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Key Points ÎThe immunologic response to subcutaneous immunotherapy is characterized by decreases in the sensitivity of end organs and changes in the humoral and cellular responses to the administered allergens. (A) ÎReduction in end-organ response with immunotherapy includes decreased early and late responses of the skin, conjunctiva, nasal mucosa, and bronchi to allergen challenge; decreased allergen- induced eosinophil, basophil, and mast cell infiltration; blunting of mucosal priming; and reduction of nonspecific bronchial sensitivity to histamine. (A) ÎShortly after initiation of immunotherapy, there is an increase in CD4+CD25+ regulatory T lymphocytes secreting IL-10 and TGF-β associated with immunologic tolerance, which is defined as a long- lived decrease in allergen-specific T cell responsiveness. With continued immunotherapy, there is some waning of this response, and immune deviation from TH2 to TH1 cytokine response to the administered allergen predominates. (A) ÎSpecific IgE levels initially increase and then gradually decrease. Levels of specific IgG1, IgG4, and IgA increase. None of these changes in antibody levels has been shown strongly and consistently to correlate with clinical improvement. (A) ÎIncreases in allergen-specific IgG levels are not predictive of the degree or duration of efficacy of immunotherapy. However, functional alterations in allergen-specific IgG levels, such as changes in avidity, affinity, or both for allergen, might play a role in determining clinical efficacy. (LB) Safety and Patient Selection Table 1. Actions to Reduce Immunotherapy Risk ÎAssess the patient's general medical condition at the time of injection (eg, recent asthma exacerbation and increased asthma symptoms). ÎIn addition to assessing asthma symptoms, consider obtaining a PEF for patients with a history of asthma before administration of the injection. The intention of assessing PEF is to alert the provider to the need for a more in-depth assessment of asthma control. If the PEF is substantially reduced compared with the patient's baseline value, the clinical condition of the patient should be evaluated before administration of the injection.

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