One and One-Half Year Experience with Unilateral and Bilateral Lung Transplantation

Lung transplantation has now become an established form of treatment for end-stage pulmonary parenchymal and vascular diseases. Despite its wide acceptance, technical aspects are still in discussion. We report on the initiation of our own lung transplant program and the technical changes we have performed during our first 1 1/2-year experience. During that period of time, we have performed 26 lung transplantations (16 single lung [SLTX] and 10 bilateral lung transplantations [BLTX]). Three-month survival for the whole group was 74% (69% for the SLTX group and 77% for the BLTX group). No instance of bronchial dehiscence was observed; however, there were eight cases of bronchial stenosis: six were managed by silicone stent insertion, one by bronchoplastic correction, and one by retransplantation. Changes in the technique of the bronchial anastomosis together with the addition of prednisone to the immediate postoperative immunosuppressive regime resulted in almost complete avoidance of these problems.     

Long-Term Outcomes of Cadaveric Lobar Lung Transplantation: An Important Surgical Option

Background: Cadaveric lobar lung transplantation (L-LTx) is developed to overcome donor–recipient size mismatch. Controversial short- and long-term outcomes following L-LTx have been reported compared to full-sized lung transplantation (F-LTx). This study reports long-term outcomes after L-LTx.Methods: We reviewed patients undergoing lung transplantation (LTx) between 2000 and 2016. The decision to perform L-LTx was made based mainly on donor–recipient height discrepancy and visual assessment of donor lungs. Predicted donor–recipient total lung capacity (TLC) ratio was calculated more recently. Primary outcome was overall survival.Results: In all, 370 bilateral LTx were performed during the study period, among those 250 (67%) underwent F-LTx and 120 (32%) underwent L-LTx, respectively. One- and 5-year survival rates were 85% vs. 90% and 53% vs. 63% for L-LTx and F-LTx, respectively (p = 0.16). Chronic lung allograft dysfunction (CLAD)-free survival at 5 years was 48% in L-LTx vs. 51% in F-LTx recipients (p = 0.89), respectively. Age, intraoperative extracorporeal membrane oxygenation (ECMO) use, intensive care unit (ICU) stay, and postoperative renal replacement therapy (RRT) were significant prognostic factors for survival using multivariate analysis.Conclusions: Overall survival and CLAD-free survival following L-LTx were comparable to F-LTx. Given the ongoing donor organ shortage, cadaveric L-LTx remains as an important resource in LTx.     

Right and Left Inverted Lobar Lung Transplantation

Adult recipients frequently withdraw from living‐donor lobar lung transplantation because of the small size of donor grafts. The right lower lobe is 120% larger than the left lower lobe. We developed a novel surgical technique in which an inverted right lower lobe graft can be transplanted into the left thorax. The first patient was a 43‐year‐old woman with end‐stage idiopathic interstitial pneumonia. Her husband was the only eligible donor for living‐donor lobar lung transplantation. His right lower lobe was estimated to provide 45% of the recipient's predicted forced vital capacity, which would provide the borderline function required for living‐donor lobar lung transplantation. Since lung perfusion scintigraphy of the recipient showed a right‐to‐left ratio of 64:36, transplanting the right lower lobe graft into the left thorax and sparing the native right lung was considered the only treatment option. We simulated this procedure using three‐dimensional models produced by a three‐dimensional printer. In living‐donor lobar lung transplantation, all anastomoses were performed smoothly as planned preoperatively. Because of the initial success, this procedure was performed successfully in two additional patients. This procedure enables larger grafts to be transplanted, potentially solving critical size matching problems in living‐donor lobar lung transplantation.     

Exacerbation of Secondary Pulmonary Hypertension by Flat Chest after Lung Transplantation

A 40-year-old woman with idiopathic pleuroparenchymal fibroelastosis (IPPFE) and flat chest underwent left single lung transplantation (SLT). Although she had developed over-systemic pulmonary arterial pressure (PAP) at transplantation, it was alleviated. However, her PAP gradually increased again. Her transplanted lung was well-inflated, but progression of fibrosis in her right native lung appeared to have caused a mediastinal shift, and her flat chest caused obstruction of the outflow tract of the pulmonary vein. She died of heart failure and associated infection 1.5 years after transplantation. An autopsy confirmed irreversible pulmonary arterial and venous changes in the transplanted lung, suggestive of chronic pressure overload. The flat chest associated with IPPFE can affect pulmonary circulation after SLT.     

