Lung transplantation (LTx) outcomes are impeded by ischemia/reperfusion injury (IRI) and subsequent chronic lung allograft dysfunction (CLAD). We examined the undefined role of receptor Mer tyrosine kinase (MerTK) on monocytic myeloid-derived suppressor cells (M-MDSCs) in efferocytosis to facilitate resolution of lung IRI. Single-cell RNA sequencing of lung tissue and bronchoalveolar lavage (BAL) from patients after LTx were analyzed. Murine lung hilar ligation and allogeneic orthotopic LTx models of IRI were used with BALB/c (WT), Cebpb ^–/– (MDSC-deficient), Mertk ^–/– , or MerTK–cleavage-resistant mice. A significant downregulation in MerTK-related efferocytosis genes in M-MDSC populations of patients with CLAD was observed compared with healthy individuals. In the murine IRI model, a significant increase in M-MDSCs, MerTK expression, and efferocytosis and attenuation of lung dysfunction was observed in WT mice during injury resolution that was absent in Cebpb ^–/– and Mertk ^–/– mice. Adoptive transfer of M-MDSCs in Cebpb ^–/– mice significantly attenuated lung dysfunction and inflammation. Additionally, in a murine orthotopic LTx model, increases in M-MDSCs were associated with resolution of lung IRI in the transplant recipients. In vitro studies demonstrated the ability of M-MDSCs to efferocytose apoptotic neutrophils in a MerTK-dependent manner. Our results suggest that MerTK-dependent efferocytosis by M-MDSCs can substantially contribute to the resolution of post-LTx IRI.

Background: Refractory end-stage pulmonary failure may benefit from extracorporeal life support (ECLS) as a bridge to lung transplantation. Veno-venous (VV) extracorporeal membrane oxygenation (ECMO) has been recommended for patients who have failed conventional medical therapy and mechanical ventilation. Veno-arterial (VA) ECMO may be used in patients with acute right ventricular (RV) failure, haemodynamic instability, or refractory respiratory failure. Peripheral percutaneous approaches, either dual-site single-lumen cannulation for veno-pulmonary (VP) ECMO or single-site dual-lumen (dl)VP ECMO, using the ProtekDuo right ventricular assist device (RVAD) cannula, has made this configuration a desirable option as a bridge to transplantation. These configurations support the right ventricle, prevent recirculation by placing the tricuspid and pulmonary valve between the drainage and return cannulas, provide the direct introduction of oxygenated blood into the pulmonary artery, and have been shown to decrease the incidence of acute kidney injury (AKI), requiring continuous renal replacement therapy (CRRT) in certain disease states. This promotes haemodynamic stability, potential sedation-weaning trials, extubation, mobilisation, and pre-transplant rehabilitation. Methods: A web-based literature search in PubMed and EMBASE was undertaken based on a combination of keywords. The PICOS and PRISMA approaches were used. Results: Four case series were identified out of 323 articles, with a total of 34 patients placed on VP ECMO as a bridge to lung transplantation. All relevant data are reviewed and integrated into the Discussion. Conclusions: Despite the limited available evidence, the use of ProtekDuo has become very promising for the management of end-stage lung disease as a bridge to lung transplantation.

Mechanical ventilation during cardiothoracic surgery is life-saving but can lead to ventilator-induced diaphragm dysfunction (VIDD) and prolong ventilator weaning and hospital length of stay. Intraoperative phrenic nerve stimulation may preserve diaphragm force production to offset VIDD; we also investigated changes in mitochondrial function after stimulation. During cardiothoracic surgeries (n = 21), supramaximal, unilateral phrenic nerve stimulation was performed every 30 min for 1 min. Diaphragm biopsies were collected after the last stimulation and analyzed for mitochondrial respiration in permeabilized fibers and protein expression and enzymatic activity of biomarkers of oxidative stress and mitophagy. Patients received, on average, 6.2 ± 1.9 stimulation bouts. Stimulated hemidiaphragms showed lower leak respiration, maximum electron transport system (ETS) capacities, oxidative phosphorylation (OXPHOS), and spare capacity compared with unstimulated sides. There were no significant differences between mitochondrial enzyme activities and oxidative stress and mitophagy protein expression levels. Intraoperative phrenic nerve electrical stimulation led to an acute decrease of mitochondrial respiration in the stimulated hemidiaphragm, without differences in biomarkers of mitophagy or oxidative stress. Future studies warrant investigating optimal stimulation doses and testing post-operative chronic stimulation effects on weaning from the ventilator and rehabilitation outcomes.

