Towards precision medicine: The application of omics technologies in asthma management

What else could be done for the management of severe asthma

Omics technology supports precision medicine in identifying the most effective treatment for different clinical phenotypes, in contrast with the “one size fits all” approach. Indeed, omics sciences contribute to the definition of new biomarkers, which can be useful as hallmarks of a specific asthma endotype or phenotype, and relevant as novel targets for pharmacology treatments. In the field of molecular biology, omics is a neologism that indicates high-throughput experimental technologies providing the tools for comprehensively monitoring the disease processes at a molecular level. The suffix “ome” comes from “chromosome” and currently includes several biological fields such as genomics, transcriptomics, proteomics, metabolomics and epigenomics. Genomics and transcriptomics have been used to identify genes associated with asthma severity (Figure 1). Recent genome-wide association studies (GWAS) have shed light on distinct pathways that contribute to asthma inflammation. Genes such as HLA, IL13, IL33, thymic stromal lymphopoietin (TSLP) involved in Th2 pathway, IL-1 receptor–like 1 (IL1RL1), encodes ST2, and the receptor for IL-33 are associated with asthma onset. In contrast, it is well-known that the risk of childhood asthma is associated with the 17q21 locus encoding the ORMDL3 and GSDML genes^6,7. Transcriptomics are focused on microRNAs (MiRNAs). MiRNAs are small non-coding single strand RNA chains involved in post-transcriptional regulation processes. MiRNAs play a key role in regulating cell functions as well as in modulating the inflammatory pathways. They may influence the single endotype profile in the complex asthma phenotype picture. MiRNAs can be collected through peripheral blood sampling, or, more invasively, through bronchial biopsies and induced sputum^8,9. Under-expression of miRNA 192 in blood was investigated in a small study, in which asthma patients underwent an allergen inhalation challenge¹⁰. The relevance of miRNA as a biomarker is increasingly investigated. Different levels of miR-1248 serum expression in asthmatic vs non-asthmatic patients have been documented. In asthmatic patients miR-1248 is also involved in the regulation of IL-5 pathway¹⁰. Among the omics, circulating miRNA deserves a specific interest. Circulating miRNAs might be a non-invasive biomarker useful in asthma diagnosis and characterisation, as demonstrated in a recent study. According to the authors, a specific subset of circulating miRNAs (miR-125b, miR-16, miR-299-5p, miR-126, miR-206, and miR-133b) was found in patients with allergic rhinitis and asthma¹¹.

Figure 1. A systems biology approach: From omics science to precision medicine.

Epigenomics represent another relevant issue. The “methylome” (the set of DNA methylation patterns) has been increasingly investigated through highly sophisticated sequence-based assays. Epigenetic mechanisms could lead to the identification of new asthma biomarkers. Recently, an epigenetic association between serum IgE concentration and methylation at different loci derived from DNA of leukocites has been described. Methylation at these CpG islands differed significantly in isolated eosinophils between subjects with and without asthma and high IgE levels¹².

Modern and advanced technologies, such as mass spectrometry, allow the detection of several proteins involved in the inflammatory mechanisms of asthma. Among the proteomics signatures characterized so far, Galectin-3 deserves to be mentioned. It has been demonstrated that this protein is expressed in omalizumab responders only. Furthermore galectin–3 seems to be associated with a more evident respiratory function improvement in asthmatic patients treated with omalizumab¹³.

The increasing interest in metabolomics, is mainly due to its prospective clinical applications. According to recent findings it is possible to define the metabolic profile through different samples including exhaled breath, urine, plasma and serum¹⁴. Currently a branch of metabolomics called “breathomics” focuses on volatile organic compounds (VOCs) from the respiratory tract. VOCs represent potential non-invasive metabolic biomarkers, particularly in the diagnosis and monitoring of pulmonary diseases including asthma¹⁵. Moreover, an electronic nose able to discriminate asthmatic from healthy controls by detecting different VOCs in exhaled breath has been developed^15,16. Therefore, metabolomics could play a key role in identifying biomarkers and improving asthma endotyping.