A System Pharmacology Multi-Omics Approach toward Uncontrolled Pediatric Asthma

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.

Multi-Omics Profiling Approach to Asthma: An Evolving Paradigm

“…Although single omics studies have contributed to a better understanding of the molecular profiles associated with asthma, they cannot fully capture the entire biological complexity of asthma. Multi-omics analysis holds great potential to molecularly characterize a wide array of complex diseases, including asthma [197,198]. Multiomics analyses take advantage of genomics, transcriptomics, epigenomics, proteomics, metabolomics, the microbiome, and other omics areas to systematically understand health and disease states and uncover new biological insights into disease mechanisms.…”

The Role of Systems Biology in Deciphering Asthma Heterogeneity

“…However, such an approach has not yet been performed in a broader range of patients, so these omics studies have only provided a partial view of the disease due to their focus on specific subtypes rather than the disease as a whole [ 76 , 120 ]. For example, “Systems Pharmacology Approach to Uncontrolled Pediatric Asthma” is a study that uses systems-wide omics in a layered manner to identify the pathophysiological mechanisms, specifically in moderate-to-severe uncontrolled pediatric asthma, rather than assessing across populations [ 121 ].…”

Medication use in uncontrolled pediatric asthma: results from the syspharmpedia study

“…The study population and design have previously been described in detail (Clinicaltrials.gov identifier: NCT04865575) (Abdel-Aziz et al, 2021). Briefly, the inclusion criteria were: (1) children age range 6 to 17 years; (2) doctor-diagnosed asthma; (3) moderate to severe asthma under GINA (Global INitiative of Asthma) (GINA, 2016) treatment Step 2 or higher.…”

“…All study participants visited the outpatient clinic of one of the tertiary hospitals to undergo the following study procedures: clinical evaluation, spirometry with bronchodilator reversibility, asthma questionnaires, and assessment of medication use (Abdel-Aziz et al, 2021). Additional clinical data were gathered from hospital patient files, physician reports, and questionnaires completed by patients or their parents.…”