Collagen Degradation and Formation Are Elevated in Exacerbated COPD Compared With Stable Disease
Articolo
Data di Pubblicazione:
2018
Citazione:
Collagen Degradation and Formation Are Elevated in Exacerbated COPD Compared With Stable Disease / D.M. Schumann, D. Leeming, E. Papakonstantinou, F. Blasi, K. Kostikas, W. Boersma, R. Louis, B. Milenkovic, J. Aerts, J.M.B. Sand, E.F.M. Wouters, G. Rohde, C. Prat, A. Torres, T. Welte, M. Tamm, M. Karsdal, D. Stolz. - In: CHEST. - ISSN 0012-3692. - 154:4(2018 Oct), pp. 798-807.
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).
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
basement membrane; C1; C4; cell turnover; collagen; COPD; ECM; lamina reticularis; type I collagen; type IV collagen; Pulmonary and Respiratory Medicine; Critical Care and Intensive Care Medicine; Cardiology and Cardiovascular Medicine
Elenco autori:
D.M. Schumann, D. Leeming, E. Papakonstantinou, F. Blasi, K. Kostikas, W. Boersma, R. Louis, B. Milenkovic, J. Aerts, J.M.B. Sand, E.F.M. Wouters, G. Rohde, C. Prat, A. Torres, T. Welte, M. Tamm, M. Karsdal, D. Stolz
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