Living-donor Lobar Lung Transplantation Research Articles

(704) - Characteristics of De Novo Donor-Specific Anti-HLA Antibodies (DSAs) in Living-Donor Lobar Lung Transplantation Might Be Different From Those in Cadaveric Lung Transplantation

(704) - Characteristics of De Novo Donor-Specific Anti-HLA Antibodies (DSAs) in Living-Donor Lobar Lung Transplantation Might Be Different From Those in Cadaveric Lung Transplantation

Postoperative pulmonary function and complications in living-donor lobectomy

Successful living-donor lobar lung transplantation largely depends on the donor's outcome. Because surgical skills and peri-operative management have evolved over time, this study evaluated the recent outcomes of donor lobectomies. Between 2008 and 2014, 48 consecutive living-donor lobar lung transplantations with 85 donor lobectomies were performed at Kyoto University. All donors were prospectively followed up regularly until 1 year after surgery. Right and left lower lobectomies were performed in 49 and 36 donors, respectively. Pulmonary arterial branches were sacrificed at equal frequency in both lobectomies, whereas pulmonary arterioplasty was only performed in left lower lobectomy (n = 9). All donors were discharged after the lobectomies, and none died during follow-up. Post-operative complications occurred in 24 donors (28%) overall, without a significant difference between donor sides. Intraoperative complications were found in 2 donors. Early and late post-operative complications were noted in 17 and 6 donors, respectively. Pneumothorax, pleuritis, and pleural effusion were the most frequent. Post-operative pulmonary function sequentially recovered more than expected and was not significantly affected by the sacrifice of pulmonary arterial branches during lobectomy. By contrast, pulmonary function at 1 year after donor lobectomy in the donors who had peri-operative complications was significantly lower than that in the donors who did not, although even post-operative pulmonary function in the donors with peri-operative complications still recovered more than expected. Living-donor lobectomies have been safely performed in recent decades with low morbidities and without mortality.

A Case Report of Living-donor Lobar Lung Transplantation for Scleroderma-associated Usual Interstitial Pneumonia: Eight Years and Counting

IntroductionScleroderma-associated interstitial lung disease is a life-limiting complication of scleroderma, often requiring lung transplantation. Living-donor lobar lung transplantation (LDLLT) is a viable alternative to deceased-donor lung transplantation in specialized centers under select circumstances. Clinical CaseA 47-year-old female underwent LDLLT after nine years of symptomatic scleroderma-associated usual interstitial pneumonia and three years awaiting deceased-donor lung transplantation. Her manifestations of scleroderma included mild sclerodactyly, periungual erythema, Raynaud's phenomenon, and gastroesophageal reflux, with positive antinuclear autoantibodies. Several years post-transplantation, manometry revealed feeble lower esophageal sphincteric pressure with ineffective esophageal motility. Bronchiolitis obliterans syndrome developed 64 months post-transplantation without evidence of aspiration or reflux on transbronchial biopsy. Currently, she has normal renal function and good allograft function [FEV1 1.52 L (73% predicted) and FVC 2.50 L (99% predicted)]. RelevanceThis is the second reported case of LDLLT in scleroderma, and the first reporting long-term pulmonary, renal, and esophageal function post-transplantation.

BOS in unilateral lung 15 years after living-donor lobar lung transplantation for idiopathic pulmonary arterial hypertension at schoolchild age in overseas travel

BOS in unilateral lung 15 years after living-donor lobar lung transplantation for idiopathic pulmonary arterial hypertension at schoolchild age in overseas travel

Unilateral chronic lung allograft dysfunction is a characteristic of bilateral living-donor lobar lung transplantation.

