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儿童难治性哮喘的药物遗传学

Pharmacogenetics of childhood uncontrolled asthma.

作者信息

Khare Manaswitha, Piparia Shraddha, Tantisira Kelan G

机构信息

Division of Pediatric Hospital Medicine, Department of Pediatrics, University of California San Diego, San Diego, CA, USA.

Division of Pediatric Hospital Medicine, Department of Pediatrics, Rady Children's Hospital of San Diego, San Diego, CA, USA.

出版信息

Expert Rev Clin Immunol. 2025 Feb;21(2):181-194. doi: 10.1080/1744666X.2023.2214363. Epub 2023 May 19.

Abstract

INTRODUCTION

Asthma is a heterogeneous, multifactorial disease with multiple genetic and environmental risk factors playing a role in pathogenesis and therapeutic response. Understanding of pharmacogenetics can help with matching individualized treatments to specific genotypes of asthma to improve therapeutic outcomes especially in uncontrolled or severe asthma.

AREAS COVERED

In this review, we outline novel information about biology, pathways, and mechanisms related to interindividual variability in drug response (corticosteroids, bronchodilators, leukotriene modifiers, and biologics) for childhood asthma. We discuss candidate gene, genome-wide association studies and newer omics studies including epigenomics, transcriptomics, proteomics, and metabolomics as well as integrative genomics and systems biology methods related to childhood asthma. The articles were obtained after a series of searches, last updated November 2022, using database PubMed/CINAHL DB.

EXPERT OPINION

Implementation of pharmacogenetic algorithms can improve therapeutic targeting in children with asthma, particularly with severe or uncontrolled asthma who typically have challenges in clinical management and carry considerable financial burden. Future studies focusing on potential biomarkers both clinical and pharmacogenetic can help formulate a prognostic test for asthma treatment response that would represent true bench to bedside clinical implementation.

摘要

引言

哮喘是一种异质性、多因素疾病,多种遗传和环境风险因素在其发病机制和治疗反应中发挥作用。了解药物遗传学有助于将个体化治疗与哮喘的特定基因型相匹配,以改善治疗效果,尤其是在控制不佳或重度哮喘中。

涵盖领域

在本综述中,我们概述了与儿童哮喘药物反应(皮质类固醇、支气管扩张剂、白三烯调节剂和生物制剂)个体间变异性相关的生物学、途径和机制的新信息。我们讨论了候选基因、全基因组关联研究以及更新的组学研究,包括表观基因组学、转录组学、蛋白质组学和代谢组学,以及与儿童哮喘相关的整合基因组学和系统生物学方法。这些文章是在2022年11月使用数据库PubMed/CINAHL DB进行一系列检索后获得的,最后一次更新。

专家观点

实施药物遗传学算法可以改善哮喘儿童的治疗靶向性,特别是对于那些在临床管理中通常面临挑战且负担相当大经济负担的重度或控制不佳的哮喘儿童。未来专注于临床和药物遗传学潜在生物标志物的研究可以帮助制定哮喘治疗反应的预后测试,这将代表真正的从实验室到床边的临床应用。

相似文献

1
Pharmacogenetics of childhood uncontrolled asthma.儿童难治性哮喘的药物遗传学
Expert Rev Clin Immunol. 2025 Feb;21(2):181-194. doi: 10.1080/1744666X.2023.2214363. Epub 2023 May 19.
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Pharmacogenetic and pharmacogenomic considerations of asthma treatment.哮喘治疗的药物遗传学和药物基因组学考量
Expert Opin Drug Metab Toxicol. 2017 Nov;13(11):1159-1167. doi: 10.1080/17425255.2017.1391215. Epub 2017 Oct 23.
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The pharmacogenetics of asthma treatment.哮喘治疗的药物遗传学
Curr Allergy Asthma Rep. 2009 Jan;9(1):10-7. doi: 10.1007/s11882-009-0002-9.
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Genetic basis for personalized medicine in asthma.哮喘个体化医学的遗传学基础。
Expert Rev Respir Med. 2012 Apr;6(2):223-36. doi: 10.1586/ers.12.9.
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Pharmacogenetics of treatment with leukotriene modifiers.白三烯调节剂治疗的药物遗传学
Curr Opin Allergy Clin Immunol. 2002 Oct;2(5):395-401. doi: 10.1097/00130832-200210000-00005.
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Pharmacogenomics in asthma therapy: where are we and where do we go?哮喘治疗中的药物基因组学:我们在哪里,我们要去哪里?
Annu Rev Pharmacol Toxicol. 2015;55:129-47. doi: 10.1146/annurev-pharmtox-010814-124543. Epub 2014 Sep 29.
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Treatment response heterogeneity in asthma: the role of genetic variation.哮喘治疗反应的异质性:遗传变异的作用。
Expert Rev Respir Med. 2018 Jan;12(1):55-65. doi: 10.1080/17476348.2018.1403318. Epub 2017 Nov 21.

本文引用的文献

6
Immunobiology of Steroid-Unresponsive Severe Asthma.类固醇无反应性重度哮喘的免疫生物学
Front Allergy. 2021 Aug 27;2:718267. doi: 10.3389/falgy.2021.718267. eCollection 2021.
7
An Overview of the Obese-Asthma Phenotype in Children.儿童肥胖型哮喘表型概述
Int J Environ Res Public Health. 2022 Jan 6;19(2):636. doi: 10.3390/ijerph19020636.

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