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 pm 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"-"-. Particles were preferentially deposited at bifurcations, specifically at carinal ridges. Evidence from other investigations indicates that mucociliary clearance may be impeded at such sites ¿n 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.

Fluid Dynamics of the Human Larynx and Upper Tracheobronchial Airways

“…The associated increased deposition efficiency may explain the enhanced bifurcation deposits of large (> 1 pm) particles observed under constant flow rates in surrogate lung systems (Martonen, 1983b;Martonen, 1991) and replica TB casts Lippman, 1972, 1976;Schlesinger et al, 1974Schlesinger et al, , 1977 with replica laryngeal casts. Indeed, the velocity field transition between Figures 9, 10, and 11 for a range of inspiratory flow rates from 15 to 60 L/min may partially explain the effects of constant versus pulsatile flows upon deposition measured in replica TB casts by Gurman et al (1984) and Sussman et al (1991aSussman et al ( , 1991b.…”

“…In aerosol therapy regimens a range of tidal volumes and breathing frequencies may be addressed to effectively target the delivery of drugs and elicit optimum benefits (Martonen, 1991). Similarly, in risk assessment protocols appropriate conditions must be employed to describe a general population exposed to atmospheric contaminants .…”

Stochastic dose estimation for inhaled particulates

“…Furthermore, if local and temporal variations in airborne concentrations are factored into the analysis, then the joint effect of environmental and biological variability produces an even wider dispersion in resulting regional and local deposition fractions (Hofmann and Daschil, 1986). Finally, the resulting variability in biological response is also affected by the local variability and inhomogeneity of sensitive target cells (Hofmann et al, 1996b) or of biological receptors on human airway walls (Martonen, 1991), thereby causing intersubject differences in the individual sensitivity to speci®c airborne particulate pollutants (Martonen and Miller, 1986).…”

Dosage regimens for inhaled therapy in children should be reconsidered

“…7 The deposition of aerosols in the human lungs is dependent on various parameters affecting the motion of aerosols. 8 These parameters are the physical and chemical characteristics of the aerosol particles produced by the inhalation device. Ventilatory function and age-dependent respiratory tract morphology also have an impact.…”

“…Accounting for age-specific characteristics of breathing patterns, inhalation devices for children have greatly improved in delivery efficiency, leading to a much higher and less variable dose administered to the patient. 1,4,5 However, studies evaluating various inhalation devices have shown that lung deposition is positively correlated with increasing age, [8][9][10][11][12][13][14] whereas oropharyngeal deposition is inversely correlated with increasing age. In other words, lung deposition increases and oropharyngeal deposition decreases with age, mainly due to changes in airway anatomy.…”