Table 1.
A summary of COPD-associated metabolomic studies.
| Author and Year | Subjects | Sample/Platform | Metabolites Name | |
|---|---|---|---|---|
| Increase | Decrease | |||
| Bowler, R.P. et al. (2015) [15] | 129 current and former smokers from the COPD Gene cohort | Plasma/HPLC-MS | Trihexosylceramides, Dihexosylceramides, Sulfatide d18.1. N16.0, Ganglioside GD1.d18.1. N16.0 (COPD exacerbations) | Ceramide, Sphingomyelin, Ganglioside, GM3, Sphingomyelin (Emphysema) Sphingomyelin, S1P (COPD exacerbations) |
| Kilk, K. et al. (2018) [4] | COPD patients (n = 25) and control individuals (n = 21) | Serum/HPLC-MS | LysoPC | SM, Hydroxylated SM, Arginine, Proline |
| Navarrete, A. et al. (2017) [20] | Control group and CS-exposed group without (n = 6, n = 10) or with (n = 10, n = 8) LGF treatment | Plasma/LC-QTOF-MS | Lysophosphatidylcholines, Mandelic acid, Hydroxymethylbenzoic acid (Before therapy), Sphingosine, Sphingosine 1-phosphate, Lysophospholipids (After LGF therapy) | Phenylalanine, Sphingosine 1-phosphate Sphingosine, Hydroxylysine, Dodecenoic acid, Oxo-methylthiobutanoic acid, (Before therapy) |
| Brajesh, S. et al. (2017) [21] | COPD patients receiving standard therapy (n = 40) and combination of doxycycline and standard therapy (n = 60) | Serum/NMR | Formate, Citrate, Imidazole, L-arginine (After doxycycline therapy compared with Pre-treatment group) | Lactate, Fatty acid (After doxycycline therapy compared with Pre-treatment group) |
| Ubhi, B. K. et al. (2012) [6] | Controls (n = 66) and GOLD stage II (n = 70), III (n = 64) and IV (n = 44) COPD patients | Serum/NMR LC-MS/MS | Glutamine, Phenylalanine, 3-methylhistidine, Ketone bodies | Lipoproteins, BCAAs, Glycine, Creatine, N, N-dimethylglycine |
| Ubhi, B. K. et al. (2012) [25] | GOLD IV patients (n = 30) and controls (n = 30) | Serum/LC-MS/MS | Glutamine, Aspartate, Arginine | Aminoadipate |
| Novotna, B. et al. (2018) [30] | COPD patients (n = 10) and healthy controls (n = 10) | Blood/HPLC-MS/MS | Carnitine, Phenylalanine/Tyrosine | Alanine, Phenylalanine, Pyroglutamate Free Carnitine/Acylcarnitine |
| Ren, X. et al. (2016) [10] | SD male rats include control, model, dexamethasone and bergenin groups, with 10 rats in each group | Serum/NMR | Isobutyrate, Acetone, Acetoacetate, Pyruvate, Glycine, Glycerol, Threonine (Before therapy). Glutamine, Glucose (After dexamethasone therapy). Glutamine (After bergenin therapy) | Isoleucine, Leucine, Valine, Lactate, Alanine, Proline, Glutamine, Glutamate, Creatine phosphate, Glucose, Serine (Before therapy). Pyruvate, Glycine, Threonine (After dexamethasone therapy). Pyruvate, Glycine, Threonine (After bergenin therapy) |
| Cruickshank-Quinn, C. I. et al. (2014) [26] | DBA/2J mice included controls group (n = 3), CS- exposed group for different time | Plasma/LC-MS | Homocitrulline, Arginine, Phenylacetylglycine, PI (36:2), PS (28:2), TG, Adenosine, AMP, Hypoxanthine | Glycerophospholipids, Glycerolipids, Pregnanetriol, Pentadecanoylglycine |
