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Type IV collagen turnover is predictive of mortality in COPD: a comparison to fibrinogen in a prospective analysis of the ECLIPSE cohort.


ABSTRACT: BACKGROUND:Identifying subjects with chronic obstructive pulmonary disease (COPD) at high risk of exacerbation and mortality is key to aid individual management of COPD. The only FDA approved blood-based drug development biomarker for patients at high risk of mortality, is plasma fibrinogen. In this study, we benchmarked two biomarkers of basement membrane remodeling, a characteristic of COPD, against plasma fibrinogen alone and as a combination. The biomarkers of basement membrane remodeling are two neoepitopes from of the alpha 3 chain of type IV collagen (COL4A3). MATERIALS AND METHODS:COL4A3 degradation was assessed by the biomarkers C4Ma3 and tumstatin (TUM) in year 1 plasma samples in 984 COPD subjects, 95 non-smoking controls and 95 smoking controls from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) cohort. They were measured by competitive ELISA using monoclonal antibodies recognizing two specific MMP-generated cleavage site within COL4A3. The level of fibrinogen was previously assessed in year 1 plasma. RESULTS:In COPD subjects, plasma C4Ma3 levels were significantly correlated with plasma fibrinogen levels (0.389 (P?

SUBMITTER: Ronnow SR 

PROVIDER: S-EPMC6444812 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Type IV collagen turnover is predictive of mortality in COPD: a comparison to fibrinogen in a prospective analysis of the ECLIPSE cohort.

Rønnow Sarah Rank SR   Sand Jannie Marie Bülow JMB   Langholm Lasse Løcke LL   Manon-Jensen Tina T   Karsdal Morten Asser MA   Tal-Singer Ruth R   Miller Bruce E BE   Vestbo Jørgen J   Leeming Diana Julie DJ  

Respiratory research 20190401 1


<h4>Background</h4>Identifying subjects with chronic obstructive pulmonary disease (COPD) at high risk of exacerbation and mortality is key to aid individual management of COPD. The only FDA approved blood-based drug development biomarker for patients at high risk of mortality, is plasma fibrinogen. In this study, we benchmarked two biomarkers of basement membrane remodeling, a characteristic of COPD, against plasma fibrinogen alone and as a combination. The biomarkers of basement membrane remod  ...[more]

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