Asthma in One Breath - Metabolic Signatures for Allergic Asthma in Children by Online Breath Analysis: An Observational Study
R. Weber, B. Streckenbach, L. Welti, D. Inci, M. Kohler, N. Perkins, R. Zenobi, S. Micic⋆, A. Moeller
Abstract
Background: There is a need to improve the diagnosis and management of pediatric asthma. Breath analysis aims to address this by non-invasively assessing altered metabolism and disease-associated processes. Our goal was to identify exhaled metabolic signatures that distinguish children with allergic asthma from healthy controls using secondary electrospray ionization high-resolution mass spectrometry (SESI-HRMS).
Methods: Breath analysis was performed via a SESI source linked to a high-resolution mass spectrometer. Significant m/z features in breath were extracted using the empirical Bayes moderated t-statistics test. Corresponding molecules were identified by MS 2 database matching and pathway analysis.
Findings: 48 allergic asthmatics and 56 healthy controls were included in the study. Among 375 significant m/z features, 134 were putatively identified. Many of these could be grouped to metabolites of common pathways or chemical families. We found several pathways that are well-represented by the significant metabolites, for example lysine degradation elevated in the asthmatic group and two arginine pathways in the healthy group. Assessing the ability of breath profiles to classify samples as asthmatic or healthy in a leave-one-out cross-validation revealed an area under the curve of 0·85.
Interpretation: For the first time, a large number of breath-derived volatile organic compounds (VOCs) that discriminate children with allergic asthma from healthy controls were identified. Many are linked to well-described metabolic pathways and chemical families involved in pathophysiological processes of asthma. Furthermore, a subset of these VOCs showed high potential for clinical diagnostic applications.
Funding: Evi Diethelm-Winteler Foundation, Childhood Research Center, Heidi Ras Stiftung, Zurich Foundation, Lotte und Adolf Hotz Stiftung
Declaration of Interest: The authors declare no conflict of interest.
Ethical Approval: The study was approved by the local ethics committee (KEK-ZH ID2018-00441) and was conducted in accordance with the Declaration of Helsinki.