Abstract
Biological agents such as omalizumab and monoclonal antibodies (mAbs) that inhibit type 2 (T2) 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 T2 inhibitors in reducing virally induced exacerbations, however, remain to be fully elucidated. Pre-clinical and clinical evidence supports the existence of a close counter-regulation of the high-affinity IgE receptor and interferon (IFN) pathways, and a potential dual mechanism of action and therapeutic benefit for omalizumab and other T2 inhibitors that inhibit IgE activity, which may enhance the prevention and treatment of virally induced asthma exacerbations. Similar evidence regarding some novel T2 inhibitor therapies, including mAbs and small-molecule inhibitors, suggests that such a dual mechanism of action with enhancement of IFN 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 T2 and T1 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 T2- and non-T2-driven asthma. Future clinical research should examine the effects of T2 inhibitors on IFN responses and other T1 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.
Abstract
T2 pathway inhibitors, including mAbs, significantly reduce asthma exacerbations, most of which are virus induced, and may act via a dual mechanism of action or counter-regulation, with targeted reduction in airway inflammation and enhanced IFN production http://ow.ly/N3zd30onQV9
Footnotes
Author contributions: J. Efthimiou conceived the idea of the review and prepared the first draft of the manuscript, and C. Poll and P.J. Barnes both reviewed and revised the first draft. J. Efthimiou, C. Poll and P.J. Barnes reviewed and revised all subsequent drafts, including the submission draft that all authors approved. All three authors reviewed the literature searches, contents, analysis and interpretation of included papers and data. The figure was created by J. Efthimiou, and then reviewed and approved by all authors. No medical writers were employed to write this review.
Conflict of interest: J. Efthimiou has nothing to disclose.
Conflict of interest: C. Poll has nothing to disclose.
Conflict of interest: P.J. Barnes reports personal fees for advisory board work from AstraZeneca, grants and personal fees for advisory board work from Boehringer Ingelheim, and personal fees for lecturing from Novartis and Chiesi, during the conduct of the review, but not directly related to the scope of the review.
- Received December 17, 2018.
- Accepted March 29, 2019.
- Copyright ©ERS 2019