Abstract
Urine metabolomics case-control studies of childhood asthma have demonstrated a discriminative ability. Here, we investigated whether urine metabolic profiles from healthy neonates were associated with the development of asthma in childhood. Untargeted metabolomics by liquid chromatography-mass spectrometry was applied to urine samples collected at age 4 weeks in 171 and 161 healthy neonates born from mothers with asthma from the COPSAC2000 and COPSAC2010 cohorts, respectively, where persistent wheeze/asthma was prospectively diagnosed using a symptom-based algorithm. Univariate and multivariate analyses were applied to investigate differences in metabolic profiles between children who developed asthma and healthy children. Univariate analysis showed 63 and 87 metabolites (q-value < 0.15) in COPSAC2000 and COPSAC2010, respectively, which is promising for discriminating between asthmatic and healthy children. Of those, 14 metabolites were common among the two cohorts. Multivariate random forest and projection to latent structures discriminant analyses confirmed the discriminatory capacity of the metabolic profiles in both cohorts with estimated errors in prediction equal to 35% and AUCpred > 0.60. Database search enabled annotation of three discriminative features: a glucoronidated compound (steroid), 3-hydroxytetradecanedioic acid (fatty acid), and taurochenodeoxycholate-3-sulfate (bile acid). The urine metabolomics profiles from healthy neonates were associated with the development of childhood asthma, but further research is needed to understand underlying metabolic pathways.
Highlights
Childhood asthma is an inflammatory airway disorder, which has recently been increasing, with the prevalence more than doubling in Westernized societies worldwide over the past decades [1].Half of young children experience asthma-like symptoms [2] and one-fifth of preschoolers develop recurrent asthma-like episodes [3], which is the main reason for hospitalization, chronic medication usage, and repeated contact with health care providers with an associated large public health care expenditure [4]
In the COPSAC2000, 171 children had an available urine sample collected before sedation with chloral hydrate
In the COPSAC2010 cohort, 161 children born to mothers with asthma had an available urine sample; 49 (30.4%) of those children developed persistent wheeze/asthma during their first 6 years of life
Summary
Childhood asthma is an inflammatory airway disorder, which has recently been increasing, with the prevalence more than doubling in Westernized societies worldwide over the past decades [1].Half of young children experience asthma-like symptoms [2] and one-fifth of preschoolers develop recurrent asthma-like episodes [3], which is the main reason for hospitalization, chronic medication usage, and repeated contact with health care providers with an associated large public health care expenditure [4]. The presence of a low-grade disease activity in early life before symptoms emerge implicates the existence of biomarkers of perturbed biochemical pathways that may help understand the mechanisms behind why some children will develop wheezing disorders and asthma during childhood. Previous urine metabolomics studies of childhood asthma have demonstrated discriminative abilities in case-control settings [12,13] as well as an ability to predict whether a child with early life wheezing will outgrow the disease or go on to develop asthma [14]. No studies have investigated whether urine metabolomics profiles from healthy neonates are associated with development of asthma during childhood
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
