Needs for Systems Approaches to Better Treat Individuals With Severe Asthma: Predicting Phenotypes and Responses to Treatments

Abstract

Asthma is a frequent heterogeneous multifactorial chronic disease whose severe forms remain largely uncontrolled despite the availability of many drugs and educational therapy. Several phenotypes and endotypes of severe asthma have been described over the last two decades. Typical type-2-immunity-driven asthma remains the most frequent phenotype, and several targeted therapies have been developed and are now available. On the contrary, non-type-2 immunity-driven severe asthma is less understood and still requires efficient innovative therapies. A personalized approach would allow improving asthma control with the help of robust biomarkers able to predict phenotypes/endotypes, exacerbations, response to targeted treatments and, in the future, possible curative options. Some data from large multicenter cohorts have emerged in recent years, especially in transcriptomics. These data have to be integrated and reproduced longitudinally to provide a systems approach for asthma care. In this focused review, the needs for such an approach and the available data will be reviewed as well as the next steps for achieving personalized medicine in asthma.

Treatable Mechanisms in Asthma

“…Such pathways can be understood as potential robust biomarkers with the needed accuracy for precision medicine that, to be successful, must be predictive, preventive, personalised and participative [ 57 ]. These biomarkers will surely help to better model asthma and provide ‘care and cure’ at an individual patient level, and thus move from dissociated fingerprints to integrative handprints [ 58 ].…”

Immunothérapie spécifique d’allergènes et médecine personnalisée : quel état des lieux en 2020 ?

“…L'intér t de Enfin, il n'est pas exclu (et probable) que l'induction de tolérance spécifique à un ou plusieurs allergènes à long terme soit sous-tendus par des mécanismes cellulaires et moléculaires propres à chaque famille d'allergène. L'apport des sciences omiques de par leur approche non supervisée et l'intégration en systèmes biologiques (génomique, transcriptomique, microbiomique, métabolomique, glycomique, lipidomique, exposomique, clinicomique, volatolomique etc..) permettrait de mettre en lumière ces différences afin de mieux les caractériser et ainsi de basculer du concept de « trait traitable » au concept de « mécanisme traitable » avec ses biomarqueurs compagnons à l'instar de ce qui est actuellement développé dans l'asthme (17,46).…”

Systems Approaches to Treatment Response to Imatinib in Severe Asthma: A Pilot Study

“…More than 60% of adults with asthma, have uncontrolled, symptomatic asthma [ 2 ]. There is an acute need for advances in pharmacologic therapies and pharmacogenetics in asthma to improve the identification of novel drug targets [ 3 ]. In a randomized clinical trial repurposing imatinib, a tyrosine kinase inhibitor of the KIT proto-oncogene receptor tyrosine kinase, for severe asthma, imatinib use improved forced expiratory volume in 1 s (FEV 1 ) compared to placebo treatment [ 4 ].…”

“…Systems biology analytic approaches are designed to capture complex biological interactions that may inform a particular clinical phenotype [ 8 ]. The application of these quantitative tools can identify biological pathways or components of those pathways that predict phenotypes/endotypes, biomarkers and drug interventions [ 3 ]. Clinically meaningful findings may contribute to personalized approaches to care.…”