Circulating 25-hydroxyvitamin D, nasopharyngeal airway metabolome, and bronchiolitis severity

Abstract

Low circulating 25-hydroxyvitamin D (25OHD) levels are a risk factor for acute respiratory infection (eg, bronchiolitis) in children. However, little is known about the relation of circulating 25OHD with the many downstream functional molecules in target organs-such as the airway-and with clinical outcomes. In this prospective multicenter study of infants (age <1 year) hospitalized with bronchiolitis, we measured serum 25OHD levels and profiled the metabolome of 144 nasopharyngeal airway samples. Among 254 metabolites identified, we defined a set of 20 metabolites that are related to lower serum 25OHD and higher vitamin D-binding protein levels. Of these metabolites, 9 metabolites were associated with a significantly higher risk of positive pressure ventilation use. These metabolites were glycerophosphocholines esterified with proinflammatory fatty acids (palmitate, arachidonate, linoleate, and stearate), sphingomyelins, alpha-hydroxyisovalerate, 2-hydroxybutyrate, and 3-(4-hydroxyphenyl)lactate (all FDR<0.05). Based on the multicenter data, vitamin D-related airway metabolites were associated with risks of bronchiolitis severity.

Keywords: airway; bronchiolitis; metabolome; severity; vitamin D.

Figure 1.. Correlations between circulating vitamin D compounds and selected nasopharyngeal airway metabolites, and their associations with risks of positive pressure ventilation among infants with bronchiolitis

The heatmap (left) shows the correlations between the circulating vitamin D-related compounds and 20 selected nasopharyngeal metabolites that were examined using hierarchical clustering with average linkage algorithm. The table (right) summarizes the adjusted associations between each of selected nasopharyngeal metabolites with risks of PPV use. Bold results are statistically significant with FDR of <0.05. OR are calculated per each incremental increase in scaled level. Abbreviations: 25OHD, 25-hydroxyvitamin D; CI, confidence interval; DBP, vitamin D-binding protein; FDR, false discovery rate; GPC, glycerophosphocholine; OR, odds ratio; sPLS, partial least squares. * Logistic regression models adjusting for patients’ age, sex, race/ethnicity, feeding status, body weight at presentation, detected virus, and serum free 25OHD levels. † Generalized linear mixed-effects models adjusting for the covariates above and accounting for potential patient clustering within the hospitals.