Exposome and pharmacogenomics: towards precision medicine in childhood asthma

Abstract

Asthma is a complex and heterogeneous disease that requires individualized management. In childhood, poor asthma control can irreversibly compromise the children's lung function. Beyond asthma phenotypes, considering disease endotypes has been assumed a crucial issue in developing tailored therapies. The interaction between genome and exposome determines the emergence of several cellular and molecular mechanisms that contribute to different asthma endotypes and clinical phenotypes. The exposome concept was introduced as an innovative approach for simultaneously assessing environmental risk factors and their impact on human health, thus encompassing the totality of the environmental exposures occurring over a lifetime. Given that different types of environmental exposures occurring throughout life have a major impact on asthma, an exposome-based approach appears to be particularly suggested, as it provides a risk profile rather than individual predictors. Pharmacogenomics refers to the genome-wide study of variants in the deoxyribonucleic acid, which evaluates the effect of genetic variants on the individual's response to treatment. Though many genetic variants have been shown to influence response to asthma treatment, results are still inconsistent and/or effect sizes are small. Furthermore, it should be considered that epigenetic changes, gene-gene and gene-environment interactions could affect pharmacogenomic associations. Sustainability and large-scale population-based studies are needed in order to improve research in exposome and pharmacogenomics. This review aims to discuss the latest developments related to childhood asthma in the fields of exposome and pharmacogenomics as well as challenges in integrating these innovative approaches into clinical practice and opportunities for future research.