Future clinical implications emerging from recent genome-wide expression studies in asthma

Abstract

Host susceptibility to environmental triggers is the most likely explanation for the development of asthma. Quantifying gene expression levels in disease-relevant tissues and cell types using fast evolving genomic technologies have generated new hypotheses about the pathogenesis of asthma and identified new therapeutic targets to treat asthma and asthma-exacerbations. New biomarkers and distinct transcriptomic phenotypes in blood, sputum and other tissues were also identified and proved effective to refine asthma classification and guide targeted therapies. The wealth of information provided by transcriptomic studies in asthma is yet to be fully exploited, but discoveries in this field may soon be implemented in clinical settings to improve diagnosis and treatment of patients afflicted with this common disease.

Keywords::

• asthma
• biomarkers
• gene expression profiling
• predictive testing
• transcriptomics

Acknowledgements

JC Bérubé is a recipient of the Pierre J. Durand doctoral recruitment scholarship award from the Faculty of Medicine of Laval University. Y Bossé was a research scholar from the Heart and Stroke Foundation of Canada and he is now recipient of a Junior 2 Research Scholar award from the Fonds de recherche Québec – Santé (FRQS). The research program of Dr. Bossé is supported by the Canadian Institutes of Health Research (MOP-102481, MOP-123369, PPP-130151), the Heart and Stroke Foundation, the Cancer Research Society and Read for the Cure, the Canadian Gene Cure Foundation, the Respiratory Health Network of the FRQS and the ‘Fondation de l’Institut universitaire de cardiologie et de pneumologie de Québec’.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Gene expression traits are highly sensitive, spatiotemporal dependent and different in nature based on rapidly evolving measurement platforms.

• Methodologies vary widely to perform genome-wide expression studies in asthma in terms of source of tissues/cells, species studied, asthma phenotypes, gene expression platforms, treatment groups and time points, which make these studies difficult to compare and summarize at this point.

• Animal models of asthma clearly demonstrated that the baseline transcriptome as well as changes that occur during development stages and following exposure to environmental triggers are genetically determined.

• Transcriptomic studies in human identified a number of new therapeutic targets that required further investigation.

• The first clinical applications of transcriptomic studies in asthma are starting to be developed and may soon improve asthma classification and guide the use of conventional and emerging drugs.