Living-donor lobar lung transplantation (LDLLT) has been established as a life-saving procedure for critically ill patients who cannot wait for cadaveric lung transplantation. Chronic lung allograft dysfunction (CLAD) is the main cause of late morbidity and mortality in lung transplantation. Studies on CLAD in cadaveric lung transplantation have been extensively reported, but few reports have been reported concerning CLAD after LDLLT. The aim of this study was to determine the prevalence, characteristics and prognosis of CLAD after LDLLT. Among 38 patients who survived more than 3 months after LDLLT at Kyoto University Hospital between June 2008 and December 2013, 8 patients (21%) were diagnosed with CLAD. The mean follow-up period after LDLLT was 33 months. Clinical course, pulmonary function and radiological findings were reviewed retrospectively in all the 38 patients as of May 2014. Six patients were female and 2 were male. The median age at LDLLT was 31 years, and the median interval between LDLLT and the initial diagnosis of CLAD was 23 months. Among 8 patients who developed CLAD, 2 patients underwent right single LDLLT and 6 patients underwent bilateral LDLLT. The former 2 patients survived 44 and 47 months after the treatment. Five out of 6 patients with bilateral LDLLT developed unilateral CLAD at the time of initial diagnosis according to ventilation scintigraphy. In 3 of these 5 patients, the progression of CLAD was halted by treatment, and the median follow-up period of 33 months after treatment. In the remaining 2 of 5 patients, CLAD progressed to the contralateral lung metachronously; 1 patient survived without oxygen supplement, but the other patient required reperformance of LDLLT 3 years after the first one. One patient with bilateral CLAD at the time of detection died of disease progression 4 years after LDLLT. Despite a relatively short observation time, CLAD developed in approximately one-fifth of the patients who survived more than 3 months after LDLLT. In bilateral LDLLT, CLAD developed unilaterally in most cases, which might be beneficial in the long term because the unaffected contralateral lung may function as a reservoir.

Outcomes after pregnancy in living lobar lung transplantation.

Pregnancy after lung transplantation has been described, but pregnancy after living donor lobar lung transplantation (LDLT) has not been reported. The aim of this study was to evaluate outcomes after pregnancy with LDLT and discuss current recommendations regarding pregnancy and lung transplantation. A total of four LDLT patients and five pregnancies were identified, all from our institution. No patient has developed worsening pulmonary function or acute or chronic rejection. The complications of pulmonary hypertension and rejection may be overestimated in this population, and recommendations for preventive sterilization at transplantation or abortion at the time of conception are likely unwarranted and unnecessary.

Living-donor lobar lung transplantation provides similar survival to cadaveric lung transplantation even for very ill patients†.

Living-donor lobar lung transplantation (LDLLT) has been performed as a life-saving procedure for critically ill patients who are unlikely to survive the long wait for cadaveric lungs. The purpose of this study was to compare the preoperative condition and outcome of LDLLT patients with those of conventional cadaveric lung transplantation (CLT) patients. A new lung transplant programme was established in 2008 at Kyoto University. Between June 2008 and January 2014, we performed 79 lung transplants, including 42 LDLLTs (10 single, 32 bilateral) and 37 CLTs (22 single, 15 bilateral). Data collected included pre- and perioperative variables and mid-term survival. All data were analysed retrospectively as of January 2014. The majority of patients were female (57.1%) in the LDLLT group and male (64.9%) in the CLT group. The average age was similar (36.6 ± 20.7 vs 39.7 ± 12.6 years, P = 0.42) between the two groups. Preoperatively, interstitial lung disease was more common in LDLLT patients than in CLT patients (47.6 vs 24.3%, P = 0.048); prior haematopoietic stem cell transplantation was performed more often in LDLLT patients than in CLT patients (33.3 vs 13.5%, P = 0.040) and there were more steroid-dependent LDLLT patients than CLT patients (64.3 vs 29.7%, P = 0.0022). Based on preoperative criteria of lower body mass index (17.2 ± 4.0 vs 19.3 ± 3.3 kg/m(2), P = 0.013), less ambulatory ability (42.9 vs 86.5%, P = 0.0001) and more ventilator dependence (11.9 vs 2.7%, P = 0.12), LDLLT patients were more debilitated than CLT patients. LDLLT patients required longer postoperative mechanical ventilation than CLT patients (15.6 ± 16.2 vs 8.5 ± 8.1 days, P = 0.025). However, 1- and 3-year survival rates were similar between the two groups (89.7 and 86.1% vs 88.3 and 83.1%, P = 0.55). All living donors returned to their previous lifestyles without restriction. Although LDLLT patients were in a worse preoperative condition than CLT patients, LDLLT patients demonstrated survival rates similar to CLT patients. LDLLT is a viable option for patients too ill to survive a long waiting time for cadaveric donors.

