Background: Matrix remodeling and immune activation characterize different forms of chronic lung disease (CLD). We targeted easily accessible, shared indicators of the progressive destruction of the gas exchange area to identify pathophysiologic processes with clinical relevance.
Methods: Prospective plasma samples from deep phenotyped age- and gender-matched CLD patients (IPF n=28; COPD n=26) and healthy subjects (KORA cohort, n=25) underwent proteomic screening (SomaLogic, Boulder, USA), followed by immunohistochemistry in lung sections. Early origin CLD (BPD) was studied in preterm infants (n=27). Informed consent was obtained for all individuals.
Results: Univariate and LASSO regression, calculated within the respective cohorts, revealed a common signature in COPD and IPF, dominated by upregulation of clotting factors such as fibrinogen, FV, prothrombin (FII) and D-dimer, together with a shared downregulation of APC, PAFAH and alpha-2-Macroglobulin, demonstrating a procoagulant state. Associated regulation of markers for endothelial function (vWF, Kallikrein) and neutrophil/macrophage activation merge on a picture of thromboinflammation. Multicolor staining localized these processes in the intravascular and interstitial lung compartment. The signature including vWF, FV and FII, correlated with lung function decline in these patients and was recapitulated in early CLD (BPD). Contrasting COPD and IPF, upregulation of MMP3, Thrombin, APC, PAFAH, Kallikrein, FVII, CD39 in BPD likely relates to neonatal platelet hyporeactivity.
Conclusion: The systemic coagulation signature links thromboinflammation and matrix remodeling, which might reflect the self-entertaining circle of alveolar-capillary destruction and could inform treatment and monitoring in CLD.