Chest
COPD: Original ResearchIdentification of Sputum Biomarkers Predictive of Pulmonary Exacerbations in COPD
Graphical Abstract
Section snippets
Patients
Patients represented a subset of participants in the previously described SPIROMICS cohort8 that included groups of healthy nonsmoking patients and patients with at least a 20-pack-year smoking history. Smokers included those with preserved spirometry as well as those with COPD grouped using Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria (GOLD stages 1-3).9 Target sample size of 980 patients was chosen to include all patients whose sputum mucin concentrations were
Results
We analyzed cell-free sputum supernatants from 980 patients (Table 1), including samples from 77 healthy nonsmokers, 341 ever smokers with preserved spirometry, and 562 patients with COPD (178 with GOLD stage 1 disease, 303 with GOLD stage 2 disease, and 81 with GOLD stage 3 disease). From the biomarker panel, we found that six metabolites were altered significantly in patients with COPD relative to healthy nonsmokers at a false discovery rate of 0.10: the mucin marker sialic acid, the
Discussion
We identified sputum biomarkers that were elevated in the airways of patients with COPD and showed significant relationships to established measures of COPD disease severity, including airway neutrophilic inflammation, GOLD status, bronchitis, and pulmonary exacerbations. The identities of these and related metabolites implicate several physiologic pathways in COPD pathogenesis, including mucus hydration, adenosine metabolism, and methionine salvage. These pathways can serve as both biomarkers
Interpretation
We identified several physiologic pathways altered in the airways of patients with COPD and associated with markers of disease severity, with the strongest relationships to metabolite biomarkers of mucus hydration and adenosine metabolism. These findings confirm previously demonstrated associations in COPD and identify new pathways. Although further validation is required, measurement of these sputum metabolites could provide a straightforward means to assess disease severity, to identify those
Acknowledgments
Author contributions: C. R. E. is responsible for the content of this manuscript. C. R. E. obtained funding, performed the analyses, wrote the manuscript, and is the guarantor of the manuscript. W. K. O., M. K., W. H. A., A. C., and R. C. B. assisted with data analysis and edited the manuscript. C. M. D., A. T. H., R. G. B., R. P. B., J. M. W., E. C. O., A. P. C., Y. T., V. K., L. M. P., C. B. C., M. K. H., Y. J. H., W. W. L., and J. L. C. contributed to SPIROMICS and edited the manuscript.
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FUNDING/SUPPORT: This work was supported by SPIROMICS, which was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health [Grants HHSN268200900013C, HHSN268200900014C, HHSN268200900015C, HHSN268200900016C, HHSN268200900017C, HHSN268200900018C, HHSN268200900019C, HHSN268200900020C, U01 HL137880, and U24 HL141762]. C. R. E. was supported by the National Institutes of Health [Grants R01-HL136961-01S1 and P30-ES10126]. R. C. B. was supported by the National Institutes of Health [Grants UH3-HL123645, P01-HL108808, P30-DK065988, P01-HL110873, P50-HL107168, and R01-HL136961].
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Collaborators from the Subpopulations and Intermediate Outcome Measures in COPD Study are listed in the Acknowledgments.