Bilateral Lung Transplantation Research Articles

Extracorporeal photopheresis (ECP) in the treatment of chronic lung allograft dysfunction (CLAD): a prospective, multicentre, open-label, randomised controlled trial studying the addition of ECP to standard care in the treatment of bilateral lung transplant patients with CLAD (E-CLAD UK)

BackgroundLong-term survival after lung transplantation is limited compared with other organ transplants. The main cause is development of progressive immune-mediated damage to the lung allograft. This damage, which can develop...

Continuous heart monitoring to evaluate treatment effects in pulmonary hypertension

BackgroundThe treatment of pulmonary hypertension (PH) has improved rapidly in recent decades. There is increasing evidence to support the role of early intervention and treatment in affecting clinical outcomes in...

P029 Successful treatment of Rapidly progressive MDA-5 with dual combination therapy as a bridge to lung transplantation

Abstract Background/Aims Anti-melanoma differentiation-associated gene 5 (MDA5) is known to be associated with rapidly progressive interstitial lung disease (RP-ILD) and is fatal in most cases. The aim of this case report is to highlight the importance of early detection and aggressive treatment in improving the survival of these patients. Methods A 48-year-old Caucasian man, ex-smoker with 20 pack year history with well-controlled asthma, GORD, hiatus hernia and chondrocalcinosis in right knee on hydroxychloroquine was noted to have finger clubbing and decreased air entry at the right lung base on routine follow up. He worked in print finishing for 18 years. Results Investigations: CXR-increased interstitial shadowing. CT chest-extensive fibrosis NSIP pattern with honey combing, traction bronchiectasis throughout both lung fields and ground glass changes at the lower lobes. FVC 2.99 (63% predicted), FEV1 2.82 (73% predicted), FEV1/FVC ratio 0.95%, TLCO 2.75 (25% predicted), KCO 0.70 (46% predicted). CK- 76, Myositis blot- MDA 5 +ve, c ANCA +ve, PR3&MPO -ve and ANA -ve. CRP 70. Bronchoscopy-normal. He received IV methyl prednisolone 1 gm x 3 followed by prednisolone 60 mg daily and tapering dose along with Cyclophosphamide IVI 1 gm x 6 cycles. Long term home oxygen was prescribed. As he did not improve on initial immunosuppressive treatment, Rituximab IVI 1 gm x 2 was administered within two months of initial therapy. He was referred for lung transplant. As maintenance, he was on mycophenolate 1.5 gm BD, prednisolone 10 mg OD, Co-trimoxazole 960 mg x 3 days per week and rituximab 1 gm at six months and 12 months. He had bilateral lung transplant in Cambridge after two years from the diagnosis. Unfortunately, he developed organizing pneumonia, primary graft dysfunction requiring a brief ITU admission and tracheostomy soon after the transplant. His current medications include Prednisolone 5mg, Mycophenolate 2g Tacrolimus 3mg mane, 2mg nocte, Azithromycin 250mg three times weekly and Septrin 480mg od. He is now managing well, cycling 10-15 miles daily. He no longer requires ambulatory oxygen. His most recent FEV1 4.1L, FVC4.9L and resting saturation 97%. Dual combination aggressive immunosuppressive therapy led to significant disease control in this patient, enabling him to be enlisted for and finally to receive a double lung transplant within a reasonable time limit. It has been reported that patients with MDA 5 ILD have a 1-year survival of 67.5% and a 3-year survival of 46.7%. Conclusion Key Learning Points: Patients with MDA5-ILD have significantly high mortality rate but early diagnosis and optimal treatment combination can lead to favourable outcomes. These patients should be monitored for opportunistic infections. Patient commitment is important. Our patient stopped smoking, reduced weight to improve fitness to optimise the transplant success. Disclosure K. Yein: None. S. Sadiq: None. S. Zeb: None. A. Ahmed: None. E. Price: None.

