Bilateral Lung Transplantation Research Articles

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.

(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

Intercostal nerve cryoablation as part of an opioid-sparing protocol reduces opioid and epidural use after lung transplant

IntroductionInadequate pain control after lung transplantation increases perioperative complications. Standard opioid-based regimens are associated with adverse effects and epidural catheters that reduce opioid use are limited by contraindications and technical challenges. We report the use of intercostal nerve cryoablation to enhance perioperative pain control as part of an opioid-sparing protocol for lung transplant recipients (LTR). MethodsWe conducted a retrospective cohort study of LTRs from 1/1/2016-12/31/2021, before (pre-cryo) and after (post-cryo) initiation of an opioid-sparing protocol utilizing intraoperative intercostal nerve cryoablation. The pre-cryo cohort included consecutive patients treated with opioids and selective use of epidural catheters. The post-cryo cohort received intercostal nerve cryoablation at levels 3-7, scheduled acetaminophen, gabapentin, and tramadol. Additional opioids or epidural catheters were used for breakthrough pain. ResultsIn total, 49 pre-cryo and 40 post-cryo patients were analyzed. Baseline demographics were similar aside from a shift to performing more bilateral lung transplants in the post-cryo cohort (57% vs 95%, p<0.0001). Total opioid usage during the index hospitalization decreased by 24% (1110 vs 841 morphine milligram equivalents [MME], p=0.027), and 28% in the bilateral LTR subgroup analysis (1168 vs 846 MME, p=0.007). Epidural use declined from 61% to 3% (p<0.0001). Median opioids prescribed at discharge decreased by 66% (450 vs 154 MME, p<0.0001). ConclusionsThe implementation of a perioperative pain management protocol that included intercostal nerve cryoablation was associated with a significant reduction in epidural utilization and opioid use during index hospitalization and upon discharge. Further research is needed to understand the impact on outcomes.

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.

Protocol for venoarterial ExtraCorporeal Membrane Oxygenation to reduce morbidity and mortality following bilateral lung TransPlantation: the ECMOToP randomised controlled trial

IntroductionLung transplantation (LTx) aims at improving survival and quality of life for patients with end-stage lung diseases. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is used as intraoperative support for LTx, despite...

Impact of anticoagulation intensity on blood transfusion for venoarterial extracorporeal membrane oxygenation during lung transplantation

Venoarterial ECMO is increasingly used for mechanical circulatory support during lung transplant. Optimal intensity of intraoperative anticoagulation would be expected to mitigate thromboembolism without increasing bleeding and blood product transfusions. Yet, the optimal intensity of intraoperative anticoagulation is unknown. We performed a retrospective cohort study of 163 patients who received a bilateral lung transplant at a single center. We categorized intensity of anticoagulation into four groups (very low to high) based on the bolus dose of unfractionated heparin given during lung transplant and compared the rates of intraoperative blood transfusions and the occurrence of thromboembolism between groups. When compared to the very low intensity group, each higher intensity group was associated with higher red blood cell, fresh frozen plasma, and platelet transfusions. The occurrence of thromboembolism was similar across groups. These preliminary data suggest that lower intensity anticoagulation may reduce the rate of intraoperative blood transfusions although further study is needed.

Impact of elexacaftor/tezacaftor/ivacaftor on respiratory colonization in an adult cystic fibrosis clinic

BackgroundLittle research has been completed on the correlation between cystic fibrosis (CF) modulator therapy and its effect on respiratory cultures in CF patients. This study evaluated the effect of elexacaftor/tezacaftor/ivacaftor (ETI) on respiratory colonization with Pseudomonas aeruginosa. MethodsThis single center, IRB approved, retrospective chart review compared patient data two years immediately prior to ETI initiation with patient data two years post-initiation from January 2017-December 2022. Patients were included in the study if they were at least 18 years old with a diagnosis of CF and had at least one month of ETI dispensed, at least one sputum culture obtained, and were currently on ETI. Those who had not been seen since ETI initiation or received a bilateral lung transplant were excluded. The primary outcome was rate of patients with respiratory colonization post-ETI. Colonization was defined as two or more positive P. aeruginosa cultures in a 12-month period. Decolonization was defined as three consecutive negative P. aeruginosa cultures after previous colonization. Key secondary outcomes included average time to discontinuation of mucolytic therapy and relative risk of pulmonary exacerbation. ResultsA significant reduction (p<0.001) in colonization with P. aeruginosa was observed with 49 patients in the pre-ETI group compared to 25 in the post-ETI group meeting the definition of colonization (n=79). Average time to discontinuation of mucolytic therapy was 14 months (p=0.002). Relative risk of pulmonary exacerbation was 4.80 (p<0.001). ConclusionsETI use resulted in reduced colonization with P. aeruginosa, discontinuation of mucolytic therapy, and decreased frequency of pulmonary exacerbation.