| Ren, X. et al. (2016) [3] | 40, 60, and 80% TS groups of rats (n = 6) and control group of rats (n = 6) | Serum/LC-MS | Lysophosphatidylethanolamine, Lysophosphatidic acid (18:1), Docosahexaenoic acid, 5-hydroxyindoleacetic acid, 5′-carboxy-γ-tocopherol | 4-imidazolone-5-propionic acid, 12-hydroxyeicosatetraenoic acid, Uridine |
| Hodgson, S. et al. (2017) [28] | HIV-associated COPD patients (n = 38), controls (n = 38) | Plasma/LC-MS/MS | Kynurenine/Tryptophan ratio, Ceramide, Fatty acids | Diacylglycero |
| De Benedetto, F. et al. (2018) [22] | 90 COPD patients received supplementation with QTer® and Creatine or placebo | Plasma/LC-MS | SM (OH) C16:1, SM C18:0 (supplementation with placebo) Lysophosphatidylcholine (Supplementation with QTer® and Creatine) | Phosphatidylcholine, Sphingomyelins (Supplementation with QTer® and Creatine) |
| Rodríguez et al. (2011) [23] | the effects of exercise on COPD patients (n = 18), healthy subjects (n = 12) | Plasma/NMR | glutamine, tyrosine, alanine, valine and isoleucine, creatine, creatinine, citrate and glucose (healthy subjects after training) | lactate, succinate and pyruvate (healthy subjects after training) lactate (COPD patients after training) |
| Wang, C. et al. (2017) [2] | Stable COPD patients with phenotype E (n = 22) and phenotype M (n = 28) | Serum/NMR | ADP, Guanosine, Choline, Glycine, Proline, Tyrosine, L-alanine, L-valine, Leucine (E and M) L-threonine, (E), Malonate (M) | Acetone, Lactate (E and M) Pyruvic acid(E), Uridine(M) |
| Tan, L.C. et al. (2018) [18] | COPD patients with phenotype E (n = 20) and phenotype M (n = 24) | Serum/NMR | Fructose, Glycine, Pyruvic acid, Pyruvate, Proline, Acetone, Lipid CH2CH2CO, Threonine, Lsopropyl alcohol (E and M), Lactate, Creatine, Citric acid, L-glutamine, Maltose Ornithine, 2-hydroxyisobutyrate, L-threonine, L-valine, Glutamic acid, β-alanine, Betaine, Cyclopentane (E); N-acetylcysteine (M) | Asparagine, pyridoxine(E) Ornithine, Guanosine, Lipoprotein(M) |
| Chen, Q. et al. (2015) [8] | Healthy smokers (n = 37), COPD smokers (n = 41) and non-smokers (n = 37) | Serum/LC-MS | Fibrinogen peptide B, Myoinositol, Dimethyluric acid, N-methylnicotinate, Cysteinsulfonic acid, Glycerophosphoinositol, Phosphatidylinositol (40:7), Creatinine | Several hydrophobic unknowns (with chromatographic retention time consistent with fatty acids and lipids) |
| Deja, S. et al. (2014) [11] | COPD patients (n = 22) and lung cancer (TNM stages I, II, III, and IV) patients (n = 77) | Serum/NMR | N-acetylated, Glycoproteins, Leucine, Lysine, Mannose, Choline, Lipid (CH3 (CH2) n) (lung cancer compared with COPD) | Acetate, Citrate, Methanol (lung cancer compared with COPD) |
| Fortis, S. et al. (2017) [31] | Stable COPD patients and acute respiratory failure patients caused by COPD exacerbation, pneumonia or heart failure | Serum Urine/NMR | Glutamine, Formate, Alanine, Proline, Histidine, Creatine, Phosphate (Serum); Cis-aconitate, Oxoglutarate (Urine, stable COPD compared with acute respiratory failure) | Mannitol, Citrate (Serum); Furoylglycine, N-oxide, Methyl-2-oxovalerate, Niacinamide Nicotinamide, (Urine, stable COPD compared with acute respiratory failure) |