Native-lung complications following single-lung transplantation for interstitial lung disease: an in-depth analysis

BackgroundInterstitial lung disease (ILD) represents a heterogeneous group of lung disorders characterized by fibrotic lung tissue changes. In regions with severe donor shortages, single-lung transplantation (SLTx) is often preferred over bilateral lung transplantation for advanced ILD. However, temporal changes and complications in the retained native lung remain poorly understood.MethodsA retrospective analysis of 149 recipients who had undergone SLTx was conducted, including 34 ILD SLTx recipients. Native-lung volume, radiological alterations, and perfusion were assessed at distinct post-SLTx time points. Statistical analyses compared ILD and non-ILD SLTx groups.ResultsOur study revealed a progressive reduction in native-lung volume over time, accompanied by radiographic deterioration and declining perfusion. Complications in the retained native lung were observed, such as pneumothorax (29.4%), pulmonary aspergillosis (11.8%), and acute exacerbation (8.9%). Long-term survival rates were similar between ILD and non-ILD SLTx recipients.ConclusionsThis study illuminates the unique challenges and complications with respect to the native lung following SLTx for ILD. Ongoing monitoring and tailored management are essential. Despite limitations, this research contributes to our understanding of the temporal progression of native-lung complications post-SLTx for ILD, underscoring the need for further investigation.

A rare case of postoperative Metamycoplasma hominis surgical site infection in a patient after bilateral lung transplantation.

Following the COVID-19 infection, the sternum dislocation and wound dehiscence resulted in an infection complicating the recovery of an immunosuppressed patient after bilateral lung transplantation. Anaerobic culture (96h) of milky cloudy wound secretion resulted in the growth of pinpoint haemolytic colonies identified as Metamycoplasma hominis (formerly Mycoplasma hominis). The search for the endogenous source of the infection found the bacterium exclusively in the patient's sputum, making a possible link to donor lung M. hominis colonization. Unfortunately, the donor samples were no longer available. The wound infection was successfully treated with 17days of clindamycin despite the continuous PCR detection of M. hominis in the sputum after the end of the treatment.

Implications of High Sensitivity Troponin Levels After Lung Transplantation.

Trends in high-sensitivity cardiac troponin I (hs-cTnI) after lung transplant (LT) and its clinical value are not well stablished. This study aimed to determine kinetics of hs-cTnI after LT, factors impacting hs-cTnI and clinical outcomes. LT recipients from 2015 to 2017 at Toronto General Hospital were included. Hs-cTnI levels were collected at 0-24h, 24-48h and 48-72h after LT. The primary outcome was invasive mechanical ventilation (IMV) >3days. 206 patients received a LT (median age 58, 35.4% women; 79.6% double LT). All patients but one fulfilled the criteria for postoperative myocardial infarction (median peak hs-cTnI = 4,820ng/mL). Peak hs-cTnI correlated with right ventricular dysfunction, >1 red blood cell transfusions, bilateral LT, use of EVLP, kidney function at admission and time on CPB or VA-ECMO. IMV>3days occurred in 91 (44.2%) patients, and peak hs-cTnI was higher in these patients (3,823 vs. 6,429ng/mL, p < 0.001 after adjustment). Peak hs-cTnI was higher among patients with had atrial arrhythmias or died during admission. No patients underwent revascularization. In summary, peak hs-TnI is determined by recipient comorbidities and perioperative factors, and not by coronary artery disease. Hs-cTnI captures patients at higher risk for prolonged IMV, atrial arrhythmias and in-hospital death.

Phenotypes and outcome of diffuse pulmonary non-amyloid light chain deposition disease.

Light chain deposition disease (LCDD) is a very rare entity. Clinical manifestations of LCDD vary according to the organs involved. Data on pulmonary LCDD are scarce and limited to small series or case reports. This study aimed to describe the characteristics and outcome of diffuse pulmonary non-amyloid LCDD localized to the lungs. A multicenter retrospective cohort study was conducted. Clinical characteristics were collected, and chest CTs were centrally reviewed. The diagnosis of pulmonary non-amyloid LCDD was confirmed by immunohistochemistry. Thirty-one cases were identified (68% female), with a median age at diagnosis of 50 years (IQR 20). Baseline FEV1/FVC was < 0.70 in 45% of patients. Mean (± SD) FEV1 and DLCO were 86% ± 26.2 and 52% ± 23.9, respectively. CT revealed peculiar patterns of thin-walled cysts (58%) and thin-walled cystic bronchiectases (27%). Increased serum kappa light chain was found in 87% of patients. Histological analysis showed kappa light chain deposits in all patients, except one with lambda chain deposits. Median annual FEV1 decline was 127 ml (IQR 178) and median DLCO decline was 4.3% (IQR 4.3). Sixteen patients received immunomodulatory treatment or chemotherapy; serum light chain levels decreased in 9 cases (75%), without significant improvement in FEV1 (p = 0.173). Overall, 48% of patients underwent bilateral lung transplantation. Transplant-free survival at 5 and 10 years were 70% and 30%, respectively. An annual FEV1 decline greater than 127 ml/year was associated with increased risk of death or transplantation (p = 0.005). Diffuse pulmonary LCDD is characterised by female predominance, a peculiar imaging pattern with bronchiectasis and/or cysts, progressive airway obstruction and severe DLCO impairment, and poor outcome. Lung transplantation is a treatment of choice.

