With R. R. Rosenthal, we developed a method for quantitative challenge of the airways with aerosols of allergen extracts and showed that the degree of response could be related to severity of disease. This method has been used to test the efficacy of many antiasthmatic drugs. Immunotherapy also minimizes the severity of the response. With R. M. Naclerio, we developed a similar technique for nasal challenge. Sampling of nasal secretions during the allergic response demonstrated appearance of mast cell and basophil mediators such as histamine and leukotrienes.
Kinins also appear in the secretions.
With P. S. Creticos we found that immunotherapy inhibited these responses. Work with allergoids, allergens modified by formaldehyde in a method developed by D. G. Marsh showed that they could be successfully used as a form of immunotherapy. My research has been directed toward understanding the mechanisms of immunotherapy, i.e. the subcutaneous administration of allergenic substances that builds up resistance to further exposure in the respiratory tract to the same allergen. Research thus far has demonstrated that immunotherapy does relatively little to reduce the amount of IgE antibodies available for mast cell mediator release although there is a modest change. On the other hand, T cell proliferation and cytokine secretion by allergen-specific T cells has been shown in several laboratories to be diminished after immunotherapy.