Author:
DiLillo Katarina M.,Norman Katy C.,Freeman Christine M.,Christenson Stephanie A.,Alexis Neil E.,Anderson Wayne H.,Barjaktarevic Igor Z.,Barr R. Graham,Comellas Alejandro P.,Bleecker Eugene R.,Boucher Richard C.,Couper David J.,Criner Gerard J.,Doerschuk Claire M.,Wells J. Michael,Han MeiLan K.,Hoffman Eric A.,Hansel Nadia N.,Hastie Annette T.,Kaner Robert J.,Krishnan Jerry A.,Labaki Wassim W.,Martinez Fernando J.,Meyers Deborah A.,O’Neal Wanda K.,Ortega Victor E.,Paine Robert,Peters Stephen P.,Woodruff Prescott G.,Cooper Christopher B.,Bowler Russell P.,Curtis Jeffrey L.,Arnold Kelly B.,
Abstract
AbstractAccelerated progression of chronic obstructive pulmonary disease (COPD) is associated with increased risks of hospitalization and death. Prognostic insights into mechanisms and markers of progression could facilitate development of disease-modifying therapies. Although individual biomarkers exhibit some predictive value, performance is modest and their univariate nature limits network-level insights. To overcome these limitations and gain insights into early pathways associated with rapid progression, we measured 1305 peripheral blood and 48 bronchoalveolar lavage proteins in individuals with COPD [n = 45, mean initial forced expiratory volume in one second (FEV1) 75.6 ± 17.4% predicted]. We applied a data-driven analysis pipeline, which enabled identification of protein signatures that predicted individuals at-risk for accelerated lung function decline (FEV1 decline ≥ 70 mL/year) ~ 6 years later, with high accuracy. Progression signatures suggested that early dysregulation in elements of the complement cascade is associated with accelerated decline. Our results propose potential biomarkers and early aberrant signaling mechanisms driving rapid progression in COPD.
Publisher
Springer Science and Business Media LLC
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