Table 2.
The 25 metabolites that are most positively-associated and 25 metabolites that are most negatively-associated with quantitative interstitial abnormalities in multivariable linear regression models
| Metabolite | HMDB ID* | Percent QIA per unit metabolite, mean [CI]† | FDR p-value | Metabolon class |
|---|---|---|---|---|
| Positively-associated with QIA | ||||
| N-acetylneuraminate | 0000230 |
1.41 [0.80 to 2.02] |
< 0.001 |
Carbohydrate; Aminosugar Metabolism |
| Pseudouridine | 0000767 |
1.35 [0.61 to 2.09] |
0.009 |
Nucleotide; Pyrimidine Metabolism, Uracil containing |
| C-glycosyltryptophan | 0240296 |
1.31 [0.69 to 1.93] |
0.002 |
Amino Acid; Tryptophan Metabolism |
| Erythronate | 0000613 |
1.23 [0.59 to 1.87] |
0.005 |
Carbohydrate; Aminosugar Metabolism |
| N-acetylserine | 0002931 |
1.23 [0.55 to 1.90] |
0.001 |
Amino Acid; Glycine, Serine and Threonine Metabolism |
| N-acetyl-L-methionine | 0011745 |
1.14 [0.57 to 1.72] |
0.004 |
Amino Acid; Methionine, Cysteine, SAM and Taurine Metabolism |
| 5–6-Dihydrouridine | 0000497 |
1.11 [0.46 to 1.76] |
0.015 |
Nucleotide; Pyrimidine Metabolism, Uracil containing |
| N-acetylthreonine | 0062557 |
1.01 [0.40 to 1.62] |
0.021 |
Amino Acid; Glycine, Serine and Threonine Metabolism |
| N2, N2-Dimethylguanosine | 0004824 |
1.01 [0.35 to 1.66] |
0.030 |
Nucleotide; Purine Metabolism, Guanine containing |
| Cytidine | 0000089 |
0.98 [0.48 to 1.48] |
0.004 |
Nucleotide; Pyrimidine Metabolism, Cytidine containing |
| Hydroxyasparagine | 0341329 |
0.98 [0.32 to 1.64] |
0.038 |
Amino Acid; Alanine and Aspartate Metabolism |
| Sphingosine | 0000252 |
0.94 [0.40 to 1.47] |
0.013 |
Lipid; Sphingosines |
|
N-Acetylgalactosamine, N-Acetyl-D-glucosamine‡ |
0000212, 000021‡ |
0.92 [0.37 to 1.47] |
0.018 |
Carbohydrate; Aminosugar Metabolism |
| N4-Acetylcytidine | 0005923 |
0.89 [0.49 to 1.30] |
0.001 |
Nucleotide; Pyrimidine Metabolism, Cytidine containing |
| N-Acetylputrescine | 0002064 |
0.89 [0.30 to 1.49] |
0.035 |
Amino Acid; Polyamine Metabolism |
| N-acetyl-isoputreanine |
0.87 [0.44 to 1.29] |
0.003 |
Amino Acid; Polyamine Metabolism |
|
| Succinylcarnitine | 0061717 |
0.85 [0.37 to 1.32] |
0.012 |
Energy; TCA Cycle |
| 1-Methyl-4-imidazoleacetate | 0002820 |
0.81 [0.35 to 1.28] |
0.013 |
Amino Acid; Histidine Metabolism |
| 3-ureido-Propionate | 0000026 |
0.78 [0.43 to 1.14] |
0.001 |
Nucleotide; Pyrimidine Metabolism, Uracil containing |
| Quinolinate | 0000232 |
0.73 [0.37 to 1.08] |
0.003 |
Cofactors and Vitamins; Nicotinate and Nicotinamide Metabolism |
| Acisoga | 0061384 |
0.66 [0.29 to 1.02] |
0.011 |
Amino Acid; Polyamine Metabolism |
| 5-(galactosylhydroxy)-L-lysine |
0.61 [0.23 to 0.98] |
0.025 |
Amino Acid; Lysine Metabolism |
|
| N-acetyltaurine | 0240253 |
0.55 [0.16 to 0.94] |
0.048 |
Amino Acid; Methionine, Cysteine, SAM and Taurine Metabolism |
| Phenylacetylglutamine | 0006344 |
0.54 [0.23 to 0.85] |
0.015 |
Peptide; Acetylated Peptides |
| 1-Carboxyethyltyrosine |
0.51 [0.22 to 0.81] |
0.015 |
Amino Acid; Tyrosine Metabolism |
|
| Negatively-associated with QIA | ||||
| Phosphatidylcholine (18:0/18:2) | 0008039 |
