Biomarkers of collagen turnover are related to annual change in FEV1 in patients with chronic obstructive pulmonary disease within the ECLIPSE study

The Evaluation of COPD Longitudinally to Identify Surrogate Endpoints (ECLIPSE) study investigators

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: Change in forced expiratory volume in one second (FEV1) is important for defining severity of chronic obstructive pulmonary disease (COPD). Serological neoepitope markers of collagen turnover may predict rate of change in FEV1. Methods: One thousand COPD subjects from the observational, multicentre, three-year ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) study (NCT00292552, trial registration in February 2006) were included. Matrix metalloproteinase (MMP)-generated fragments of collagen type I, and type VI (C1M and C6M) were assessed in month six serum samples. A random-coefficient model with both a random intercept and a random slope was used to test the ability of the markers to predict post-dose bronchodilator FEV1 (PD-FEV1) change over two years adjusting for sex, age, BMI, smoking, bronchodilator reversibility, prior exacerbations, emphysema and chronic bronchitis status at baseline. Results: Annual change of PD-FEV1 was estimated from a linear model for the two-year study period. Serum C1M and C6M were independent predictors of lung function change (p = 0.007/0.005). Smoking, bronchodilator reversibility, plasma hsCRP and emphysema were also significant predictors. The effect estimate between annual change in PD-FEV1 per one standard deviation (1SD) increase of C1M and C6M was +10.4 mL/yr. and +8.6 mL/yr. C1M, and C6M, had a significant association with baseline FEV1. Conclusion: We demonstrated that markers of tissue turnover were significantly associated with lung function change. These markers may function as prognostic biomarkers and possibly as efficacy biomarkers in clinical trials focusing on lung function change in COPD. Trial registration:NCT00292552 , Retrospectively registered, trial registration in February 2006.

Original languageEnglish (US)
Article number164
JournalBMC Pulmonary Medicine
Volume17
Issue number1
DOIs
StatePublished - Dec 4 2017

Fingerprint

Bronchodilator Agents
Chronic Obstructive Pulmonary Disease
Collagen
Biomarkers
Emphysema
Lung
Smoking
Aptitude
Chronic Bronchitis
Forced Expiratory Volume
Collagen Type I
Serum
Matrix Metalloproteinases
Linear Models
Clinical Trials

Keywords

  • COPD
  • Extracellular matrix
  • Lung function change
  • Prognosis
  • Serological marker

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Biomarkers of collagen turnover are related to annual change in FEV1 in patients with chronic obstructive pulmonary disease within the ECLIPSE study. / The Evaluation of COPD Longitudinally to Identify Surrogate Endpoints (ECLIPSE) study investigators.

In: BMC Pulmonary Medicine, Vol. 17, No. 1, 164, 04.12.2017.

