From Expert Review of Respiratory Medicine

Genetic Basis for Personalized Medicine in Asthma

Michael Portelli; Ian Sayers

Abstract and Introduction

Abstract

There is heterogeneity in patient responses to current asthma medications. Significant progress has been made identifying genetic polymorphisms that influence the efficacy and potential for adverse effects to asthma drugs, including; β₂-adrenergic receptor agonists, corticosteroids and leukotriene modifiers. Pharmacogenetics holds great promise to maximise clinical outcomes and minimize adverse effects. Asthma is heterogeneous with respect to clinical presentation and inflammatory mechanisms underlying the disease, which is likely to contribute to variable results in clinical trials targeting specific inflammatory mediators. Genome-wide association studies have begun to identify genes underlying asthma (e.g., IL1RL1), which represent future therapeutic targets. In this article, we review and update the pharmacogenetics of current asthma therapies and discuss the genetics underlying selected Phase II and future targets.

Introduction

Asthma is characterised by reversible airway obstruction, increased bronchial hyper-responsiveness (BHR) and chronic inflammation. However, it is recognized that asthma is heterogeneous regarding the underlying clinical and inflammatory phenotypes present. In the UK, 5.4 million people are currently receiving treatment for asthma, which represents a major burden with respect to mortality, morbidity and National Health Service costs – estimated to be GB£1 billion per year. Current asthma medications (Figure 1) are effective in most but not all patients, with a subgroup of patients (<5%) that have limited disease control, persistent symptoms and exacerbations despite medication use.^[1] There is a need for alternative therapies for these refractory patients and a need to target existing drugs towards those subjects most likely to gain clinical benefit.

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