Abstract

Allergic asthma is a chronic, airway inflammatory disease in which exposure to allergen causes intermittent attacks of breathlessness, airway hyper-reactivity, wheezing and cough. Allergic asthma has been called a "syndrome" resulting from a complex interplay between genetic and environmental factors. Worldwide more than 300 million individuals are affected by this disease and in the US alone, it is estimated that more than 35 million people, mostly children, suffer from asthma. Although animal models, linkage analyses and genome-wide association studies have identified numerous candidate genes a solid definition of allergic asthma has not yet emerged; however, such studies have contributed to our understanding of the multiple pathways to this syndrome. In contrast to the animal models in which T-helper 2 (TH2) cell response is the dominant feature, in the human disease, initial exposure to allergen results in TH2-dependent stimulation of immune response that mediates the production of immunoglobulin E (IgE) and cytokines. Re-exposure to allergen then activates mast cells, which release mediators such as histamines and leukotrienes that recruit other cells including TH2 cells, which mediate the inflammatory response in the lungs. In this review, we discuss the current understanding of how associated genetic and environmental factors increase the complexity of allergic asthma and the challenges it poses for the development of novel approaches to effective treatment and prevention.