Living-donor Lobar Lung Transplantation Research Articles

Living-donor Lobar Lung Transplantation - Initiation and Development - Secondary Publication.

Due to the difficulty of finding brain-dead donors, in October 1998, I performed the first living-donor lobar lung transplantation (LDLLT) for a ventilator-dependent 24-year-old female patient with bronchiectasis using lobes from her parents. The patient is still alive and in good health 25 years after the transplantation. Over time, the indications for LDLLT have expanded to include pulmonary hypertension, pulmonary fibrosis, congenital genetic diseases, pulmonary complications after stem cell transplantation, and, more recently, severe lung injury due to COVID-19 infection. In 2022, we successfully performed an ABO-incompatible LDLLT. To address size mismatches, we have developed new LDLLT techniques, such as right-to-left inverted transplantation, upper lobe-sparing transplantation, and segmental lung transplantation. Our published studies cover a range of topics, encompassing both basic and clinical research. Of particular significance is the observation that LDLLT offers immunological advantages over cadaveric lung transplantation (CLT). Having conducted 353 cases of lung transplantation, including 161 LDLLTs and 192 CLTs, our 5-year survival rates were 83% after LDLLT and 74% after CLT, surpassing the 55% 5-year survival rate reported by the International Society for Heart and Lung Transplantation. We have hosted numerous observers and research fellows from 15 countries. In addition, I have contributed to LDLLT procedures not only in Japan but also abroad. It brings me great satisfaction to think that my educational efforts may ultimately lead to saving the lives of those suffering from end-stage respiratory failure around the world.

Postoperative Complications in Living Donors for Lung Transplantation.

Living donor lobar lung transplantation is a life-saving procedure for critically ill patients. This requires 2 healthy donors exposed to risks and without medical benefit. Therefore, the donor's safety and minimal postoperative complications are crucial. This study aimed to investigate the short-term outcomes and identify the risk factors affecting these outcomes. The data of 175 living donors enrolled between 1998 and 2022 were analyzed. Donors were divided into era 1 (1998-2009) and era 2 (2010-2022). The overall incidence of postoperative complications was 39%, of which 7% were major complications. Donors who underwent surgery on the right side had a higher incidence of delayed pulmonary fistulae (P = 0.01) and elevated liver enzyme levels (P = 0.028). Living donor surgery on the right side (P = 0.01), era 2 (P = 0.01), and the need for plasty (P = 0.04) were predictors of postoperative complications. Updated data on complications and their correlation with postoperative quality of life from this study could aid in the selection of potential donors and facilitate informed consent.

(606) - Long-Term Maintenance of Pulmonary Function in the Contralateral Unaffected Lung with Chronic Lung Allograft Dysfunction After Bilateral Living-Donor Lobar Lung Transplantation

(606) - Long-Term Maintenance of Pulmonary Function in the Contralateral Unaffected Lung with Chronic Lung Allograft Dysfunction After Bilateral Living-Donor Lobar Lung Transplantation

(914) - Comparison of Perioperative Outcomes Between Living-Donor Lobar Lung Transplant Versus Deceased-Donor Lung Transplant

(914) - Comparison of Perioperative Outcomes Between Living-Donor Lobar Lung Transplant Versus Deceased-Donor Lung Transplant

Successful Living-donor Lobar Lung Transplantation With BK Virus-related Hemorrhagic Cystitis Throughout the Perioperative Period

Successful Living-donor Lobar Lung Transplantation With BK Virus-related Hemorrhagic Cystitis Throughout the Perioperative Period

Readmissions and costs in cadaveric and living-donor lobar lung transplantation: Analysis using a national database

Readmissions and costs in cadaveric and living-donor lobar lung transplantation: Analysis using a national database