| Naz, S. et al. (2017) [29] | Healthy, smokers and smokers with COPD | Serum/LC–MS | Asymmetric, Asymmetric/symmetric dimethylarginine, Fatty acid, Sphingolipid pathways (female); cAMP signaling (male) | Acetyl–ornithine/Ornithine, Arginine/(citrulline+ornithine) (female) |
| Wang, L. et al. (2013) [9] | COPD patients (n = 32) and healthy controls (n = 21) | Urine/NMR | Acetate, Ketone bodies, Pyruvate, Carnosine, M-hydroxyphenylacetate, Phenylacetyglycine, | 1-methylnicotinamide, Creatinine, Lactate |
| Huang, Q. et al. (2018) [34] | 41 Chinese elderly participants including COPD patients and their healthy spouses | Urine/ICP-MS | N-formyl-l-methionine, CPA, Decanoylcarnitine, L-histidine, Spermine, Acetylcarnosine, L-octanoylcarnitine, D-glucose (COPD) Indolelactic acid, 5-phosphoribosylamine (PM2.5 exposure) | Suberylglycine, 3-dehydrocarnitine (COPD), Uric acid, Glyceric acid, 1,3-biphosphate, Methyluric acid, 4-pyridoxic acid, Dopamine 4-sulfate, (PM2.5 exposure) |
| Airoldi, C. et al. (2016) [38] | ZZ-α1-antitrypsin deficient COPD patients (n = 11) and healthy controls (n = 11) | EBC/NMR | Acetate, 2,3-butanediol propionic acid, Lactate, Butyrate acetone, Benzoate, fatty acid, Formate, Alanine, Ethanol, Acetoin, Isopropanol acetoin, Propionate, Acetate | No report |
| Laurentiis, G. et al. (2013) [41] | Healthy smokers (n = 20), COPD smokers (n = 15), PLCH patients (n = 15) | EBC/NMR | Acetate (COPD and PLCH) 2-propanol (COPD) Isobutyrate (PLCH) | 1-methylimidazole (COPD and PLCH) Isobutyrate (COPD) 2-propanol (PLCH) |
| Ishikawa, S. et al. (2019) [46] | 3D bronchial tissue | 3D bronchial tissues/LC-MS/MS | 6-phosphogluconate, Erythrose 4-phosphate Ribose 5phosphate (R5P) | Glucose 6-phosphate, Fructose 6-phosphate, Glutathione, Oxidized glutathione, ADP, ATP |
| Li, J. et al. (2017) [47] | COPD rats treated with normal saline (n = 10) and aminophylline (APL) (n = 10) | Lung tissue/LC-QTOF/MS | LTA4, 5-HETE, 20-OH-LTB4, LXA4, PGE2 (Before ALP therapy) | LTA4, 5-HETE, LTB4, LXA4, PGE2 (After ALP therapy) |
| Yang, L. et al. (2015) [48] | SD rats included control group (n = 40), COPD group (n = 40), and BYF therapy group (n = 40) | Lung tissue/HPLC-Q-TOF/MS | Linoleic acid, Acetylcholine, Arachidonic acid, 2-methoxyestradiol 20-hydroxy-PGE2, 5-HEPE, 7-Oxo-11-dodecenoic acid, Acetyl-l-leucine (Before BYF therapy) Phenylpyruvic acid, Sphinganine PC (18:1) (After BYF therapy) | Phenylpyruvic acid, Sphinganine PC (18:1) (Before BYF therapy) Linoleic acid, Acetylcholine, Arachidonic acid, 2-methoxyestradiol 20-hydroxy-PGE2, 5-HEPE, 7-Oxo-11-dodecenoic acid, Acetyl-l-leucine (After BYF therapy) |
| Zhao, P. et al. (2017) [5] | COPD rats treated with normal saline, BJF, and aminophylline | Lung tissue/LC-MS | Glutathione (After BJF therapy) | Arachidonic acid, Linoleic acid, Glycerophospholipid (After BJF therapy) |
| van der Doesa, A. M. (2018) [7] | Smoking controls, COPD patients in a stable or acute exacerbation phase | Sputum/LC-MS | No report | ALA, EPA, LA, HEPEs, HDHAs, HETEs, LTB4 |