Serum amino acid concentrations and clinical outcomes in smokers: SPIROMICS metabolomics study.

TitleSerum amino acid concentrations and clinical outcomes in smokers: SPIROMICS metabolomics study.
Publication TypePublication
Year2019
AuthorsLabaki WW, Gu T, Murray S, Curtis JL, Yeomans L, Bowler RP, R Barr G, Comellas AP, Hansel NN, Cooper CB, Barjaktarevic I, Kanner RE, Paine R, McDonald M-LN, Krishnan JA, Peters SP, Woodruff PG, O'Neal WK, Diao W, He B, Martinez FJ, Standiford TJ, Stringer KA, Han MK
JournalSci Rep
Volume9
Issue1
Pagination11367
Date Published2019 08 06
ISSN2045-2322
KeywordsAmino Acids, Female, Humans, Isoleucine, Leucine, Male, Metabolomics, Middle Aged, Patient Outcome Assessment, Proton Magnetic Resonance Spectroscopy, Pulmonary Disease, Chronic Obstructive, Smokers, Tryptophan, Valine
Abstract

Metabolomics is an emerging science that can inform pathogenic mechanisms behind clinical phenotypes in COPD. We aimed to understand disturbances in the serum metabolome associated with respiratory outcomes in ever-smokers from the SPIROMICS cohort. We measured 27 serum metabolites, mostly amino acids, by H-nuclear magnetic resonance spectroscopy in 157 white ever-smokers with and without COPD. We tested the association between log-transformed metabolite concentrations and one-year incidence of respiratory exacerbations after adjusting for age, sex, current smoking, body mass index, diabetes, inhaled or oral corticosteroid use, study site and clinical predictors of exacerbations, including FEV% predicted and history of exacerbations. The mean age of participants was 53.7 years and 58% had COPD. Lower concentrations of serum amino acids were independently associated with 1-year incidence of respiratory exacerbations, including tryptophan (β = -4.1, 95% CI [-7.0; -1.1], p = 0.007) and the branched-chain amino acids (leucine: β = -6.0, 95% CI [-9.5; -2.4], p = 0.001; isoleucine: β = -5.2, 95% CI [-8.6; -1.8], p = 0.003; valine: β = -4.1, 95% CI [-6.9; -1.4], p = 0.003). Tryptophan concentration was inversely associated with the blood neutrophil-to-lymphocyte ratio (p = 0.03) and the BODE index (p = 0.03). Reduced serum amino acid concentrations in ever-smokers with and without COPD are associated with an increased incidence of respiratory exacerbations.

DOI10.1038/s41598-019-47761-w
Alternate JournalSci Rep
PubMed ID31388056
PubMed Central IDPMC6684630
Grant ListR00 HL121087 / HL / NHLBI NIH HHS / United States
P30 ES005605 / ES / NIEHS NIH HHS / United States
K24 HL137013 / HL / NHLBI NIH HHS / United States
HHSN268200900015C / HL / NHLBI NIH HHS / United States
HHSN268200900016C / HL / NHLBI NIH HHS / United States
I01 CX000911 / CX / CSRD VA / United States
U01 HL137880 / HL / NHLBI NIH HHS / United States
R01 HL122438 / HL / NHLBI NIH HHS / United States
HHSN268200900018C / HL / NHLBI NIH HHS / United States
HHSN268200900013C / HL / NHLBI NIH HHS / United States
HHSN268200900014C / HL / NHLBI NIH HHS / United States
T32 HL007749 / HL / NHLBI NIH HHS / United States
HHSN268200900019C / HL / NHLBI NIH HHS / United States
HHSN268200900017C / HL / NHLBI NIH HHS / United States
HHSN268200900020C / HL / NHLBI NIH HHS / United States
K24 HL138188 / HL / NHLBI NIH HHS / United States
R01 GM111400 / GM / NIGMS NIH HHS / United States
MS#: 
MS145
Manuscript Full Title: 
Serum amino acid concentrations and clinical outcomes in smokers: SPIROMICS metabolomics study.
Manuscript Lead/Corresponding Author Affiliation: 
Clinical Center: Michigan (University of Michigan)
ECI: 
Manuscript Status: 
Published and Public