Living-donor lobar lung transplantation

Living-donor lobar lung transplantation (LDLLT) is indicated for critically ill patients who would not survive the waiting period in the case of severe brain-dead donor shortage. It is essential to confirm that potential donors are willing to donate without applying psychological pressure from others. In standard LDLLT, the right and left lower lobes donated by 2 healthy donors are implanted into the recipient under cardiopulmonary support. LDLLT can be applied to various lung diseases including restrictive, obstructive, infectious, and vascular lung diseases in both adult and pediatric patients if size matching is acceptable. Functional size matching by measuring donor pulmonary function and anatomical size matching by 3-dimensional computed tomography volumetry are very useful. When 2 donors with ideal size matching are not available, various transplant procedures, such as single lobe, segmental, recipient lobe-sparing, and inverted lobar transplants are valuable options. There seems to be immunological advantages in LDLLT as compared to cadaveric lung transplantation (CLT). Unilateral chronic allograft dysfunction is a unique manifestation after bilateral LDLLT, which may contribute to better prognosis. The growth of adult lung graft implanted into growing pediatric recipients is suggested by radiologic evaluation. Although only 2 lobes are implanted, postoperative pulmonary function is equivalent between LDLLT and CLT. The long-term outcome after LDLLT is similar to or better than that after CLT. The author has performed 164 LDLLTs resulting in 71.6% survival rate at 10years. All living-donors returned to their previous life styles. Because of possible serious morbidity in donors, LDLLT should be applied only for critically ill patients.

Roles and practice of living-related lobar lung transplantation.

Living-donor lobar lung transplantation (LDLLT) was first performed in the USA and thereafter it was introduced in Japan in 1998 as an alternative modality to brain-dead donor lung transplantation (BDLT). Although the LDLLT procedure was employed for rapidly deteriorating patients who were hospitalized and mechanically ventilated at the time of transplantation, LDLLT demonstrated better or comparable post-transplant outcomes in comparison to BDLT. Less injured lobar grafts and a significantly shorter graft ischemic time possibly contributed to a significantly lower incidence of severe primary graft dysfunction (PGD) after LDLLT in comparison to BDLT. In standard LDLLT, patients obtained lobar grafts from two different donors, and thus most patients developed chronic lung allograft dysfunction (CLAD) only in the unilateral lung graft. This indicates that the contralateral unaffected lung graft could reserve lung function after the unilateral development of CLAD. In our transplant program, the incidence of CLAD per donor in LDLLT (14.4%) was also significantly lower in comparison to BDLT (24.7%). The 1-, 5- and 10-year survival rates after LDLLT were 90.9%, 75.5% and 57.2%, respectively, which were equivalent to those after BDLT (92.9%, 73.4% and 62.2%). The inherent surgical risk to the living donors should always be considered. In our experience, living-donor surgery was associated with a complication rate of 12.7%, and importantly, all living donors finally returned to their previous social lives. Precise functional and anatomical size matching between donor lobar graft and recipient could provide a favorable pulmonary function after LDLLT. We recently established multimodal surgical approaches, such as native upper lobe-sparing, right-to-left horizontally rotated, segmental, and single-lobe transplantation, in order to resolve the issue of size mismatch between the donor lobar graft and the recipient.

Long-term management and outcome of lung transplantation in Japan.

The long-term survival after lung transplantation (LT) is favorable in Japan. However, long-term survivors after LT are subject to late complications, including chronic lung allograft dysfunction (CLAD), malignancy, infection, and chronic kidney disease (CKD) because of the need for lifelong immunosuppression. The rates of single cadaveric LT (CLT) and living-donor lobar LT (LDLLT) are higher than that of bilateral CLT in Japan. Here, we will describe the management of late complications and long-term outcome after LT in Japan. Attention should be paid to not only the phenotype of CLAD but also the difference in CLAD after CLT and after LDLLT as well as the timing of lung re-transplantation for advanced CLAD, especially after single CLT. Since post-transplant lymphoproliferative disorder is the most common malignancy after LT, infection monitoring for infection-related malignancies and appropriate screening are keys to the early diagnosis and treatment of malignancy after LT. The long-term management of infection after LT is also important, especially with regard to community-acquired pathogens, Aspergillus, and cytomegalovirus. When providing long-term care after LT, physicians should be aware of CKD and the timing of renal replacement therapy in cases with severe CKD. The widespread use of computed tomography and dialysis in Japan are beneficial for long-term survivors of LT. The similar survival outcomes of single CLT and LDLLT, compared with bilateral CLT, might contribute to improved long-term survival in Japan. Pulmonologists are encouraged to become further involved in long-term management after LT in Japan.

