Abstract
Asthma is a heterogeneous and multifactorial respiratory disease with an important impact on childhood. Difficult-to-treat asthma is not uncommon among children, and it causes a high burden to the patient, caregivers, and society. This review aims to summarize the recent findings on pediatric asthma treatment response revealed by different omic approaches conducted in 2018–2019. A total of 13 studies were performed during this period to assess the role of genomics, epigenomics, transcriptomics, metabolomics, and the microbiome in the response to short-acting beta agonists, inhaled corticosteroids, and leukotriene receptor antagonists. These studies have identified novel associations of genetic markers, epigenetic modifications, metabolites, bacteria, and molecular mechanisms involved in asthma treatment response. This knowledge will allow us establishing molecular biomarkers that could be integrated with clinical information to improve the management of children with asthma.
Highlights
Asthma is the most prevalent chronic disease in children and youth [1]
In contrast to the past, when most pharmacogenomic studies of childhood asthma were focused on European-descent populations [16,17], within the reviewed period, the pharmacogenomic studies of childhood asthma have analyzed two underrepresented populations with a high burden of asthma and failure in treatment response [24]: African Americans from the Study of African Americans, Asthma, Genes and Environments (SAGE) and Hispanic/Latinos from the Genes-Environment and Admixture in Latino Americans (GALA II) (Table 1, Table S2). In these two studies (GALA II and SAGE), genomic studies of Short-acting beta-agonists (SABAs) treatment response were carried out by means of genome-wide association studies (GWAS), based on both genotyping arrays and whole-genome sequencing (WGS) data [25,26], and by performing admixture mapping [26]. The latter approach is a type of analysis that can be applied to admixed populations in order to identify genomic regions in which local ancestry is associated with a trait, based on the differences in allele frequency of the single nucleotide polymorphisms (SNPs) depending on their ancestral background [24]
Three pharmacogenomic, three epigenomic, three transcriptomic, one metabolomic, one microbiome, and two integrative omic studies evaluated the responsiveness to SABAs, inhaled corticosteroids (ICSs), or leukotriene receptor antagonists (LTRAs) in children with asthma
Summary
Asthma is the most prevalent chronic disease in children and youth [1]. Globally, its prevalence reaches 11.7% and 14.1% in children aged 6–7 and 13–14 years old, respectively [2]. Personalized medicine has recently emerged aimed to select the most appropriate therapy for each patient based on identifying different asthma phenotypes and endotypes [11]. This review aims to provide an update on the latest findings in omic studies of pediatric asthma treatment response. Studies were eligible if they met the following inclusion criteria: (1) omic studies of treatment response focused on children and youth with asthma, (2) publication date between 1 January 2018 and 31 December 2019, and (3) studies written in English. The criteria to exclude studies were: (1) lack of assessment of asthma treatment response, (2) publications focused on individuals without asthma, (3) studies that did not apply omic approaches, (4) studies focused on animal models, and (5) manuscripts reporting literature reviews, editorials, or opinion articles. All the manuscripts were reviewed by at least three independent authors
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