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Personalized management of asthma exacerbations: lessons from genetic studies.

ABSTRACT: INTRODUCTION:The genetics of severe asthma and asthma exacerbations are distinct from milder forms of asthma. Gene-environmental interactions contribute to the complexity and heterogeneity of severe asthma and asthma exacerbations, and pharmacogenomic studies have also identified genes that affect susceptibility to asthma exacerbations. AREAS COVERED:Studies on the genetics, gene-environment interactions, and pharmacogenomics of asthma exacerbations are reviewed. Multiple individual genetic variants have been identified to be associated with asthma exacerbations but each genetic polymorphism explains only a fraction of the disease and by itself is not able to translate into clinical practice. Research is shifting from candidate gene studies and genome wide association studies towards more integrative approaches to translate genetic findings into clinical diagnostic and therapeutic tools. EXPERT COMMENTARY:Integrative approaches combining polygenic or genomic data with multi-omics technologies have the potential to discover new biologic mechanisms and biomarkers for severe asthma and asthma exacerbations. Greater understanding of genomics and underlying biologic pathways will also lead to improved prevention and treatment, lowering costs, morbidity, and mortality. The utilization of genomic testing and personalized medicine may revolutionize asthma management, in particular for patients with severe, refractory asthma.

SUBMITTER: Wang AL

PROVIDER: S-EPMC5642928 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Personalized management of asthma exacerbations: lessons from genetic studies.

Wang Alberta L AL Tantisira Kelan G KG

Expert review of precision medicine and drug development 20161220 6

<h4>Introduction</h4>The genetics of severe asthma and asthma exacerbations are distinct from milder forms of asthma. Gene-environmental interactions contribute to the complexity and heterogeneity of severe asthma and asthma exacerbations, and pharmacogenomic studies have also identified genes that affect susceptibility to asthma exacerbations.<h4>Areas covered</h4>Studies on the genetics, gene-environment interactions, and pharmacogenomics of asthma exacerbations are reviewed. Multiple individu ...[more]

PMID: 29051920

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Project description:There is a need for improved therapies for severe asthma. Lebrikizumab, a humanized monoclonal antibody that binds to interleukin (IL)-13, is under development for the treatment of poorly controlled asthma. This article reviews the potential role of IL-13 in the pathogenesis of asthma, the efficacy and safety of lebrikizumab in humans, and progress in patient selection for lebrikizumab therapy. IL-13 is a T-helper (Th2) cell-derived cytokine implicated in inflammatory responses in asthma, including serum immunoglobulin-E synthesis, mucus hypersecretion, and subepithelial fibrosis. Blocking the pro-inflammatory effects of IL-13 with lebrikizumab has the potential to improve asthma control. Published data on the efficacy and safety of lebrikizumab in the treatment of asthma are relatively limited. The late asthmatic response after inhaled allergen challenge is reduced by almost 50%, following treatment with lebrikizumab. In a Phase II study performed in 219 adults with poorly controlled asthma despite inhaled corticosteroids (MILLY trial), lebrikizumab produced an improvement in prebronchodilator forced expiratory volume in 1 second of 5.5% compared with placebo at 12 weeks, but had no effects on other efficacy end points. Adverse effects were similar to placebo, except that musculoskeletal side effects occurred slightly more often with lebrikizumab. Stratifying patients into a high Th2 phenotype using serum periostin, which is upregulated in lung epithelial cells by IL-13, may identify individuals responsive to blockade of IL-13. In the MILLY trial, lebrikizumab treatment was associated with greater improvement in lung function in patients with elevated serum periostin levels compared with those with low periostin levels. Two large Phase III randomized controlled trials in patients with uncontrolled asthma are underway to establish the safety and efficacy of lebrikizumab when administered over a 52-week period. These studies will also help to determine whether identifying patients with a Th2 high inflammatory phenotype using serum periostin allows a personalized approach to the treatment of asthma.

Dataset Information

Personalized management of asthma exacerbations: lessons from genetic studies.

Publications

Personalized management of asthma exacerbations: lessons from genetic studies.

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