Impact of perioperative airway pathogens on living-donor lobar lung transplantation outcomes.

To elucidate the clinical impact of pathogenic organism (PO) positivity early after transplantation, we evaluated the impact of perioperative airway POs on outcomes after living-donor lobar lung transplantation (LDLLT), where the graft airway is supposed to be sterile from a healthy donor. A retrospective review of 67 adult LDLLT procedures involving 132 living donors was performed. Presence of POs in the recipients' airways was evaluated preoperatively and postoperatively in intensive-care units. POs were detected preoperatively in 13 (19.4%) recipients. No POs were isolated from the donor airways at transplantation. POs were detected in 39 (58.2%) recipients postoperatively; most were different from the POs isolated preoperatively. Postoperative PO isolation was not associated with short-term outcomes other than prolonged postoperative ventilation. The 5-year overall survival was significantly better in the PO-negative group than in the PO-positive group (89.1% vs. 63.7%, P = 0.014). In the multivariate analysis, advanced age (hazard ratio [HR]: 1.041 per 1-year increase, P = 0.033) and posttransplant PO positivity in the airway (HR: 3.684, P = 0.019) significantly affected the survival. The airways of the living-donor grafts were microbiologically sterile. PO positivity in the airway early after transplantation negatively impacted long-term outcomes.

Restrictive allograft dysfunction rather than bronchiolitis obliterans syndrome had a major impact on the overall survival after living-donor lobar lung transplantation.

Chronic lung allograft dysfunction (CLAD) is a known long-term fatal disorder after lung transplantation. In this study, we evaluated the CLAD classification of the International Society for Heart and Lung Transplantation (ISHLT) for living-donor lobar lung transplantation (LDLLT). We conducted a single-center retrospective review of data from 73 patients who underwent bilateral LDLLT between 1998 and 2019. Factors related to opacity on computed tomography (CT) and restriction on pulmonary function tests (PFTs) were also analyzed. Overall, 26 (36%) patients were diagnosed with CLAD, including restrictive allograft syndrome (RAS), n = 10 (38.5%); bronchiolitis obliterans syndrome (BOS), n = 8 (30.8%); mixed, n = 1 (3.8%); undefined, n = 2 (7.7%); and unclassified, n = 5 (19.2%). The 5-year survival rate after the CLAD onset was 60.7%. The survival of patients with BOS was significantly better than that of patients with RAS (p = 0.012). In particular, patients with restriction on PFT had a significantly worse survival than those without restriction (p = 0.001). CLAD after bilateral LDLLT does not have a major impact on the recipient survival, especially in patients with BOS. Restrictionon PFT may predict a particularly poor prognosis in patients with CLAD after bilateral LDLLT.

Impact of Spousal Donation on Postoperative Outcomes of Living-donor Lobar Lung Transplantation.

The effect of human leukocyte antigen mismatches between donors and recipients on postoperative outcomes of lung transplantation remains controversial. We retrospectively reviewed adult recipients receiving living-donor lobar lung transplantation (LDLLT) to examine the difference in de novo donor-specific antibody (dnDSA) development and clinically diagnosed unilateral chronic lung allograft dysfunction per graft (unilateral CLAD) between lung grafts donated by spouses (nonblood relatives) and nonspouses (relatives within the third degree). We also investigated the difference in prognoses between recipients undergoing LDLLTs including spouse donors (spousal LDLLTs) and not including spouse donors (nonspousal LDLLTs). In this study, 63 adult recipients undergoing LDLLTs (61 bilateral and 2 unilateral LDLLTs from 124 living donors) between 2008 and 2020 were enrolled. The cumulative incidence of dnDSAs per lung graft was calculated, and prognoses were compared between recipients undergoing spousal and nonspousal LDLLTs. The cumulative incidence of both dnDSAs and unilateral CLAD in grafts donated by spouses was significantly higher than that in grafts donated by nonspouses (5-y incidence of dnDSAs: 18.7% versus 6.4%, P = 0.038; 5-y incidence of unilateral CLAD: 45.6% versus 19.4%, P = 0.011). However, there were no significant differences in the overall survival or chronic lung allograft dysfunction-free survival between recipients undergoing spousal and nonspousal LDLLTs ( P > 0.99 and P = 0.434, respectively). Although there were no significant differences in prognoses between spousal and nonspousal LDLLTs, more attention should be paid to spousal LDLLTs because of the higher development rate of dnDSAs and unilateral CLAD.

