Impact of Biologics on Oscillometry Defined Small Airway Dysfunction in Uncontrolled Asthma

Small airways dysfunction (SAD) is a recognised treatable trait within severe asthma, associated with worse symptom control and increased exacerbations. It can be measured using forced oscillometry technique (FOT). FOT is an effective and effort-independent method of measuring peripheral lung resistance and compliance. Type 2 inflammation can affect the small airways via eosinophilic inflammation, mucus plugging and smooth muscle inflammation. These are all potential targets of monoclonal antibody therapy. Clinical trials have shown that mepolizumab, dupilumab and tezepelumab all effect both significant and clinically meaningful improvements in oscillometry-defined SAD; however, benralizumab does not. Furthermore, in indirect matched head-to-head comparisons, dupilumab exerts greater improvements compared to either benralizumab or tezepelumab. Future research should consider oscillometry-defined SAD being incorporated as a key clinical outcome in phase 2 studies as new monoclonal antibodies are developed, such as bispecifics, especially both dual upstream (IL33/TSLP) or downstream blockade (IL4/5/13).