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Am J Respir Crit Care Med. 2017 Feb 15;195(4):473-481. doi: 10.1164/rccm.201607-1330OC.

Biomarkers Predictive of Exacerbations in the SPIROMICS and COPDGene Cohorts.

Author information

1
1 University of Colorado Anschutz Medical Campus, Aurora, Colorado.
2
2 National Jewish Health, Denver, Colorado.
3
3 Department of Biostatics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
4
4 Department of Medicine, Morehouse School of Medicine, Atlanta, Georgia.
5
5 Marsico Lung Institute/Cystic Fibrosis Research Center, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
6
6 Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, Ann Arbor, Michigan.
7
7 VA Ann Arbor Healthcare System, Ann Arbor, Michigan.
8
8 Division of Pulmonary and Critical Care Medicine, University of Nebraska, Omaha, Nebraska.
9
9 Department of Medicine, Columbia University Medical Center, New York, New York.
10
10 Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, North Carolina.
11
11 Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Utah, Salt Lake City, Utah.
12
12 Division of Pulmonary and Critical Care Medicine, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.
13
13 Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
14
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.
15
15 Department of Medicine, Weill Cornell Medical College, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, New York.

Abstract

RATIONALE:

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.

OBJECTIVES:

To determine the value of adding blood biomarkers to clinical variables to predict exacerbations.

METHODS:

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 FEV1, self-reported gastroesophageal reflux, St. George's Respiratory Questionnaire score, smoking status). We used the Stouffer-Liptak test to combine P values for metaanalysis.

MEASUREMENTS AND MAIN RESULTS:

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 α2-macroglobulin increased predictive value for future severe exacerbations.

CONCLUSIONS:

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.

KEYWORDS:

COPD; biomarker; exacerbation

PMID:
27579823
PMCID:
PMC5378424
DOI:
10.1164/rccm.201607-1330OC
[Indexed for MEDLINE]
Free PMC Article

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