Catecholamine Support at the Initiation of Epoprostenol Therapy in Pulmonary Arterial Hypertension

Epoprostenol is a first-line therapy for patients with pulmonary arterial hypertension (PAH) in World Health Organization functional class IV who often have low cardiac output and hypotension. However, initiation of epoprostenol can cause hemodynamic collapse in these vulnerable patients. Inotropic agent support may prevent the hemodynamic instability caused by initiation of epoprostenol; however, a protocol for supportive therapy has not been established. To assess the reliability and prognostic effects of dobutamine and dopamine support at the initiation of epoprostenol therapy in patients with PAH. We initiated epoprostenol therapy in 71 patients with PAH. Hemodynamics at the initiation of epoprostenol were measured by right heart catheterization. We initiated dobutamine when a patient's mixed venous oxygen saturation was less than 60% or cardiac index was less than 2.0 L/min/m(2) or when right ventricular failure was clinically suspected. We initiated dopamine when a patient's systolic blood pressure was less than 90 mm Hg or urine volume was less than 20 ml/h. At the initiation of epoprostenol, dobutamine and/or dopamine were required to support 46 patients according to protocol. Eight patients died during the hospitalization and one patient received a living-donor lobar lung transplant after the initiation of epoprostenol therapy. Neither inotropic agent was an independent risk factor for short-term mortality (dobutamine: hazard ratio, 1.63; 95% confidence interval, 0.33-8.11; dopamine: hazard ratio, 0.22; 95% confidence interval, 0.03-1.70). Sixty-two patients were discharged for home infusion of epoprostenol. Transplant-free survival rates at 5 years were 80.0% for patients who did not require inotropic support at the start of epoprostenol and 76.6% for patients with who did require dopamine and/or dobutamine support (P = 0.45). Temporary use of dobutamine and dopamine appears to be safe for hemodynamic support at the initiation of epoprostenol therapy for selected patients with PAH with low cardiac output and hypotension. The protocol presented here requires validation at other centers.

Living-Donor Lobar Lung Transplantation for Treatment of Idiopathic Pulmonary Arterial Hypertension With Severe Pulmonary Arterial Dilation

Living-Donor Lobar Lung Transplantation for Treatment of Idiopathic Pulmonary Arterial Hypertension With Severe Pulmonary Arterial Dilation

Once-daily oral administration of cyclosporine in a lung transplant patient with a history of renal toxicity of calcineurin inhibitors: Figure 1:

Cyclosporine is usually administered orally in two divided doses every 12 h in transplant patients. However, some patients have difficulty in achieving therapeutic levels after transplantation. In fact, cyclosporine is reportedly administered once daily in renal and liver transplantation cases, but not in lung transplantation cases. We report a patient with a history of calcineurin inhibitor-induced renal toxicity who successfully underwent living-donor lobar lung transplantation (LDLLT) with the novel immunosuppressive strategy of once-daily administration of cyclosporine. An 18-year old man with progressive respiratory insufficiency after bone marrow transplantation was referred to our hospital for lung transplantation. He had a history of renal toxicity due to calcineurin inhibitors. Based on his history of tacrolimus- and cyclosporine-induced renal toxicity, we decided to initiate basiliximab as induction therapy, followed by once-daily cyclosporine administration to obtain high enough blood cyclosporine concentrations at 2 h post-dose (C2) and lowered trough blood concentrations (C0) for protection of renal function as maintenance therapy. LDLLT was successfully performed, and the postoperative course was uneventful and free of rejection episodes. Cyclosporine dosing was adjusted with intensive therapeutic drug monitoring of blood cyclosporine levels. One year after LDLLT, the patient is alive and well with no problems with daily life activities.

