Table 2– Metabolites that significantly distinguish all chronic obstructive pulmonary disease patients (COPD) and Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages III and IV patients from control subjects, and emphysema patients from non-emphysema patients
Metabolic pathway/processMetabolite#All COPD patients versus controlGOLD III patients versus controlGOLD IV patients versus controlEmphysema versus non-emphysema patients
Microbial trimethylamine metabolismTrimethylamine+,§27.6++
Creatine biosynthesis/glycine degradationCreatine¶,§-13.2++
Glycine+,§,ƒ-10.7++
N,N-dimethylglycine¶,+,§-30.6++-54§§-35.4++
BCAA degradation3-hydroxyisobutyrateƒ-17++-15.4++
Isobutyrate+,§,ƒ-14.5++
Isoleucine¶,##-16.1++-11.3++
Leucine¶,##-10.9++
Valine¶,##-24.9++-12.3++
Muscle-protein catabolism3-methylhistidine+,ƒ37§§43.2§§53.5§§34.5++
Several pathwaysGlutamine¶,§,##30.4§§38.2§§52.4§§17.4++
Cysteine and methionine metabolismMethionine§-12++
Phenylalanine and tyrosine metabolismPhenylalanine¶,+,§,ƒ24.7§§29.7§§25.9++17.9++
Lipid metabolismHDL¶,##-15.4++-12.3++
LDL/VLDL¶,##-31++-31.5++-28.3++
Polyunsaturated lipid¶,+,##-24.2++-26.8++-21.7++
Monoglyceride+,§,ƒ-11.5++
Glycerol+,§,ƒ-20.1++-24.6++
Ketone bodies3-hydroxybutyrate¶,+,§,ƒ15.3§§20.3§§26.6§§17.1++
Acetoacetate¶,§25.9++42.2¶¶
VitaminAscorbateƒ,##30.8++41.3++
Post-translational glycoprotein acetylationO-acetylated glycoproteins-14.3¶¶-16.2++
N-acetylated glycoproteins-12.7++
  • Data presented as % positive or negative mean fold change (MFC). BCAA: branched-chain amino acid; HDL: high-density lipoproteins; LDL: low-density lipoproteins; VLDL: very low-density lipoproteins. #: unassigned metabolites also discriminated between each of the patient groups, the largest effect being an MFC of 106% (more information is included in the online supplementary material). : assigned from the literature of Tukiainen and co-workers [10, 11]. +: assigned from GlaxoSmithKline database of standards (unpublished data). §: assigned using Chenomx software. ƒ: assigned from the Human Metabolome Database. ##: assigned from two-dimensional nuclear magnetic resonance correlation spectroscopy, total correlation spectroscopy, heteronuclear single-quantum correlation, and heteronuclear multiple-bond correlation on selected GOLD stage IV and control subjects’ samples. The t-test raw p-value thresholds corresponding to α 0.05, 0.1 and 0.15 for each group were: GOLD III male and female p<0.0013, p<0.0048 and p=0.0075, respectively; GOLD IV male and female p<0.0031, p<0.011 and p=0.0335, respectively; all COPD patients (i.e. GOLD II, III, and IV male and female) p<0.0013, p<0.0151 and p=0.0266, respectively; combined GOLD III and IV male and female versus control p<0.0027, p<0.0110 and p=0.0250. ¶¶: false discovery rate (FDR) α<0.15; ++: FDR α<0.10; §§: FDR α<0.05.