Table 4.
A The 25 metabolites that have highest odds of QIA-predominant phenotype and B 25 metabolites that have the lowest odds of QIA-predominant phenotype compared to emphysema-predominant phenotype in multinomial logistic regression
| Metabolite | HMDB ID* | Odds of QIA-predominant over emphysema-predominant, mean [CI]† |
FDR p-value | Metabolon class |
|---|---|---|---|---|
| Symmetric dimethylarginine (SMDA), Asymmetric dimethylarginine (ADMA)‡ |
0003334, 0001539‡ |
5.19 [2.01–13.40] |
0.021 |
Amino Acid; Urea cycle; Arginine and Proline Metabolism |
| Phenylalanine | 0000159 |
5.04 [1.73–14.72] |
0.040 |
Amino Acid; Phenylalanine Metabolism |
| Asparagine | 0000168 |
4.79 [1.99–11.54] |
0.018 |
Amino Acid; Alanine and Aspartate Metabolism |
| Sulfate | 01448 |
4.05 [1.79–9.17] |
0.022 |
Xenobiotics; Chemical |
| Proline |
0000162, 0003411 |
3.36 [1.61–7.03] |
0.028 |
Amino Acid; Urea cycle; Arginine and Proline Metabolism |
| Kynurenine | 0000684 |
2.82 [1.48–5.34] |
0.031 |
Amino Acid; Tryptophan Metabolism |
| Erythronate | 0000613 |
2.71 [1.46–5.04] |
0.031 |
Carbohydrate; Aminosugar Metabolism |
| N-acetyl-isoputreanine |
2.64 [1.73–4.04] |
0.002 |
Amino Acid; Polyamine Metabolism |
|
| Alpha-Ketoglutaramate | 0001552 |
2.57 [1.46–4.50] |
0.026 |
Amino Acid; Glutamate Metabolism |
| Gamma-Glutamylphenylalanine | 0000594 |
2.49 [1.40–4.42] |
0.031 |
Peptide; Gamma-glutamyl Amino Acid |
| Phosphatidylethanolamine (16:0/18:2) | 0005322 |
2.37 [1.65–3.40] |
< 0.001 |
Lipid; Phosphatidylethanolamine (PE) |
| Phosphatidylethanolamine (16:0/18:1) | 0005320 |
2.31 [1.66–3.23] |
< 0.001 |
Lipid; Phosphatidylethanolamine (PE) |
| Aspartate | 0000191 |
2.25 [1.40–3.61] |
0.022 |
Amino Acid; Alanine and Aspartate Metabolism |
| Lysophosphatidylethanolamine (16:0/0:0) | 0011503 |
2.16 [1.30–3.58] |
0.039 |
Lipid; Lysophospholipid |
| Phosphatidylethanolamine (18:0/20:4) | 0009003 |
2.10 [1.39–3.18] |
0.018 |
Lipid; Phosphatidylethanolamine (PE) |
| Phosphatidylethanolamine (16:0/20:4) | 0005323 |
2.09 [1.43–3.04] |
0.011 |
Lipid; Phosphatidylethanolamine (PE) |
| 3-Ureidopropionate | 0000026 |
1.99 [1.40–2.83] |
0.011 |
Nucleotide; Pyrimidine Metabolism, Uracil containing |
| N-formylanthranilic acid | 0004089 |
1.97 [1.32–2.95] |
0.026 |
Amino Acid; Tryptophan Metabolism |
| Phosphatidylethanolamine (18:0/18:2) | 0008994 |
1.94 [1.37–2.74] |
0.011 |
Lipid; Phosphatidylethanolamine (PE) |
| Succinylcarnitine | 0061717 |
1.92 [1.22–3.01] |
0.049 |
Energy; TCA Cycle |
| Quinolinate | 0000232 |
1.89 [1.35–2.66] |
0.011 |
Cofactors and Vitamins; Nicotinate and Nicotinamide Metabolism |
| Gulonate | 0003290 |
1.89 [1.25–2.87] |
0.037 |
Cofactors and Vitamins; Ascorbate and Aldarate Metabolism |
| Methionine sulfone | 0062174 |
1.85 [1.26–2.70] |
0.031 |
Amino Acid; Methionine, Cysteine, SAM and Taurine Metabolism |
| 1-Carboxyethylphenylalanine |
1.81 [1.34–2.43] |
0.011 |
Amino Acid; Phenylalanine Metabolism |
|
| Glutamate | 0000148 |
1.80 [1.25–2.61] |
0.031 |
Amino Acid; Glutamate Metabolism |
|
Sphingomyelin (D18:1/20:1(11Z)), Sphingomyelin (D18:2/20:0)‡ |
0240610, 0240632‡ |
0.31 [0.16–0.63] |
0.026 |
Lipid; Sphingomyelins |
| Thyroxine | 0000248 |