Living-donor lobar lung transplantation: a viable option for recipients with pulmonary hypertension.

Journal Article Accepted manuscript Living-donor lobar lung transplantation: a viable option for recipients with pulmonary hypertension Get access Hidenao Kayawake, Hidenao Kayawake Department of Thoracic Surgery, Kyoto University, Kyoto, JapanDepartment of Thoracic Surgery, Kobe City Medical Center General Hospital, Kobe, Japan https://orcid.org/0000-0003-2357-7024 Search for other works by this author on: Oxford Academic PubMed Google Scholar Hiroshi Date Hiroshi Date Department of Thoracic Surgery, Kyoto University, Kyoto, Japan Corresponding author: Hiroshi Date, Department of Thoracic Surgery, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan, Tel.: +81-75-751-4975, Fax: +81-86-751-4974, E-mail: hdate@kuhp.kyoto-u.ac.jp https://orcid.org/0000-0001-7262-6000 Search for other works by this author on: Oxford Academic PubMed Google Scholar European Journal of Cardio-Thoracic Surgery, ezad132, https://doi.org/10.1093/ejcts/ezad132 Published: 04 April 2023 Article history Received: 29 March 2023 Accepted: 01 April 2023 Published: 04 April 2023

Diagnostic value of circulating microRNA-21 in chronic lung allograft dysfunction after bilateral cadaveric and living-donor lobar lung transplantation

BackgroundMicroRNAs (miRNAs) involved in the pathogenesis of pulmonary fibrosis have been shown to be associated with the development of chronic lung allograft dysfunction (CLAD) after lung transplantation (LT). We investigated the role of circulating miRNAs in the diagnosis of CLAD after bilateral LT, including cadaveric LT (CLT) and living-donor lobar LT (LDLLT). MethodsThe subjects of this retrospective study were 37 recipients of bilateral CLT (n = 23) and LDLLT (n = 14), and they were divided into a non-CLAD group (n = 24) and a CLAD group (n = 13). The plasma miRNA levels of the two groups were compared, and correlations between their miRNAs levels and percent baseline forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and total lung capacity (TLC) values were calculated from one year before to one year after the diagnosis of CLAD. ResultsThe plasma levels of both miR-21 and miR-155 at the time of the diagnosis of CLAD were significantly higher in the CLAD group than in the non-CLAD group (miR-21, P = 0.0013; miR-155, P = 0.042). The miR-21 levels were significantly correlated with the percent baseline FEV1, FVC, and TLC value of one year before and at the time of diagnosis of CLAD (P < 0.05). A receiver operating characteristic curve analysis of the performance of miR-21 levels in the diagnosis of CLAD yielded an area under the curve of 0.89. ConclusionCirculating miR-21 appears to be of potential value in diagnosing CLAD after bilateral LT.

Living-donor lobar lung transplantation for pulmonary hypertension: living on the edge?

Journal Article Accepted manuscript Living-donor lobar lung transplantation for pulmonary hypertension: living on the edge? Get access Dirk Van Raemdonck, MD, PhD, Dirk Van Raemdonck, MD, PhD Departments of Thoracic Surgery, University Hospitals LeuvenDepartment of Chronic Diseases and Metabolism, Katholieke Universiteit Leuven, Leuven, Belgium Corresponding Author Contact Information: Dirk Van Raemdonck, MD, PHD, Department of Thoracic Surgery, University Hospital Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. E-mail: dirk.vanraemdonck@uzleuven.be Phone:+32 16 34 68 23, Facsimile:+32 16 34 68 24 https://orcid.org/0000-0003-1261-0992 Search for other works by this author on: Oxford Academic PubMed Google Scholar Robin Vos, MD, PhD, Robin Vos, MD, PhD Departments of Respiratory Diseases, University Hospitals LeuvenDepartment of Chronic Diseases and Metabolism, Katholieke Universiteit Leuven, Leuven, Belgium https://orcid.org/0000-0002-3468-9251 Search for other works by this author on: Oxford Academic PubMed Google Scholar Geert M Verleden, MD, PhD, Geert M Verleden, MD, PhD Departments of Respiratory Diseases, University Hospitals LeuvenDepartment of Chronic Diseases and Metabolism, Katholieke Universiteit Leuven, Leuven, Belgium https://orcid.org/0000-0003-3048-2429 Search for other works by this author on: Oxford Academic PubMed Google Scholar Laurens J Ceulemans, MD, PhD Laurens J Ceulemans, MD, PhD Departments of Thoracic Surgery, University Hospitals LeuvenDepartment of Chronic Diseases and Metabolism, Katholieke Universiteit Leuven, Leuven, Belgium https://orcid.org/0000-0002-4261-7100 Search for other works by this author on: Oxford Academic PubMed Google Scholar European Journal of Cardio-Thoracic Surgery, ezad097, https://doi.org/10.1093/ejcts/ezad097 Published: 23 March 2023 Article history Received: 03 March 2023 Accepted: 13 March 2023 Published: 23 March 2023

