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A blood and bronchoalveolar lavage protein signature of rapid FEV1 decline in smoking-associated COPD
Journal article   Open access   Peer reviewed

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, …
Scientific reports, Vol.13(1), 8228
05/22/2023
DOI: 10.1038/s41598-023-32216-0
PMCID: PMC10203309
PMID: 37217548
url
https://doi.org/10.1038/s41598-023-32216-0View
Published (Version of record) Open Access

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 (FEV 1 ) 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 (FEV 1 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.
Systems Biology Chronic obstructive pulmonary disease Proteome informatics

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