0.32 [0.16–0.64] |
0.028 |
Amino Acid; Tyrosine Metabolism |
|
Sphingomyelin (D18:1/18:1), Sphingomyelin (D18:2/18:0)‡ |
0012101 |
0.32 [0.16–0.66] |
0.031 |
Lipid; Sphingomyelins |
| Sphingomyelin (D18:1/18:0) | 0001348 |
0.33 [0.16–0.68] |
0.038 |
Lipid; Sphingomyelins |
| Citrulline | 0000904 |
0.41 [0.22–0.74] |
0.043 |
Amino Acid; Urea cycle; Arginine and Proline Metabolism |
| Sphingomyelin (D18:2/18:1) |
0.43 [0.26–0.69] |
0.020 |
Lipid; Sphingomyelins |
|
| Eicosenoylcarnitine |
0.47 [0.31–0.70] |
0.011 |
Lipid; Fatty Acid Metabolism (Acyl Carnitine, Monounsaturated) |
|
| Oleoylcarnitine | 0005065 |
0.49 [0.30–0.80] |
0.049 |
Lipid; Fatty Acid Metabolism (Acyl Carnitine, Monounsaturated) |
| Stearoylethanolamide | 0013078 |
0.50 [0.31–0.80] |
0.045 |
Lipid; Endocannabinoid |
| Glycerol | 0000131 |
0.53 [0.38–0.74] |
0.011 |
Lipid; Glycerolipid Metabolism |
| N6,N6,N6-Trimethyl-L-lysine | 0001325 |
0.55 [0.38–0.81] |
0.033 |
Amino Acid; Lysine Metabolism |
| Homostachydrine | 0033433 |
0.59 [0.43–0.81] |
0.024 |
Xenobiotics; Food Component/Plant |
| 9-Decenoylcarnitine | 0013205 |
0.61 [0.44–0.84] |
0.037 |
Lipid; Fatty Acid Metabolism (Acyl Carnitine, Monounsaturated) |
| 9-Hexadecenoylcarnitine | 0013207 |
0.62 [0.45–0.86] |
0.049 |
Lipid; Fatty Acid Metabolism (Acyl Carnitine, Monounsaturated) |
| 10-undecylenate | 0033724 |
0.63 [0.47–0.85] |
0.037 |
Lipid; Medium Chain Fatty Acid |
| Myristoleoylcarnitine | 0240588 |
0.63 [0.49–0.82] |
0.018 |
Lipid; Fatty Acid Metabolism (Acyl Carnitine, Monounsaturated) |
| Trans-2-Dodecenoylcarnitine | 13,326 |
0.64 [0.49–0.84] |
0.031 |
Lipid; Fatty Acid Metabolism (Acyl Carnitine, Monounsaturated) |
| Dodecadienoate |
0.66 [0.52–0.85] |
0.028 |
Lipid; Fatty Acid, Dicarboxylate |
|
| Decanoylcarnitine | 0000651 |
0.67 [0.52–0.87] |
0.034 |
Lipid; Fatty Acid Metabolism (Acyl Carnitine, Medium Chain) |
| Octanoylcarnitine | 0000791 |
0.68 [0.53–0.88] |
0.037 |
Lipid; Fatty Acid Metabolism (Acyl Carnitine, Medium Chain) |
|
Linoelaidic acid, Linoleic acid‡ |
0006270, 0000673‡ |
0.69 [0.54–0.87] |
0.033 |
Lipid; Long Chain Polyunsaturated Fatty Acid (n3 and n6) |
|
gamma-Linolenic acid, alpha-Linolenic acid‡ |
0003073, 0001388‡ |
0.71 [0.57–0.88] |
0.031 |
Lipid; Long Chain Polyunsaturated Fatty Acid (n3 and n6) |
|
Vaccenic acid, Elaidic acid, cis-Vaccenic acid, Oleic acid‡ |
0003231, 0000573, 0240219, 0000207‡ |
0.71 [0.56–0.90] |
0.049 |
Lipid; Long Chain Monounsaturated Fatty Acid |
| 10Z-Heptadecenoic acid | 0060038 |
0.74 [0.61–0.90] |
0.041 |
Lipid; Long Chain Monounsaturated Fatty Acid |
| 7Z,10Z-Hexadecadienoic acid | 0000477 |
0.74 [0.61–0.89] |
0.031 |
Lipid; Long Chain Polyunsaturated Fatty Acid (n3 and n6) |
CI 95% confidence interval, FDR Benjamini–Hochberg False Discovery Rate, HMDB Human Metabolome Database, QIA quantitative interstitial abnormalities
*Wishart DS, Guo AC, Oler E, et al., HMDB 5.0: the Human Metabolome Database for 2022. Nucleic Acids Res. 2022. Jan 7;50(D1):D622–31
†Multinomial regression models adjusted for age, sex, body mass index, smoking status, pack-years, and inhaled corticosteroid use. QIA-predominant was initially used as the reference group
‡Cannot be analytically differentiated