Abstract CT278: [DREAM] Double lung transplant registry aimed for lung-limited malignancies - a prospective registry study for medically refractory cancers

Abstract BackgroundAdenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) are listed as ‘special circumstances’ for lung transplantation according to a consensus document from the International Society for Heart and Lung Transplantation (ISHLT) (Weill D et al., 2015). Five studies have reported on lung transplantation in carefully selected subsets of patients with multifocal lung adenocarcinoma (Raemdonck DV et al., 2016; Glanville AR et al., 2018). The 5-year survival rate of bilateral sequential lung transplantation was estimated at over 50% in patients with multifocal BAC, invasive adenocarcinoma, and NSCLC (Ahmad U et al., 2012; Paloyan EB et al., 2000; Zorn GL et al., 2003; de Perrot M et al., 2004). Another a case series reported a post-transplant recurrence-free survival of 23 to 56 months in three patients (Garver RI et al., 1999). Moreover, there is an unmet need for patients who have lung-limited metastasis after successful treatment for primary tumors such as sarcomas or colorectal cancer (CRC). As with liver transplantation for CRC patients who have liver-confined metastases (Dueland S et at., 2020; Hernandez-Alejandro R et al., 2022), the applicability of lung transplantation in lung-limited metastatic patients should be explored. There is also an unmet need for patients with respiratory failure with a history of cancer in the last 5 years. MethodsThis is a prospective registration trial to evaluate outcomes of patients who undergo double lung transplantation for the treatment of the select groups of medically refractory cancers (primary lung cancers or metastatic cancers in lungs). Overall survival (OS), disease-free survival (DFS), allograft rejection (AR) and allograft survival (AS) as well as molecular and genetic biomarkers will be monitored to investigate the correlation with prognosis.The study duration will be 10 years including surveillance. Recruitment is to occur during the first 5 years of the study. The goal is to enroll 125 participants through the Northwestern Medicine Clinical Programs.Essential Criteria:1.The tumor should be without any extrapulmonary metastasis as determined by standard of care diagnostic and staging workup.2.All standard of care or experimental oncological treatments known to improve survival should have failed or deemed infeasible 3.Patients should meet the general criteria for lung transplant evaluation and listing Study cohorts:•Cohort A: Primary lung cancers - Examples include, but not limited to, invasive mucinous/non-mucinous non-small cell lung cancers and multifocal carcinomas.•Cohort B: Metastatic cancers to the lung only - Examples include, but not limited to, germ cell tumors, head &amp; neck tumors, colorectal tumors, renal cell tumors, testicular cancers.•Cohort C: Respiratory failure with a history of cancer in the last 5 years- Examples include, but not limited to interstitial lung disease (ILD), pulmonary fibrosis (idiopathic or secondary), advanced chronic obstructive pulmonary disease (COPD), bronchiectasis, emphysema, cystic fibrosis (CF), emphysema due to alpha-1 antitrypsin deficiency, and pulmonary arterial hypertension (PAH) Clinical trial registry number : NCT05671887.Enrollment began November 16, 2022. Trial is open and continues to enroll participants as of Jan 8, 2024. Citation Format: Young Kwang Chae, Liam Il-Young Chung, Rade Tomic, Ankit Bharat. [DREAM] Double lung transplant registry aimed for lung-limited malignancies - a prospective registry study for medically refractory cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT278.

Lung transplantation following prior cardiac surgical procedures

IntroductionAs lung transplant candidates are older with increased comorbidities, we sought to examine the prevalence and outcomes of lung transplant recipients after prior cardiac surgery. MethodsLung transplants were identified from the United Network for Organ Sharing/Organ Procurement and Transplantation Network Database. Patients were stratified based on prior cardiac surgery (No Surgery [NS], Prior coronary artery bypass grafting [CABG], Prior Valve [Valve]). Unadjusted comparisons were performed amongst all groups, and propensity matching was utilized for adjusted comparisons. Survival was examined with Kaplan-Meier methods. Results28,710 patients were identified, 467 (1.6%) had prior CABG and 84 (0.3%) had prior valvular surgery. Prior to matching, the NS group was significantly younger, less commonly male, and had lower lung allocation scores. There were significantly fewer bilateral lung transplants in the CABG and Valve groups. Length of stay was shortest in the CABG group, but there were no significant differences in postoperative stroke, dialysis, or in-hospital mortality. There was an increased incidence of cardiac/cerebrovascular cause of death in CABG recipients (18.3%) and malignancy death in Valve recipients (23.3%). Following matching, CABG 5-year survival was lower than NS (p<0.01), while there was no significant difference between NS and Valve groups (p=0.4). ConclusionsCABG and Valve recipients had decreased survival, however not at levels prohibitive to transplantation. Due to potentially increased risk of cardiovascular mortality, providers should evaluate the burden of vascular disease in potential recipients with prior CABG to improve patient selection and maximize post-transplant survival.

