Scientific Reports (May 2023)
A blood and bronchoalveolar lavage protein signature of rapid FEV1 decline in smoking-associated COPD
- Katarina M. DiLillo,
- Katy C. Norman,
- Christine M. Freeman,
- Stephanie A. Christenson,
- Neil E. Alexis,
- Wayne H. Anderson,
- Igor Z. Barjaktarevic,
- R. Graham Barr,
- Alejandro P. Comellas,
- Eugene R. Bleecker,
- Richard C. Boucher,
- David J. Couper,
- Gerard J. Criner,
- Claire M. Doerschuk,
- J. Michael Wells,
- MeiLan K. Han,
- Eric A. Hoffman,
- Nadia N. Hansel,
- Annette T. Hastie,
- Robert J. Kaner,
- Jerry A. Krishnan,
- Wassim W. Labaki,
- Fernando J. Martinez,
- Deborah A. Meyers,
- Wanda K. O’Neal,
- Victor E. Ortega,
- Robert Paine,
- Stephen P. Peters,
- Prescott G. Woodruff,
- Christopher B. Cooper,
- Russell P. Bowler,
- Jeffrey L. Curtis,
- Kelly B. Arnold,
- SPIROMICS investigators
Affiliations
- Katarina M. DiLillo
- Department of Biomedical Engineering, University of Michigan
- Katy C. Norman
- Department of Biomedical Engineering, University of Michigan
- Christine M. Freeman
- Research Service, VA Ann Arbor Healthcare System
- Stephanie A. Christenson
- Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California San Francisco
- Neil E. Alexis
- Center for Environmental Medicine, Asthma, and Lung Biology, University of North Carolina at Chapel Hill
- Wayne H. Anderson
- Marsico Lung Institute/Pulmonary and Critical Care Medicine, University of North Carolina at Chapel Hill
- Igor Z. Barjaktarevic
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California Los Angeles
- R. Graham Barr
- Department of Medicine, Columbia University Medical Center
- Alejandro P. Comellas
- Division of Pulmonary, Critical Care and Occupational Medicine, University of Iowa
- Eugene R. Bleecker
- Division of Genetics, Genomics and Precision Medicine, University of Arizona Health Sciences
- Richard C. Boucher
- Marsico Lung Institute/Cystic Fibrosis Research Center, Department of Medicine, University of North Carolina at Chapel Hill
- David J. Couper
- Collaborative Studies Coordinating Center, Department of Biostatistics, University of North Carolina at Chapel Hill
- Gerard J. Criner
- Department of Thoracic Medicine and Surgery, Temple University
- Claire M. Doerschuk
- Marsico Lung Institute/Cystic Fibrosis Research Center, Department of Medicine, University of North Carolina at Chapel Hill
- J. Michael Wells
- Department of Medicine, University of Alabama at Birmingham
- MeiLan K. Han
- Division of Pulmonary & Critical Care Medicine, University of Michigan
- Eric A. Hoffman
- Department of Radiology, University of Iowa
- Nadia N. Hansel
- Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine
- Annette T. Hastie
- Department of Internal Medicine, Wake Forest School of Medicine, Atrium Health
- Robert J. Kaner
- Department of Medicine, Weill Cornell Medical Center
- Jerry A. Krishnan
- Division of Pulmonary, Critical Care, Sleep and Allergy, University of Illinois at Chicago
- Wassim W. Labaki
- Division of Pulmonary & Critical Care Medicine, University of Michigan
- Fernando J. Martinez
- Department of Medicine, Weill Cornell Medical Center
- Deborah A. Meyers
- Division of Genetics, Genomics and Precision Medicine, University of Arizona Health Sciences
- Wanda K. O’Neal
- Marsico Lung Institute/Cystic Fibrosis Research Center, Department of Medicine, University of North Carolina at Chapel Hill
- Victor E. Ortega
- Department of Internal Medicine, Division of Respiratory Medicine, Mayo Clinic
- Robert Paine
- Division of Respiratory, Critical Care, and Occupational Pulmonary Medicine, University of Utah
- Stephen P. Peters
- Department of Internal Medicine, Wake Forest School of Medicine, Atrium Health
- Prescott G. Woodruff
- Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California San Francisco
- Christopher B. Cooper
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California Los Angeles
- Russell P. Bowler
- Division of Pulmonary and Critical Care, National Jewish Health
- Jeffrey L. Curtis
- Division of Pulmonary & Critical Care Medicine, University of Michigan
- Kelly B. Arnold
- Department of Biomedical Engineering, University of Michigan
- SPIROMICS investigators
- DOI
- https://doi.org/10.1038/s41598-023-32216-0
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 14
Abstract
Abstract Accelerated 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.
