A review of metabolomics approaches and their application in identifying causal pathways of childhood asthma

Abstract

Because asthma is a disease that results from host-environment interactions, an approach that allows assessment of the effect of the environment on the host is needed to understand the disease. Metabolomics has appealing potential as an application to study pathways to childhood asthma development. The objective of this review is to provide an overview of metabolomics methods and their application to understanding host-environment pathways in asthma development. We reviewed recent literature on advances in metabolomics and their application to study pathways to childhood asthma development. We highlight the (1) potential of metabolomics in understanding the pathogenesis of disease and the discovery of biomarkers; (2) choice of metabolomics techniques, biospecimen handling, and data analysis; (3) application to studying the role of the environment on asthma development; (4) review of metabolomics applied to the outcome of asthma; (5) recommendations for application of metabolomics-based -omics data integration in understanding disease pathogenesis; and (6) limitations. In conclusion, metabolomics allows use of biospecimens to identify useful biomarkers and pathways involved in disease development and subsequently to inform a greater understanding of disease pathogenesis and endotypes and prediction of the clinical course of childhood asthma phenotypes.

Therapeutic suppression of pulmonary neutrophilia and allergic airway hyperresponsiveness by an RORγt inverse agonist

“…Currently, phenotypic parameters, such as age of onset, blood and sputum eosinophil levels, biomarkers, corticosteroid sensitivity, and extent of obesity are used to infer endotypes (47). It is likely, however, that more accurate assignments of endotypes will eventually be revealed through a combination of noninvasive tests that could include genetic screening, assessments of occupational and domestic exposures, and metabolomics, in addition to T cell lineage-specific cytokines (48). These types of approaches should identify individuals with Th17-dependent exacerbations predicted to be controlled by inverse agonists of RORγt.…”

Metabolomic Profiling of Infants With Recurrent Wheezing After Bronchiolitis

“…When metabolomics was applied to asthmatic children in an effort to improve our understanding of the pathogenesis of asthma and better characterize its different phenotypes [25], it led to the identification of specific metabolic patterns in these individuals [26][27][28][29]. Although viruses are known to be capable of reprogramming metabolic pathways, very few published studies have applied metabolomics to bronchiolitis.…”

Obesity-Associated Metabolic Signatures Correlate to Clinical and Inflammatory Profiles of Asthma: A Pilot Study

“…Thirdly, lack of validation of the identified metabolites in an additional population set as well as lack of healthy controls and obese subjects without asthma limits the interpretation of the differential metabolites in relation to asthma pathophysiology, while our validation analysis by exploring the relationships of differential metabolites with obesity assessments and clinical or inflammation profiles of asthma would strengthen the results. 50 Fourthly, as for the libraries and unavailability of reference standards, some of the detected metabolites are unidentified, which somewhat limits the exploring of the potential metabolic signature.…”