Collagen Degradation and Formation Are Elevated in Exacerbated COPD Compared With Stable Disease
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).
|Keywords||basement membrane, C1, C4, cell turnover, collagen, COPD, ECM, lamina reticularis, type I collagen, type IV collagen|
|Persistent URL||dx.doi.org/10.1016/j.chest.2018.06.028, hdl.handle.net/1765/114487|
|Journal||Chest: the cardiopulmonary and critical care journal|
Schumann, D.M. (Desiree M.), Leeming, D. (Diana), Papakonstantinou, E. (Eleni), Blasi, F, Kostikas, K. (Konstantinos), Boersma, W.G, … Stolz, D. (Daiana). (2018). Collagen Degradation and Formation Are Elevated in Exacerbated COPD Compared With Stable Disease. Chest: the cardiopulmonary and critical care journal, 154(4), 798–807. doi:10.1016/j.chest.2018.06.028