Bridge to Thoracic Organ Transplantation in Patients with Pulmonary Arterial Hypertension Using a Pumpless Lung Assist Device

We describe a novel technique of pumpless extracorporeal life support in four patients with cardiogenic shock due to end-stage pulmonary hypertension (PH) including patients with veno-occlusive disease (PVOD) using a pumpless lung assist device (LAD). The device was connected via the pulmonary arterial main trunk and the left atrium, thereby creating a septostomy-like shunt with the unique addition of gas exchange abilities in parallel to the lung. Using this approach, all four patients were successfully bridged to bilateral lung transplantation and combined heart–lung transplantation, respectively. Although all patients presented in cardiogenic shock, hemodynamic unloading of the right ventricle using the low-resistance LAD stabilized the hemodynamic situation immediately so that no pump support was subsequently required.     

双肺移植治疗终末期原发性肺动脉高压

双肺移植治疗原发性肺动脉高压１例。男病人，３０岁。多年来有气短等症状，晕厥４次，反复咯血４年，近期大咯血３次。肺动脉压２０．３／７．３（１３．７）ｋＰａ，全肺阻力３５４．９７８ｋＰａ·ｓ／Ｌ，有中至重度三尖瓣关闭不全。１９９８年１月２０日在体外循环（心脏不停跳）支持下手术。术毕肺动脉压基本正常，三尖瓣关闭不全及反流消失。术后给予三联免疫抑制剂。围手术期有明显的血液动力学紊乱，无明确的急性排斥发生，最主要的并发症是左主支气管吻合口、右上叶及中间干支气管狭窄，目前仍间断行球囊扩张治疗。病人已生存８个多月，状态稳定，在扩张狭窄的支气管后可出院外自由活动     

Lung Transplantation in Japan

The first successful living-donor lobar lung transplant (LDLLT) in Japan was performed at Okayama University in October 1998 after a long period of waiting for the legalization of thoracic organ transplantation. By May 2003, a further 41 lung transplants had been performed; 28 from living donors and 13 from cadaveric donors. The indications for a lung transplant are very specialized in Japan, the most common being primary pulmonary hypertension. Although the number of lung transplants is still small, survival in Japan, at 72% after 4 years, is better than the world average. Because the number of available cadaveric donors for lung transplantation is limited, at less than 5 per year, LDLLT is a realistic option for properly selected candidates.     

Successful Lung Transplantation in a Case With Diffuse Pulmonary Arteriovenous Malformations and Hereditary Hemorrhagic Telangiectasia

Diffuse pulmonary arteriovenous malformations (AVMs) are associated with a poor prognosis and the therapeutic strategy remains controversial. We describe a pediatric patient with diffuse pulmonary AVMs associated with hereditary hemorrhagic telangiectasia (HHT), who presented with two cerebral AVMs in the parietal and occipital lobes as well. Of note, successful bilateral lung transplantation not only improved the hypoxemia but also resulted in size reduction of the cerebral AVMs. Although it is essential to consider involvements other than pulmonary AVMs, especially brain AVMs, to decide the indication, lung transplantation can be a viable therapeutic option for patients with diffuse pulmonary AVMs and HHT.     

Cost-Effectiveness of Lung Transplantation in Relation to Type of End-Stage Pulmonary Disease

The purpose of this study was to explore the relationship between diagnosis and the cost-effectiveness and cost-utility of lung transplantation. A microsimulation model was used, based on empirical data from the Dutch lung transplantation program, collected between 1991 and 1999. We assessed life-years, quality-adjusted life-years, and costs with and without transplantation for the diagnostic categories alfa-1 antitrypsin deficiency, COPD/emphysema, bronchiectasis, primary and secondary pulmonary hypertension, cystic fibrosis, and pulmonary fibrosis. Alfa-1 antitrypsin deficiency and bronchiectasis had the highest survival gain. Secondary pulmonary hypertension and pulmonary fibrosis had the lowest survival gain and the lowest gain of quality-adjusted life-years. As compared with COPD/emphysema, alfa-1 antitrypsin deficiency, bronchiectasis, and CF had 25%, 40% and 19% more favorable cost-effectiveness ratios, respectively. Cost-utility ratios varied less, with values of -7%, -14% and -11% for alfa-1 antitrypsin deficiency, bronchiectasis, and primary pulmonary hypertension, respectively, compared with COPD. In conclusion, our model suggests that there is considerable variation in cost-effectiveness and, to a lesser degree, in cost-utility between the different diagnostic categories. These variations are the result of differences in survival and in quality of life with and without lung transplantation.     

