Spatially Distinct Immunothrombotic Signatures in Patients with Pneumonia-Related Acute Respiratory Distress Syndrome: Insights from Lung Alveolar and Blood Circulation Profiles

Abstract

Abstract Background The role of immunothrombosis in the pathogenesis of pulmonary acute respiratory distress syndrome (ARDS) is increasingly recognized, but its implications in extrapulmonary complications remain inadequately understood. This study aimed to compare the immunothrombotic signatures in patients with pneumonia-related ARDS (p-ARDS) at both pulmonary and systemic levels and to assess their clinical relevance. Methods This prospective observational study included consecutive patients with p-ARDS admitted to the intensive care unit between July and November 2022. Concurrently hospitalized patients with common pneumonia in the general ward were included as controls. Paired bronchoalveolar lavage fluid (BALF) and serum samples were utilized to quantify 15 biomarkers and characterize pulmonary and systemic immunothrombotic signatures, respectively. The clinical relevance of these biomarkers was explored using Spearman correlation, receiver operating characteristic, and binary logistic regression analyses. Results A total of 23 patients with p-ARDS and 10 pneumonia controls were included for analysis. Among the p-ARDS cohort, 10 out of 23 patients experienced mortality within 28 days of admission. Our results revealed significant signatures of pulmonary inflammation and systemic endothelial injury in patients with p-ARDS, in comparison to the pneumonia controls. Specially, BALF IL-6 showed a negative correlation with PaO2/FiO2 ratio (Spearman r = − 0.67, P < 0.001), while serum a disintegrin and metalloproteinase with thrombospondin type 1 motif, 13 (ADAMTS-13) and soluble thrombomodulin (TM) exhibited close correlations with SOFA and DIC score. The combination of BALF IL-6 and serum TM showed promise in distinguishing p-ARDS from common pneumonia (area under the curve [AUC] = 0.955; 95% confidence interval [CI]: 0.895 − 1.000). Furthermore, BALF H3cit was significantly associated with 28-day mortality, even after adjusting for the SOFA score upon admission (odds ratio [OR] = 6.71; 95% CI: 1.05 − 42.44; P = 0.043). Conclusions This preliminary investigation revealed compartment-specific differences in the immunothrombotic signature between patients with p-ARDS and those with pneumonia alone. These findings provide insights into the pathophysiology underlying p-ARDS and its complications, with potential to facilitate the development of precision medicine approaches for its clinical management.