精准医学时代对哮喘发病机制的认识
2022/10/17
摘要
哮喘是一种临床表型极其多样的综合征，其发病、严重程度和治疗反应由许多遗传和环境因素的复杂相互作用决定。环境因素表观遗传影响基因表达，疾病是由一个多维动态网络驱动的，该网络涉及RNA和来自基因表达的蛋白质分子以及各种代谢产物。换言之，特定的病理生理机制或内型是一种动态网络，它是对个体基因型和个体出生前就暴露于的各种环境因素（如饮食、感染、空气污染、吸烟、抗生素使用、肠道、皮肤和肺部的菌群）作出反应而产生的。哮喘基因组扫描的一个关键特征是它们有潜力揭示导致发病的分子途径。导致疾病的内型对哮喘患者的表型有重要影响，包括他们的药物反应性。了解内切型将不仅有助于实施针对患者病情的特定分子网络的治疗，还将有助于制定针对个体内切型的治疗策略，以及精准健康，这将有助于从早期高度准确地预测疾病发生，并实施基于内型的预防策略。了解内型将为哮喘诊疗中的精准医学实践铺平道路，即远离“一刀切”的医学和不考虑个人易感性的人群预防方法。
The understanding of asthma pathogenesis in the era of precision medicine
Nobuyuki Hizawa
Abstract
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.
哮喘是一种临床表型极其多样的综合征，其发病、严重程度和治疗反应由许多遗传和环境因素的复杂相互作用决定。环境因素表观遗传影响基因表达，疾病是由一个多维动态网络驱动的，该网络涉及RNA和来自基因表达的蛋白质分子以及各种代谢产物。换言之，特定的病理生理机制或内型是一种动态网络，它是对个体基因型和个体出生前就暴露于的各种环境因素（如饮食、感染、空气污染、吸烟、抗生素使用、肠道、皮肤和肺部的菌群）作出反应而产生的。哮喘基因组扫描的一个关键特征是它们有潜力揭示导致发病的分子途径。导致疾病的内型对哮喘患者的表型有重要影响，包括他们的药物反应性。了解内切型将不仅有助于实施针对患者病情的特定分子网络的治疗，还将有助于制定针对个体内切型的治疗策略，以及精准健康，这将有助于从早期高度准确地预测疾病发生，并实施基于内型的预防策略。了解内型将为哮喘诊疗中的精准医学实践铺平道路，即远离“一刀切”的医学和不考虑个人易感性的人群预防方法。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(Allergol Int. 2022 Oct 1;S1323-8930(22)00110-1. doi: 10.1016/j.alit.2022.09.001.)
(Allergol Int. 2022 Oct 1;S1323-8930(22)00110-1. doi: 10.1016/j.alit.2022.09.001.)
The understanding of asthma pathogenesis in the era of precision medicine
Nobuyuki Hizawa
Abstract
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.
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支气管上皮细胞低CC16 mRNA表达水平与哮喘严重程度相关
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