− 2.09 [− 3.26 to − 0.91] |
0.013 |
Lipid; Phosphatidylcholine (PC) |
| Phosphatidylcholine (16:0/18:2) | 0007973 |
− 1.92 [− 3.25 to − 0.59] |
0.044 |
Lipid; Phosphatidylcholine (PC) |
| Lysophosphatidylcholine (16:0/0:0) | 0010382 |
− 1.71 [− 2.76 to − 0.66] |
0.024 |
Lipid; Lysophospholipid |
| Phosphatidylcholine (18:2/20:4) | 0008147 |
− 1.59 [− 2.21 to − 0.97] |
< 0.001 |
Lipid; Phosphatidylcholine (PC) |
| Phosphatidylcholine (16:0/18:0) | 0007970 |
− 1.45 [− 2.31 to − 0.59] |
0.018 |
Lipid; Phosphatidylcholine (PC) |
| Lysophosphatidylcholine (18:0/0:0) | 0010384 |
− 1.45 [− 2.19 to − 0.70] |
0.005 |
Lipid; Lysophospholipid |
| Sphingomyelin (D18:1/20:0) | 0012102 |
− 1.40 [− 2.22 to − 0.57] |
0.017 |
Lipid; Sphingomyelins |
| Vitamin A | 0000305 |
− 1.16 [− 1.74 to − 0.57] |
0.004 |
Cofactors and Vitamins; Vitamin A Metabolism |
|
Sphingomyelin (D18:2(4E,14Z)/14:0), Sphingomyelin (D18:1/14:1(9Z))‡ |
0240637, 0240612‡ |
− 1.15 [− 1.63 to − 0.66] |
< 0.001 |
Lipid; Sphingomyelins |
| Thyroxine | 0000248 |
− 1.13 [− 1.83 to − 0.42] |
0.025 |
Amino Acid; Tyrosine Metabolism |
| L-alpha-Aminobutyric acid | 0000452 |
− 1.13 [− 1.69 to − 0.57] |
0.003 |
Amino Acid; Glutathione Metabolism |
| Phosphatidylinositol (18:0/20:4) | 0009815 |
− 1.10 [− 1.80 to − 0.39] |
0.028 |
Lipid; Phosphatidylinositol (PI) |
| Lysophosphatidylcholine (0:0/16:0) | 0061702 |
− 1.10 [− 1.68 to − 0.53] |
0.005 |
Lipid; Lysophospholipid |
| 3-methyl-2-oxobutyrate | 0000019 |
− 1.06 [− 1.75 to − 0.37] |
0.030 |
Amino Acid; Leucine, Isoleucine and Valine Metabolism |
| Gamma-glutamyl-2-aminobutyrate |
− 1.06 [− 1.48 to − 0.64] |
< 0.001 |
Peptide; Gamma-glutamyl Amino Acid |
|
| Lysophosphatidylcholine (18:1/0:0) | 0002815 |
− 1.04 [− 1.69 to − 0.39] |
0.025 |
Lipid; Lysophospholipid |
| Lysophosphatidylcholine (18:2/0:0) | 0010386 |
− 1.04 [− 1.69 to − 0.39] |
0.025 |
Lipid; Lysophospholipid |
|
Sphingomyelin (D17:2/16:0) Sphingomyelin (D18:2/15:0)‡ |
0240677 |
− 1.02 [− 1.47 to − 0.58] |
< 0.001 |
Lipid; Sphingomyelins |
| Arachidoylcarnitine | 0006460 |
− 1.00 [− 1.52 to − 0.48] |
0.005 |
Lipid; Fatty Acid Metabolism (Acyl Carnitine, Long Chain Saturated) |
| Phosphatidylcholine (18:2/18:2) | 0008138 |
− 0.98 [− 1.53 to − 0.44] |
0.010 |
Lipid; Phosphatidylcholine (PC) |
|
Sphingomyelin (D17:1/14:0), Sphingomyelin (D16:1/15:0)‡ |
− 0.95 [− 1.33 to − 0.57] |
< 0.001 |
Lipid; Sphingomyelins |
|
| Ceramide (D18:2/22:0) |
− 0.93 [− 1.38 to − 0.47] |
0.003 |
Lipid; Ceramides |
|
| Citrulline | 0000904 |
− 0.92 [− 1.56 to − 0.29] |
0.043 |
Amino Acid; Urea cycle; Arginine and Proline Metabolism |
|
Ceramide (D20:1/18:0), Ceramide (D16:1/22:0), Ceramide (D18:1/20:0)‡ |
0240684, 0240682, 0004951‡ |
− 0.91 [− 1.40 to − 0.41] |
0.009 |
Lipid; Ceramides |
| Lysophosphatidylcholine (24:0/0:0) | 0010405 | − 0.84 [− 1.25 to − 0.43] | 0.003 |
Lipid; Lysophospholipid |
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
†Multivariable regression models adjusted for age, sex, body mass index, smoking status, pack-years, and inhaled corticosteroid use
‡ Cannot be analytically differentiated