**Genetics of Allergic Asthma and Current Perspectives on Therapeutic Management**

Mina Youssef, Cynthia Kanagaratham, Mohamed I. Saad and Danuta Radzioch

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/63651

#### **Abstract**

Globally, more than 300 million people are asthmatics and this number has been estimated to become 400 million by 2025. Asthma is a chronic inflammatory condition, which, although has no cure, is treatable in most patients. The most common structural alterations in asthmatic airways include thickening of the epithelial and sub epithelial layers, increased airway smooth muscle mass, and angiogenesis. Several genetically control‐ led factors greatly influence the predisposition and severity of allergic asthma. Twin studies have attributed as much as 75% of asthma susceptibility to heredity. Particular‐ ly, genome-wide association studies (GWASs) have discovered several asthma and/or atopy susceptibility genes. Current treatment protocols for managing asthma involve the use of corticosteroids and β-agonists. Over the last 40 years, there has been a marked development-targeted therapy for asthma, such as anti-leukotrienes, anti-immunoglo‐ bulin (Ig)E, anti-tumor necrosis factor (TNF)-α, and anti-interleukins (ILs) (Th2 cytokines). To identify novel targets and to develop newer drug generations, better understanding of asthma molecular pathophysiology is required. Furthermore, the pharmacogenetic studies, focusing on better understanding of beneficial or/and adverse effects to antiasthma drugs, will also facilitate the development of more effective and targeted treatments in specific subpopulations of patients suffering from asthma.

**Keywords:** asthma, asthma therapies, genetics, pharmacogenetics

#### **1. Introduction**

Asthma is an inflammatory chronic condition that has reached globally epidemic levels. Although no cure exists, symptoms are treatable in most patients [1]. Statistically, the number

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of asthmatic cases has been on the rise over the past 10 years and affecting up to 10% of adults and 20% of children worldwide [2]. Globally, more than 300 million people are asthmatics, and this estimate is predicted to become 400 million by 2025 [3]. The worldwide economic burden caused by asthma is predicted to be more than that of both acquired immunod eficiency syndrome (AIDS) and tuberculosis combined together. For example, in the United States of America, the annual asthma care costs exceed US\$6 billion [4]. Moreover, these numbers are due to the fact that more than 50% of asthmatic cases are poorly controlled by medication, since the response to treatments varies considerably among patients despite having similar clinical features [3, 5]. Asthma is characterized by altered and distinct clinical changes in the lung airways obstructing the flow of air into the lungs. The most prominent airway remodel‐ ing features include epithelial and subepithelial layer thickening, increased airway smooth muscle (ASM) mass, and angiogenesis [6]. Different classes of asthma therapies address one or more of the phenotypes of asthma; however, the heterogeneous nature of the disease prevents homogeneous clinical outcomes in response to the current treatment guidelines [7].

In the past two decades, the field of human genetics has evolved due to the advancements in the human genome project and high-throughput sequencing technologies [8, 9]. Currently, the advances in genetic, pharmacodynamic, and pharmacokinetic studies, analyzing responsive‐ ness of patients to various therapies, may eventually allow to prescribe personalized treatment and to shift asthma therapies from classical standards, using mostly corticosteroids and βadrenergic agonists, to a highly tailored approach [10]. Future genetic profiles of the popula‐ tion would form the basis of tomorrow's treatments in order to potentiate the required therapeutic benefits, and to diminish any possible adverse effect risks. Overall, there remains a great need for comprehensive drug research, paralleled with high-throughput genetic profiling, in order to treat asthma in a personalized or stratified manner [11].
