PHARMACOGENETICS OF INHALED CORTICOSTEROID RESPONSE IN CHILDREN AND ADOLESCENTS WITH ASTHMA

Abstract

Variability in response to inhaled corticosteroids in childhood asthma reflects a combination of genetic characteristics, inflammatory endotype, and actual drug exposure, in which the risk of exacerbation during prescribed treatment does not always characterize biological drug sensitivity. The aim of the review is to critically compare clinical publications on pharmacogenetic and regulatory response markers in children and adolescents, assessing the reproducibility of associations and the evidence supporting personalized treatment; an analysis was conducted with a targeted audit of 25 sources, and the synthesis of quantitative findings was restricted to publications with accessible full texts. Genotype-phenotype observations, genome-wide associations, pharmacoepigenetic markers, prediction models, and treatment-selection trials were considered separately. Russian and Belarusian observations are limited by heterogeneous exposure and the composition of comparator groups, while several international genomic signals received only nominal support; in independent validation of a model combining clinical characteristics with three microRNAs, the area under the receiver operating characteristic curve was 0.72 versus 0.65 for the clinical model. The association of PDGFD with adrenal suppression was replicated in a pediatric validation cohort, although clinical selection and concomitant systemic steroids limit the generalizability of the estimate. Trials of genotype-guided treatment escalation did not identify a significant improvement in the primary symptom-control outcome, while retaining a favorable signal for the secondary exacerbation outcome. Three analytical matrices distinguish outcomes, exposure, replication, and clinical utility; published associations support further independent evaluation of markers but do not, by themselves, justify genotype-based treatment changes.