Aerosol Therapy Implications of Particle Deposition Patterns in Simulated Human Airways

Abstract

The efficacy of inhalation therapy may be improved by the selective deposition of aerosolized medicines, by explicitly targeting and delivering drugs to prescribed lung sites. This may be accomplished by controlling particle sizes and regulating breathing patterns. Here, the deposition patterns of 1.9-10.6 μm mass median aerodynamic diameter test aerosols, mapped in surrogate respiratory tracts consisting of replica laryngeal casts and fabricated tracheobronchial models, are analyzed. Configurations of the laryngeal casts corresponded to inspiratory flow rates of 15, 30 and 60 Lmin-l. Particles were preferentially deposited at bifurcations, specifically at carinal ridges. Evidence from other investigations indicates that mucociliary clearance may be impeded at such sites in vivo. When these two effects, enhanced deposition and impaired clearance, are coupled, the findings suggest that epithelial cells and receptors at airway branching sites may receive concentrated doses of inhaled pharmacological agents. To focus the effects of airborne drugs the lung should, therefore, be considered as a serial network of Y-shaped bifurcation units. The findings have important implications to current aerosol therapy using metered-dose inhalers and nebulizers, and future protocols including: (1) the treatment of bronchogenic carcinomas because malignant tumors have a predilection for upper airway bifurcations; and, (2) lung diseases related to the afferent nervous system since components of neural pathways frequent such locations.