Aerosols Used In Clinical Investigations Of Disease

Several diagnostic tests utilizing specific-size nonradioactive aerosols and also radioactive aerosols with standard nuclear medicine technology are practiced in respiratory medicine (Table 2). For example, inhalation of aerosols of methacholine and histamine is widely used to assess nonspecific bronchial responsiveness in asthma; the concentration of the challenge aerosol that provokes a specific fall in FEV1 gives an indication of the severity of the disease. Changes in the disease with treatment or with exposure to sensitizing agents can be monitored over time with repeated measurements. These measurements are coupled with clinical outcomes such as spirometry and pharmacokinetic and pharmacodynamic measurements in the same group of subjects. In the research laboratory, measurements using radioactive aerosols of these challenge agents have determined the change in distribution effected with changes in airway caliber [124,125] as well as compared techniques and outcomes in inhalation challenge testing [126-128].

Mucociliary clearance (MCC), a measure of the surface transport properties of the lung, and lung epithelial permeability (LEP), a measure of the integrity of the alveolar-capillary membrane, can be assessed using radiotracers and imaging. MCC is determined from the rate of removal (from ciliated airways) of an inhaled tracer aerosol, while LEP is determined from the rate of removal of an inhaled tracer resulting from absorption across the alveolated surface of the lung and into the circulation. Table 3 lists the factors affecting these measurements, some of which need to be controlled when performing these studies [31].

MCC is measured by imaging the lung over time to obtain the retention of an inhaled radioaerosol. Planar imaging is used mainly, and serial measurements are required. Because aerosol size and ventilatory parameters affect where aerosol is initially deposited in the lung and because the rate of transport is more rapid from proximal airways than peripheral airways, changes to the initial deposition pattern as a result of treatment or the factors listed in Table 3 will

Table 3 Factors Affecting the Measurement of Lung Mucociliary Clearance (MCC) and Lung Epithelial Permeability (LEP)

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