• Desiree M Schumann, Diana Leeming, Eleni Papakonstantinou, Francesco Blasi, Konstantinos Kostikas, Wim Boersma, Renaud Louis, Branislava Milenkovic, Joachim Aerts, Sand Jannie M B JMB Nordic Bioscience, Fibrosis Biology and Biomarkers, Herlev, Denmark., Wouters Emiel F M EFM Department of Respiratory Medicine, Maastricht University Medical Center, Maastricht the Netherlands., Gernot Rohde, Christina Prat, Antoni Torres, Tobias Welte, Michael Tamm, Morten Karsdal, and Daiana Stolz.
• Clinic of Pneumology and Pulmonary Cell Research, University Hospital Basel, Basel, Switzerland.
• Chest. 2018 Oct 1; 154 (4): 798-807.

BackgroundThe 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.MethodsIn 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.ResultsAt 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.ConclusionsSerologically 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).Copyright © 2018. Published by Elsevier Inc.

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