학술논문
Identification of Sputum Biomarkers Predictive of Pulmonary Exacerbations in COPD.
Document Type
Academic Journal
Author
Esther CR Jr; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC. Electronic address: charles_esther@med.unc.edu.; O'Neal WK; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC.; Anderson WH; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC.; Kesimer M; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC.; Ceppe A; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC.; Doerschuk CM; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC.; Alexis NE; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC.; Hastie AT; Department of Internal Medicine, School of Medicine, Wake Forest University, Winston-Salem, NC.; Barr RG; Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY.; Bowler RP; Department of Medicine, National Jewish Health, Denver, CO.; Wells JM; Lung Health Center, Division of Pulmonary Allergy and Critical Care, University of Alabama at Birmingham, Birmingham, AL.; Oelsner EC; Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY.; Comellas AP; Division of Pulmonary, Critical Care and Occupational Medicine, University of Iowa, Iowa City, IA.; Tesfaigzi Y; Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.; Kim V; Pulmonary and Critical Care Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA.; Paulin LM; Department of Medicine and Epidemiology, Dartmouth-Hitchcock Medical Center, Geisel School of Medicine, Hanover, NH.; Cooper CB; Department of Medicine and Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.; Han MK; Division of Pulmonary and Critical Care Medicine, University of Michigan Ann Arbor, Ann Arbor, MI.; Huang YJ; Division of Pulmonary and Critical Care Medicine, University of Michigan Ann Arbor, Ann Arbor, MI.; Labaki WW; Division of Pulmonary and Critical Care Medicine, University of Michigan Ann Arbor, Ann Arbor, MI.; Curtis JL; Division of Pulmonary and Critical Care Medicine, University of Michigan Ann Arbor, Ann Arbor, MI; Medicine Service, VA Ann Arbor Healthcare System, Ann Arbor, MI.; Boucher RC; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Source
Publisher: Elsevier Country of Publication: United States NLM ID: 0231335 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1931-3543 (Electronic) Linking ISSN: 00123692 NLM ISO Abbreviation: Chest Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Improved understanding of the pathways associated with airway pathophysiologic features in COPD will identify new predictive biomarkers and novel therapeutic targets.
Research Question: Which physiologic pathways are altered in the airways of patients with COPD and will predict exacerbations?
Study Design and Methods: We applied a mass spectrometric panel of metabolomic biomarkers related to mucus hydration and inflammation to sputa from the multicenter Subpopulations and Intermediate Outcome Measures in COPD Study. Biomarkers elevated in sputa from patients with COPD were evaluated for relationships to measures of COPD disease severity and their ability to predict future exacerbations.
Results: Sputum supernatants from 980 patients were analyzed: 77 healthy nonsmokers, 341 smokers with preserved spirometry, and 562 patients with COPD (178 with Global Initiative on Chronic Obstructive Lung Disease [GOLD] stage 1 disease, 303 with GOLD stage 2 disease, and 81 with GOLD stage 3 disease) were analyzed. Biomarkers from multiple pathways were elevated in COPD and correlated with sputum neutrophil counts. Among the most significant analytes (false discovery rate, 0.1) were sialic acid, hypoxanthine, xanthine, methylthioadenosine, adenine, and glutathione. Sialic acid and hypoxanthine were associated strongly with measures of disease severity, and elevation of these biomarkers was associated with shorter time to exacerbation and improved prediction models of future exacerbations.
Interpretation: Biomarker evaluation implicated pathways involved in mucus hydration, adenosine metabolism, methionine salvage, and oxidative stress in COPD airway pathophysiologic characteristics. Therapies that target these pathways may be of benefit in COPD, and a simple model adding sputum-soluble phase biomarkers improves prediction of pulmonary exacerbations.
Trial Registry: ClinicalTrials.gov; No.: NCT01969344; URL: www.
Clinicaltrials: gov.
(Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)
Research Question: Which physiologic pathways are altered in the airways of patients with COPD and will predict exacerbations?
Study Design and Methods: We applied a mass spectrometric panel of metabolomic biomarkers related to mucus hydration and inflammation to sputa from the multicenter Subpopulations and Intermediate Outcome Measures in COPD Study. Biomarkers elevated in sputa from patients with COPD were evaluated for relationships to measures of COPD disease severity and their ability to predict future exacerbations.
Results: Sputum supernatants from 980 patients were analyzed: 77 healthy nonsmokers, 341 smokers with preserved spirometry, and 562 patients with COPD (178 with Global Initiative on Chronic Obstructive Lung Disease [GOLD] stage 1 disease, 303 with GOLD stage 2 disease, and 81 with GOLD stage 3 disease) were analyzed. Biomarkers from multiple pathways were elevated in COPD and correlated with sputum neutrophil counts. Among the most significant analytes (false discovery rate, 0.1) were sialic acid, hypoxanthine, xanthine, methylthioadenosine, adenine, and glutathione. Sialic acid and hypoxanthine were associated strongly with measures of disease severity, and elevation of these biomarkers was associated with shorter time to exacerbation and improved prediction models of future exacerbations.
Interpretation: Biomarker evaluation implicated pathways involved in mucus hydration, adenosine metabolism, methionine salvage, and oxidative stress in COPD airway pathophysiologic characteristics. Therapies that target these pathways may be of benefit in COPD, and a simple model adding sputum-soluble phase biomarkers improves prediction of pulmonary exacerbations.
Trial Registry: ClinicalTrials.gov; No.: NCT01969344; URL: www.
Clinicaltrials: gov.
(Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)