Repeated exposure to antigens via inhalation is the primary cause of hypersensitivity pneumonitis, a form of interstitial pneumonia. The chronic form of hypersensitivity pneumonitis leads to progressive loss of respiratory function; lung transplantation is the only therapeutic option for chronically ill patients. The ESTS Lung Transplantation Working Group conducted a retrospective multicentred cohort study to increase the body of knowledge available on this rare indication for lung transplantation. Data were collected for every patient who underwent lung transplant for hypersensitivity pneumonitis in participating centres between December 1996 and October 2019. Primary outcome was overall survival; secondary outcome was freedom from chronic lung allograft dysfunction. A total of 114 patients were enrolled from 9 centres. Almost 90% of patients were diagnosed with hypersensitivity pneumonitis before transplantation, yet the antigen responsible for the infection was identified in only 25% of cases. Eighty per cent of the recipients received induction therapy. Survival at 1, 3, and 5 years was 85%, 75%, and 70%, respectively. 85% of the patients who survived 90 days after transplantation were free from chronic lung allograft dysfunction after 3 years. The given study presents a large cohort of HP patients who underwent lung transplants. Overall survival rate is higher in transplanted hypersensitivity pneumonitis patients than in those suffering from any other interstitial lung diseases. Hypersensitivity pneumonitis patients are good candidates for lung transplantation.

Intraoperative venoarterial extracorporeal membrane oxygenation (VA ECMO) is becoming the most common mode of extracorporeal life support (ECLS) in lung transplantation (LTx). We compared rates of primary graft dysfunction (PGD) and other perioperative outcomes in patients who underwent LTx using VA ECMO with either central or peripheral arterial cannulation. We analyzed bilateral lung transplants using intraoperative VA ECMO which were entered into the multicenter international ECLS in LTx registry between 1/2016 and 8/2024. Our primary outcome included Grade 3 Primary Graft Dysfunction (PGD3) at 48-72 hours. Secondary outcomes included postoperative complications and survival. There were 501 transplants that met inclusion criteria: 315 in the central group and 186 in the peripheral group. The incidence of PGD3 at 48-72 hours was 26.3% in the central group and 30.1% in the peripheral group (p = 0.42). In the logistic regression analysis, central vs peripheral cannulation was not associated with increased risk of PGD3 (OR 1.64, 95% CI 0.657-4.209, p = 0.294). We found no difference between groups in other graft-related outcomes nor cannulation-related complications including stroke. In the Cox regression analysis, central vs peripheral cannulation was not associated with overall survival (HR 1.5, 95% CI 0.70-3.20, p = 0.298). The choice of arterial cannulation strategy for intraoperative VA ECMO support did not impact the risk of PGD3, graft- or cannulation-related complications, nor mid-term survival. The decision regarding arterial cannulation site strategy should be tailored to meet patient and procedural needs.

Lung transplantation (LTx) is performed as soon as donor organs are made available to minimize cold ischemic time. Studies have suggested that an extended static preservation of donor lung allografts at 10°C may offer similar clinical outcomes with the added benefits of surgery being performed as a semi-elective (SE) procedure. The purpose of our study was to compare the clinical outcomes between a cohort of patients who underwent LTx in the traditional fashion and after a period of static preservation at 10°C. Unlike previous studies, we also provide an account of the recipients’ pre-transplant health status. This is a prospective, nonrandomized, open label study with propensity matching. Controls were matched using a 2:1 greedy matching algorithm based on LAS within the timeframe of the study (2021–2023), resulting in 15 SE and 30 matched controls. In the SE arm, no LTx was performed between 1800 and 0500 hours. When donor lungs were accepted and the donor cross clamp time occurred between 1800 and 0400 hours, OR time (anesthesia start) was moved to 0600 or later. On arrival, donor lungs were stored at 10°C static preservation. The maximum allowed time between donor cross clamp and recipient anesthesia initiation was 12 hours. No statistical difference between baseline characteristics was identified between the 2 groups (Table 1). 2/3 of patients were already admitted at the time of transplantation and 15% were on ECMO pre-operatively, indicating a sick patient cohort. Left lung ischemic time (performed second at our institution) was significantly longer in the SE group (722 minutes vs 318 minutes). Post-operative outcomes, including PGD at 72 hours, prolonged MV, ICU and hospital LOS, rejection, re-exploration, and re-admissions were not statistically different between the 2 groups. 1- year survival was 93% for SE patients, and 100% for controls. One-year outcomes of semi-elective lung transplantation is comparable to traditional transplantation recipients, even in a sick cohort of patients.