Jason D Keene1, Sean Jacobson2, Katerina Kechris3, Gregory L Kinney3, Marilyn G Foreman4, Claire M Doerschuk5, Barry J Make2, Jeffrey L Curtis6,7, Stephen I Rennard8, R Graham Barr9, Eugene R Bleecker10, Richard E Kanner11, Eric C Kleerup12, Nadia N Hansel13, Prescott G Woodruff14, MeiLan K Han6, Robert Paine11, Fernando J Martinez15, Russell P Bowler2, Wanda K O'Neal5. 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.
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.
Authors: Robert Marcun; Ivan Stankovic; Radosav Vidakovic; Jerneja Farkas; Sasa Kadivec; Biljana Putnikovic; Ivan Ilic; Aleksandar N Neskovic; Mitja Lainscak Journal: Intern Emerg Med Date: 2015-09-30 Impact factor: 3.397
Authors: Elizabeth A Regan; David A Lynch; Douglas Curran-Everett; Jeffrey L Curtis; John H M Austin; Philippe A Grenier; Hans-Ulrich Kauczor; William C Bailey; Dawn L DeMeo; Richard H Casaburi; Paul Friedman; Edwin J R Van Beek; John E Hokanson; Russell P Bowler; Terri H Beaty; George R Washko; MeiLan K Han; Victor Kim; Song Soo Kim; Kunihiro Yagihashi; Lacey Washington; Charlene E McEvoy; Clint Tanner; David M Mannino; Barry J Make; Edwin K Silverman; James D Crapo Journal: JAMA Intern Med Date: 2015-09 Impact factor: 21.873
Authors: Brendan J Carolan; Yu-il Kim; André A Williams; Katerina Kechris; Sharon Lutz; Nichole Reisdorph; Russell P Bowler Journal: Am J Respir Crit Care Med Date: 2013-09-01 Impact factor: 21.405
Authors: Brendan J Carolan; Grant Hughes; Jarrett Morrow; Craig P Hersh; Wanda K O'Neal; Stephen Rennard; Sreekumar G Pillai; Paula Belloni; Debra A Cockayne; Alejandro P Comellas; Meilan Han; Rachel L Zemans; Katerina Kechris; Russell P Bowler Journal: Respir Res Date: 2014-10-12
Authors: Wassim W Labaki; Meng Xia; Susan Murray; Jeffrey L Curtis; R Graham Barr; Surya P Bhatt; Eugene R Bleecker; Nadia N Hansel; Christopher B Cooper; Mark T Dransfield; J Michael Wells; Eric A Hoffman; Richard E Kanner; Robert Paine; Victor E Ortega; Stephen P Peters; Jerry A Krishnan; Russell P Bowler; David J Couper; Prescott G Woodruff; Fernando J Martinez; Carlos H Martinez; MeiLan K Han Journal: Respir Med Date: 2018-06-05 Impact factor: 3.415
Authors: Rola Harmouche; Samuel Y Ash; Rachel K Putman; Gary M Hunninghake; Ruben San Jose Estepar; Fernando J Martinez; Augustine M Choi; David A Lynch; Hiroto Hatabu; MeiLan K Han; Russell P Bowler; Ravi Kalhan; Ivan O Rosas; George R Washko; Raul San Jose Estepar Journal: Chest Date: 2019-06-22 Impact factor: 9.410
Authors: Diego J Maselli; Surya P Bhatt; Antonio Anzueto; Russell P Bowler; Dawn L DeMeo; Alejandro A Diaz; Mark T Dransfield; Ashraf Fawzy; Marilyn G Foreman; Nicola A Hanania; Craig P Hersh; Victor Kim; Gregory L Kinney; Nirupama Putcha; Emily S Wan; J Michael Wells; Gloria E Westney; Kendra A Young; Edwin K Silverman; MeiLan K Han; Barry J Make Journal: Chest Date: 2019-05-30 Impact factor: 9.410
Authors: Laura M Raffield; Hong Dang; Katherine A Pratte; Sean Jacobson; Lucas A Gillenwater; Elizabeth Ampleford; Igor Barjaktarevic; Patricia Basta; Clary B Clish; Alejandro P Comellas; Elaine Cornell; Jeffrey L Curtis; Claire Doerschuk; Peter Durda; Claire Emson; Christine M Freeman; Xiuqing Guo; Annette T Hastie; Gregory A Hawkins; Julio Herrera; W Craig Johnson; Wassim W Labaki; Yongmei Liu; Brett Masters; Michael Miller; Victor E Ortega; George Papanicolaou; Stephen Peters; Kent D Taylor; Stephen S Rich; Jerome I Rotter; Paul Auer; Alex P Reiner; Russell P Tracy; Debby Ngo; Robert E Gerszten; Wanda K O'Neal; Russell P Bowler Journal: Proteomics Date: 2020-06 Impact factor: 3.984
Authors: Elizabeth A Regan; Craig P Hersh; Peter J Castaldi; Dawn L DeMeo; Edwin K Silverman; James D Crapo; Russell P Bowler Journal: Am J Respir Cell Mol Biol Date: 2019-08 Impact factor: 6.914
Authors: Suresh Garudadri; Prescott G Woodruff; MeiLan K Han; Jeffrey L Curtis; R Graham Barr; Eugene R Bleecker; Russell P Bowler; Alejandro Comellas; Christopher B Cooper; Gerard Criner; Mark T Dransfield; Nadia N Hansel; Robert Paine; Jerry A Krishnan; Stephen P Peters; Annette T Hastie; Fernando J Martinez; Wanda K O'Neal; David J Couper; Neil E Alexis; Stephanie A Christenson Journal: Chest Date: 2019-01-23 Impact factor: 9.410
Authors: Russell P Bowler; Nadia N Hansel; Sean Jacobson; R Graham Barr; Barry J Make; MeiLan K Han; Wanda K O'Neal; Elizabeth C Oelsner; Richard Casaburi; Igor Barjaktarevic; Chris Cooper; Marilyn Foreman; Robert A Wise; Dawn L DeMeo; Edwin K Silverman; William Bailey; Kathleen F Harrington; Prescott G Woodruff; M Bradley Drummond Journal: J Gen Intern Med Date: 2017-09-07 Impact factor: 5.128