Collagen Degradation and Formation Are Elevated in Exacerbated COPD Compared With Stable Disease.

Abstract

The role of the extracellular matrix (ECM) structure and remodeling thereof in lung diseases is gaining importance. Pathology-related changes in ECM turnover may result in deleterious changes in lung architecture, leading to disease in the small airways. Here, degradation fragments of type I (C1M), type IV (α1 chain, C4M2), and type IV (α3 chain, C4Ma3) collagen, all degraded by metalloproteinases and the pro-form of collagen type V (PRO-C5) were investigated and associated with COPD severity and outcome. In a prospective, observational, multicenter study including 498 patients with COPD Gold Initiative for Chronic Obstructive Lung Disease stage 2 to 4, ECM markers were assessed in serum at stable state, exacerbation, and at follow-up 4 weeks after exacerbation. At stable state, there was a significant inverse association between FEV₁ % predicted and C1M, C4Ma3, and Pro-C5. C1M, C4M2, C4Ma3, and Pro-C5 were associated with BMI, airflow obstruction, dyspnea, and exercise capacity (BODE) index and the modified Medical Research Council (MMRC) score. C1M, C4M2, C4Ma3, and Pro-C5 were significantly increased from stable state to exacerbation and decreased at follow-up. Furthermore, the biomarkers were significantly higher during severe exacerbation compared with moderate exacerbation. Multivariate analysis adjusted for BMI, MMRC score, unadjusted Charlson score, and FEV₁ %predicted showed a significant influence of C1M, C4Ma3, and C4M2 on time to exacerbation. None of the biomarkers were predictors for mortality. Serologically assessed collagen remodeling appears to play a significant role in COPD severity (airflow limitation, dyspnea) and disease outcome (time to exacerbation and prognosis as assessed by the BODE index).