Lung Transplantation in Pulmonary Arterial Hypertension: The Portuguese Experience

In patients with pulmonary arterial hypertension (PAH), refractory to medical therapy, lung transplantation emerges as an option. This study describes the outcomes of 8 PAH patients who underwent lung transplantation. A retrospective, single-center study was conducted among patients with PAH who underwent lung transplantation in our center. Patients had a median age of 46 years, with female sex predominance (75%). Causes of HAP were pulmonary veno-occlusive disease (n = 5, 62.5%), idiopathic PAH (n = 2, 25%), and heritable PAH (n = 1, 12.5%). Pre-transplant hemodynamics revealed a median mean pulmonary artery pressure of 58.5 mm Hg (48-86). All patients received bilateral lung transplants with extracorporeal membrane oxygenation support, displaying immediate post-transplant hemodynamic improvement. Primary graft dysfunction grade 3 (PGD 3) was observed in 75% of patients. Five patients (62.5%) died, with a 72.9% survival at 12 months and 29.2% at 24 months post-transplantation. Our study reveals the complexity and challenges of lung transplants in patients with PAH. Despite notable immediate hemodynamic improvements, high rates of PGD 3 and the survival rate remain a concern. Further research to define optimal peri and post-transplant management to improve survival is required.

Unveiling the complexities of lung transplantation in situs inversus

BackgroundLung transplantation for situs inverse is considered technically challenging because of the reverse positioning of the organs. By providing a detailed description of the surgical procedure, perioperative care, and post-transplant follow-up, we aim to contribute valuable information to the existing knowledge base. We presented two cases of successful bilateral sequential lung transplantation in situs inverse patients.Case presentationOur first patient was a 28-year-old, non-smoking woman with Kartagener syndrome and advanced bronchiectasis that developed into pneumonia and required repeated hospital admissions. She underwent double lung transplantation. During the lung transplant procedure, venoarterial extracorporeal membrane oxygenation (VA ECMO) support was provided. The recipient’s morphologically right (anatomically left) lung was explanted. The right main bronchus was anastomosed, followed by the pulmonary artery and left atrial anastomoses. Afterward, we proceeded with the left side. Similar to the right side, left pneumonectomy and implantation were performed using the same methods. The duration of VA ECMO support was 147 min with a 328-min ischemic time. Because of the significant size mismatch, nonanatomic lung volume reduction over the right middle and left upper lobes was necessary. The patient had no complications postoperatively and was discharged on post-operative day (POD) 12. Our second patient was a 51-year- old man with scleroderma-associated interstitial lung disease with situs inversus. Bilateral sequential lung transplantation was performed. Similar to case 1, a clamshell incision was made at the fourth intercostal space entry. The patient then received VA ECMO support identical to that in case 1. The total VA ECMO support time was 155 min with 295 min of ischemic time. The patient recovered uneventfully and was discharged on POD 13.ConclusionsLung transplantation for situs inverse can be a viable treatment option without modifying established transplantation procedures.

Fungal Infections and Colonization after Bilateral Lung Transplant: A Six-Year Single-Center Experience.

Fungal infections (FIs) are one of the leading causes of morbidity and mortality within the first year of lung transplant (LT) in LT recipients (LTRs). Their prompt identification and treatment are crucial for a favorable LTR outcome. The objectives of our study were to assess (i) the FI incidence and colonization during the first year after a bilateral LT, (ii) the risk factors associated with FI and colonization, and (iii) the differences in fungal incidence according to the different prophylactic strategies. All bilateral LTRs admitted to the intensive care unit of Padua University Hospital were retrospectively screened, excluding patients <18 years of age, those who had been re-transplanted, and those who had received ventilation and/or extracorporeal membrane oxygenation before LT. Overall, 157 patients were included. A total of 13 (8%) patients developed FI, and 36 (23%) developed colonization, which was mostly due to Aspergillus spp. We did not identify independent risk factors for FI. Groups of patients receiving different prophylactic strategies reported a similar incidence of both FI and colonization. The incidence of FI and fungal colonization was 8% and 23%, respectively, with no differences between different antifungal prophylaxes or identified predisposing factors. Further studies with larger numbers are needed to confirm our results.

