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Collagen- and elastin-derived biomarkers and acute severe exacerbations in COPD: a sub study of the CORTICO-COP trial

Year: 2026

Type: article

Abstract: Extracellular matrix (ECM) turnover and neutrophil protease activity contribute to chronic obstructive pulmonary disease (COPD) pathobiology, but the prognostic value of circulating neoepitopes for acute exacerbations (AECOPD) is uncertain. In a prospective cohort from the CORTICO-COP trial, the biomarkers C5M and C6M (type V/VI collagen degradation), ELP-3 (proteinase 3-generated elastin fragment), and CPa9-HNE (neutrophil elastase-generated calprotectin fragment) were measured in plasma at hospital admission for AECOPD (exacerbation phase; n = 299) and at day-30 follow-up (stable phase; n = 200). The primary endpoint was time to a composite of readmission with AECOPD or all-cause mortality within 12 months; the secondary endpoint was all-cause mortality. Cox models were adjusted for age, sex, pack-years, Charlson Comorbidity Index, and randomization arm. Single-time-point levels were not associated with the composite endpoint or with mortality at exacerbation or at stable phase. In a post-hoc analysis of paired data, a larger decline in CPa9-HNE from admission to day-30 (lowest quartile of change) was associated with a shorter time to the composite endpoint (HR 1.88, 95% CI 1.18-3.01) but not with mortality. This exploratory signal suggests within-patient decline in plasma CPa9-HNE may mark early re-exacerbation risk, but this requires validation in independent cohorts.

Source: Scientific Reports

DOI: 10.1038/s41598-026-51575-y