(487) - How Donor Graft Lungs Behave in a Recipient Thorax After Living-Donor Lobar Lung Transplantation: 2-Year Follow-up

Purpose: In living-donor lobar lung transplantation (LDLLT), there is a wide range of size discrepancies between donor and recipient. The aim of this study was to investigate how such donor grafts behave in the new recipient thorax after LDLLT. Methods: Twenty-six donor grafts in 13 bilateral LDLLT were enrolled in this study. The recipient's original diseases were bronchiolitis obliterans in 5 patients, pulmonary fibrosis in 5, bronchiectasis in 2, and pulmonary hypertension in 1. Pulmonary function tests and three-dimensional computed tomography (3D-CT) volumetry were performed before LDLLT and 3, 6, 12, and 24 months after LDLLT. Postoperative changes of pulmonary function and volume in the donor grafts were further investigated. Results: Donor graft volume ranged from 39 to 180% of the hemilateral tho- racic volume of the recipient. Only 2 recipients grew taller by 7cm and 11cm in 2 years. Graft forced vital capacities (FVC) increased over time, reaching 102 ± 39% and 109 ± 42% of preoperatively estimated values at 12 and 24 months after LDLLT, respectively. Graft volume also increased over time, reaching 122 ± 39% and 130 ± 39% of the original size at 12 and 24 months postoperatively. As for the association between postoperative donor graft volume ratio to the original value and preoperative 3D-CT volumetry size matching, there was a significant correlation between these parameters throughout postoperative timings (3, 6, 12, 24 months after LDLLT, p < 0.05). In contrast, there w as no significant correlation between postoperative donor graft FVC ratio to the preoperatively estimated value and preoperative 3D-CT volumetry size match- ing throughout postoperative timings. Furthermore, postoperative donor graft volume was significantly correlated with preoperative hemithorax volume of the recipient throughout postoperative timings (p < 0.01). Conclusion: We found that both lung function and volume in donor grafts significantly improved even 2 years after LDLLT. Furthermore, donor grafts adapted themselves to the recipient's thoracic cage by overinflating or under- inflating to the extent that they could maintain their own function in a new recipient environment.

(814) - The Impact of Incomplete Pulmonary Fissures of Living Lobar Lung Transplant Donors on Bronchial Stenosis of Lung Recipients

Bronchial complications are among the most challenging problems after living-donor lobar lung transplantation (LDLLT), although the ischemic time of living-donor lungs can be minimized compared to cadaveric lung transplantation. To prevent bronchial complications, maintaining the pulmonary blood flow is critical for the bronchial healing. However, in the donor lobectomy of LDLLT, the inadequate dissection of interlobar fissures could cause unexpected obstruction of the pulmonary vessels and decreased blood flow to the bronchial anastomosis. The purpose of this study was to examine the relationships between incomplete pulmonary fissures of living-donor lungs and bronchial stenosis of LDLLT recipients. We retrospectively analyzed 127 donors and 69 recipients of bilateral and unilateral LDLLT at our institution between October 1998 and October 2013. According to Craig’s classification of pulmonary fissures, interlobar fissures of donor lungs were Grade 1 in 43, Grade 2 in 73, Grade 3 in 11 and Grade 4 in no donor. Postoperative lung perfusion scintigraphy was available in 119 of 127 transplanted lungs after LDLLT. Lung perfusion scintigraphy showed segmental defect or reduced blood flow in the lobar apex in 12 transplanted lungs (Group A), and homogenous distribution of blood flow in 107 transplanted lungs (Group B). Grade of interlobar fissures in Group A was significantly higher than that in Group B (2.1 ± 0.15 v.s. 1.7 ± 0.059; p < 0.05). While 3 of 12 (25 %) transplanted lungs in Group A revealed bronchial stenosis after LDLLT, no bronchial stenosis was encountered in 107 transplanted lungs of Group B. Our experience suggests that the incomplete pulmonary fissure of living-donors is a possible risk factor for bronchial stenosis of lung recipients in LDLLT. Careful dissection of incomplete pulmonary fissures should be required to maintain the pulmonary blood flow in the living-donor lobectomy.

