Dynamic and prognostic proteomic associations with FEV 1 decline in chronic obstructive pulmonary disease

Lisa Ruvuna; Kahkeshan Hijazi; Daniel E. Guzman; Claire Guo; Joseph Loureiro; Edward Khokhlovich; Melody Morris; Ma’en Obeidat; Katherine A. Pratte; Katarina M. DiLillo; Sunita Sharma; Katerina Kechris; Antonio Anzueto; Igor Barjaktarevic; Eugene R. Bleecker; Richard Casaburi; Alejandro Comellas; Christopher B. Cooper; Dawn L. DeMeo; Marilyn Foreman; Eric L. Flenaugh; MeiLan K. Han; Nicola A. Hanania; Craig P. Hersh; Jerry A. Krishnan; Wassim W. Labaki; Fernando J. Martinez; Wanda K. O’Neal; Robert Paine; Stephen P. Peters; Prescott G. Woodruff; J Michael Wells; Christine H. Wendt; Kelly B. Arnold; R. Graham Barr; Jeffrey L. Curtis; Debby Ngo; Russell P. Bowler

doi:10.1101/2024.08.07.24311507

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Dynamic and prognostic proteomic associations with FEV 1 decline in chronic obstructive pulmonary disease

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Dynamic and prognostic proteomic associations with FEV 1 decline in chronic obstructive pulmonary disease

Lisa Ruvuna, Kahkeshan Hijazi, Daniel E. Guzman, Claire Guo, Joseph Loureiro, Edward Khokhlovich, Melody Morris, Ma’en Obeidat, Katherine A. Pratte, Katarina M. DiLillo, …

medRxiv

Cold Spring Harbor Laboratory

08/08/2024

DOI: 10.1101/2024.08.07.24311507

PMCID: PMC11326337

PMID: 39148837

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https://doi.org/10.1101/2024.08.07.24311507View

Preprint (Author's original) This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

Rationale: Identification and validation of circulating biomarkers for lung function decline in COPD remains an unmet need. Objective: Identify prognostic and dynamic plasma protein biomarkers of COPD progression. Methods: We measured plasma proteins using SomaScan from two COPD-enriched cohorts, the Subpopulations and Intermediate Outcomes Measures in COPD Study (SPIROMICS) and Genetic Epidemiology of COPD (COPDGene), and one population-based cohort, Multi-Ethnic Study of Atherosclerosis (MESA) Lung. Using SPIROMICS as a discovery cohort, linear mixed models identified baseline proteins that predicted future change in FEV1 (prognostic model) and proteins whose expression changed with change in lung function (dynamic model). Findings were replicated in COPDGene and MESA-Lung. Using the COPD-enriched cohorts, Gene Set Enrichment Analysis (GSEA) identified proteins shared between COPDGene and SPIROMICS. Metascape identified significant associated pathways. Measurements and main results: The prognostic model found 7 significant proteins in common (p < 0.05) among all 3 cohorts. After applying false discovery rate (adjusted p < 0.2), leptin remained significant in all three cohorts and growth hormone receptor remained significant in the two COPD cohorts. Elevated baseline levels of leptin and growth hormone receptor were associated with slower rate of decline in FEV1. Twelve proteins were nominally but not FDR significant in the dynamic model and all were distinct from the prognostic model. Metascape identified several immune related pathways unique to prognostic and dynamic proteins. Conclusion: We identified leptin as the most reproducible COPD progression biomarker. The difference between prognostic and dynamic proteins suggests disease activity signatures may be different from prognosis signatures.

Disease Progression

Proteomics

Spirometry

Details

Title: Subtitle: Dynamic and prognostic proteomic associations with FEV 1 decline in chronic obstructive pulmonary disease
Creators: Lisa Ruvuna - University of Colorado Denver
Kahkeshan Hijazi - Novartis (United States)
Daniel E. Guzman - Columbia University Irving Medical Center
Claire Guo - National Jewish Health
Joseph Loureiro - Novartis (United States)
Edward Khokhlovich - Novartis (United States)
Melody Morris - Novartis (United States)
Ma’en Obeidat - Novartis (United States)
Katherine A. Pratte - National Jewish Health
Katarina M. DiLillo - University of Michigan
Sunita Sharma - University of Colorado Denver
Katerina Kechris - University of Colorado Anschutz Medical Campus
Antonio Anzueto - The University of Texas at San Antonio Health Science Center
Igor Barjaktarevic - University of California, Los Angeles
Eugene R. Bleecker - Mayo Clinic in Arizona
Richard Casaburi - The Lundquist Institute
Alejandro Comellas - University of Iowa
Christopher B. Cooper - University of California, Los Angeles
Dawn L. DeMeo - Brigham and Women's Hospital
Marilyn Foreman - Morehouse School of Medicine
Eric L. Flenaugh - Morehouse School of Medicine
MeiLan K. Han - University of Michigan
Nicola A. Hanania - Baylor College of Medicine
Craig P. Hersh - Brigham and Women's Hospital
Jerry A. Krishnan - University of Illinois Chicago
Wassim W. Labaki - University of Michigan
Fernando J. Martinez - Cornell University
Wanda K. O’Neal - University of North Carolina at Chapel Hill
Robert Paine - University of Utah
Stephen P. Peters - Wake Forest University
Prescott G. Woodruff - University of California, San Francisco
J Michael Wells - University of Alabama at Birmingham
Christine H. Wendt - VA Ann Arbor Healthcare System
Kelly B. Arnold - University of Michigan
R. Graham Barr - Columbia University Irving Medical Center
Jeffrey L. Curtis - VA Ann Arbor Healthcare System
Debby Ngo - Novartis (United States)
Russell P. Bowler - Cleveland Clinic
Resource Type: Preprint
Publication Details: medRxiv
DOI: 10.1101/2024.08.07.24311507
PMID: 39148837
PMCID: PMC11326337
Publisher: Cold Spring Harbor Laboratory
Language: English
Date posted: 08/08/2024
Academic Unit: Pulmonary, Critical Care, and Occupational Medicine; Psychiatry; ICTS; Internal Medicine
Record Identifier: 9984697360102771

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