TY - JOUR
T1 - Collagen Degradation and Formation Are Elevated in Exacerbated COPD Compared With Stable Disease
AU - Schumann, Desiree M.
AU - Leeming, Diana
AU - Papakonstantinou, Eleni
AU - Blasi, Francesco
AU - Kostikas, Konstantinos
AU - Boersma, Wim
AU - Louis, Renaud
AU - Milenkovic, Branislava
AU - Aerts, Joachim
AU - Sand, Jannie M. B.
AU - Wouters, Emiel F. M.
AU - Rohde, Gernot
AU - Prat, Christina
AU - Torres, Antoni
AU - Welte, Tobias
AU - Tamm, Michael
AU - Karsdal, Morten
AU - Stolz, Daiana
PY - 2018/10/1
Y1 - 2018/10/1
N2 - 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 (alpha 1 chain, C4M2), and type IV (alpha 3 chain, C4Ma3) collagen, all degraded by metalloproteinases and the pro-form of collagen type V (PRO-05) were investigated and associated with COPD severity and outcome. METHOD: 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-05. C1M, C4M2, C4Ma3, and Pro-05 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-05 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).
AB - 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 (alpha 1 chain, C4M2), and type IV (alpha 3 chain, C4Ma3) collagen, all degraded by metalloproteinases and the pro-form of collagen type V (PRO-05) were investigated and associated with COPD severity and outcome. METHOD: 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-05. C1M, C4M2, C4Ma3, and Pro-05 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-05 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).
KW - basement membrane
KW - C1
KW - C4
KW - cell turnover
KW - collagen
KW - COPD
KW - ECM
KW - lamina reticularis
KW - type I collagen
KW - type IV collagen
KW - OBSTRUCTIVE PULMONARY-DISEASE
KW - BIOMARKERS
KW - FIBROSIS
KW - LUNG
KW - CORTICOSTEROIDS
KW - TURNOVER
KW - PROFILE
KW - ASTHMA
KW - URINE
U2 - 10.1016/j.chest.2018.06.028
DO - 10.1016/j.chest.2018.06.028
M3 - Article
C2 - 29966667
SN - 0012-3692
VL - 154
SP - 798
EP - 807
JO - Chest
JF - Chest
IS - 4
ER -