A System Pharmacology Multi-Omics Approach toward Uncontrolled Pediatric Asthma
Mahmoud I. Abdel‐Aziz, Anne H. Neerincx, Susanne J. H. Vijverberg, Simone Hashimoto, Paul Brinkman, Mario Gorenjak, Antoaneta A. Toncheva, Susanne Harner, Susanne Brandstetter, Christine Wolff, Javier Pérez-García, Anna M. Hedman, Catarina Almqvist, Paula Corcuera, Javier Korta‐Murua, Olaia Sardón‐Prado, Maria Pino‐Yanes, Uroš Potočnik, Michael Kabesch, Aletta D. Kraneveld, Anke H. Maitland‐van der Zee
Abstract
There is a clinical need to identify children with poor asthma control as early as possible, to optimize treatment and/or to find therapeutic alternatives. Here, we present the "Systems Pharmacology Approach to Uncontrolled Pediatric Asthma" (SysPharmPediA) study, which aims to establish a pediatric cohort of moderate-to-severe uncontrolled and controlled patients with asthma, to investigate pathophysiological mechanisms underlying uncontrolled moderate-to-severe asthma in children on maintenance treatment, using a multi-omics systems medicine approach. In this multicenter observational case-control study, moderate-to-severe asthmatic children (age; 6-17 years) were included from four European countries (Netherlands, Germany, Spain, and Slovenia). Subjects were classified based on asthma control and number of exacerbations. Demographics, current and past patient/family history, and clinical characteristics were collected. In addition, systems-wide omics layers, including epi(genomics), transcriptomics, microbiome, proteomics, and metabolomics were evaluated from multiple samples. In all, 145 children were included in this cohort, 91 with uncontrolled (median age = 12 years, 43% females) and 54 with controlled asthma (median age = 11.7 years, 37% females). The two groups did not show statistically significant differences in age, sex, and body mass index z-score distribution. Comprehensive information and diverse noninvasive biosampling procedures for various omics analyses will provide the opportunity to delineate underlying pathophysiological mechanisms of moderate-to-severe uncontrolled pediatric asthma. This eventually might reveal novel biomarkers, which could potentially be used for noninvasive personalized diagnostics and/or treatment.