(882) - Comparison of Local Ventilation in Patients Very Early After Bilateral Lung Transplantation and Healthy Subjects Using Magnetic Resonance Imaging

(882) - Comparison of Local Ventilation in Patients Very Early After Bilateral Lung Transplantation and Healthy Subjects Using Magnetic Resonance Imaging

Long-Term Survival Following Primary Graft Dysfunction Development in Lung Transplantation

IntroductionPrimary graft dysfunction (PGD) is a known risk factor for early mortality following lung transplant (LT). However, the outcomes of patients who achieve long-term survival following index hospitalization are unknown. We aimed to determine the long-term association of PGD grade 3 (PGD3) in patients without in-hospital mortality. MethodsLT recipients were identified from the United Network for Organ Sharing Database. Patients were stratified based on the grade of PGD at 72 h (No PGD, Grade 1/2 or Grade 3). Groups were assessed with comparative statistics. Long-term survival was evaluated using Kaplan–Meier methods and a multivariable shared frailty model including recipient, donor, and transplant characteristics. ResultsThe PGD3 group had significantly increased length of stay, dialysis, and treated rejection post-transplant (P < 0.001). Unadjusted survival analysis revealed a significant difference in long-term survival (P < 0.001) between groups; however, following adjustment, PGD3 was not independently associated with long-term survival (hazard ratio: 0.972; 95% confidence interval: 0.862-1.096). Increased mortality was significantly associated with increased recipient age and treated rejection. Decreased mortality was significantly associated with no donor diabetes, bilateral LT as compared to single LT, transplant in 2015-2016 and 2017-2018, and no post-transplant dialysis. ConclusionsWhile PGD3 remains a challenge post LT, PGD3 at 72 h is not independently associated with decreased long-term survival, while complications such as dialysis and rejection are, in patients who survive index hospitalization. Transplant providers should be aggressive in preventing further complications in recipients with severe PGD to minimize the negative association on long-term survival.

Quantifying the effects of training in lung transplantation: Lessons from NASA

IntroductionSequential lung transplantation is a complex procedure. The traditional training model continues to centre around operative experience with progressively increasing delegation of stages of the procedure. However, little evidence exists on the effects this has on surgical trainers. The NASA-TLX is a subjective, multi-dimensional assessment tool that rates perceived workload. We sought to employ this as a means of assessing the impact that training in lung transplantation has on trainers. MethodsWe prospectively collected the NASA-TLX data for 60 patients undergoing bilateral sequential lung transplantation. In 30 cases the operation was performed entirely by the senior surgeon (SS) who implanted both lungs. In 30 operations the senior surgeon implanted the right lung (SSR) and supervised a trainee implanting the left lung (TL). ResultsThe overall weighted rating was significantly lower for the surgeon undertaking the case themselves rather than training (p <0.001). Cases were comparable in terms of case type, donor ischaemic time and peri-operative characteristics. Mental and temporal demand were greater throughout training cases (p<0.001, p<0.05). There was less effect on frustration, physical demand and effort. Perceived performance showed no significant difference between the groups. ConclusionThe NASA task load index can be used to inform the effects of training lung transplantation on trainers. Training leads to greater mental and temporal demands with less effect on other factors. Crucially, there was no significant difference in perceived performance. As the specialty continues to be confronted with diverse challenges, this study should give confidence to those training the transplant surgeons of the future, as well as providing them with a mechanism to reflect on their own training performance. ACGME CompetenciesInterpersonal and communication skillsPractice-based learning and improvement

(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

(1026) - ECMO Bridge to Bilateral Lung Transplant for Castleman Disease

(1026) - ECMO Bridge to Bilateral Lung Transplant for Castleman Disease

(1271) - Bilateral Lung Transplantation Combining Pulmonary Artery Reconstruction for Giant Pulmonary Artery Aneurysm with Severe Pulmonary Artery Hypertension