(806) - Outcomes Following Pregnancy in Living Lobar Lung Transplantation

Pregnancy following lung transplantation has been described, but pregnancy following living donor lobar lung transplantation (LDLT) has not been reported. LDLT was originally developed to decrease transplant waiting list mortality due to a lack of available organs. As female patients with LDLT matured, physicians were faced with advising patients on family planning. Generally, most physicians recommend abstaining from pregnancy after lung transplantation due to the required alterations in immunosuppressive therapy that could increase the risk of rejection.

Living Donor Lobar Lung Transplantation: A Longstanding Concept Being Revisited with the Same Old Nemesis

Living donor lobar lung transplantation (LDLLT) has been successfully used in select patient populations. A 29-year-old male, who underwent bilateral LDLLT 12 years earlier with allografts donated by father and paternal uncle, developed bronchiolitis obliterans syndrome at distinctly different rates. LDLLT can be done successfully with unique management issues.

Gastroparesis after living-donor lobar lung transplantation: report of five cases

Gastroparesis is a challenging gastrointestinal complication of deceased-donor lung transplantation and heart-lung transplantation, but it has not been reported after living-donor lobar lung transplantation (LDLLT). To better understand this complication after LDLLT, we reviewed our institutional experiences. Among the 32 patients who survived for at least 3 months after LDLLT, five (16 %) developed symptomatic gastroparesis. All five patients had undergone bilateral LDLLT, and gastroparesis was diagnosed within 2 months after transplantation. Neither adult patients who received single lobar LDLLT nor pediatric patients who received either bilateral or single lobar LDLLT developed gastroparesis. Although gastroparesis-related symptoms improved after medical treatment in three patients, two patients died of complications related to gastroparesis. We conclude that gastroparesis can occur after LDLLT and may cause grave complications unless carefully managed.

Effect of hypogammaglobulinemia after lung transplantation: a single-institution study

Recent studies suggest hypogammaglobulinemia (HGG) is frequently associated with infection after solid organ transplantation, although the effects of HGG after lung transplantation are not well recognized. We investigated the incidence and degree of HGG after lung transplantation and its association with infection. A retrospective cohort study analysing pre- and post-transplant IgA, IgG and IgM levels and infectious events in patients undergoing living-donor lobar and cadaveric lung transplantation at Kyoto University Hospital between June 2008 and March 2013. Overall, post-transplant immunoglobulin (Ig) levels were significantly lower than pretransplant levels. In almost all patients who received transplants for bronchiolitis obliterans (BO) after haematopoietic stem cell transplantation (HSCT), interstitial lung diseases and bronchiectasis, post-transplant IgA and IgG levels decreased and were significantly lower than pretransplant levels; pre- and post-transplant IgA and pretransplant IgG levels were significantly lower in patients transplanted for BO after HSCT than in the others. Post-transplant IgG levels in patients transplanted for BO after HSCT also tended to be lower than those in the others, but not significantly. Nineteen of 29 patients had HGG after lung transplantation (65.5%) and had more infections than the normal gammaglobulinemia group, although there was no significant difference. Among them, 2 patients transplanted for BO after HSCT with quite low HGG had severe pneumonia and finally died. Post-transplant Ig levels were significantly lower than pretransplant levels. Although without significant difference, HGG patients had more infections, above all, those with severe HGG transplanted for BO after HSCT could have lethal infections. Ig levels in HGG should be monitored carefully because severe HGG was associated with poor prognosis.

Continuous carbon dioxide partial pressure monitoring in lung transplant recipients.

