Background:

A significant proportion of patients with severe asthma achieve a complete response to anti-IL5 biologics, but at present, we lack understanding of prerequisites for immune remission in response to biological treatment. Impaired wound healing can be considered a functional marker of epithelial dysfunction and immune dysregulation in severe asthma.

Aim: To assess the association between ability to down-titrate anti-IL5 treatment, and airway wound healing ability in patients undergoing titration of anti-IL5.

Methods: 

The OPTIMAL study is a multicenter, open-label randomized clinical trial evaluating an algorithm for titration of anti-IL5 biologics, in patients with severe asthma, who have obtained complete control on anti-IL5. In a subset of participants, nasal epithelial cells (NEC?s) were cultured and assessed with a wound healing assay. NEC?s were cultured into wells and, when confluent, a wound/scratch was made across the well with the Sartorius Woundmaker tool. Cell confluence in the wound was assessed hourly in an Incucyte live cell imaging tool, and compared between groups after 24 hours.

Results: NEC?s were obtained from 19 patients at baseline. 13 were successful at titrating anti-IL5 biologics and 6 were unsuccessful. Patients unable to downtitrate anti-IL5 tended to have poorer wound healing ability already before down-titration (58 % relative wound confluence versus 68 %, p=0.24).

Conclusion: Patients, who are unable to down-titrate their anti-IL5, tended to have impaired wound healing even before down-titration of biologics, suggesting that epithelial dysfunction could be a marker of incomplete immune remission on treatment.