Computational fluid dynamics model predictions of inhaled corticosteroid deposition in patients with severe asthma

This is the authors' abstract. We don't add key points for this paper.

Background Some patients with severe asthma have persistent type-2 inflammation despite being treated with high-dose inhaled corticosteroids (ICS). The variability in ICS deposition between patients with severe asthma is not well-understood and could contribute to this persistence. Objectives To characterise and compare model-predicted deposition of fine-particle and extrafine-particle ICS in patients with severe asthma based on biomarkers of type-2 inflammation, airway morphology and airway function. Methods Twenty-eight patients with severe asthma performed full-inspiration and full-expiration chest CT on the same day that biomarkers of type-2 inflammation were measured. Functional respiratory imaging and computational fluid dynamics were used to simulate and predict intrathoracic, central and peripheral airway deposition, and central-to-peripheral airway deposition (C:P) ratio of fine-particle ICS (fluticasone-propionate HFA) (ICS FP ) and extrafine-particle ICS (beclomethasone-dipropionate HFA) (ICS EFP ). CT-derived wall area percent (WA%), lumen area (LA) and mucus burden were quantified to characterise airway morphology. Results Simulated deposition of ICS EFP was higher than ICS FP in the intrathoracic, central and peripheral airways (all p<0.0001). Greater WA% and smaller LA were correlated with greater C:P ratio of ICS FP (r=0.60, p=0.0068; r=−0.60, p=0.0072) and ICS EFP (r=0.54, p=0.028; r=−0.54, p=0.026). Participants with elevated sputum eosinophils had a greater C:P ratio, irrespective of particle size (ICS FP , p=0.045; ICS EFP , p=0.021). Conclusions In severe asthma patients with thicker airway walls, narrower airway lumens and elevated biomarkers of type-2 inflammation, a smaller ratio of ICS FP reached the peripheral airways. ICS EFP did not fully mitigate this. Patient-specific airway morphology may impact regional ICS deposition and contribute to persistent inflammation.