Ischemia-reperfusion injury, a form of sterile inflammation, is the leading risk factor for both short-term mortality following pulmonary transplantation and chronic lung allograft dysfunction. While it is well recognized that neutrophils are critical mediators of acute lung injury, processes that guide their entry into pulmonary tissue are not well understood. Here, we found that CCR2+ classical monocytes are necessary and sufficient for mediating extravasation of neutrophils into pulmonary tissue during ischemia-reperfusion injury following hilar clamping or lung transplantation. The classical monocytes were mobilized from the host spleen, and splenectomy attenuated the recruitment of classical monocytes as well as the entry of neutrophils into injured lung tissue, which was associated with improved graft function. Neutrophil extravasation was mediated by MyD88-dependent IL-1β production by graft-infiltrating classical monocytes, which downregulated the expression of the tight junction-associated protein ZO-2 in pulmonary vascular endothelial cells. Thus, we have uncovered a crucial role for classical monocytes, mobilized from the spleen, in mediating neutrophil extravasation, with potential implications for targeting of recipient classical monocytes to ameliorate pulmonary ischemia-reperfusion injury in the clinic.
Perioperative factors can affect outcomes of liver transplantation (LT) in recipients with hepatitis C virus (HCV) infection. This study was conducted to investigate whether the immunomodulatory effects of packed red blood cells (PRBC) and platelets administered in the perioperative period might affect immune responses to HCV and thus outcomes in LT recipients.Data for a total of 257 HCV LT recipients were analysed. Data on clinical demographics including perioperative transfusion (during and within the first 24 h), serum cytokine concentration, HCV-specific interferon-γ (IFN-γ) and interleukin-17 (IL-17) producing cells, and outcomes including graft and patient survival were analysed.Patient survival was higher in HCV LT recipients who did not receive transfusions (Group 1, n = 65) than in those who did (Group 2, n = 192). One-year patient survival was 95% in Group 1 and 88% in Group 2 (P = 0.02); 5-year survival was 77% in Group 1 and 66% in Group 2 (P = 0.05). Group 2 had an increased post-transplant viral load (P = 0.032) and increased incidence of advanced fibrosis at 1 year (P = 0.04). After LT, Group 2 showed increased IL-10, IL-17, IL-1β and IL-6, and decreased IFN-γ, and a significantly increased rate of IL-17 production against HCV antigen. Increasing donor age (P = 0.02), PRBC transfusion (P < 0.01) and platelets administration were associated with worse survival.Transfusion had a negative impact on LT recipients with HCV. The associated early increase in pro-HCV IL-17 and IL-6, with decreased IFN-γ, suggests that transfusion may be associated with the modulation of HCV-specific responses, increased fibrosis and poor transplant outcomes.
Transfer of select, medically refractory acute respiratory distress syndrome patients to lung transplant centers requires extensive resources. Here, we report 270 consecutive lung transplant patient referrals to our center for medically refractory ARDS from June 2021 to April 2022, following the implementation of clinical care pathways for intake of these patients. Eighty-seven of 270 patients (32.2%) met screening criteria and were evaluated for transfer within a median of 12 days, during which 38 of 87 patients (43.7%) died and 12 of 87 patients (13.8%) transferred elsewhere. Thirty-seven of 87 patients (42.5%) were accepted for transfer of which 16 of 37 patients (43.2%) successfully transferred to our center with a median transfer waiting period of 12 days. Because of resource constraints, 21 of 37 accepted patients (56.8%) could not be transferred of which 9 of 21 patients (42.9%) died while waiting. Nine of 16 transferred patients (56.2%) eventually underwent lung transplantation with over 80% 6-month survival. ARDS patients referred for transplantation have high risk of mortality and, therefore, require well-described pathways for evaluation and transfer.
Purpose of review The purpose of this review is to analyze the most recent and relevant literature involving lung transplantation for coronavirus disease 2019 (COVID-19) associated acute respiratory distress syndrome (ARDS), the pathological mechanisms of lung injury, selection criteria and outcomes. Recent findings Pathological analysis of lungs after COVID-19 ARDS has shown architectural distortion similar to that observed in explanted lungs from patients undergoing lung transplantation for end-stage lung diseases such as emphysema. Short-term outcomes after lung transplantation for COVID-19 associated respiratory failure are comparable to those performed for other indications. Summary Lung transplantation after COVID-19 ARDS is a potentially life-saving procedure for appropriately selected patients with no evidence of lung function recovery despite maximal treatment. Lung transplantation should be ideally performed in high-volume centers with expertise.
