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

Abstract

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. 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. 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. 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). 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.