Breathomics in Asthmatic Children Treated with Inhaled Corticosteroids

Abstract

Background: “breathomics” enables indirect analysis of metabolic patterns underlying a respiratory disease. In this study, we analyze exhaled breath condensate (EBC) in asthmatic children before (T0) and after (T1) a three-week course of inhaled beclomethasone dipropionate (BDP). Methods: we recruited steroid-naive asthmatic children for whom inhaled steroids were indicated and healthy children, evaluating asthma control, spirometry and EBC (in asthmatics at T0 and T1). A liquid-chromatography–mass-spectrometry untargeted analysis was applied to EBC and a mass spectrometry-based target analysis to urine samples. Results: metabolomic analysis discriminated asthmatic (n = 26) from healthy children (n = 16) at T0 and T1, discovering 108 and 65 features relevant for the discrimination, respectively. Searching metabolomics databases, seven putative biomarkers with a plausible role in asthma biochemical–metabolic processes were found. After BDP treatment, asthmatic children, in the face of an improved asthma control (p < 0.001) and lung function (p = 0.01), showed neither changes in EBC metabolomic profile nor in urinary endogenous steroid profile. Conclusions: “breathomics” can discriminate asthmatic from healthy children, with prostaglandin, fatty acid and glycerophospholipid as putative markers. The three-week course of BDP—in spite of a significant clinical improvement—was not associated with changes in EBC metabolic arrangement and urinary steroid profile.

Application of Metabolomics in Pediatric Asthma: Prediction, Diagnosis and Personalized Treatment

“…The detection of phosphatidylglycerol, N-acryloylglycine and tiglylglycine in earlyonset asthma [21] are associated with fatty acid metabolism, which is consistent with data suggesting lipid dysregulation in asthma [120,123]. Glycerophospholipid metabolism has been shown to be altered in BALF from animal models of allergic asthma [136] and in asthmatic subjects indicating the possible role of glycerophospholipid in the pathogenesis of asthma and of airway epithelial injury [50,137].…”

“…When comparing the non-severe asthma group to severe asthma, Carraro et al measured metabolites in EBC related to inflammation, 20-hydroxy-PGF2a, thromboxane B2, and 6-keto-prostaglandin F1a [ 30 ]. The occurrence of inflammatory mediators in EBC is a common phenomenon in pediatric [ 120 ] and adult asthma [ 121 , 122 ]. A high omega-6 to omega-3 fatty acid ratio has been suggested to be pro-inflammatory and pro-allergic.…”

Latest Progresses in Allergic Diseases Biomarkers: Asthma and Atopic Dermatitis

“…New techniques include the use of -omics technology, such as transcriptomics, proteomics and metabolomics, to create a detailed profile of the asthma features. One of the latest applications is the metabolic profiling of the breath of asthma patients before and after ICS treatment ( Ferraro et al, 2020 ). Moreover, the aim of the ongoing SMART clinical trial (NCT04194814), started in 2019, is to test new non-invasive methods to evaluate biomarkers for skin structure and function variations.…”

Research Progress of Metabolomics in Asthma

“…Another clinical trial showed that the relative abundance of four metabolites, i.e., lactate, formate, butyrate, and isobutyrate, were significantly higher in EBCs of children with asthma than in healthy controls [ 22 ]. Three metabolites (prostaglandins, fatty acids, and glycerol phospholipids) can be used as biomarkers of breathomics to distinguish asthma children from healthy children [ 23 ]. Obesity and asthma are closely linked, and, interestingly, the EBC metabolomics of obese asthmatics is characterized by a unique metabolic spectrum compared to obesity or asthma alone [ 84 ].…”