AimAnti IL5/anti-IL5R biologics are highly effective in asthma by targeting eosinophilic inflammation and reducing exacerbations, but their effects on lung function are less clear. The aim of the study was to explore whether a novel lung function index, σlnCL, provided by a new technique, computed cardiopulmonography (CCP), is modified following treatment with these biologic therapies in patients with severe type-2 high asthma. σlnCL measures inhomogeneity (unevenness) in lung tissue inflation/deflation and is a sensitive index of small-airways disease.MethodsThis was an observational study at a tertiary asthma clinic. Fifty-four patients with type- 2 high asthma were evaluated at baseline and following their 4th biologic injection with an anti-IL5 or anti-IL5R agent 3 or 4 months later, respectively. Assessments included CCP (as described in [1]) and standard spirometry, both pre- and post-bronchodilation with salbutamol, and measurements of blood eosinophil count (BEC), FeNO and ACQ5.ResultsBiologic therapy significantly improved both FEV1%pred and σlnCL (p<0.01 and p<0.005, respectively), as did bronchodilation (p<0.001 for both), regardless of the specific biologic used (linear mixed-effects modelling). When considering BEC, FeNO, and ACQ5 as predictors in the models, BEC and ACQ5 significantly influenced FEV1%pred (F-ratio 22.7 and 22.6, respectively, both p<0.001). However, only BEC strongly affected σlnCL values (F-ratio 34.1, p<0.001), while ACQ5 had a weaker effect (F-ratio 5.4, p<0.05). FeNO did not show statistical significance.The change in post-bronchodilator σlnCL following biologics followed a bimodal distribution (Akaike information criterion). Patients responding with a fall in σlnCL also had a significant increase in FEV1%pred compared to those without σlnCL changes (t-test, 13.1% vs. -1.6%, p<0.001, figure 1). S94 Figure 1‘σlnCL Responders’, i.e. patients who exhibited a decrease in σlnCL (standard deviation for the natural logarithm of standardized lung compliance) following their fourth biologic injection (B) also experienced a significant improvement in FEV1%pred (forced expiratory volume in one second as a percentage of predicted) compared to ‘σlnCL Non- Responders’, i.e. those who did not show the changes in σlnCL, (A)ConclusionsCCP categorized patients into two groups: responders and non-responders to biologics in terms of lung function changes. Although the effectiveness of anti-IL5 therapy may not rely on direct lung function changes, a subgroup of patients experienced early and significant lung function improvement. Additionally, our findings revealed a strong association between σlnCL and systemic eosinophilic inflammation levels (BEC) in type-2 high asthma, both at baseline and after biologic treatment.ReferenceMagor-Elliot, et al. 2022. doi:10.1152/japplphysiol.00436.2022Please refer to page A286 for declarations of interest related to this abstract.