The understanding of asthma pathogenesis in the era of precision medicine

抄録

Asthma is a syndrome with extremely diverse clinical phenotypes in which the onset, severity, and response to treatment are defined by the complex interplay of many genetic and environmental factors. Environmental factors epigenetically affect gene expression, and the disease is driven by a multidimensional dynamic network involving RNA and protein molecules derived from gene expression, as well as various metabolic products. In other words, specific pathophysiological mechanisms or endotypes are dynamic networks that arise in response to individual genotypes and the various environmental factors to which individuals have been exposed since before birth, such as diet, infection, air pollution, smoking, antibiotic use, and the bacterial flora of the intestinal tract, skin, and lungs. A key feature of asthma genome scans is their potential to reveal the molecular pathways that lead to pathogenesis. Endotypes that drive the disease have a significant impact on the phenotypes of asthma patients, including their drug responsiveness. Understanding endotypes will lead to not only the implementation of therapies that are tailored to the specific molecular network(s) underlying the patient's condition, but also to the development of therapeutic strategies that target individual endotypes, as well as to precision health, which will enable the prediction of disease onset with high accuracy from an early stage and the implementation of preventive strategies based on endotypes. Understanding of endotypes will pave the way for the practice of precision medicine in asthma care, moving away from ‘one-size-fits-all’ medicine and population-based prevention approaches that do not take individuals' susceptibility into account.