Pulmonary Hypertension Associated with Lung Transplantation Obliterative Bronchiolitis and Vascular Remodeling of the Allograft

Pathologic obliterative bronchiolitis (OB)/Bronchiolitis obliterans syndrome (pathologic OB/BOS) is the major obstacle to long-term survival post-lung transplantation (LT). Our group has demonstrated that pulmonary hypertension (PH) complicates the course of chronic inflammatory lung diseases that have similarities to pathologic OB/BOS and that vascular remodeling of the bronchial circulation occurs during BOS. Consequently, we hypothesized that PH is associated with pathologic OB/BOS and may result from a vasculopathy of the allograft pulmonary circulation.
We conducted a single-center, retrospective study and examined the presence of PH and vasculopathy in patients with pathologic OB/BOS. Fifty-two pathologic specimens post-LT were recovered from January 10, 1997 to January 5, 2007 and divided into two groups, those with and without pathologic OB/BOS.PH was defined as a mean pulmonary artery pressure (mPAP) > 25 mmHg by right heart catheterization (RHC) or right ventricular systolic pressure (RVSP) ≥45 mmHg by transthoracic echocardiogram (TTE).
PH was more prevalent in those LT recipients with pathologic OB/BOS (72% vs. 0%, p = 0.003). Furthermore, pulmonary arteriopathy and venopathy were more prevalent in patients with pathologic OB/BOS (84% vs. 4%, p < 0.0001, and 77% vs. 35%, p = 0.004, respectively).
PH is common in LT recipients with pathologic OB/BOS and is associated with a vasculopathy of the allograft pulmonary circulation.     

Pulmonary thromboembolism as a complication of lung transplantation

Post‐transplantation mortality after lung transplantation (LTX) is higher than for other solid organ transplantations. Thoracic surgery is associated with increased risk of thromboembolic complications, and as LTX recipients lack the collateral bronchial circulation, pulmonary thromboembolism (PTE) may represent a pertinent yet largely underdiagnosed cause of post‐transplantation respiratory failure. In this systematic review, we sought to elucidate the occurrence and predilection site of PTE after LTX, and its potential impact on LTX‐associated mortality. Based on twelve original articles identified by a systematic search strategy in PubMed, we found that PTE was reported in 4% of LTX recipients, and 38% of these events occurred within the first 30 days after the LTX procedure. In single‐lung transplantation (SLTX) recipients, 12% were diagnosed with PTE, with 92% of these affecting the allograft. Of LTX patients diagnosed with PTE, 11% died within 1 year after LTX and 75% of these deaths occurred within the first 30 days. Our findings suggest that PTE is a potentially underdiagnosed cause of early post‐LTX respiratory failure. This should be confirmed in larger studies with systematic follow‐up diagnostic imaging.     

Effects of Nitric Oxide After Cardiac Transplantation in the Setting of Recipient Pulmonary Hypertension

Background. Recipient pulmonary hypertension secondary to chronic congestive heart failure is a significant risk factor for right ventricular failure after cardiac transplantation. In this study, the hemodynamic and inotropic effects of nitric oxide (NO) were examined after bicaval cardiac transplantation in the setting of monocrotaline pyrrole-induced recipient chronic pulmonary hypertension.

Methods. Twenty dogs underwent 10 successfully completed transplantation experiments. Recipients underwent pulmonary artery injection of 3 mg/kg monocrotaline pyrrole 4 months before transplantation. Measurements were taken 1 hour after cessation of cardiopulmonary bypass and after NO inhalation. Pulmonary vascular impedance was calculated using Fourier analysis, and cardiac function was assessed with load-insensitive means (preload recruitable stroke work).

Results. At the time of transplantation, the precardiopulmonary bypass levels of pulmonary vascular resistance in recipient animals were significantly greater when compared with donor levels, and were further significantly increased after cardiopulmonary bypass. Three recipients died after transplantation secondary to acute right ventricular failure. In the surviving animals, NO led to significant improvements in pulmonary vascular resistance and vascular impedance, which occurred in association with significant increases in transpulmonary efficiency. No significant changes were observed in right and left ventricular preload recruitable stroke work after NO inhalation.

Conclusions. These data suggest that NO may be an effective means to improve vascular impedance and pulmonary vascular efficiency after cardiac transplantation in the setting of recipient chronic pulmonary hypertension.     

In Vivo Molecular Imaging Characterizes Pulmonary Gene Expression During Experimental Lung Transplantation

Experimental gene therapy is a promising strategy to prevent ischemia-reperfusion (I/R) injury and allograft rejection after lung transplantation, and methods will eventually be needed to characterize pulmonary transgene expression in vivo in humans. Therefore, we studied positron emission tomography (PET) as a means of performing in vivo molecular imaging in rodent models of lung transplantation. Rats were transfected endotracheally with adenovirus encoding a fusion gene of a mutant Herpes simplex virus-1 thymidine kinase and the green fluorescent protein gene (the former serving as an imaging reporter gene). Twenty-four hours after transfection, lungs were transplanted in groups representing normal transplantation, I/R injury and acute allograft rejection. Imaging was obtained either 24 h after transplantation to study reperfusion injury or 4 days after transplantation to study graft rejection. After imaging, lungs were excised and analyzed for thymidine kinase activity. Imaging detected transgene expression in transplanted lungs even in the presence of acute rejection or I/R injury. The PET imaging signal correlated with in vitro lung tissue assays of thymidine kinase activity (r(2) = 0.534). Thus, noninvasive molecular imaging with PET is a feasible, sensitive and quantitative method for characterizing pulmonary transgene expression in experimental lung transplantation.     

