tight junctions, promotes the relaxation of constricted bronchial smooth muscle, and stimulates the heart. Antihistamines that target the H1 receptor reduce the symptoms that follow the release of histamine from mast cells in allergic rhinoconjunctivitis and IgE-triggered urticaria. In urticaria, for example, the relevant H1 receptors include those on blood vessels and unmyelinated nerve fibers in the skin. Anticholinergic drugs bronchodilate constricted airways and reduce respiratory secretions. Antileukotriene drugs act as antagonists of leukotriene receptors on smooth muscle, endothelial cells, and mucous-gland cells, and are also used to relieve the symptoms of allergic rhinoconjunctivitis and asthma. Inhaled bronchodilators that act on β-adrenergic receptors to relax constricted muscle relieve acute asthma attacks. In chronic allergic disease it is extremely important to treat and prevent the chronic inflammatory injury to tissues, and regular use of inhaled corticosteroids is now recommended in persistent asthma to help suppress inflammation. Topical corticosteroids are used to suppress the chronic inflammatory changes seen in eczema.
A new type of allergy suppressive therapy that is beginning to gain significant use is blockade of IgE function by treatment with monoclonal anti-IgE antibodies, omalizumab being an example. This antibody binds the Fc portion of IgE at the same site that binds the FcεRI on basophils and mast cells. The portion of the Fc domain of IgE that binds to the low-affinity IgE receptor (FcεRII) that is expressed on a variety of leukocytes other than basophils and mast cells is different from the domain that binds the high-affinity FcεRI; omalizumab by steric hindrance blocks binding of IgE to the low-affinity receptor as well as to FcεRI. Prevention of binding of IgE to its receptors on basophils results in downregulation of these receptors on these cells, making them less easily activated by exposure to allergens. Omalizumab also appears to act in chronic allergic asthma to reduce IgE-mediated antigen trapping and presentation by dendritic cells, thus preventing the activation of new allergen-specific TH2 cells. Altogether, these actions lead to suppression of the late-phase response to allergen challenge (see Section 14-9). The antibody is administered by subcutaneous injections once every 2 to 4 weeks. This treatment has been shown to be highly effective for patients with chronic urticaria and also appears to be effective in individuals with severe chronic asthma. Of special interest is that in studies of children with moderate to severe asthma who were treated for 4 years with omalizumab, most remained symptom free without any anti-asthma treatment, suggesting that the anti-IgE therapy modified the natural history of the disease.