Distinct Metabolic Profile of Inhaled Budesonide and Salbutamol in Asthmatic Children during Acute Exacerbation

Abstract

Inhaled budesonide and salbutamol represent the most important and frequently used drugs in asthmatic children during acute exacerbation. However, there is still no consensus about their resulting metabolic derangements; thus, this study was conducted to determine the distinct metabolic profiles of these two drugs. A total of 69 children with asthma during acute exacerbation were included, and their serum and urine were investigated using high-resolution nuclear magnetic resonance (NMR). A metabolomics analysis was performed using a principal component analysis and orthogonal signal correction-partial least squares using SIMCA-P. The different metabolites were identified, and the distinct metabolic profiles were analysed using MetPA. A high-resolution NMR-based serum and urine metabolomics approach was established to study the overall metabolic changes after inhaled budesonide and salbutamol in asthmatic children during acute exacerbation. The perturbed metabolites included 22 different metabolites in the serum and 21 metabolites in the urine. Based on an integrated analysis, the changed metabolites included the following: increased 4-hydroxybutyrate, lactate, cis-aconitate, 5-hydroxyindoleacetate, taurine, trans-4-hydroxy-l-proline, tiglylglycine, 3-hydroxybutyrate, 3-methylhistidine, glucose, cis-aconitate, 2-deoxyinosine and 2-aminoadipate; and decreased alanine, glycerol, arginine, glycylproline, 2-hydroxy-3-methylvalerate, creatine, citrulline, glutamate, asparagine, 2-hydroxyvalerate, citrate, homoserine, histamine, sn-glycero-3-phosphocholine, sarcosine, ornithine, creatinine, glycine, isoleucine and trimethylamine N-oxide. The MetPA analysis revealed seven involved metabolic pathways: arginine and proline metabolism; taurine and hypotaurine metabolism; glycine, serine and threonine metabolism; glyoxylate and dicarboxylate metabolism; methane metabolism; citrate cycle; and pyruvate metabolism. The perturbed metabolic profiles suggest potential metabolic reprogramming associated with a combination treatment of inhaled budesonide and salbutamol in asthmatic children.Glucocorticoids and beta2 agonists represent the most important and frequently used drugs for symptom control in asthmatic children during acute exacerbation [1,2]. Current guidelines recommend the combined use of glucocorticoids and beta2 agonists as the preferred therapy for asthmatic children during acute exacerbation [3,4]. The glucocorticoid and beta2 agonist therapies are effective at controlling airway inflammation, reducing asthma symptoms, decreasing airway hyper-responsiveness and reducing the frequency and severity of exacerbations as well as asthma mortality. Despite their undoubted effectiveness and safety, there is still no consensus about the resulting metabolic derangements, including the development of dyslipidaemia, insulin resistance, glucose intolerance, diabetes, central adiposity and skeletal muscle wasting [5][6][7].Both glucocorticoids and beta2 agonists have the potential to influence glucose, lipid and protein...

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