Bridge to transplant using a flow-adaptive extracorporeal total artificial lung system following bilateral pneumonectomy

Abstract

Background: Severe acute respiratory distress syndrome (ARDS) complicated by necrotizing pneumonia and septic shock carries a mortality exceeding 80%. Lung transplantation is rarely pursued because persistent sepsis, uncertainty regarding the reversibility of parenchymal injury, and profound hemodynamic instability preclude candidacy.

Methods: We developed an extracorporeal total artificial lung (TAL) system to enable bilateral pneumonectomy for source control in a patient with ARDS complicated by necrotizing pneumonia and refractory septic shock. The system incorporated a flow-adaptive right pulmonary artery-to-right atrial shunt to compensate for loss of pulmonary vascular capacitance, extracorporeal oxygenation, and dual left atrial return conduits to maintain physiologic transcardiac blood flow. In parallel, we performed single-cell and spatial transcriptomic profiling of the explanted lungs to define associated cellular and molecular changes.

Findings: Following pneumonectomy, vasopressor requirements resolved, and the patient remained fully supported until transplant. Transcriptomic profiling revealed diffuse, uniform destruction across all regions, with dense infiltration by neutrophils, monocyte-derived alveolar macrophages, and activated T cells. These inflammatory changes coexisted with marked expansion of aberrant basaloid epithelial cells and CTHRC1-positive myofibroblasts, with near-complete loss of normal alveolar architecture. Molecular signatures recapitulated end-stage fibrotic lung disease and were consistent with irreversible injury rather than a recoverable ARDS phenotype. The patient demonstrates excellent cardiopulmonary function 2 years after transplantation.

Conclusions: An extracorporeal TAL system can permit safe bilateral pneumonectomy for source control in otherwise non-transplantable patients with medically refractory pneumonia, providing a viable salvage strategy to bridge selected patients to successful lung transplantation.

Funding: This project was funded through NIH grants HL145478, HL147575, HL173940, and P0HL169188.

Keywords: ARDS; TAL; Translation to patients; bilateral pneumonectomy; lung transplant; sepsis.