Identification of Sputum Biomarkers Predictive of Pulmonary Exacerbations in COPD.

TitleIdentification of Sputum Biomarkers Predictive of Pulmonary Exacerbations in COPD.
Publication TypePublication
Year2022
AuthorsEsther CR, O'Neal WK, Anderson WH, Kesimer M, Ceppe A, Doerschuk CM, Alexis NE, Hastie AT, R Barr G, Bowler RP, J Wells M, Oelsner EC, Comellas AP, Tesfaigzi Y, Kim V, Paulin LM, Cooper CB, Han MK, Huang YJ, Labaki WW, Curtis JL, Boucher RC
Corporate AuthorsSubpopulations and Intermediate Outcome Measures in COPD Study
JournalChest
Volume161
Issue5
Pagination1239-1249
Date Published2022 May
ISSN1931-3543
Keywordsbiomarkers, Humans, Hypoxanthines, N-Acetylneuraminic Acid, Pulmonary Disease, Chronic Obstructive, Sputum
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.

DOI10.1016/j.chest.2021.10.049
Alternate JournalChest
PubMed ID34801592
PubMed Central IDPMC9131049
Grant ListHHSN268200900019C / HL / NHLBI NIH HHS / United States
P50 HL107168 / HL / NHLBI NIH HHS / United States
UH3 HL123645 / HL / NHLBI NIH HHS / United States
HHSN268200900015C / HL / NHLBI NIH HHS / United States
HHSN268200900014C / HL / NHLBI NIH HHS / United States
P01 HL110873 / HL / NHLBI NIH HHS / United States
R01 HL136961 / HL / NHLBI NIH HHS / United States
U24 HL141762 / HL / NHLBI NIH HHS / United States
P30 ES010126 / ES / NIEHS NIH HHS / United States
HHSN268200900016C / HL / NHLBI NIH HHS / United States
U01 HL137880 / HL / NHLBI NIH HHS / United States
HHSN268200900020C / HL / NHLBI NIH HHS / United States
HHSN268200900017C / HL / NHLBI NIH HHS / United States
R01 HL148215 / HL / NHLBI NIH HHS / United States
HHSN268200900018C / HL / NHLBI NIH HHS / United States
R01 AI129958 / AI / NIAID NIH HHS / United States
HHSN268200900013C / HL / NHLBI NIH HHS / United States
P30 DK065988 / DK / NIDDK NIH HHS / United States
P01 HL108808 / HL / NHLBI NIH HHS / United States
MS#: 
MS153
Manuscript Full Title: 
Identification of Sputum Biomarkers Predictive of Pulmonary Exacerbations in COPD.
Manuscript Lead/Corresponding Author Affiliation: 
Genomics and Informatics Center (University of North Carolina at Chapel Hill)
ECI: 
Manuscript Status: 
Published and Public