Aerosol penetration and mucociliary transport in the healthy human lung. Effect of low serum theophylline levels.

The effect of theophylline on the penetration of an inhaled radioaerosol in the lung, bronchial clearance, and tracheal mucociliary transport rate (TMTR) was investigated in 13 healthy volunteers. Following a randomized, double-blind, crossover protocol, subjects ingested 4 mg/kg twice daily of theophylline or placebo for three days which resulted in stable, low therapeutic serum levels. Aerosol penetration, assessed by the skew of the initial distribution of lung radioactivity, was more peripheral (p less than 0.025) with theophylline, indicating bronchodilation that was not detectable by standard pulmonary function tests. The TMTR increased in ten of 13 subjects after theophylline, but not to a significant level. Bronchial clearance was not significantly different with theophylline despite the longer clearance pathway created by the increased peripheral aerosol deposition. This finding suggests that mucus transport rates in the intrapulmonary airways were increased by theophylline.

Clinical aerosols II. Therapeutic aerosols.

The current uses of clinical aerosols such as water, saline, mucolytics, bronchodilators, cromolyn sodium, corticosteroids, and antimicrobials have been reviewed. The benefits of water, saline, and detergent aerosols continue to be surrounded by uncertainty and controversy. Aerosolized mucolytic and proteolytic agents have not been conclusively shown to be of substantial value in the improvement of respiratory disorders. Favorable bronchodilator therapy is achieved with aerosols of certain sympathomimetic and anticholinergic agents. However, successful therapy depends on the dose administered and the site of aerosol deposition in the lung. The prophylactic use of cromolyn sodium in patients with asthma is another useful application of aerosols. Topically active corticosteroid aerosols are increasingly being used since they may reduce risks of systemic effects from corticosteroids. Research on uncommonly aerosolized agents has widened the spectrum of therapeutic applications of aerosols.

Clinical aerosols. I. Characterization of aerosols and their diagnostic uses.

Characterization of an aerosol is of major importance for the understanding of its pathogenic, diagnostic, or therapeutic effect. The parameters necessary for such characterization as well as the methods for obtaining them are reviewed. The factors that determine site of deposition in the human lung are discussed. Further, we have reviewed methods employed to produce aerosols for diagnostic, therapeutic, and clinical research uses. Basic and relatively simple knowledge of aerosol characterization can increase the usefulness of clinical aerosols. Using this knowledge, general principles for aerosol administration are developed. Finally, the application of aerosols in the diagnosis of respiratory diseases is presented; these aerosols include contrast agents, radioactive aerosols, and bronchospastic agents.