The Association of Post-Lung Transplant Pulmonary Embolism With the Development of Chronic Lung Allograft Dysfunction.

Pulmonary embolism (PE) is a rare yet serious postoperative complication for lung transplant recipients (LTRs). The association between timing and severity of PE and the development of chronic allograft lung dysfunction (CLAD) has not been described. A single-center, retrospective cohort analysis of first LTRs included bilateral or single lung transplants and excluded multiorgan transplants and retransplants. PEs were confirmed by computed tomography angiography or ventilation/perfusion (VQ) scans. Infarctions were confirmed on computed tomography angiography by a trained physician. The PE severity was defined by the Pulmonary Embolism Severity Index (PESI) score, a 30-d post-PE mortality risk calculator, and stratified by low I and II (0-85), intermediate III and IV (85-125), and high V (>125). PE and PESI were analyzed in the outcomes of overall survival, graft failure, and chronic lung allograft dysfunction (CLAD). We identified 57 of 928 patients (6.14%) who had at least 1 PE in the LTR cohort with a median follow-up of 1623 d. In the subset with PE, the median PESI score was 85 (75.8-96.5). Most of the PESI scores (32/56 available) were in the low-risk category. In the CLAD analysis, there were 49 LTRs who had a PE and 16 LTRs (33%) had infarction. When treating PE as time-dependent and adjusting for covariates, PE was significantly associated with death (hazard ratio [HR] 1.8; 95% confidence interval [CI], 1.3-2.5), as well as increased risk of graft failure, defined as retransplant, CLAD, or death (HR 1.8; 95% CI, 1.3-2.5), and CLAD (HR 1.7; 95% CI, 1.2-2.4). Infarction was not associated with CLAD or death. The PESI risk category was not a significant predictor of death or CLAD. PE is associated with decreased survival and increased hazard of developing CLAD. PESI score was not a reliable predictor of CLAD or death in this lung transplant cohort.

Red blood cell transfusion-related dynamics of extracellular vesicles in intensive care patients: a prospective subanalysis

Extracellular vesicles (EVs) accumulate during packed red blood cell (PRBC) storage. To date, the involvement of EVs in transfusion-related immunomodulation (TRIM) has not been prospectively evaluated in intensive care unit (ICU) patients. This was a prospective subanalysis of a recent observational feasibility study in postoperative ICU patients after: (1) open aortic surgery (Aorta), (2) bilateral lung transplantation (LuTx), and (3) other types of surgery (Comparison). Patient plasma was collected three times each before and after leukoreduced PRBC transfusion at 30-min intervals. The total number of EVs and EVs derived from erythrocytes (EryEVs), total platelets (total PEVs), activated platelets, granulocytes (GEVs), monocytes, and myeloid cells in PRBC samples and patient plasma were analyzed by flow cytometry. Statistical analysis was performed by Spearman’s correlation test, linear mixed models and pairwise comparisons by Wilcoxon matched-pairs test. Twenty-three patients (Aorta n = 5, LuTx n = 9, Comparison n = 9) were included in the final analysis. All EV subgroups analyzed were detectable in all PRBCs samples (n = 23), but concentrations did not correlate with storage time. Moreover, all EVs analyzed were detectable in all plasma samples (n = 138), and EV counts were consistent before transfusion. Concentrations of total EVs, EryEVs, total PEVs, and GEVs increased after transfusion compared with baseline in the entire cohort but not in specific study groups. Furthermore, the change in plasma EV counts (total EVs and EryEVs) after transfusion correlated with PRBC storage time in the entire cohort. Extracellular vesicles were detectable in all PRBC and plasma samples. Individual EV subtypes increased after transfusion in the entire cohort, and in part correlated with storage duration. Future clinical studies to investigate the role of EVs in TRIM are warranted and should anticipate a larger sample size.Trial registration: Clinicaltrials.gov: NCT03782623.

Resistin Pathway as Novel Mechanism of Post-lung Transplantation Bronchial Stenosis.

