Serum metabolite biomarkers discriminate healthy smokers from COPD smokers

Qiuying Chen, Ruba S. Deeb, Yuliang Ma, Michelle R. Staudt, Ronald Crystal, Steven S. Gross

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

COPD (chronic obstructive pulmonary disease) is defined by a fixed expiratory airflow obstruction associated with disordered airways and alveolar destruction. COPD is caused by cigarette smoking and is the third greatest cause of mortality in the US. Forced expiratory volume in 1 second (FEV1) is the only validated clinical marker of COPD, but it correlates poorly with clinical features and is not sensitive enough to predict the early onset of disease. Using LC/MS global untargeted metabolite profiling of serum samples from a well-defined cohort of healthy smokers (n = 37), COPD smokers (n = 41) and non-smokers (n = 37), we sought to discover serum metabolic markers with known and/or unknown molecular identities that are associated with early-onset COPD. A total of 1,181 distinct molecular ions were detected in 95% of sera from all study subjects and 23 were found to be differentiallyexpressed in COPD-smokers vs. healthy-smokers. These 23 putative biomarkers were differentially- correlated with lung function parameters and used to generate a COPD prediction model possessing 87.8%sensitivity and 86.5% specificity. In an independent validation set, this model correctly predicted COPD in 8/10 individuals. These serum biomarkers included myoinositol, glycerophopshoinositol, fumarate, cysteinesulfonic acid, a modified version of fibrinogen peptide B (mFBP), and three doubly-charged peptides with undefined sequence that significantly and positively correlate with mFBP levels. Together, elevated levels of serum mFBP and additional disease-associated biomarkers point to a role for chronic inflammation, thrombosis, and oxidative stress in remodeling of the COPD airways. Serum metabolite biomarkers offer a promising and accessible window for recognition of early-stage COPD.

Original languageEnglish
Article numbere0143937
JournalPLoS One
Volume10
Issue number12
DOIs
Publication statusPublished - 1 Dec 2015
Externally publishedYes

Fingerprint

Pulmonary diseases
Biomarkers
Metabolites
blood serum
respiratory tract diseases
Chronic Obstructive Pulmonary Disease
biomarkers
metabolites
Serum
fibrinogen
peptides
Fibrinogen
Pulmonary Ventilation
Fumarates
Oxidative stress
smoking (habit)
thrombosis
lung function
Forced Expiratory Volume
Inositol

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Chen, Q., Deeb, R. S., Ma, Y., Staudt, M. R., Crystal, R., & Gross, S. S. (2015). Serum metabolite biomarkers discriminate healthy smokers from COPD smokers. PLoS One, 10(12), [e0143937]. https://doi.org/10.1371/journal.pone.0143937

Serum metabolite biomarkers discriminate healthy smokers from COPD smokers. / Chen, Qiuying; Deeb, Ruba S.; Ma, Yuliang; Staudt, Michelle R.; Crystal, Ronald; Gross, Steven S.

In: PLoS One, Vol. 10, No. 12, e0143937, 01.12.2015.

Research output: Contribution to journalArticle

Chen, Qiuying ; Deeb, Ruba S. ; Ma, Yuliang ; Staudt, Michelle R. ; Crystal, Ronald ; Gross, Steven S. / Serum metabolite biomarkers discriminate healthy smokers from COPD smokers. In: PLoS One. 2015 ; Vol. 10, No. 12.
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