Living-Donor Lobar Lung Transplantation: A Powerful BUT Still Undervalued Resource To Overcome Donor Shortage.

Journal Article Accepted manuscript Living-Donor Lobar Lung Transplantation: A Powerful BUT Still Undervalued Resource To Overcome Donor Shortage Get access Paula Moreno, Paula Moreno Thoracic Surgery and Lung Transplantation UnitGroup for the Study of Thoracic Neoplasms and Lung Transplantation, IMIBIC (Instituto Maimónides de Investigación Biomédica de Córdoba), University of Córdoba, Córdoba, Spain CORRESPONDING AUTHOR: Paula Moreno, MD, PhD, Thoracic surgery and lung transplantation Unit. University Hospital Reina Sofia. Avenida Menéndez Pidal s/n. 14004. Córdoba. Spain. Tel:+34 957010445, Email: pmoreno39@gmail.com Search for other works by this author on: Oxford Academic PubMed Google Scholar Antonio Álvarez Antonio Álvarez Thoracic Surgery and Lung Transplantation UnitGroup for the Study of Thoracic Neoplasms and Lung Transplantation, IMIBIC (Instituto Maimónides de Investigación Biomédica de Córdoba), University of Córdoba, Córdoba, Spain Search for other works by this author on: Oxford Academic PubMed Google Scholar European Journal of Cardio-Thoracic Surgery, ezad081, https://doi.org/10.1093/ejcts/ezad081 Published: 16 March 2023 Article history Received: 24 February 2023 Accepted: 01 March 2023 Published: 16 March 2023

Donor's long-term quality of life following living-donor lobar lung transplantation.

Living-donor lobar lung transplantation is an alternative procedure to deceased donation lung transplantation. It involves graft donation from healthy donors; however, only a few reports have discussed its long-term prognosis in living lung donors and their associated health-related quality of life. This study aimed to examine living lung donors' health-related quality of life. In our cross-sectional survey of living lung donors, we assessed health-related quality of life-based on three key aspects (physical, mental, and social health) using the 36-Item Short Form Health Survey. We also evaluated chronic postoperative pain and postoperative breathlessness using the numeric rating scale and the modified Medical Research Council Dyspnea scale, respectively. We obtained consent from 117 of 174 living lung donors. The average scores of the living lung donors on the 36-Item Short Form Health Survey were higher than the national average. However, some donors had poorer physical, mental, and social health, with lower summary scores than the national averages. Low mental component summary predictors included donor age (<40 years; odds ratio=10.2; p<.001) and recipient age (<18 years; odds ratio=2.73; p<.032). Low role-social component summary predictors included high lung allocation score (≥50; odds ratio=3.94, p<.002) and recipient death (odds ratio=3.64; p=.005). There were no predictors for a physical component summary. Additionally, many donors did not complain of pain or dyspnea. Living lung donors maintained an acceptable long-term health-related quality of life after surgery. Potential donors should be informed of relevant risk factors, and high-risk donors should receive appropriate support.

Comparison of living-donor lobar lung transplantation and cadaveric lung transplantation for pulmonary hypertension.

