Journal article
Identification of Sputum Biomarkers Predictive of Pulmonary Exacerbations in COPD
Chest, Vol.161(5), pp.1239-1249
05/01/2022
DOI: 10.1016/j.chest.2021.10.049
PMCID: PMC9131049
PMID: 34801592
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.
Details
- Title: Subtitle
- Identification of Sputum Biomarkers Predictive of Pulmonary Exacerbations in COPD
- Creators
- Charles R. Esther - University of North Carolina at Chapel HillWanda K. O'Neal - University of North Carolina at Chapel HillWayne H. Anderson - University of North Carolina at Chapel HillAgathe Ceppe - University of North Carolina at Chapel HillClaire M. Doerschuk - University of North Carolina at Chapel HillNeil E. Alexis - University of North Carolina at Chapel HillAnnette T. Hastie - Wake Forest UniversityR. Graham Barr - Columbia UniversityRussell P. Bowler - National Jewish HealthJ. Michael Wells - University of Alabama at BirminghamElizabeth C. Oelsner - Columbia UniversityAlejandro P. Comellas - University of IowaYohannes Tesfaigzi - Brigham and Women's HospitalVictor Kim - Temple UniversityLaura M. Paulin - Dartmouth–Hitchcock Medical CenterChristopher B. Cooper - University of California, Los AngelesMeiLan K. Han - University of Michigan–Ann ArborYvonne J. Huang - University of Michigan–Ann ArborWassim W. Labaki - University of Michigan–Ann ArborJeffrey L. Curtis - VA Ann Arbor Healthcare SystemRichard C. Boucher - University of North Carolina at Chapel HillSubpopulations and Intermediate Outcome Measures in COPD Study
- Contributors
- Eric A Hoffman (Contributor) - University of Iowa, Radiology
- Resource Type
- Journal article
- Publication Details
- Chest, Vol.161(5), pp.1239-1249
- Publisher
- Elsevier
- DOI
- 10.1016/j.chest.2021.10.049
- PMID
- 34801592
- PMCID
- PMC9131049
- ISSN
- 0012-3692
- eISSN
- 1931-3543
- Number of pages
- 11
- Grant note
- HHSN268200900013C; HHSN268200900014C; HHSN268200900015C; HHSN268200900016C; HHSN268200900017C; HHSN268200900018C; HHSN268200900019C; HHSN268200900020C; U01 HL137880; U24 HL141762 / SPIROMICS - National Heart, Lung, and Blood Institute of the National Institutes of Health UH3-HL123645; P01-HL108808; P30-DK065988; P01-HL110873; P50-HL107168; R01-HL136961; R01-HL136961-01S1; P30-ES10126 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 05/01/2022
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Pulmonary, Critical Care, and Occupational Medicine; ICTS; Internal Medicine
- Record Identifier
- 9984318718602771
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