunity for therapeutic intervention to render marginal lungs viable for transplantation. This ultimately aligns with the need of the lung transplant field to increase the number of available donor organs given critical shortages. As transplantation is the only option for patients with end-stage lung disease, advancements in technology are needed to decrease wait-list time and mortality. This review summarizes the results from the application of EVLP as a therapeutic intervention and focuses on the use of the platform with regard to cell therapies, cell product therapies, and cytokine filtration among other technologies. This review will summarize both the clinical and translational science being conducted in these aspects and will highlight the opportunities for EVLP to be developed as a powerful tool to increase the donor lung supply. Full article
(This article belongs to the Special Issue Advances in Lung Transplantation)
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