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

Acute respiratory distress syndrome (ARDS), when complicated by secondary pneumonias caused by nosocomial antibiotic-resistant pathogens and septic shock, can carry mortality rates exceeding 80%. We performed single-cell RNA sequencing and Visium HD spatial transcriptomics on an explanted lung from a 33-year-old patient with influenza-associated ARDS complicated by carbapenem-resistant Pseudomonas aeruginosa pneumonia and refractory septic shock. Our results demonstrated diffuse and uniform tissue destruction in the affected lung, with dense infiltration by neutrophils, monocyte-derived alveolar macrophages, and activated T cells. We also observed marked expansion of aberrant basaloid epithelial cells and CTHRC1-positive myofibroblasts coexisting with widespread inflammation, accompanied by near-complete loss of normal alveolar architecture. The resulting molecular signatures recapitulated those seen in end-stage fibrotic lung disease and were consistent with irreversible injury rather than a recoverable ARDS phenotype.