In cases of septic shock arising from severe Acute Respiratory Distress Syndrome (ARDS) accompanied by necrotizing pneumonia (pneumonia characterized by the death of lung tissue), mortality rates can exceed 80%. Within this clinical context, lung transplantation is generally not considered a viable option due to the persistent risk of infection and uncertainties regarding the recoverability of the organ. Although existing mechanical ventilation and Extracorporeal Membrane Oxygenation (ECMO) methods support gas exchange, they may be insufficient to correct the profound circulatory disturbances caused by sepsis. The primary challenge in this domain lies in the absence of a strategy capable of controlling the source of infection while maintaining the patient’s circulatory system in a stable condition until the transplantation process.
The study conducted by Yan and colleagues aimed to develop and test the feasibility of a novel extracorporeal Total Artificial Lung (TAL) system that would prepare the patient for transplantation following the complete surgical removal of infected lungs unresponsive to standard treatments (bilateral pneumonectomy). The study additionally sought to perform advanced molecular analyses on the excised lung tissues in order to determine whether the tissue damage was reversible in situations where existing diagnostic methods were insufficient. The researchers investigated whether this approach could, in selected cases, eliminate the source of infection and establish a bridge to successful lung transplantation.
In the study, an extracorporeal TAL system was employed, incorporating a specially designed flow-adaptive right pulmonary artery–right atrium shunt (blood passageway) to compensate for the loss of the pulmonary circulation and dual left atrial return channels to maintain physiological blood flow. After both lungs were removed to control the infectious focus, circulation was sustained through this system. Concurrently, single-cell and spatial transcriptomic (gene expression mapping) analyses were performed on tissue samples obtained from the excised organs. These molecular examinations were utilized to map, in detail, the cellular alterations and structural deterioration within the tissue. During the critical 48-hour period following the complete removal of the patient’s infected lungs, the developed flow-adaptive TAL system fully assumed vital functions. Throughout this interval, the physiological support provided by the system rapidly corrected the patient’s circulatory dysfunction, lactate levels returned to normal, and by the 12th postoperative hour, the need for vasopressor support was entirely eliminated. Despite the absence of systemic anticoagulation, the system operated for 48 hours without causing any clot formation or technical malfunction, preserving right ventricular function and bringing the patient into the most physiologically optimal condition for the transplantation procedure. One of the most significant elements validating the scientific basis of the treatment process was the advanced computational analyses performed on the excised tissues. The researchers examined the tissue samples using single-cell RNA sequencing and spatial transcriptomics and employed advanced machine learning–based software and algorithms (e.g., scvi-tools, CellTypist) to process the complex datasets obtained. These computational analyses demonstrated at the cellular level that the damage within the lung tissue was not regional but rather a homogeneous and irreversible destruction extending throughout the entire organ. The molecular mapping revealed that the tissue’s regenerative capacity had been exhausted and that fibrosis-inducing mechanisms had become predominant, thereby confirming the biological necessity of the decision to remove the lungs.
As a result, the implementation of the developed system was observed to eliminate the patient’s requirement for vasopressors and to achieve complete hemodynamic stabilization during the pre-transplantation period. Molecular analyses identified an irreversible pattern of damage characterized by widespread neutrophil infiltration and fibrosis (increase in connective tissue), with complete loss of normal alveolar architecture across the tissue. These findings molecularly confirmed that the lung damage in the present case did not represent a recoverable ARDS phenotype and indicate that, in selected patients, this method may constitute a feasible strategy for transition to lung transplantation.
Reference: Yan, Y., Chandrasekhar, A., Yang, H. C., Devarakonda, T., Reynolds, A., Yeldandi, A. V., Arunachalam, A., Kurihara, C., Budinger, G. R. S., & Bharat, A. (2026). Bridge to transplant using a flow-adaptive extracorporeal total artificial lung system following bilateral pneumonectomy. Med (New York, N.Y.), 100985. Advance online publication. https://doi.org/10.1016/j.medj.2025.100985