Lung Dose, Distribution, and Clinical Response to Therapeutic Aerosols

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Abstract
The response to therapeutic aerosols is considered to be a function of the dose deposited at the target site in the lung. The dose, in turn, is dependent upon the system producing the aerosol, the particle size characteristics of the inhaled aerosol, the mode of inhalation, and the calibre of the airways. The influence of the pattern of deposition of the inhaled dose, i.e., selective delivery to the central vs. small, peripheral airways, on the response is not as well defined. Distribution of therapeutic aerosols in the lung has been measured using a variety of tracer methods; correlations with clinical response have been obtained in a limited number of these same studies. Systems used to provide unit doses of therapeutic aerosols are the metered dose inhaler (MDI), containing drug in a pressurized formulation, and the dry powder inhalers (DPI). Efficiency of delivery is on the order of 5–15% for these systems, even under optimal inhalation conditions. Continuous aerosol is provided by the jet or ultrasonic nebulizer with delivery efficiencies ranging from 1 to 5% for the former and approximately 10% for the latter. The particle size of aerosol from these devices ranges from < 1 μm mass median aerodynamic diameter (MMAD) to 12 μm MMAD. However, the “effect” of particle size, once the inspiratory flow rate is taken into account, can be much greater, shifting the deposition pattern to more proximal airways, as does airway narrowing owing to the presence of lung disease. Increased flow rates and changes in airway geometry can alter both the dose deposited and the response and may necessitate the adjustment of dosing levels to meet the needs of the individual patient. By using a variety of methods, deposition efficiency can be improved and medication “targeted” to the lower respiratory tract to minimize local and systemic side effects. Practically, these methods consist of baffling and the addition of valved spacer devices to the MDI. New formulations and delivery systems are being developed to provide finer, and more respirable aerosols, with sustained action. Knowledge of the lung dose and distribution of inhaled aerosols from these systems is critical for the assessment of their performance in vivo.