Untargeted metabolomics of childhood asthma exacerbations from retrospectively collected serum samples

Asthma is a common chronic inflammatory disease of the airways, affecting 360 million people globally. It is characterised by chronic inflammation, recurrent episodes of bronchoconstriction and mucosal hypersecretion. Symptoms include chest tightness, shortness of breath, coughing and wheezing. Oral corticosteroids used for the treatment of asthma have adverse effects, including bone mineralisation and adrenal suppression. Not all children with acute asthma-like symptoms will have persistent asthma in the future. This is particularly common at a pre-school age. This persistence is only known retrospectively. Identifying children early in their disease course can better direct treatment. Additionally, further understanding of the underlying disease mechanisms can direct novel therapies. Metabolomics is the systematic study of metabolites in a biological system. Metabolites are low molecular weight biochemical that are reactants, intermediates and end products of biological reactions. They are highly sensitive and are a snapshot of a particular biochemistry and/or pathophysiology. However, they are also highly sensitive to analytical variation. Thus, there were three aims in this study: to assess the impact of potentially limiting factors of retrospectively collected serum samples on metabolomic analysis; to determine whether metabolomics can identify potential biomarkers to distinguish wheeze/asthma exacerbation and control groups; and to determine whether metabolomics-derived biomarkers can identify differences between preschool-aged and school-aged phenotypes. Serum samples were curated from the Mechanisms of Acute Viral Respiratory Infections in Children (MAVRIC) study. This cohort study recruited children upon presentation to the emergency department at Princess Margaret Hospital with acute lower respiratory illnesses including wheeze/asthma. One–hundred and sixty-one samples were from children with acute wheeze/asthma, and 51 were from healthy controls. Samples