Research output: Contribution to journalArticle

The Evaluation of COPD Longitudinally to Identify Surrogate Endpoints (ECLIPSE) study investigators. / Biomarkers of collagen turnover are related to annual change in FEV1 in patients with chronic obstructive pulmonary disease within the ECLIPSE study. In: BMC Pulmonary Medicine. 2017 ; Vol. 17, No. 1.
@article{519da382761d4f4e99262150f509ebbf,
title = "Biomarkers of collagen turnover are related to annual change in FEV1 in patients with chronic obstructive pulmonary disease within the ECLIPSE study",
abstract = "Background: Change in forced expiratory volume in one second (FEV1) is important for defining severity of chronic obstructive pulmonary disease (COPD). Serological neoepitope markers of collagen turnover may predict rate of change in FEV1. Methods: One thousand COPD subjects from the observational, multicentre, three-year ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) study (NCT00292552, trial registration in February 2006) were included. Matrix metalloproteinase (MMP)-generated fragments of collagen type I, and type VI (C1M and C6M) were assessed in month six serum samples. A random-coefficient model with both a random intercept and a random slope was used to test the ability of the markers to predict post-dose bronchodilator FEV1 (PD-FEV1) change over two years adjusting for sex, age, BMI, smoking, bronchodilator reversibility, prior exacerbations, emphysema and chronic bronchitis status at baseline. Results: Annual change of PD-FEV1 was estimated from a linear model for the two-year study period. Serum C1M and C6M were independent predictors of lung function change (p = 0.007/0.005). Smoking, bronchodilator reversibility, plasma hsCRP and emphysema were also significant predictors. The effect estimate between annual change in PD-FEV1 per one standard deviation (1SD) increase of C1M and C6M was +10.4 mL/yr. and +8.6 mL/yr. C1M, and C6M, had a significant association with baseline FEV1. Conclusion: We demonstrated that markers of tissue turnover were significantly associated with lung function change. These markers may function as prognostic biomarkers and possibly as efficacy biomarkers in clinical trials focusing on lung function change in COPD. Trial registration:NCT00292552 , Retrospectively registered, trial registration in February 2006.",
keywords = "COPD, Extracellular matrix, Lung function change, Prognosis, Serological marker",
author = "{The Evaluation of COPD Longitudinally to Identify Surrogate Endpoints (ECLIPSE) study investigators} and Leeming, {Diana J.} and Inger Byrjalsen and Sand, {Jannie M.B.} and Bihlet, {Asger R.} and Peter Lange and Ruth Thal-Singer and Miller, {Bruce E.} and Karsdal, {Morten A.} and J{\o}rgen Vestbo and Y. Ivanov and K. Kostov and J. Bourbeau and M. Fitzgerald and P. Hern{\'a}ndez and K. Killian and R. Levy and F. Maltais and D. O'Donnell and J. Krepelka and J. Vestbo and E. Wouters and D. Quinn and P. Bakke and M. Kosnik and A. Agusti and Jaume Sauleda and Y. Feschenko and V. Gavrisyuk and L. Yashina and W. MacNee and D. Singh and J. Wedzicha and Anzueto, {Antonio R} and S. Braman and R. Casaburi and B. Celli and G. Giessel and M. Gotfried and G. Greenwald and N. Hanania and D. Mahler and B. Make and S. Rennard and C. Rochester and P. Scanlon and D. Schuller and F. Sciurba and A. Sharafkhaneh and T. Siler and E. Silverman",
year = "2017",
month = "12",
day = "4",
doi = "10.1186/s12890-017-0505-4",
language = "English (US)",
volume = "17",
journal = "BMC Pulmonary Medicine",
issn = "1471-2466",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Biomarkers of collagen turnover are related to annual change in FEV1 in patients with chronic obstructive pulmonary disease within the ECLIPSE study

AU - The Evaluation of COPD Longitudinally to Identify Surrogate Endpoints (ECLIPSE) study investigators

AU - Leeming, Diana J.

AU - Byrjalsen, Inger

AU - Sand, Jannie M.B.

AU - Bihlet, Asger R.

AU - Lange, Peter

AU - Thal-Singer, Ruth

AU - Miller, Bruce E.

AU - Karsdal, Morten A.

AU - Vestbo, Jørgen

AU - Ivanov, Y.

AU - Kostov, K.

AU - Bourbeau, J.

AU - Fitzgerald, M.

AU - Hernández, P.

AU - Killian, K.

AU - Levy, R.

AU - Maltais, F.

AU - O'Donnell, D.

AU - Krepelka, J.

AU - Vestbo, J.

AU - Wouters, E.

AU - Quinn, D.

AU - Bakke, P.

AU - Kosnik, M.

AU - Agusti, A.

AU - Sauleda, Jaume

AU - Feschenko, Y.

AU - Gavrisyuk, V.

AU - Yashina, L.

AU - MacNee, W.

AU - Singh, D.

AU - Wedzicha, J.

AU - Anzueto, Antonio R

AU - Braman, S.

AU - Casaburi, R.

AU - Celli, B.

AU - Giessel, G.

AU - Gotfried, M.

AU - Greenwald, G.

AU - Hanania, N.

