Predicting childhood asthma development: are early life metabolite levels the philosopher’s stone to unlock the puzzle?

Background There are critical gaps in our understanding of the temporal relationships between metabolites and subsequent asthma development. This is the first study to examine metabolites from newborn screening in the etiology of early childhood wheezing. Methods 1,951 infants enrolled between 2012–2014 from pediatric practices located in Middle Tennessee in the population-based birth cohort study, the Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure Study (INSPIRE), were linked with metabolite data from the Tennessee Newborn Screening Program. The association between levels of 37 metabolites and number of wheezing episodes in the past 12 months was assessed at 1, 2, and 3 years of life. Results Several metabolites were significantly associated with number of wheezing episodes. Two acylcarnitines, C10:1 and C18:2, showed robust associations. Increasing levels of C10:1 were associated with increasing number of wheezing episodes at 2-years (OR 2.11, 95% CI 1.41–3.17) and 3-years (OR 2.56, 95% CI 1.59–4.11), while increasing levels of C18:2 were associated with increasing number of wheezing episodes at 1-year (OR 1.38, 95% CI 1.12–1.71) and 2-years (OR 1.47, 95% CI 1.17–1.84). Conclusions Identification of specific metabolites and associated pathways involved in wheezing pathogenesis offer insights into potential targets to prevent childhood asthma morbidity.