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

Nandhitha Ragunayakam; Ashutosh Thakar; Hosein Sadafi; Carmen Venegas Garrido; Yonni Friedlander; Melanie Kjarsgaard; Kayla Zhang; Anna Dvorkin-Gheva; Manali Mukherjee; Myrna B Dolovich; Ben R Lavon; Mark Inman; Parameswaran Nair; Sarah Svenningsen

doi:10.1136/thorax-2024-222444

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

Thorax. 2025 Mar 27:thorax-2024-222444. doi: 10.1136/thorax-2024-222444. Online ahead of print.

Authors

Nandhitha Ragunayakam^{1

2}, Ashutosh Thakar^{1

2}, Hosein Sadafi³, Carmen Venegas Garrido^{1

2}, Yonni Friedlander^{1

4}, Melanie Kjarsgaard^{1

2}, Kayla Zhang^{1

2}, Anna Dvorkin-Gheva^{1

2}, Manali Mukherjee^{1

2}, Myrna B Dolovich^{1

2}, Ben R Lavon³, Mark Inman^{1

2}, Parameswaran Nair^{1

2}, Sarah Svenningsen^{5

2

4}

Affiliations

¹ Firestone Institute for Respiratory Health, St Joseph's Healthcare Hamilton, Hamilton, Ontario, Canada.
² Department of Medicine, Division of Respirology, McMaster University, Hamilton, Ontario, Canada.
³ FLUIDDA Inc, New York, New York, USA.
⁴ Imaging Research Centre, St Joseph's Healthcare Hamilton, Hamilton, Ontario, Canada.
⁵ Firestone Institute for Respiratory Health, St Joseph's Healthcare Hamilton, Hamilton, Ontario, Canada svennins@mcmaster.ca.

PMID: 40147931
DOI: 10.1136/thorax-2024-222444

Abstract

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.

Keywords: Asthma; Imaging/CT MRI etc.