Biomarkers Predictive of Exacerbations in the SPIROMICS and COPDGene Cohorts.

MS#: 
MS026
TitleBiomarkers Predictive of Exacerbations in the SPIROMICS and COPDGene Cohorts.
Publication TypePublication
Year2017
AuthorsKeene JD, Jacobson S, Kechris K, Kinney GL, Foreman MG, Doerschuk CM, Make BJ, Curtis JL, Rennard SI, R Barr G, Bleecker ER, Kanner RE, Kleerup EC, Hansel NN, Woodruff PG, Han MK, Paine R, Martinez FJ, Bowler RP, O'Neal WK
Corporate AuthorsCOPDGene and SPIROMICS Investigators ‡
JournalAm J Respir Crit Care Med
Volume195
Issue4
Pagination473-481
Date Published2017 02 15
ISSN1535-4970
Keywordsbiomarkers, Disease Progression, Female, Forced Expiratory Volume, Gastroesophageal Reflux, Humans, Male, Middle Aged, Predictive Value of Tests, Proportional Hazards Models, Prospective Studies, Pulmonary Disease, Chronic Obstructive, Regression Analysis, Retrospective Studies, Severity of Illness Index, smoking
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 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.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 α-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.

DOI10.1164/rccm.201607-1330OC
Alternate JournalAm. J. Respir. Crit. Care Med.
PubMed ID27579823
PubMed Central IDPMC5378424
Grant ListR01 HL089897 / HL / NHLBI NIH HHS / United States
HHSN268200900019C / HL / NHLBI NIH HHS / United States
HHSN268200900009C / WH / WHI NIH HHS / United States
S10 OD018526 / OD / NIH HHS / United States
U01 HL089897 / HL / NHLBI NIH HHS / United States
R01 HL095432 / HL / NHLBI NIH HHS / United States
R01 HL089856 / HL / NHLBI NIH HHS / United States
R01 HL126838 / HL / NHLBI NIH HHS / United States
U01 HL089856 / HL / NHLBI NIH HHS / United States
HHSN268200900015C / HL / NHLBI NIH HHS / United States
HHSN268200900016C / HL / NHLBI NIH HHS / United States
I01 CX000911 / CX / CSRD VA / United States
U01 HL137880 / HL / NHLBI NIH HHS / United States
HHSN268200900018C / HL / NHLBI NIH HHS / United States
HHSN268200900017C / HL / NHLBI NIH HHS / United States
HHSN268200900020C / HL / NHLBI NIH HHS / United States
HHSN268200900013C / HL / NHLBI NIH HHS / United States
HHSN268200900014C / HL / NHLBI NIH HHS / United States
U54 MD008149 / MD / NIMHD NIH HHS / United States
Manuscript Lead/Corresponding Author Affiliation: 
Clinical Center: Denver (National Jewish Health)
ECI: 
Manuscript Status: 
Published