Department of Respiratory Medicine, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands.
Department of Pediatric Pneumology and Allergy, University Children's Hospital Regensburg (KUNO), Regensburg, Germany.
Pediatr Pulmonol. 2018 Jun;53(6):836-845. doi: 10.1002/ppul.23976. Epub 2018 Mar 1.
Asthma is a complex multifactorial disease and it is the most common chronic disease in children. There is a high variability in response to asthma treatment, even in patients with good adherence to maintenance treatment, and a correct inhalation technique. Distinct underlying disease mechanisms in childhood asthma might be the reason of this heterogeneity. A deeper knowledge of the underlying molecular mechanisms of asthma has led to the recent development of advanced and mechanism-based treatments such as biologicals. However, biologicals are recommended only for patients with specific asthma phenotypes who remain uncontrolled despite high dosages of conventional asthma treatment. One of the main unmet needs in their application is lack of clinically available biomarkers to individualize pediatric asthma management and guide treatment. Pharmacogenomics, epigenomics, and transcriptomics are three omics fields that are rapidly advancing and can provide tools to identify novel asthma mechanisms and biomarkers to guide treatment. Pharmacogenomics focuses on variants in the DNA, epigenomics studies heritable changes that do not involve changes in the DNA sequence but lead to alteration of gene expression, and transcriptomics investigates gene expression by studying the complete set of mRNA transcripts in a cell or a population of cells. Advances in high-throughput technologies and statistical tools together with well-phenotyped patient inclusion and collaborations between different centers will expand our knowledge of underlying molecular mechanisms involved in disease onset and progress. Furthermore, it could help to select and stratify appropriate therapeutic strategies for subgroups of patients and hopefully bring precision medicine to daily practice.
哮喘是一种复杂的多因素疾病,也是儿童中最常见的慢性疾病。即使患者对维持治疗和正确的吸入技术具有良好的依从性,对哮喘治疗的反应也存在很大的差异。儿童哮喘的不同潜在疾病机制可能是这种异质性的原因。对哮喘潜在分子机制的深入了解导致了最近先进的、基于机制的治疗方法的发展,如生物制剂。然而,生物制剂仅推荐用于特定哮喘表型的患者,这些患者尽管接受了高剂量的常规哮喘治疗,但仍未得到控制。在其应用中,一个主要的未满足需求是缺乏临床可用的生物标志物来个体化儿科哮喘管理和指导治疗。药物基因组学、表观基因组学和转录组学是三个快速发展的组学领域,它们可以提供工具来识别新的哮喘机制和生物标志物来指导治疗。药物基因组学侧重于 DNA 中的变异,表观基因组学研究不涉及 DNA 序列变化但导致基因表达改变的可遗传变化,转录组学通过研究细胞或细胞群体中的完整 mRNA 转录本来研究基因表达。高通量技术和统计工具的进步,以及具有良好表型的患者纳入和不同中心之间的合作,将扩展我们对疾病发生和进展中涉及的潜在分子机制的认识。此外,它还有助于为患者亚组选择和分层适当的治疗策略,并有望将精准医学带入日常实践。