Background

Small airways disease(SAD) in severe asthma is associated with higher disease burden. Effective treatment of SAD could improve disease control. Aerosol deposition is affected by structural airway changes. To date it is unknown whether SAD affects aerosol deposition. End-expiratory flows(FEF75 and FEF25-75) are sensitive spirometry indicators of SAD. Computational fluid dynamic(CFD) modelling is a validated technique to predict aerosol deposition.

Aim

To compare regional aerosol deposition of two inhalers between severe asthma patients with SAD and without SAD.

Methods

CFD simulations were performed on 20 chest CT scans of children with severe asthma (age 10 ± 3.2 years), 10 with and 10 without SAD. SAD was defined as: FEF25-75 and FEF75 z-score <-1.645 and FVC>-1.645. No SAD was defined as: FEV1, FEF25-75, FEF75 and FVC z-score >-1.645. Central and peripheral aerosol deposition was predicted for beclomethasone/formoterol(100/6µg) dry powder inhaler(DPI) and pressurized metered dose inhaler with valved holding chamber(pMDI). Device and age-specific inhalation manoeuvres for DPI and pMDI were simulated. Primary outcome: mean difference in central- and peripheral airways deposition (absolute dose in µg) between the SAD and no SAD group for both devices.

Results

For both DPI and pMDI central airway deposition was higher in the SAD group, 2.8µg (95% CI 0.1? 5.6; p=.043) and 3.9µg (95% CI 0.9 ? 6.9; p=.013) resp., in comparison to the no SAD group. Peripheral airway deposition for DPI and pMDI was lower for patients with SAD, 1.9 (95% CI 0.7 ? 4.5; p=.133) and 3.4µg (95% CI 0.3 ? 7.0; p=.066) resp., however not significant.

Conclusion
SAD affects regional deposition in children with severe asthma.