Biomarkers predictive of exacerbations in the SPIROMICS and COPDGene cohorts

Jason D. Keene, 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, Mei Lan K. Han, Robert Paine, Fernando J. Martinez, Russell P. Bowler, Wanda K. O'Neal

Research output: Contribution to journalArticle

  • 12 Citations

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.

LanguageEnglish (US)
Pages473-481
Number of pages9
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume195
Issue number4
DOIs
StatePublished - Feb 15 2017

Fingerprint

Chronic Obstructive Pulmonary Disease
Cohort Studies
Biomarkers
Outcome Assessment (Health Care)
Gastroesophageal Reflux
Disease Progression
Decorin
Macroglobulins
Molecular Epidemiology
Health
Health Care Costs
Hospital Emergency Service
Blood Proteins
Adrenal Cortex Hormones
Hospitalization
Smoking
Oxygen
Anti-Bacterial Agents
Mortality
Therapeutics

Keywords

  • Biomarker
  • COPD
  • Exacerbation

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Biomarkers predictive of exacerbations in the SPIROMICS and COPDGene cohorts. / Keene, Jason D.; Jacobson, Sean; Kechris, Katerina; Kinney, Gregory L.; Foreman, Marilyn G.; Doerschuk, Claire M.; Make, Barry J.; Curtis, Jeffrey L.; Rennard, Stephen I.; Barr, R. Graham; Bleecker, Eugene R.; Kanner, Richard E.; Kleerup, Eric C.; Hansel, Nadia N.; Woodruff, Prescott G.; Han, Mei Lan K.; Paine, Robert; Martinez, Fernando J.; Bowler, Russell P.; O'Neal, Wanda K.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 195, No. 4, 15.02.2017, p. 473-481.

Research output: Contribution to journalArticle

Keene, JD, Jacobson, S, Kechris, K, Kinney, GL, Foreman, MG, Doerschuk, CM, Make, BJ, Curtis, JL, Rennard, SI, Barr, RG, Bleecker, ER, Kanner, RE, Kleerup, EC, Hansel, NN, Woodruff, PG, Han, MLK, Paine, R, Martinez, FJ, Bowler, RP & O'Neal, WK 2017, 'Biomarkers predictive of exacerbations in the SPIROMICS and COPDGene cohorts' American Journal of Respiratory and Critical Care Medicine, vol 195, no. 4, pp. 473-481. DOI: 10.1164/rccm.201607-1330OC
Keene, Jason D. ; Jacobson, Sean ; Kechris, Katerina ; Kinney, Gregory L. ; Foreman, Marilyn G. ; Doerschuk, Claire M. ; Make, Barry J. ; Curtis, Jeffrey L. ; Rennard, Stephen I. ; Barr, R. Graham ; Bleecker, Eugene R. ; Kanner, Richard E. ; Kleerup, Eric C. ; Hansel, Nadia N. ; Woodruff, Prescott G. ; Han, Mei Lan K. ; Paine, Robert ; Martinez, Fernando J. ; Bowler, Russell P. ; O'Neal, Wanda K./ Biomarkers predictive of exacerbations in the SPIROMICS and COPDGene cohorts. In: American Journal of Respiratory and Critical Care Medicine. 2017 ; Vol. 195, No. 4. pp. 473-481
@article{ed8346290a7749b597c4820900d984fe,
title = "Biomarkers predictive of exacerbations in the SPIROMICS and COPDGene cohorts",
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 = "Biomarker, COPD, Exacerbation",
author = "Keene, {Jason D.} and Sean Jacobson and Katerina Kechris and Kinney, {Gregory L.} and Foreman, {Marilyn G.} and Doerschuk, {Claire M.} and Make, {Barry J.} and Curtis, {Jeffrey L.} and Rennard, {Stephen I.} and Barr, {R. Graham} and Bleecker, {Eugene R.} and Kanner, {Richard E.} and Kleerup, {Eric C.} and Hansel, {Nadia N.} and Woodruff, {Prescott G.} and Han, {Mei Lan K.} and Robert Paine and Martinez, {Fernando J.} and Bowler, {Russell P.} and O'Neal, {Wanda K.}",
year = "2017",
month = "2",
day = "15",
doi = "10.1164/rccm.201607-1330OC",
language = "English (US)",
volume = "195",
pages = "473--481",
journal = "American Journal of Respiratory and Critical Care Medicine",
issn = "1073-449X",
publisher = "American Thoracic Society",
number = "4",

}

TY - JOUR

T1 - Biomarkers predictive of exacerbations in the SPIROMICS and COPDGene cohorts

AU - Keene,Jason D.

AU - Jacobson,Sean

AU - Kechris,Katerina

AU - Kinney,Gregory L.

AU - Foreman,Marilyn G.

AU - Doerschuk,Claire M.

AU - Make,Barry J.

AU - Curtis,Jeffrey L.

AU - Rennard,Stephen I.

AU - Barr,R. Graham

AU - Bleecker,Eugene R.

AU - Kanner,Richard E.

AU - Kleerup,Eric C.

AU - Hansel,Nadia N.

AU - Woodruff,Prescott G.

AU - Han,Mei Lan K.

AU - Paine,Robert

AU - Martinez,Fernando J.

AU - Bowler,Russell P.

AU - O'Neal,Wanda K.

PY - 2017/2/15

Y1 - 2017/2/15

N2 - 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.

AB - 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.

KW - Biomarker

KW - COPD

KW - Exacerbation

UR - http://www.scopus.com/inward/record.url?scp=85014916073&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85014916073&partnerID=8YFLogxK

U2 - 10.1164/rccm.201607-1330OC

DO - 10.1164/rccm.201607-1330OC

M3 - Article

VL - 195

SP - 473

EP - 481

JO - American Journal of Respiratory and Critical Care Medicine

T2 - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

SN - 1073-449X

IS - 4

ER -