A new method to evaluate plume characteristics of hydrofluoroalkane and chlorofluorocarbon metered dose inhalers.

Two concerns raised when comparing metered dose inhalers (MDIs) to other inhalation devices are their relatively high throat deposition and the 'cold-Freon' effect seen in a small number of patients. The cold-Freon effect is presumed to be a result of the cold, forceful MDI plume impacting on the back of a patient's throat. This in vitro study uses a new plume characterization method to determine the spray force and plume temperature of various MDIs. Spray force measurements were made for 28 marketed products consisting of bronchodilators, steroids, press-and-breathe, breath-actuated and nasal inhalers. Results show that chlorofluorocarbon (CFC)-containing MDIs produce extremely forceful and cold plumes. Several hydrofluoralkane (HFA)-containing MDIs produced much softer and warmer plumes, but two HFA products had spray forces similar to the CFC products. Although the type of propellant used can affect spray force, actuator orifice diameter is the most important factor. Data obtained from marketed products and experimental inhalers show that MDIs that have a low spray force also have low throat deposition.

Estimation of guinea pig tracheobronchial transport rates using a compartmental model.

Mucociliary clearance in the tracheobronchial tree of guinea pigs was examined using monodisperse 7.9 micrometers MMAD polystyrene particles. Animals were exposed for approximately 1 h by inhalation via an intratracheal tube to aerosols tagged with gold-198 and fluorescent dyes. Following exposure, animals were radioactively monitored and sacrificed at predetermined times. The lungs were removed, freeze-dried, sectioned completely, and examined with a fluorescent microscope. Measurements were made of airway diameters where particles were found. An anatomic model for guinea pig lung morphology was used to assign ranges of airway diameters to five zones, which were incorporated into a compartmental model for lung clearance. Kinetic analysis of particle distributions in the zones led to development of first-order equations describing the compartmental clearance. Rate constants obtained from the kinetic analysis were used to estimate mucociliary transport rates in specific bronchial generations, which ranged from approximately 0.001 mm/min in the distal bronchioles to approximately 8 mm/min in the trachea, and resulted in a calculated 24-h clearance time for tracheobronchial clearance in the guinea pig. No evidence for either bronchial penetration by particles or relatively prolonged bronchial retention of particles was found in this study.

Deposition of inhaled monodisperse aerosols in small rodents.

Aerosols of five different sizes varying from about 0.05 micron to 3 micron in aerodynamic equivalent diameter were prepared from spherical aluminosilicate particles (p=2.2 g/cm3) labelled with 169Yb. Fifty hamsters and fifty rats were exposed, while anaesthetized, to these monodisperse aerosols under controlled laboratory conditions to determine quantitatively deposition in the respiratory airways with respect to particle size and volume of air inhaled. Ten animals of each species were exposed to each of the particle sizes. Five animals were exposed simultaneously for 20 min in an inhalation exposure apparatus which provided automatic recordings of respiratory rates and volumes using individual whole-body plethymographs; three were sacrificed immediately after exposure and the remaining two after 20 h had elapsed for radioanalysis of selected tissues to determine deposition quantities and organ distribution. Detailed results are given for the observed deposition fractions for the different aerosols in the various parts of the respiratory tract. The lowest fractional total deposition occurred for particles between 0.5 micron and 1 micron in aerodynamic equivalent diameter. Relative deposition among the various lung lobes showed remarkable consistency with respect to particle size. Based upon the results of morphometric measurements of replica casts of lungs of the two species, interpretations are made relating the observed deposition phenomena to tracheobronchial anatomy.

A stereoradiographic technique and its application to the evaluation of lung casts.

Stereoradiographs have been used on occasion for three-dimensional reconstruction and measurement of objects in radiology and radiotherapy. The lack of a good stereoradiographic technique has limited the uses of steroradiographic exposures. In this paper, the principle of the double-image is outlined and a method of applying this principle to stereoradiographic exposures is developed. A computer program has been developed from geometrical considerations to analyze the stereobronchogram and to calculate the dimensions of the objects in question. The applications of this technique are discussed and its use in evaluating lung casts is described.