Selective hemoadsorption of cytokines and platelet-neutrophil complexes mitigates lung microvascular hyperpermeability in an ovine acute lung injury model

Background: Acute respiratory distress syndrome (ARDS) is a life-threatening disease that is characterized by noncardiogenic pulmonary edema, respiratory distress, and hypoxemia, and has high mortality. Uncontrolled activation of neutrophils and formation of platelet-neutrophil complexes (PNCs) contribute significantly to its pathogenesis. In this study, we investigated whether suppression of systemic inflammation through simultaneous adsorption of inflammatory mediators, including PNCs, reduces lung invasion and offers an effective treatment strategy for ARDS. Materials and methods: We investigated the efficacy of a novel hemoadsorption column, NOA-001, which simultaneously removes cytokines and PNCs, in an ovine model of smoke inhalation-induced ARDS. Animals were assigned to two groups: treatment with NOA-001 (n = 6) or a control group with a blood circuit without the column (n = 5). The impact on neutrophil dynamics, lung injury, edema formation, and inflammatory markers was assessed. Results: Neutrophil capture rates by NOA-001 were significantly higher at 4 and 6 h compared to controls, with a trend toward lower circulating neutrophil counts. Flow cytometry confirmed that NOA-001 predominantly removed PNCs (CD62⁺/CD11b^low or CD11b^high). At 27 h, the NOA-001 group had significantly improved oxygenation (oxygenation index: 10.3 ± 3.0 vs. 18.8 ± 3.2, p < 0.05) and significantly lower lung injury scores (1.9 ± 0.3 vs. 2.8 ± 0.2, p < 0.05) compared to controls. Lung edema was significantly attenuated, as evidenced by reduced lung lymph flow (27.3 ± 6.4 vs. 57.8 ± 6.4 mL/h), lower wet-to-dry weight ratios in lung (7.4 ± 0.3 vs. 9.2 ± 0.6) and trachea (2.7 ± 0.1 vs. 3.0 ± 0.1), and decreased thoracic exudate volume (90 ± 69 vs. 620 ± 183 mL, p < 0.05). Pulmonary protein leakage and neutrophil migration indices were also significantly lower in the NOA-001 group. Interleukin-6 levels in bronchoalveolar lavage fluid tended to be lower in the NOA-001 group (p = 0.08). No adverse events were observed. Conclusions: Simultaneous removal of cytokines and PNCs using NOA-001 significantly reduced ARDS severity by attenuating pulmonary edema and improving pulmonary gas exchange. These results suggest that NOA-001 may be a novel and promising therapeutic strategy for ARDS.