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

Desiree M. Schumann, Diana Leeming, Eleni Papakonstantinou, Francesco Blasi, Konstantinos Kostikas, Wim Boersma, Renaud Louis, Branislava Milenkovic, Joachim Aerts, Jannie M.B. Sand, Emiel F.M. Wouters, Gernot Rohde, Christina Prat, Antoni Torres, Tobias Welte, Michael Tamm, Morten Karsdal, Daiana Stolz

Research output: Contribution to journalArticlepeer-review

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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).

Original languageEnglish
Pages (from-to)798-807
Number of pages10
JournalChest
Volume154
Issue number4
DOIs
Publication statusPublished - Oct 1 2018

Keywords

  • basement membrane
  • C1
  • C4
  • cell turnover
  • collagen
  • COPD
  • ECM
  • lamina reticularis
  • type I collagen
  • type IV collagen

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

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