Identification of Sputum Biomarkers Predictive of Pulmonary Exacerbations in COPD.
adenosine
glutathione
inflammation
metabolomics
methionine salvage
mucus
Journal
Chest
ISSN: 1931-3543
Titre abrégé: Chest
Pays: United States
ID NLM: 0231335
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
received:
10
06
2021
revised:
15
10
2021
accepted:
29
10
2021
pubmed:
22
11
2021
medline:
11
5
2022
entrez:
21
11
2021
Statut:
ppublish
Résumé
Improved understanding of the pathways associated with airway pathophysiologic features in COPD will identify new predictive biomarkers and novel therapeutic targets. Which physiologic pathways are altered in the airways of patients with COPD and will predict exacerbations? 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. 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. 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. ClinicalTrials.gov; No.: NCT01969344; URL: www. gov.
Sections du résumé
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.
Identifiants
pubmed: 34801592
pii: S0012-3692(21)04377-4
doi: 10.1016/j.chest.2021.10.049
pmc: PMC9131049
pii:
doi:
Substances chimiques
Biomarkers
0
Hypoxanthines
0
N-Acetylneuraminic Acid
GZP2782OP0
Banques de données
ClinicalTrials.gov
['NCT01969344']
Types de publication
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1239-1249Subventions
Organisme : NHLBI NIH HHS
ID : HHSN268200900019C
Pays : United States
Organisme : NHLBI NIH HHS
ID : P50 HL107168
Pays : United States
Organisme : NHLBI NIH HHS
ID : UH3 HL123645
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268200900015C
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268200900014C
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL110873
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL136961
Pays : United States
Organisme : NHLBI NIH HHS
ID : U24 HL141762
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES010126
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268200900016C
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL137880
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268200900020C
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268200900017C
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL148215
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268200900018C
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI129958
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268200900013C
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK065988
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL108808
Pays : United States
Investigateurs
Neil E Alexis
(NE)
Wayne H Anderson
(WH)
Mehrdad Arjomandi
(M)
Igor Barjaktarevic
(I)
R Graham Barr
(RG)
Lori A Bateman
(LA)
Surya P Bhatt
(SP)
Eugene R Bleecker
(ER)
Richard C Boucher
(RC)
Russell P Bowler
(RP)
Stephanie A Christenson
(SA)
Alejandro P Comellas
(AP)
Christopher B Cooper
(CB)
David J Couper
(DJ)
Gerard J Criner
(GJ)
Ronald G Crystal
(RG)
Jeffrey L Curtis
(JL)
Claire M Doerschuk
(CM)
Mark T Dransfield
(MT)
Brad Drummond
(B)
Christine M Freeman
(CM)
Craig Galban
(C)
MeiLan K Han
(MK)
Nadia N Hansel
(NN)
Annette T Hastie
(AT)
Eric A Hoffman
(EA)
Yvonne Huang
(Y)
Robert J Kaner
(RJ)
Richard E Kanner
(RE)
Eric C Kleerup
(EC)
Jerry A Krishnan
(JA)
Lisa M LaVange
(LM)
Stephen C Lazarus
(SC)
Fernando J Martinez
(FJ)
Deborah A Meyers
(DA)
Wendy C Moore
(WC)
John D Newell
(JD)
Robert Paine
(R)
Laura Paulin
(L)
Stephen P Peters
(SP)
Cheryl Pirozzi
(C)
Nirupama Putcha
(N)
Elizabeth C Oelsner
(EC)
Wanda K O'Neal
(WK)
Victor E Ortega
(VE)
Sanjeev Raman
(S)
Stephen I Rennard
(SI)
Donald P Tashkin
(DP)
J Michael Wells
(JM)
Robert A Wise
(RA)
Prescott G Woodruff
(PG)
Informations de copyright
Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.
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