AU - Mahler, D.

AU - Make, B.

AU - Rennard, S.

AU - Rochester, C.

AU - Scanlon, P.

AU - Schuller, D.

AU - Sciurba, F.

AU - Sharafkhaneh, A.

AU - Siler, T.

AU - Silverman, E.

PY - 2017/12/4

Y1 - 2017/12/4

N2 - Background: Change in forced expiratory volume in one second (FEV1) is important for defining severity of chronic obstructive pulmonary disease (COPD). Serological neoepitope markers of collagen turnover may predict rate of change in FEV1. Methods: One thousand COPD subjects from the observational, multicentre, three-year ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) study (NCT00292552, trial registration in February 2006) were included. Matrix metalloproteinase (MMP)-generated fragments of collagen type I, and type VI (C1M and C6M) were assessed in month six serum samples. A random-coefficient model with both a random intercept and a random slope was used to test the ability of the markers to predict post-dose bronchodilator FEV1 (PD-FEV1) change over two years adjusting for sex, age, BMI, smoking, bronchodilator reversibility, prior exacerbations, emphysema and chronic bronchitis status at baseline. Results: Annual change of PD-FEV1 was estimated from a linear model for the two-year study period. Serum C1M and C6M were independent predictors of lung function change (p = 0.007/0.005). Smoking, bronchodilator reversibility, plasma hsCRP and emphysema were also significant predictors. The effect estimate between annual change in PD-FEV1 per one standard deviation (1SD) increase of C1M and C6M was +10.4 mL/yr. and +8.6 mL/yr. C1M, and C6M, had a significant association with baseline FEV1. Conclusion: We demonstrated that markers of tissue turnover were significantly associated with lung function change. These markers may function as prognostic biomarkers and possibly as efficacy biomarkers in clinical trials focusing on lung function change in COPD. Trial registration:NCT00292552 , Retrospectively registered, trial registration in February 2006.

AB - Background: Change in forced expiratory volume in one second (FEV1) is important for defining severity of chronic obstructive pulmonary disease (COPD). Serological neoepitope markers of collagen turnover may predict rate of change in FEV1. Methods: One thousand COPD subjects from the observational, multicentre, three-year ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) study (NCT00292552, trial registration in February 2006) were included. Matrix metalloproteinase (MMP)-generated fragments of collagen type I, and type VI (C1M and C6M) were assessed in month six serum samples. A random-coefficient model with both a random intercept and a random slope was used to test the ability of the markers to predict post-dose bronchodilator FEV1 (PD-FEV1) change over two years adjusting for sex, age, BMI, smoking, bronchodilator reversibility, prior exacerbations, emphysema and chronic bronchitis status at baseline. Results: Annual change of PD-FEV1 was estimated from a linear model for the two-year study period. Serum C1M and C6M were independent predictors of lung function change (p = 0.007/0.005). Smoking, bronchodilator reversibility, plasma hsCRP and emphysema were also significant predictors. The effect estimate between annual change in PD-FEV1 per one standard deviation (1SD) increase of C1M and C6M was +10.4 mL/yr. and +8.6 mL/yr. C1M, and C6M, had a significant association with baseline FEV1. Conclusion: We demonstrated that markers of tissue turnover were significantly associated with lung function change. These markers may function as prognostic biomarkers and possibly as efficacy biomarkers in clinical trials focusing on lung function change in COPD. Trial registration:NCT00292552 , Retrospectively registered, trial registration in February 2006.

KW - COPD

KW - Extracellular matrix

KW - Lung function change

KW - Prognosis

KW - Serological marker

UR - http://www.scopus.com/inward/record.url?scp=85037639407&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85037639407&partnerID=8YFLogxK

U2 - 10.1186/s12890-017-0505-4

DO - 10.1186/s12890-017-0505-4

M3 - Article

VL - 17

JO - BMC Pulmonary Medicine

JF - BMC Pulmonary Medicine

SN - 1471-2466

IS - 1

M1 - 164

ER -