Inhaled corticosteroid delivery is markedly affected by breathing pattern and valved holding chamber model

<bold>Background:</bold> Independent high-quality research is lacking on valved holding chambers (VHCs) especially regarding the drug delivery (DD) of inhaled corticosteroids (ICS). Fluticasone propionate (FP) is the most widely used ICS for children globally. <bold>Methods:</bold> In an in vitro setting the DD and fine particle dose (FPD) of FP from a pressurized metered dose inhaler (pMDI, Flixotide Evohaler®) was tested with AeroChamber plus Flow-Vu (AC), Babyhaler (BH), EasyChamber (EC) and Optichamber Diamond (OD) using a Next Generation Impactor. The pMDI+VHC setup was connected to a child throat model without a facemask. Breathing patterns representing calm tidal breathing of 4 and 6-year-old children, and a steady 3-sec inhalation, were simulated using volumes ranging from 150–1000 ml. <bold>Results:</bold> OD showed the lowest proportion of FP trapped in the throat with all breathing patterns. AC had similar FPD in the respirable (1–5 µm) range irrespective of breathing pattern. OD and EC showed higher DD as well as higher concentrations in the 1–5 µm range with both tidal breathing compared to 3-s inhalation. Compared to EC, the FPD of the other VHCs were skewed towards <2 µm particles. BH performed poorly (low DD and low FPD in the respirable range) in all scenarios. <bold>Conclusions:</bold> The DD and FPD of FP is significantly influenced by both the breathing pattern and the type of VHC used. Consistent and effective drug delivery within the respirable range is crucial, particularly when using ICS. It is imperative to utilize well-tested, high-quality VHCs to optimize therapeutic outcomes while minimizing potential local side effects.