The use of pharmacogenomics, epigenomics, and transcriptomics to improve childhood asthma management: Where do we stand?

Abstract

Asthma is a complex multifactorial disease and it is the most common chronic disease in children. There is a high variability in response to asthma treatment, even in patients with good adherence to maintenance treatment, and a correct inhalation technique. Distinct underlying disease mechanisms in childhood asthma might be the reason of this heterogeneity. A deeper knowledge of the underlying molecular mechanisms of asthma has led to the recent development of advanced and mechanism-based treatments such as biologicals. However, biologicals are recommended only for patients with specific asthma phenotypes who remain uncontrolled despite high dosages of conventional asthma treatment. One of the main unmet needs in their application is lack of clinically available biomarkers to individualize pediatric asthma management and guide treatment. Pharmacogenomics, epigenomics, and transcriptomics are three omics fields that are rapidly advancing and can provide tools to identify novel asthma mechanisms and biomarkers to guide treatment. Pharmacogenomics focuses on variants in the DNA, epigenomics studies heritable changes that do not involve changes in the DNA sequence but lead to alteration of gene expression, and transcriptomics investigates gene expression by studying the complete set of mRNA transcripts in a cell or a population of cells. Advances in high-throughput technologies and statistical tools together with well-phenotyped patient inclusion and collaborations between different centers will expand our knowledge of underlying molecular mechanisms involved in disease onset and progress. Furthermore, it could help to select and stratify appropriate therapeutic strategies for subgroups of patients and hopefully bring precision medicine to daily practice.

Recent findings in the genetics and epigenetics of asthma and allergy

“…As predicted [70], individualized medicine in this first phase which has started now will rather restrict access to drugs than tailor new drugs to individual needs. Using genetic and nongenetic data such as transcriptomics, epigenetics, and metabolomics, asthma and allergy patients may be first characterized as nonresponders to standard therapy as discussed in a previous conceptual paper [71]. In those patients, even though high doses of steroids and other drugs are administered, their disease is not controlled, leading to ever-increasing amounts of drugs with side effects, uncontrolled symptoms, ER visits, and hospital admissions.…”

Pharmacogenomic associations of adverse drug reactions in asthma: systematic review and research prioritisation

“…The most important ADRs by consensus for each drug class varied; for beta-2 agonists (SABA or LABA) it was tachycardia, for corticosteroids it was both adrenal suppression/crisis and reduced growth, for LTAs it was sleep/ behaviour disturbances, and for theophylline it was nausea and vomiting. Not all participants completed the survey for (14) Adrenal suppression crisis (11) Sleep/behaviour disturbances (12) Nausea and vomiting (9) Arrhythmias (9) Reduced growth (11) Headache 7Arrhythmias 7Fine Tremor (8) Candidiasis (4) Nausea and vomiting (5) Headache (5) Hypokalaemia 6 ADRs of each drug. For theophylline, 39% reported that the drug was no longer used in current treatment steps.…”

“…In addition, a patient’s genotype can affect outcomes of treatment in asthma [ 6 – 8 ]. The data from these pharmacogenomic studies of asthma medication efficacy in children have progressed to the point where there are now polymorphisms approaching clinical utility [ 9 ].…”

Precision Medicine in Childhood Asthma: Omic Studies of Treatment Response

“…In the last year, the role of different omics in asthma treatment response has been recapitulated in different reviews [16][17][18][19][20][21]. This review aims to provide an update on the latest findings in omic studies of pediatric asthma treatment response.…”