Biomarkers Predictive of Exacerbations in the SPIROMICS and COPDGene Cohorts

Sean Jacobson; Katerina Kechris; Gregory L Kinney; Marilyn G Foreman; Claire M Doerschuk; Barry J Make; Jeffrey L Curtis; Stephen I Rennard; R Graham Barr; Eugene R Bleecker; Richard E Kanner; Eric C Kleerup; Nadia N Hansel; Prescott G Woodruff; MeiLan K Han; Robert Paine III; Fernando J Martinez; Russell P Bowler; Wanda K O'Neal; COPDGene Investigators; SPIROMICS Investigators

doi:10.1164/rccm.201607-1330OC

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Biomarkers Predictive of Exacerbations in the SPIROMICS and COPDGene Cohorts

Journal article

Open access

Peer reviewed

Biomarkers Predictive of Exacerbations in the SPIROMICS and COPDGene Cohorts

Sean Jacobson, Katerina Kechris, Gregory L Kinney, Marilyn G Foreman, Claire M Doerschuk, Barry J Make, Jeffrey L Curtis, Stephen I Rennard, R Graham Barr, Eugene R Bleecker, …

American journal of respiratory and critical care medicine, Vol.195(4), pp.473-481

02/15/2017

DOI: 10.1164/rccm.201607-1330OC

PMCID: PMC5378424

PMID: 27579823

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Abstract

Chronic obstructive pulmonary disease exacerbations are associated with disease progression, higher healthcare cost, and increased mortality. Published predictors of future exacerbations include previous exacerbation, airflow obstruction, poor overall health, home oxygen use, and gastroesophageal reflux. To determine the value of adding blood biomarkers to clinical variables to predict exacerbations. Subjects from the SPIROMICS (Subpopulations and Intermediate Outcomes Measures in COPD Study) (n = 1,544) and COPDGene (Genetic Epidemiology of COPD) (n = 602) cohorts had 90 plasma or serum candidate proteins measured on study entry using Myriad-RBM multiplex panels. We defined total exacerbations as subject-reported worsening in respiratory health requiring therapy with corticosteroids and/or antibiotics, and severe exacerbations as those leading to hospitalizations or emergency room visits. We assessed retrospective exacerbations during the 12 months before enrollment and then documented prospective exacerbations in each cohort. Exacerbations were modeled for biomarker associations with negative binomial regression including clinical covariates (age, sex, percent predicted FEV , self-reported gastroesophageal reflux, St. George's Respiratory Questionnaire score, smoking status). We used the Stouffer-Liptak test to combine P values for metaanalysis. Between the two cohorts, 3,471 total exacerbations (1,044 severe) were reported. We identified biomarkers within each cohort that were significantly associated with a history of exacerbation and with a future exacerbation, but there was minimal replication between the cohorts. Although established clinical features were predictive of exacerbations, of the blood biomarkers only decorin and α -macroglobulin increased predictive value for future severe exacerbations. Blood biomarkers were significantly associated with the occurrence of exacerbations but were not robust between cohorts and added little to the predictive value of clinical covariates for exacerbations.

Severity of Illness Index

Smoking - adverse effects

Predictive Value of Tests

Prospective Studies

Smoking - blood

Humans

Middle Aged

Gastroesophageal Reflux - etiology

Proportional Hazards Models

Male

Biomarkers - blood

Pulmonary Disease, Chronic Obstructive - complications

Disease Progression

Forced Expiratory Volume

Regression Analysis

Pulmonary Disease, Chronic Obstructive - blood

Female

Retrospective Studies

Details

Title: Subtitle: Biomarkers Predictive of Exacerbations in the SPIROMICS and COPDGene Cohorts
Creators: Sean Jacobson - 2 National Jewish Health, Denver, Colorado
Katerina Kechris - 3 Department of Biostatics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado
Gregory L Kinney - 3 Department of Biostatics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado
Marilyn G Foreman - 4 Department of Medicine, Morehouse School of Medicine, Atlanta, Georgia
Claire M Doerschuk - 5 Marsico Lung Institute/Cystic Fibrosis Research Center, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
Barry J Make - 2 National Jewish Health, Denver, Colorado
Jeffrey L Curtis - 7 VA Ann Arbor Healthcare System, Ann Arbor, Michigan
Stephen I Rennard - 8 Division of Pulmonary and Critical Care Medicine, University of Nebraska, Omaha, Nebraska
R Graham Barr - 9 Department of Medicine, Columbia University Medical Center, New York, New York
Eugene R Bleecker - 10 Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, North Carolina
Richard E Kanner - 11 Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Utah, Salt Lake City, Utah
Eric C Kleerup - 12 Division of Pulmonary and Critical Care Medicine, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California
Nadia N Hansel - 13 Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
Prescott G Woodruff - 14 Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine and Cardiovascular Research Institute, University of California San Francisco, School of Medicine, San Francisco, California; and
MeiLan K Han - 6 Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, Ann Arbor, Michigan
Robert Paine III - 11 Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Utah, Salt Lake City, Utah
Fernando J Martinez - 15 Department of Medicine, Weill Cornell Medical College, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, New York
Russell P Bowler - 2 National Jewish Health, Denver, Colorado
Wanda K O'Neal - 5 Marsico Lung Institute/Cystic Fibrosis Research Center, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
COPDGene Investigators
SPIROMICS Investigators
Contributors: Eric A Hoffman (Contributor) - University of Iowa, Radiology
Resource Type: Journal article
Publication Details: American journal of respiratory and critical care medicine, Vol.195(4), pp.473-481
DOI: 10.1164/rccm.201607-1330OC
PMID: 27579823
PMCID: PMC5378424
NLM abbreviation: Am J Respir Crit Care Med
ISSN: 1073-449X
eISSN: 1535-4970
Publisher: United States
Grant note: HHSN268200900017C / NHLBI NIH HHS HHSN268200900019C / NHLBI NIH HHS HHSN268200900020C / NHLBI NIH HHS U01 HL089897 / NHLBI NIH HHS U01 HL137880 / NHLBI NIH HHS R01 HL089856 / NHLBI NIH HHS HHSN268200900015C / NHLBI NIH HHS I01 CX000911 / CSRD VA HHSN268200900013C / NHLBI NIH HHS R01 HL126838 / NHLBI NIH HHS R01 HL095432 / NHLBI NIH HHS U01 HL089856 / NHLBI NIH HHS HHSN268200900016C / NHLBI NIH HHS HHSN268200900018C / NHLBI NIH HHS HHSN268200900014C / NHLBI NIH HHS S10 OD018526 / NIH HHS HHSN268200900009C / WHI NIH HHS R01 HL089897 / NHLBI NIH HHS U54 MD008149 / NIMHD NIH HHS
Language: English
Date published: 02/15/2017
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Radiology; Psychiatry; Internal Medicine
Record Identifier: 9984051548102771

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