Abstract
Biological agents such as omalizumab and monoclonal antibodies that inhibit type 2 immunity significantly reduce exacerbations, which are mainly due to viral infections, when added to inhaled corticosteroids in patients with severe asthma. The mechanisms for the therapeutic benefit of type 2 inhibitors in reducing virally-induced exacerbations, however, remain to be fully elucidated. Preclinical and clinical evidence supports the existence of a close counter-regulation of the high-affinity IgE receptor and interferon pathways, and a potential dual mechanism of action and therapeutic benefit for omalizumab and other type 2 inhibitors that inhibit IgE activity, which may enhance the prevention and treatment of virally-induced asthma exacerbations. Similar evidence regarding some novel type 2 inhibitor therapies, including biological and small molecule inhibitors, suggest that such a dual mechanism of action with enhancement of interferon production working through non-IgE pathways, might also exist. The specific mechanisms for this dual effect could be related to the close counter-regulation between type 2 and type 1 immune pathways and potential key underlying mechanisms are discussed. Further basic research and better understanding of these underlying counter-regulatory mechanisms could provide novel therapeutic targets for the prevention and treatment of virally-induced asthma exacerbations, as well as type 2 and non-type 2 driven asthma. Future clinical research should examine the effects of type 2 inhibitors on interferon responses and other type 1 immune pathways, in addition to any effects on the frequency and severity of viral and other infections and related exacerbations in patients with asthma as a priority.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: Dr. Efthimiou has nothing to disclose.
Conflict of interest: Dr. Poll has nothing to disclose.
Conflict of interest: Prof. Barnes reports personal fees from AstraZeneca, grants and personal fees from Boehringer-Ingelheim, personal fees from Novartis, personal fees from Chiesi, during the conduct of the review, but not directly related to the scope of the review.
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