This article summarizes and provides commentary regarding guidelines on the administration of immunotherapy (IT) for allergic airway disease. Recent investigations have provided important insights into the immunologic mechanism of IT and the prominent role of interleukin-10-producing regulatory T lymphocytes. The most important aspect of successful IT is the administration of an appropriate dose of an extract containing a sufficient concentration of the relevant allergen. This is largely possible now only with standardized extracts. When the major allergen content of successful IT extracts was quantified, efficacy was demonstrated across a surprisingly narrow concentration range (approximately 5-24 μg per injection), irrespective of the extract. This presumably reflects the concentration of an antigen that drives an immune response toward tolerance. It may be predicted that as major allergen content is quantified in currently nonstandardized extracts, effective IT will also be achieved by administering a dose in this range, in contrast to current practices involving fairly arbitrary dosing decisions. With the availability of nonsedating antihistamines, intranasal corticosteroids, and the leukotriene modifiers, inadequate pharmacologic response or intolerable side effects are less commonly the major indications for starting IT for allergic rhinitis (AR). However, with the recognition that a relatively short course (3-5 years) of IT can provide long-term immunomodulation and clinical benefit, a desire to avoid long-term pharmacotherapy and the associated high costs may be the primary indication for IT in AR cases. While evidence overwhelmingly supports the beneficial influences of IT in asthma cases, the positioning of IT for this disorder is not established. The observed prevention of asthma in children who have AR is intriguing, but further studies are required to assess the extent to which the prevalence and severity of chronic asthma will be reduced when these children reach adulthood. Similarly, safety issues overwhelmingly suggest that uncontrolled asthma is the greatest risk factor for mortality associated with IT and that IT therefore may be contraindicated for most patients who have inadequate pharmacologic responses or are unable to tolerate useful pharmacologic agents. Paradoxically, these are the patients for whom a response to IT may be most desirable
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