More than 400 US pulmonologists and allergists enrolled 4,756 patients ≥6 years of age in the study. Patients were eligible for inclusion in this study if they had been diagnosed with severe or difficult-to-treat asthma by their physician; if they had received care from their physician or healthcare provider for at least one year; had a smoking history of ≤30 pack-years, and had either high use of the healthcare system or high medication use in the previous 12 months. During the three-year study period, patients had seven study visits and completed questionnaires assessing healthcare coverage, characteristics of asthma, medical history, comorbid medical conditions, and selfreported allergen exposure.The results found a common lack of disease control in patients with moderate-tosevere asthma. Hospitalizations, emergency department visits, history of intubation, and use of steroid bursts were consistently high in all age groups, with higher than expected healthcare utilization and missed work or schooldays in patients with the most severe disease.

Treatment of Asthma
A major advance in the treatment of allergic diseases occurred with the advent of biologically derived therapeutic agents made possible by recent advances in molecular biology. These agents have allowed for the development of treatment strategies that selectively attack the molecular mediators responsible for allergic inflammation. Central to this approach is utilization of cell lines or modified bacteria to produce proteins, antibodies, mediator receptors or modified mediators all with the goal of specifically interfering with the function of critical mediators involved in allergic inflammatory responses. This technology potentially allows development of highly specific therapeutic agents that selectively intercept mediators of the allergic immune response in a manner that, potentially, is not only highly targeted but also should provide minimal likelihood of adverse events induced by the therapy.This is a dramatic departure from earlier nonselective immunomodulatory strategies that suppress immune responses by altering the production of inflammatory mediators via effects on transcription of DNA and effects on mediator biosynthetic pathways leading to potential for diverse adverse clinical consequences.

The first biological agent approved as therapy for moderate to severe allergic asthma, omalizumab, is available for treatment of patients who have failed to respond to medium to high dosages of inhaled corticosteroids. Omalizumab is a recombinant humanized monoclonal antibody that targets the part of the IgE antibody that binds to mast cells and basophils. IgE is a central mediator of allergic responses. IgE is the antibody that binds to those proteins known as allergens that induce the wide range of allergic diseases including allergic rhinitis, allergic asthma, food allergies, and allergic urticaria, or hives. IgE is produced consequent to an elegant immunologic cascade of events.The protein that forms the allergen first must gain access to cells, known as antigen presenting cells or dendritic cells, which ingest and modify the allergen for subsequent presentation to a T helper-2 lymphocyte.This cell then interacts with a Bcell, which transforms into a plasma cell, which produces IgE, which is selectively able to bind to the allergen.The allergen-specific IgE is released into the serum and binds to mast cells and basophils, which possess high affinity receptors for IgE. Mast cells are located throughout the respiratory tract, the skin, the eye, and the gut. When allergens are encountered by the IgE bound to the mast cell, adjacent IgE molecules can bind to the specific allergen, thereby cross-linking the IgE molecules and initiating an internal cellular series of events that activate the mast cell.The activated mast cell releases inflammatory mediators stored in secretory granules such as histamine and proteolytic enzymes, while simultaneously forming new mediators, including leukotrienes and prostaglandins, derived from membrane bound phophlipids. Histamine can induce itching, sneezing, wheezing, vasodilation, and microvascular leakage, leading to signs and symptoms of rhinitis, asthma, and hives. Leukotrienes are also able to induce vasodilation and microvascular leakage, in addition to being powerful bronchoconstrictors, and can help recruit inflammatory cells such as eosinophils to the site of the allergic reaction, thus playing a critical rolel in asthma and rhinitis. The activated mast also produces a wide range of cytokines that orchestrate allergic inflammatory responses.The IgE-dependent activation of mast cells is thus the pivotal event in the development of symptoms of allergic diseases, including asthma and rhinitis. By interfering with the ability of serum IgE to bind to mast cells and basophils, omalizumab deprives these cells of the ability to be activated readily by allergens that depend on IgE for triggering cell activation.