RT Journal Article
SR Electronic
T1 Dual mechanism of action of T2 inhibitor therapies in virally induced exacerbations of asthma: evidence for a beneficial counter-regulation
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1802390
DO 10.1183/13993003.02390-2018
VO 54
IS 1
A1 John Efthimiou
A1 Chris Poll
A1 Peter J. Barnes
YR 2019
UL http://erj.ersjournals.com/content/54/1/1802390.abstract
AB 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.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