P166 Use of in silico deposition modelling to evaluate the lung deposition patterns of budesonide delivered from different inhaler devices in patients with severe asthma

Abstract

Introduction and objectives Small airways dysfunction and inflammation in the periphery of the lungs contribute substantially to airflow limitation in asthma (Burgel, et al. Eur Respir Rev 2011;20:23–33). Glucocorticoid receptors are widely distributed in the respiratory tract, with increased density in the peripheral airways (Adcock, et al. Am J Respir Crit Care Med 1996:771–782). Therefore, improving the deposition of inhaled corticosteroids within the small airways in asthma is important. In silico lung deposition-modelling via Computational Fluid Dynamics is a method via which to study the drug delivery characteristics of inhaler devices. The objective of this study was to assess the lung deposition patterns achieved for aerosolised budesonide delivered from different inhaler systems in patients with severe asthma. Methods These deposition-modelling experiments used Computed Tomography (CT) images of lungs from 10 patients with severe asthma and translated them into 3D computer models that were then exposed to representative therapeutic doses of budesonide aerosol delivered via simulated inhalation manoeuvres characteristic of the devices being studied. Budesonide was delivered via representative aerosol suspensions (1 mg/2 mL) from a smart nebuliser (FAVOLIR®) or a standard jet nebuliser or 200 µg delivered via a dry-powder inhaler (DPI), a medium-resistance passive device, at 2 inhaled mean flow rates (30 L/min [slow] or 60 L/min [fast]). Results Extrathoracic deposition was higher with the DPI than either of the nebulisers (table 1), even though the in vitro aerodynamic particle size distribution was smaller with the DPI than for either nebuliser device. The smart nebuliser consistently delivered a substantially higher budesonide dose to the intrathoracic region compared with the standard nebuliser and the DPI devices (table 1), both as a consequence of the smart nebuliser being breath-triggered, but also because of its guided long, slow, and deep inhalation manoeuvre. In particular, the smart nebuliser was more effective at targeting the small airways than either the standard nebuliser or the DPI. Conclusions The modelling suggests that the smart nebuliser (FAVOLIR®) delivers aerosolised budesonide to the lungs, and particularly the small airways, of patients with severe asthma much more effectively than a standard jet nebuliser or the DPI studied herein.