Serum metabolomic profiling reveals important difference between infants with and without subsequent recurrent wheezing in later childhood after RSV bronchiolitis

Abstract

We aimed to use serum metabolomics to discriminate infants with severe respiratory syncytial virus (RSV) bronchiolitis who later developed subsequent recurrent wheezing from those who did not and to investigate the relationship between serum metabolome and host immune responses with regard to the subsequent development of recurrent wheezing. Fifty‐one infants who were hospitalized during an initial episode of severe RSV bronchiolitis at 6 months of age or less were included and followed for up to the age of 3 years. Of them, 24 developed subsequent recurrent wheezing and 27 did not. Untargeted serum metabolomics was performed by ultraperformance liquid chromatography coupled with high‐resolution mass spectrometry (UPLC‐MS/MS). Cytokines were measured by multiplex immunoassay. Difference in serum metabolomic profiles was observed between infants who developed recurrent wheezing and those who did not. L‐lactic acid level was significantly higher in infants with recurrent wheezing than those without. Pyrimidine metabolism, glycerophospholipid metabolism, and arginine biosynthesis were identified as the most significant changed pathways between the two groups. Moreover, L‐lactic acid level was positively associated with serum CXCL8 level. This exploratory study showed that differential serum metabolic signatures during severe RSV bronchiolitis in early infancy were associated with the development of subsequent recurrent wheezing in later childhood.

Nasopharyngeal lipidomic endotypes of infants with bronchiolitis and risk of childhood asthma: a multicentre prospective study

“…For example, a recent analysis of three cohort studies of bronchiolitis in the USA and Finland has revealed that the phenotype characterised by a history of breathing problems, allergic predisposition and rhinovirus infection had a significantly increased risk for asthma12—which is in line with the present analysis. Additionally, previous reports using global metabolomics (ie, not lipidomics) have suggested pathobiological roles of complex lipids in the pathobiology of both acute respiratory infections17 38–42 and asthma 19 43 44. For example, concordant with the endotype B (clinical severe lipid sphingolipids-high ) observed in the current study, a metabolomic analysis of 144 infants with bronchiolitis has reported a positive association of sphingolipids in the upper airway with higher bronchiolitis severity 15.…”

Metabolomics of bronchoalveolar lavage in children with persistent wheezing

“…This allowed us to speculate that there could be a clear association between airway metabolomic compositions and wheezing recurrence. Previous studies suggested that serum L-lactic acid level was significantly higher in infants with recurrent wheezing than those without; glycerophospholipid metabolism and arginine biosynthesis were the most significant changed pathways between those infants with and without subsequent recurrent wheezing [ 38 ]. The elevated urine levels of bile acid taurochenodeoxycholate-3-sulfate and fatty acid 3-hydroxytetradecanedioic acid in healthy neonates could indicate an increased risk of asthma later in life [ 39 ].…”

Metabolomics in pediatric lower respiratory tract infections and sepsis: a literature review

“…23,24 To our knowledge, four prospective studies have been conducted wherein the metabolic profiles of children with bronchiolitis were analyzed, and the children were then followed to determine if they developed a wheeze. 27,[35][36][37] Zhu et al collected nasopharyngeal samples from 918 infants and clustered them into five different metabotypes. The metabotype rich in amino acids and low in polyunsaturated fatty acids was found to be associated with an increased risk for asthma at 5 years old.…”

“…37 The goal of the remaining three studies was to identify metabolic pathways involved in the pathogenesis of wheeze following bronchiolitis and did not include clinical models for the prediction of wheeze. 27,35,36 Nonetheless, significant metabolites were reported in two studies that were associated with wheeze 2-3 years after bronchiolitis (Supplemental Tables S8 and S9). 35,36 There are a number of clinical tools that have been developed for predicting asthma in children based on features including age, sex, personal and family history of atopic conditions, and serum eosinophil and immunoglobulin E levels.…”

“…27,35,36 Nonetheless, significant metabolites were reported in two studies that were associated with wheeze 2-3 years after bronchiolitis (Supplemental Tables S8 and S9). 35,36 There are a number of clinical tools that have been developed for predicting asthma in children based on features including age, sex, personal and family history of atopic conditions, and serum eosinophil and immunoglobulin E levels. 38 Unfortunately, each clinical tool has its own drawbacks, and are often limited by poor negative likelihood ratios.…”