肾移植术后肺部感染致ARDS的治疗

目的：总结。肾移植术后重度肺部感染致急性呼吸窘迫综合征（ARDS）的治疗经验。方法：回顾性分析2000年7月-2009年1月期间24例肾移植术后重症肺部感染致ARDS患耆的临床资料：肺部感染致ARDS多在肾移植术后1～12个月发生。尤以术后2～6个月多见．且大剂量激素冲击多为诱因。24例患者均采用综合治疗方案,并按照抗排斥反应药物治疗方案分为三个阶段进行治疗。结果：24例患者中。9例死亡,2例放弃治疗．死亡率为37．5％;其中两个或两个以上器官障碍者死亡8例,最多见于上消化道出血和肾功能衰竭。1例最长呼吸机辅助呼吸达33灭．最终痊愈出院。本组患者肺部感染多为混合性感染,多以巨细胞病毒、真菌、耐药菌群和条件致病菌感染为主。结论：移植肾功能的保护或替代是治愈的决定因素;合理、及时调整抗生素是治愈的关键;肠内营养支持是治愈的基础;早期有利的呼吸功能支持是主要手段。     

Lobar Torsion After Lung Transplantation—A Case Report and Review of the Literature

Lobar torsion is a rare complication following lung transplantation. Early detection and immediate therapeutic intervention can lead to a favorable outcome. We report an unusual case of left lingular torsion following single lung transplantation performed for idiopathic pulmonary fibrosis. The patient experienced severe ventilatory compromise immediately after leaving the operating room, and a chest X-ray revealed a well-demarcated area of consolidation involving the left mid- and lower lung zones. Lingular torsion was promptly diagnosed and corrected surgically. The possibility of acute lobar torsion should be considered in lung transplant recipients who experience acute respiratory compromise in the early postoperative period. Early diagnosis and correction can avoid pulmonary infarction and the need for lobar resection.     

Racial and Ethnic Disparities in Survival in Lung Transplant Candidates with Idiopathic Pulmonary Fibrosis

Minority patients have worse outcomes than nonminority patients in a variety of pulmonary diseases. We aimed to compare the survival of Black and Hispanic patients to that of others with idiopathic pulmonary fibrosis (IPF). We performed a retrospective cohort study of patients with IPF who were evaluated for lung transplantation at our center. Kaplan-Meier survival curves and Cox proportional hazards models were used to compare survival between groups. Black and Hispanic patients had spirometry, lung volumes and diffusion capacity that were similar to others, but had worse exercise capacity. Minority patients had a significantly increased risk of death compared to others independent of transplantation status (hazard ratio = 3.3, 95% CI 1.2-8.9, p = 0.02). Differences in exercise capacity, pulmonary hemodynamics and socioeconomic factors appeared to account for some of the differences in survival. Black and Hispanic patients with IPF had an increased risk of death following referral for lung transplantation. This finding may be due to differences in disease progression and/or differences in access to medical care among minority patients. Future studies should confirm our findings in a larger cohort. The elimination of racial and ethnic disparities in outcome should be a priority for clinicians and researchers in this field.     

Adaptation Over a Wide Range of Donor Graft Lung Size Discrepancies in Living‐Donor Lobar Lung Transplantation

Living‐donor lobar lung transplantation (LDLLT), unlike deceased donor lung transplantation, often involves a wide range of size discrepancies between donors and recipients. The aim of this study was to evaluate the function of donor lung grafts in the recipient thorax in 14 cases of bilateral LDLLT involving 28 successfully transplanted lower‐lobe grafts. Pulmonary function tests and three‐dimensional computed tomography (3D‐CT) volumetry were performed perioperatively. According to 3D‐CT size matching, donor graft volumes ranged from 40% to 161% of the hemilateral thoracic volumes of the recipients. Graft forced vital capacity (FVC) values increased over time, reaching 102 ± 39% of preoperatively estimated values at 12 months postoperatively. Graft volumes also increased over time, reaching 120 ± 38% of the original values at 12 months postoperatively. Undersized donor grafts expanded more after LDLLT than oversized donor grafts, producing greater FVC values than those estimated preoperatively, whereas oversized donor grafts became inflated to their original size and maintained FVC values that approached the preoperative estimates. Thus, donor grafts were found to overinflate or underinflate to the extent that they could preserve their native function in the new recipient's environment.