PMID- 26674646
OWN - NLM
STAT- MEDLINE
DCOM- 20160627
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 12
DP  - 2015
TI  - Serum Metabolite Biomarkers Discriminate Healthy Smokers from COPD Smokers.
PG  - e0143937
LID - 10.1371/journal.pone.0143937 [doi]
LID - e0143937
AB  - 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 differentially-expressed 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.
FAU - Chen, Qiuying
AU  - Chen Q
AD  - Department of Pharmacology, Weill Cornell Medicine, 1300 York Avenue, New York, 
      NY, 10065, United States of America.
FAU - Deeb, Ruba S
AU  - Deeb RS
AD  - Department of Genetic Medicine, Weill Cornell Medicine, 1300 York Avenue, New 
      York, NY, 10065, United States of America.
FAU - Ma, Yuliang
AU  - Ma Y
AD  - Department of Pharmacology, Weill Cornell Medicine, 1300 York Avenue, New York, 
      NY, 10065, United States of America.
FAU - Staudt, Michelle R
AU  - Staudt MR
AD  - Department of Genetic Medicine, Weill Cornell Medicine, 1300 York Avenue, New 
      York, NY, 10065, United States of America.
FAU - Crystal, Ronald G
AU  - Crystal RG
AD  - Department of Genetic Medicine, Weill Cornell Medicine, 1300 York Avenue, New 
      York, NY, 10065, United States of America.
FAU - Gross, Steven S
AU  - Gross SS
AD  - Department of Pharmacology, Weill Cornell Medicine, 1300 York Avenue, New York, 
      NY, 10065, United States of America.
LA  - eng
GR  - R37 HL087062/HL/NHLBI NIH HHS/United States
GR  - P20 HL113443/HL/NHLBI NIH HHS/United States
GR  - R37HL087062/HL/NHLBI NIH HHS/United States
GR  - R01HL1189541/HL/NHLBI NIH HHS/United States
GR  - R01 HL107882/HL/NHLBI NIH HHS/United States
GR  - R01HL107882/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20151216
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Biomarkers)
SB  - IM
MH  - Adult
MH  - Biomarkers
MH  - Case-Control Studies
MH  - Chromatography, Liquid
MH  - Cluster Analysis
MH  - Female
MH  - Forced Expiratory Volume
MH  - Healthy Volunteers
MH  - Humans
MH  - Male
MH  - Mass Spectrometry
MH  - *Metabolome
MH  - *Metabolomics/methods
MH  - Middle Aged
MH  - Pulmonary Disease, Chronic Obstructive/*blood/physiopathology
MH  - Reproducibility of Results
MH  - Respiratory Function Tests
MH  - Smoking/*blood
PMC - PMC4682670
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/12/18 06:00
MHDA- 2016/06/28 06:00
PMCR- 2015/12/16
CRDT- 2015/12/18 06:00
PHST- 2015/05/05 00:00 [received]
PHST- 2015/11/11 00:00 [accepted]
PHST- 2015/12/18 06:00 [entrez]
PHST- 2015/12/18 06:00 [pubmed]
PHST- 2016/06/28 06:00 [medline]
PHST- 2015/12/16 00:00 [pmc-release]
AID - PONE-D-15-19036 [pii]
AID - 10.1371/journal.pone.0143937 [doi]
PST - epublish
SO  - PLoS One. 2015 Dec 16;10(12):e0143937. doi: 10.1371/journal.pone.0143937. 
      eCollection 2015.