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 journalArticle

6 Citations (Scopus)

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

Fingerprint

Complement C5
Chronic Obstructive Pulmonary Disease
Collagen
Dyspnea
Extracellular Matrix
Biomedical Research
Biomarkers
Collagen Type V
Exercise
Metalloproteases
Gold
Lung Diseases
Multicenter Studies
Observational Studies
Multivariate Analysis
Pathology
Lung
Mortality
Serum

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

Cite this

Schumann, D. M., Leeming, D., Papakonstantinou, E., Blasi, F., Kostikas, K., Boersma, W., ... Stolz, D. (2018). Collagen Degradation and Formation Are Elevated in Exacerbated COPD Compared With Stable Disease. Chest, 154(4), 798-807. https://doi.org/10.1016/j.chest.2018.06.028

Collagen Degradation and Formation Are Elevated in Exacerbated COPD Compared With Stable Disease. / Schumann, Desiree M.; Leeming, Diana; Papakonstantinou, Eleni; Blasi, Francesco; Kostikas, Konstantinos; Boersma, Wim; Louis, Renaud; Milenkovic, Branislava; Aerts, Joachim; Sand, Jannie M.B.; Wouters, Emiel F.M.; Rohde, Gernot; Prat, Christina; Torres, Antoni; Welte, Tobias; Tamm, Michael; Karsdal, Morten; Stolz, Daiana.

In: Chest, Vol. 154, No. 4, 01.10.2018, p. 798-807.

Research output: Contribution to journalArticle

Schumann, DM, Leeming, D, Papakonstantinou, E, Blasi, F, Kostikas, K, Boersma, W, Louis, R, Milenkovic, B, Aerts, J, Sand, JMB, Wouters, EFM, Rohde, G, Prat, C, Torres, A, Welte, T, Tamm, M, Karsdal, M & Stolz, D 2018, 'Collagen Degradation and Formation Are Elevated in Exacerbated COPD Compared With Stable Disease', Chest, vol. 154, no. 4, pp. 798-807. https://doi.org/10.1016/j.chest.2018.06.028
Schumann DM, Leeming D, Papakonstantinou E, Blasi F, Kostikas K, Boersma W et al. Collagen Degradation and Formation Are Elevated in Exacerbated COPD Compared With Stable Disease. Chest. 2018 Oct 1;154(4):798-807. https://doi.org/10.1016/j.chest.2018.06.028
Schumann, Desiree M. ; Leeming, Diana ; Papakonstantinou, Eleni ; Blasi, Francesco ; Kostikas, Konstantinos ; Boersma, Wim ; Louis, Renaud ; Milenkovic, Branislava ; Aerts, Joachim ; Sand, Jannie M.B. ; Wouters, Emiel F.M. ; Rohde, Gernot ; Prat, Christina ; Torres, Antoni ; Welte, Tobias ; Tamm, Michael ; Karsdal, Morten ; Stolz, Daiana. / Collagen Degradation and Formation Are Elevated in Exacerbated COPD Compared With Stable Disease. In: Chest. 2018 ; Vol. 154, No. 4. pp. 798-807.
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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).",
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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

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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 (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).

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 (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).

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KW - C1

KW - C4

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KW - COPD

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KW - type IV collagen

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