Structure–function–treatment relationships of aerosol deposition in patients with severe asthma

Abstract

Inhaled aerosols, the cornerstone in the everyday therapeutic management of patients with asthma, target drug directly to their pathophysiological site of action within the lungs. Asthma is a disease of the whole airway tree1; that is, the central and peripheral airways, where the peripheral airways are considered a treatable trait.2 However, the complex architecture of the lungs with varied morphologic airway structures and disease pathologies results in variable, heterogeneous and patchy deposition patterns of inhaled drug. This leads to varying sensitivity from the multiple cell types targeted within the lungs, and the resultant therapeutic efficacy depends not only on drug pharmacology but also on the extent, site and degree of penetration of aerosol deposition in the airways.3 Radiolabelling of inhaled aerosols, coupled with direct in vivo lung imaging, has determined that smaller drug particles achieve deeper penetration into the lungs in patients with asthma.4 The study by Ragunayakam et al 5 forwards our understanding of structure–function–treatment relationships of inhaled corticosteroid (ICS) deposition and distribution in the lungs of patients with severe asthma, stratified by biomarkers of T2 inflammation. The authors assessed extrafine particles (<2 µm) of beclometasone compared with fine-particle fluticasone propionate (where CT-derived in silico airways modelling was used to predict ICS deposition in the lungs), with physiological, radiological and T2 inflammatory factors. Greater intrathoracic, central and peripheral airway deposition was observed with extrafine-particles compared with fine-particle ICS, confirming the …