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 - 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, A.
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.
AU - Wanner, A.
N1 - Publisher Copyright:
© 2017 The Author(s).
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
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U2 - 10.1186/s12890-017-0505-4
DO - 10.1186/s12890-017-0505-4
M3 - Article
C2 - 29202744
AN - SCOPUS:85037639407
SN - 1471-2466
VL - 17
JO - BMC Pulmonary Medicine
JF - BMC Pulmonary Medicine
IS - 1
M1 - 164
ER -