Image-based modelling of inhaler deposition during respiratory exacerbation

Abstract

AbstractFor many of the one billion sufferers of respiratory diseases worldwide, managing their disease with inhalers improves their ability to breathe. Poor disease management and rising pollution can trigger exacerbations which require urgent relief. Higher drug deposition in the throat instead of the lungs limits the impact on patient symptoms. To optimise delivery to the lung, patient-specific computational studies of aerosol inhalation can be used. How-ever in many studies, inhalation modelling does not represent an exacerbation, where the patient’s breath is much faster and shorter. Here we compare differences in deposition of inhaler particles (10, 4 µm) in the airways of a healthy male, female lung cancer and child cystic fibrosis patient. We aimed to evaluate deposition differences during an exacerbation compared to healthy breathing with image-based healthy and diseased patient models. We found that the ratio of drug in the lower to upper lobes was 35% larger during healthy breathing than an exacerbation. For smaller particles the upper airway deposition was similar in all patients, but local deposition hotspots differed in size, location and intensity. Our results identify that image-based airways must be used in respiratory modelling. Various inhalation profiles should be tested for optimal prediction of inhaler deposition.HighlightsRegional and local drug deposition was modelled in three patients during normal, sinusoidal inhalation and an exacerbation.Local drug deposition changes with airway shape and inhalation profile, even when regional deposition is similar.Image-based models were combined with highly-resolved particle tracking including particle contact and cohesion.Fluid model validated by comparing gas velocity field with in vitro experiments.