Living-donor lobar lung transplantation (LDLLT) is a life-saving procedure for critically ill patients with various lung diseases, including pulmonary hypertension (PH). However, there are concerns regarding the development of heart failure with pulmonary oedema after LDLLT in which only 1 or 2 lobes are implanted. This study aimed to compare the preoperative conditions and postoperative outcomes of LDLLT with those of cadaveric lung transplantation (CLT) in PH patients. Between 2008 and 2021, 34 lung transplants for PH, including 12 LDLLTs (5 single and 7 bilateral) and 22 bilateral CLTs, were performed. Preoperative variables and postoperative outcomes were retrospectively compared between the 2 procedures. Based on the preoperative variables of less ambulatory ability (41.7% vs 100%, P < 0.001), a higher proportion of World Health Organization class 4 (83.3% vs 18.2%, P < 0.001) and higher mean pulmonary artery pressure (74.4 vs 57.3 mmHg, P = 0.040), LDLLT patients were more debilitated than CLT patients. Nevertheless, hospital death was similar between the 2 groups (8.3% vs 9.1%, P > 0.99, respectively). Furthermore, the 5-year overall survival rate was similar between the 2 groups (90.0% vs 76.3%, P = 0.489). Although LDLLT patients with PH had worse preoperative conditions and received smaller grafts than CLT patients, LDLLT patients demonstrated similar perioperative outcomes and prognoses as CLT patients. LDLLT is a viable treatment option for patients with PH.

Outcome and growth of lobar graft after pediatric living-donor lobar lung transplantation

Living-donor lobar lung transplantation (LDLLT) remains a life-saving option for pediatric patients with respiratory failure. However, the long-term survival and post-transplant quality of adult lobar grafts transplanted into children are unknown. Therefore, this study aimed to evaluate the outcomes of pediatric LDLLT and post-transplant graft growth. We retrospectively reviewed the prospectively collected clinical data of 25 living-donor lung transplantations performed in 24 pediatric recipients aged ≤17 years. The annual pulmonary function test data and computed tomography scans of 12 recipients, followed up for >5 years without significant complications, were used to evaluate growth in height, graft function, and radiological changes. The Kaplan-Meier method and simple linear regression were performed for analysis. Bilateral lower lobe transplantation was performed in 12 patients, unilateral lower lobe transplantation in 12, and bilateral middle lobe transplantation in 1. The median volumetric size matching at transplantation was 142% (range, 54%-457%). The 5- and 10-year overall survival rates were 87.7% and 75.1༅, respectively. Chronic lung allograft dysfunction occurred in 2 patients. During a median follow-up of 6 years, the median increases in height and vital capacity were 14.4% (range, 0.80%-43.5%) and 58.5% (range, 6.7%-322%), respectively. Graft weight was positively correlated with graft volume (r2=0.622, p<0.001) after the graft volume exceeded the original lobar volume in the donor. This study shows that pediatric LDLLT offers satisfactory long-term survival, with the growth of mature adult lobes transplanted into growing children.

Living Donor Lobar Lung Transplant for a Patient With Lung Disease Caused by ABCA3 Gene Mutations: A Case Report

Recessive gene mutations in ABCA3 cause lethal neonatal respiratory distress, and pediatric and adult interstitial lung disease. The effectiveness of medical treatments is limited and a subset of such patients will eventually require lung transplantation. A 20 months old boy developed interstitial lung disease and was treated with hydroxychloroquine, which had a significant effect. Sequence analysis of ABCA3 gene revealed newly discovered compound heterozygous mutations. His respiratory dysfunction gradually progressed over years and he underwent living-donor lobar lung transplantation (LDLLT) at 8 years of age with his parents serving as bilateral lobar donors. The parents had been genetically examined beforehand and found to be carriers who had one allele with an ABCA3 gene mutation and the other with no mutation. The recipient has been well without chronic lung allograft dysfunction and his parents have been enjoying healthy social lives for 7 years since the operations. LDLLT appears to be a valid option for selected children with ABCA3 gene mutations who are too ill to wait for cadaveric lung transplantation. When relatives of the recipient with ABCA3 gene mutation are deemed potential donors for LDLLT, sequence analyses of the donors are indispensable to exclude the possibility that they are late-onset patients of this recessive hereditary disease.