Bronchial stenosis remains a significant source of morbidity among lung transplant recipients. Though infection and anastomotic ischemia have been proposed etiologies of the development of bronchial stenosis, the pathophysiologic mechanism has not been well elucidated. In this single-centered prospective study, from January 2013 through September 2015, we prospectively collected bronchoalveolar lavage (BAL) and endobronchial epithelial brushings from the direct anastomotic site of bronchial stenosis of bilateral lung transplant recipients who developed unilateral post-transplant bronchial stenosis. Endobronchial epithelial brushings from the contralateral anastomotic site without bronchial stenosis and BAL from bilateral lung transplant recipients who did not develop post-transplant bronchial stenosis were used as controls. Total RNA was isolated from the endobronchial brushings and real-time polymerase chain reaction reactions were performed. Electrochemiluminescence biomarker assay was used to measure 10 cytokines from the BAL. Out of 60 bilateral lung transplant recipients, 9 were found to have developed bronchial stenosis with 17 samples adequate for analysis. We observed a 1.56 to 70.8 mean-fold increase in human resistin gene expression in the anastomotic bronchial stenosis epithelial cells compared with nonstenotic airways. Furthermore, IL-1β (21.76±10.96pg/mL; control 0.86±0.44pg/mL; P <0.01) and IL-8 levels (990.56±326.60pg/mL; control 20.33±1.17pg/mL; P <0.01) were significantly elevated in the BAL of the lung transplant patients who developed anastomotic bronchial stenosis. Our data suggest that the development of postlung transplantation bronchial stenosis may be in part mediated through the human resistin pathway by IL-1β induced transcription factor nuclear factor-κβ activation and downstream upregulation of IL-8 in alveolar macrophages. Further study is needed in the larger patient cohorts and to determine its potential therapeutic role in the management of post-transplant bronchial stenosis.

폐이식 수혜자에 대해 적용한 장기간 호흡재활프로그램의 효과

Purpose: The purpose of this study was to provide long-term pulmonary rehabilitation program (PR) to lung transplant recipients for more than a year and verify their effectiveness.&#x0D; Methods: A 52-year-old female patient who had bilateral lung transplantation received an outpatient PR 3 times a week for a total of 97 weeks. The PR applied was composed of aerobic exercise, strength exercise, breathing exercise, flexibility exercise, and home exercise education. Evaluation was performed on the participant at 3, 6, 9, 12, and 24 months after surgery. For each period, the following parameters were determined: 6-minute walk distance (6MWD), grip strength, respiratory muscle strength, lung function, peak cough flow rate, skeletal muscle mass (SMM), and skeletal muscle index (SMI).&#x0D; Results: The 6MWD increased up to 12 months following surgery, and exercise-induced hypoxemia occurred only 3 months following surgery. The grip strength increased up to 12 months after surgery and decreased at 24 months after surgery. The MIP increased up to 12 months after surgery, and the MEP increased until 24 months after surgery. The FVC increased up to 12 months following surgery and FEV1 increased up to 24 months following surgery. PCF increased up to 12 months after surgery. Body weight also increased steadily until 24 months postoperatively. SMM and SMI increased up to 12 months after surgery, and SMI decreased at 24 months following surgery.&#x0D; Conclusion: It is essential that the PR for lung transplant recipients be applied intensively in less than 12 months after surgery, and the goal of the PR should be configured for the purpose of management in more than 12 months following surgery.

Impulse Oscillometry Versus Spirometry to Detect Bronchiolitis Obliterans Syndrome in Bilateral Lung Transplant Recipients: A Prospective Diagnostic Study.

Chronic lung allograft dysfunction (CLAD), and especially bronchiolitis obliterans syndrome (BOS), remain dominant causes of morbidity and mortality after lung transplantation. Interest is growing in the forced oscillation technique, of which impulse oscillometry (IOS) is a form, as a tool to improve our understanding of these disorders. However, data remain limited and no longitudinal studies have been published, meaning there is no information regarding any capacity IOS may have for the early detection of CLAD. We conducted a prospective longitudinal study enrolling a consecutive sample of adult bilateral lung transplant recipients with healthy lung allografts or CLAD and performed ongoing paired IOS and spirometry tests on a clinically determined basis. We assessed for correlations between IOS and spirometry and examined any predictive value either modality may hold for the early detection of BOS. We enrolled 91 patients and conducted testing for 43 mo, collecting 558 analyzable paired IOS and spirometry tests, with a median of 9 tests per subject (interquartile range, 5-12) and a median testing interval of 92 d (interquartile range, 62-161). Statistically significant moderate-to-strong correlations were demonstrated between all IOS parameters and spirometry, except resistance at 20 Hz, which is a proximal airway measure. No predictive value for the early detection of BOS was found for IOS or spirometry. This study presents the first longitudinal data from IOS after lung transplantation and adds considerably to the growing literature, showing unequivocal correlations with spirometry but failing to demonstrate a predictive value for BOS.