Living-donor lobar lung transplantation (LDLLT) recipients often have hypercapnia preoperatively, which confers a risk of worsened hypercapnia intraoperatively. We reviewed our experience with continuous carbon dioxide partial pressure (PtcCO2) monitoring in LDLLT to evaluate its accuracy and feasibility. We also assessed preoperative and intraoperative carbon dioxide levels in LDLLT recipients. Twenty-six LDLLT recipients without pulmonary hypertension underwent preoperative nocturnal and intraoperative PtcCO2 monitoring, determined with a TOSCA-500 monitor. Maximal preoperative nocturnal PtcCO2 (72.7 ± 19.3 mmHg) was significantly correlated with preoperative resting arterial carbon dioxide partial pressure (PaCO2; 55.1 ± 11.6 mmHg, r(2)=0.84). PtcCO2 was more correlated with PaCO2 (range, 39-192 mmHg) during LDLLT (r(2)=0.93) than with end-tidal carbon dioxide partial pressure (r(2)=0.38). Intraoperative continuous PtcCO2 monitoring was useful for evaluating real-time carbon dioxide levels. Intraoperative PtcCO2 did not exceed maximal preoperative nocturnal PtcCO2 in 13 recipients (50%) but temporarily exceeded it in 11 recipients (42%). PtcCO2 was further elevated in 2 recipients (8%) requiring the early establishment of cardiopulmonary bypass. There were no complications related to PtcCO2 monitoring. PtcCO2 monitoring in LDLLT recipients is useful as a means for determining intraoperative carbon dioxide levels, which increase dramatically and can be predicted preoperatively and assessed in a timely manner.

Redo living-donor lobar lung transplantation for bronchiolitis obliterans associated with antibody-mediated rejection

Living-donor lobar lung transplantation (LDLLT) is an established therapy for patients with end-stage lung disease, but living-donor lobar lung retransplantation (re-LDLLT) is rarely reported. We previously reported a case of unilateral antibody-mediated rejection after LDLLT in the presence of newly formed donor-specific antibodies against a right-lobe donor. The same patient developed contralateral bronchiolitis obliterans, resulting in bilateral bronchiolitis obliterans, but re-LDLLT was successful. Pathological findings of the explanted lungs were consistent with the clinical course of the patient. One year after re-LDLLT, the patient is doing well without any anti-human leukocyte antigen antibodies. Four lobes from four different donors were transplanted in this patient. The first two lobes were rejected eventually, but the two lobes implanted later presented no signs of rejection at least for 1 year after the transplant. Herein, we report this rare case and compare the clinical course and pathological findings.

A Prospective Study Analyzing One-Year Multidimensional Outcomes in Living Lung Transplant Donors

The success of living-donor lobar lung transplantation (LDLLT) largely depends on donor outcome; but to date, no authors have studied health-related quality of life (HRQOL) of donors. We prospectively evaluated multidimensional outcomes before and 1 year after donor lobectomies. Patient-reported HRQOL, dyspnea, psychological status and sleep quality, and physiological pulmonary function were determined. All donors were alive without any limitations in their activities of daily living after 1 year. Postoperative pulmonary function was better than the estimated preoperative values; but, with respect to HRQOL, four of the eight subscales of the Medical Outcomes Study 36-item short form (SF-36) deteriorated significantly after donation. In addition, dyspnea assessed by the modified Medical Research Council scale also worsened significantly. In contrast, postoperative anxiety assessed by the Hospital Anxiety and Depression Scale significantly improved from baseline. The donors whose recipients died reported lower SF-36 scores with worsening sleep quality measured by Pittsburgh Sleep Quality Index. Thus, although postoperative pulmonary functions in donors were preserved, their HRQOL and dyspnea deteriorated postoperatively. Moreover, HRQOL and sleep quality were impaired in recipients who experienced poor outcomes. To capture the comprehensive outcomes in LDLLT donors after donation, patient-reported outcomes should be analyzed separately from physiological outcomes.

Broncho-Bronchiolitis Obliterans After Living-Donor Lung Transplantation

Broncho-Bronchiolitis Obliterans After Living-Donor Lung Transplantation