(1271) - Bilateral Lung Transplantation Combining Pulmonary Artery Reconstruction for Giant Pulmonary Artery Aneurysm with Severe Pulmonary Artery Hypertension

(1266) - Bilateral Lung Transplantation for Pulmonary Emphysema Associated with Cutis Laxa

(1266) - Bilateral Lung Transplantation for Pulmonary Emphysema Associated with Cutis Laxa

(1052) - A Case of Takotsubo Cardiomyopathy in a Bilateral Lung Transplant Recipient

(1052) - A Case of Takotsubo Cardiomyopathy in a Bilateral Lung Transplant Recipient

(1269) - Successful Bilateral Lung Transplantation for a Patient with Severe Post-COVID-19 Fibrosis and a History of Multiple Thoracic Procedures

(1269) - Successful Bilateral Lung Transplantation for a Patient with Severe Post-COVID-19 Fibrosis and a History of Multiple Thoracic Procedures

The Right Ventricle in Pulmonary Arterial Hypertension: An Organ at the “Heart of the Problem”

Abstract: Pulmonary Arterial Hypertension (PAH) is a progressive disease with no cure. A major determinant of outcome is the function of the right ventricle (RV). Unfortunately, progressive RV dysfunction and failure can occur despite PAH-specific therapies. While initial adaptive hypertrophic changes occur to maintain cardiac output and preserve contractile function and reserve, maladaptive changes occur in the RV muscle that contribute to RV systolic and diastolic dysfunction and failure. These include impaired angiogenesis / decreased capillary density with ischemia, fibrosis, cardiomyocyte apoptosis and impaired autophagy, inflammation, enhanced oxidative stress, altered metabolism, etc. Of note, there are no therapies currently approved that offset these changes and treatment of RV dysfunction is largely supportive only. Further patients often do not qualify for bilateral lung transplantation because of co-morbidities such as renal impairment. Thus, a dire unmet need exists regarding the management of RV dysfunction and failure in patients with PAH. In this State-of-the-Art review, we comprehensively outline the unique features of the RV compared to the left ventricle (LV) under normal circumstances and highlight the unique challenges faced by the RV when confronted with increased afterload as occurs in PAH. We provide detailed insights into the basis for the adaptive hypertrophic phase as well as detailed commentary into the pathophysiology of the maladapted dysfunctional state as well as the pathobiological aberrations occurring in the RV muscle that underlines the progressive dysfunction and failure that commonly ensues. We also review comprehensively the evaluation of RV function using all currently employed imaging, hemodynamic and other modalities and provide a balanced outline of strengths and limitations of such approaches with the treating clinician in mind. We outline the current approaches, albeit limited to chronic multi-modal management of RV dysfunction and failure. We further outline new possible approaches to treatment that include novel pharmacologic approaches, possible use of cellular/stem cell therapies and mechanical approaches. This review is directed to the treating clinician to provide comprehensive insights regarding the RV in patients with PAH.

Gram-negative bacterial colonizations before bilateral lung transplant. The impact of ‘targeted’ versus ‘standard’ surgical prophylaxis

BackgroundInfections are one of the most common causes of death after lung transplant (LT). However, the benefit of ‘targeted’ prophylaxis in LT recipients pre-colonized by Gram-negative (GN) bacteria is still unclear.MethodsAll consecutive bilateral LT recipients admitted to the Intensive Care Unit of the University Hospital of Padua (February 2016–2023) were retrospectively screened. Only patients with pre-existing GN bacterial isolations were enrolled and analyzed according to the antimicrobial surgical prophylaxis (‘standard’ vs. ‘targeted’ on the preoperative bacterial isolation).ResultsOne hundred eighty-one LT recipients were screened, 46 enrolled. Twenty-two (48%) recipients were exposed to ‘targeted’ prophylaxis, while 24 (52%) to ‘standard’ prophylaxis. Overall prevalence of postoperative multi-drug resistant (MDR) GN bacteria isolation was 65%, with no differences between the two surgical prophylaxis (p = 0.364). Eleven (79%) patients treated with ‘standard’ prophylaxis and twelve (75%) with ‘targeted’ therapy reconfirmed the preoperative GN pathogen (p = 0.999). The prevalence of postoperative infections due to MDR GN bacteria was 50%. Of these recipients, 4 belonged to the ‘standard’ and 11 to the ‘targeted’ prophylaxis (p = 0.027).ConclusionsThe administration of a ‘targeted’ prophylaxis in LT pre-colonized recipients seemed not to prevent the occurrence of postoperative MDR GN infections.