Table 4.
Multivariable associations of serum discriminatory metabolites (respiratory syncytial virus vs rhinovirus-A) with clinical outcomes
| Metabolites* | Superpathway | Positive pressure ventilation† | Recurrent wheezing‡ | Asthma§ | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| OR§ | 95% CI | P-value | OR§ | 95% CI | P-value | OR§ | 95% CI | P-value | ||
| Tricosanoyl sphingomyelin (d18:1/23:0) | Lipid | 0.99 | 0.56–1.75 | 0.97 | 1.50 | 1.05–2.15 | 0.03 | 1.15 | 0.77–1.73 | 0.50 |
| Fructose | Carbohydrate | 1.14 | 0.78–1.66 | 0.49 | 0.58 | 0.41–0.84 | 0.004 | 0.96 | 0.68–1.37 | 0.83 |
| Behenoyl sphingomyelin (d18:1/22:0) | Lipid | 0.77 | 0.46–1.29 | 0.32 | 1.54 | 1.06–2.23 | 0.02 | 1.07 | 0.70–1.64 | 0.76 |
| Lignoceroylcarnitine (C24) | Lipid | 0.20 | 0.08–0.48 | <0.001 | 0.99 | 0.68–1.44 | 0.95 | 0.73 | 0.45–1.17 | 0.19 |
| Leucylalanine | Peptide | 2.08 | 0.90–4.85 | 0.09 | 0.77 | 0.55–1.08 | 0.14 | 1.16 | 0.65–2.09 | 0.61 |
| Cerotoylcarnitine (C26) | Lipid | 0.41 | 0.19–0.93 | 0.03 | 1.01 | 0.53–1.94 | 0.97 | 1.15 | 0.55–2.40 | 0.71 |
| Isobutyrylglycine | Amino acid | 1.01 | 0.45–2.28 | 0.98 | 1.77 | 1.15–2.73 | 0.009 | 1.50 | 0.97–2.32 | 0.07 |
| Pregnenediol disulfate (C21H34O8S2) | Lipid | 0.95 | 0.56–1.59 | 0.84 | 0.67 | 0.47–0.96 | 0.03 | 1.00 | 0.65–1.54 | 0.99 |
| Dihomo-linoleoylcarnitine (C20:2) | Lipid | 0.42 | 0.15–1.20 | 0.10 | 1.11 | 0.66–1.86 | 0.69 | 1.22 | 0.63–2.37 | 0.55 |
| Nervonoylcarnitine (C24:1) | Lipid | 0.52 | 0.25–1.09 | 0.08 | 1.26 | 0.70–2.25 | 0.44 | 0.88 | 0.47–1.65 | 0.70 |
| Behenoylcarnitine (C22) | Lipid | 0.14 | 0.02–0.81 | 0.03 | 1.32 | 0.52–3.37 | 0.56 | 0.68 | 0.39–1.18 | 0.17 |
| Ximenoylcarnitine (C26:1) | Lipid | 0.51 | 0.25–1.05 | 0.07 | 1.17 | 0.73–1.89 | 0.51 | 1.04 | 0.45–2.40 | 0.93 |
| Glycosyl-N-palmitoyl-sphingosine (d18:1/16:0) | Lipid | 1.25 | 0.45–3.48 | 0.67 | 1.15 | 0.71–1.86 | 0.58 | 0.71 | 0.39–1.32 | 0.28 |
| Lactosyl-N-nervonoyl-sphingosine (d18:1/24:1) | Lipid | 1.51 | 0.84–2.72 | 0.17 | 1.41 | 0.98–2.01 | 0.06 | 1.15 | 0.74–1.77 | 0.53 |
| Pregnenediol sulfate (C21H34O5S) | Lipid | 0.72 | 0.46–1.11 | 0.14 | 0.66 | 0.50–0.88 | 0.004 | 0.88 | 0.53–1.46 | 0.62 |
| Arachidonoylcarnitine (C20:4) | Lipid | 0.42 | 0.16–1.09 | 0.08 | 1.00 | 0.64–1.54 | 0.99 | 1.09 | 0.56–2.10 | 0.81 |
| Dihomo-linolenoylcarnitine (C20:3n3 or 6) | Lipid | 0.38 | 0.20–0.70 | 0.002 | 1.11 | 0.74–1.68 | 0.61 | 1.14 | 0.61–2.15 | 0.68 |
| Citrate | Energy | 0.46 | 0.17–1.25 | 0.13 | 1.05 | 0.58–1.9 | 0.88 | 1.08 | 0.60–1.95 | 0.80 |
| Stearoylcarnitine (C18) | Lipid | 1.02 | 0.61–1.71 | 0.93 | 1.47 | 0.90–2.42 | 0.12 | 1.00 | 0.64–1.56 | 0.99 |
| N6-methyladenosine | Nucleotide | 0.85 | 0.44–1.65 | 0.64 | 0.81 | 0.54–1.21 | 0.30 | 0.75 | 0.56–1.01 | 0.06 |
| Thyroxine | Amino acid | 0.45 | 0.26–0.80 | 0.01 | 0.87 | 0.47–1.62 | 0.66 | 0.84 | 0.59–1.20 | 0.34 |
| Linoleoylcarnitine (C18:2) | Lipid | 0.39 | 0.12–1.24 | 0.11 | 1.72 | 1.28–2.32 | <0.001 | 1.70 | 1.03–2.81 | 0.04 |
| Phenylacetylcarnitine | Peptide | 0.32 | 0.07–1.55 | 0.16 | 0.97 | 0.59–1.6 | 0.91 | 1.38 | 0.89–2.13 | 0.15 |
Abbreviations: CI, confidence interval; OR, odds ratio
Bold results are statistically significant.
The discriminatory metabolites that have a false discovery rate of <0.05 in the virus-metabolite model (Table 2) are selected
Defined as use of invasive and/or non-invasive mechanical ventilation (e.g., continuous positive airway pressure ventilation).
Defined by parental report of at least two corticosteroid-requiring breathing problems in six months or at least four wheezing episodes in one year that last at least one day and affect sleep.
Defined by physician-diagnosis of asthma by age five years, plus either asthma medication use (e.g., albuterol inhaler, inhaled corticosteroids, montelukast) or asthma-related symptoms in the preceding year.
The multivariable logistic regression models adjusted for age and potential batch effect, as well as clustering within hospitals (with the use of generalized estimating equations). Odds ratio is calculated per each standard deviation of corresponding metabolite intensity.