Genetic Determinants of Poor Response to Treatment in Severe Asthma

Abstract

Severe asthma is a multifactorial disorder with marked phenotypic heterogeneity and complex interactions between genetics and environmental risk factors, which could, at least in part, explain why during standard pharmacologic treatment, many patients remain poorly controlled and at an increased risk of airway remodeling and disease progression. The concept of “precision medicine” to better suit individual unique needs is an emerging trend in the management of chronic respiratory diseases. Over the past few years, Genome-Wide Association Studies (GWAS) have revealed novel pharmacogenetic variants related to responses to inhaled corticosteroids and the clinical efficacy of bronchodilators. Optimal clinical response to treatment may vary between racial/ethnic groups or individuals due to genetic differences. It is also plausible to assume that epigenetic factors play a key role in the modulation of gene expression patterns and inflammatory cytokines. Remarkably, specific genetic variants related to treatment effectiveness may indicate promising pathways for novel therapies in severe asthma. In this review, we provide a concise update of genetic determinants of poor response to treatment in severe asthma and future directions in the field.

Exploring Factors Underlying Poorly-Controlled Asthma in Adults by Integrating Phenotypes and Genotypes Associated with Obesity and Asthma: A Case-Control Study

“…In contrast to the reported SNPs associated with poorly-controlled asthma in previous studies, 38 we obtained 16 obesity-associated SNPs from a matched-case control study in an Asian population, which might be attributed to ethnic differences, and we did not access pharmacogenomic analysis for therapeutic responses to ICS or bronchodilators. The current predictive biological function of SNPs genes reflects the possible obesity-asthma shared genetic effects, involving the pro-inflammatory effects of adipose tissue fetal programming and epigenetics.…”

Impact of frailty in elderly patients with moderate to severe asthma

“…Additionally, accurate interpretation of lung function tests can be challenging because physiologic age-related respiratory changes mimic obstructive functional patterns and neurocognitive function could eventually impair the ability to perform spirometry in some patients [ 23 ]. Furthermore, epigenetic mechanisms mediate nonstructural changes in gene expression that are regulated by DNA methylation patterns, microRNA expression and histone modifications have been described with advancing age [ 24 ]. It is possible that some of the changes noted above might be associated with airway remodelling and poor treatment response.…”

Predictive genetic panel for adult asthma using machine learning methods

“… 5 Identifying genetic variations associated with asthma and discovering the molecular interactions between the omics that confer risk of developing this disease will help us to unravel the biological pathways involved in the pathogenesis of asthma, resulting in improved treatment. 6 , 7 …”