Small Airways Disease Affects Aerosol Deposition in Children with Severe Asthma: A Functional Respiratory Imaging Study

Background: Small airways disease (SAD) in severe asthma (SA) is associated with high disease burden. Effective treatment of SAD could improve disease control. Reduced end-expiratory flows (forced expiratory flow [FEF]_25-75 and FEF₇₅) are considered sensitive indicators of SAD. Inhaled medication should be delivered to the smaller peripheral airways to treat SAD effectively. Aerosol deposition is affected by structural airway changes. Little is known about the effect of SAD on aerosol delivery to the smaller peripheral airways. Functional respiratory imaging (FRI) is a validated technique using 3D reconstructed chest computed tomography (CT) and computational fluid dynamics to predict aerosol deposition in the airways. Aim: This study aims to compare central and peripheral (= small airways) deposition between children with SA and SAD and children with SA without SAD, with different inhaler devices and inhalation profiles. Methods: FRI was used to predict the deposition of beclomethasone/formoterol dry powder inhaler (DPI), beclomethasone/formoterol pressurized metered dose inhaler with valved holding chamber (pMDI/VHC), and salbutamol pMDI/VHC for different device-specific inhalation profiles in chest-CT of 20 children with SA (10 with and 10 without SAD). SAD was defined as FEF_25-75 and FEF₇₅ z-score < -1.645 and forced vital capacity (FVC) z-score > -1.645. No SAD was defined as forced expiratory volume (FEV)₁, FEF_25-75, FEF₇₅, and FVC z-score > -1.645. The intrathoracic, central, and peripheral airways depositions were determined. Primary outcome was difference in central-to-peripheral (C:P) deposition ratio between children with SAD and without SAD. Results: Central deposition was significantly higher (∼3.5%) and peripheral deposition was lower (2.9%) for all inhaler devices and inhalation profiles in children with SAD compared with children without SAD. As a result C:P ratios were significantly higher for all inhaler devices and inhalation profiles, except for beclomethasone administered through DPI (p = .073), in children with SAD compared with children without SAD. Conclusion: Children with SA and SAD have higher C:P ratios, that is, higher central and lower peripheral aerosol deposition, than children without SAD. The intrathoracic, central, and peripheral deposition of beclomethasone/formoterol using DPI was lower than using pMDI/VHC.