Therapeutic aerosols and airway secretions

Despite common misconceptions, airway mucus is not an impermeable barrier that entraps and clears all inhaled material. To be therapeutically effective, an aerosol medication must efficiently deposit in the airway and then diffuse or translocate across the mucous barrier while retaining bioactivity. Characteristics of aerosols that affect their ability to penetrate the mucous barrier include particle charge, solubility, and size. Aerosol medications can also change the biophysical properties of secretions and influence how rapidly mucus is cleared. Surfactant is probably responsible for the displacement of inhaled particles through the mucous layer (Schürch et al., 1990). As well, exogenous surfactant has been shown to increase tracheal mucociliary clearance in anesthetized dogs (de Sanctis et al., 1994) and to improve the mucociliary clearability of secretions from babies with neonatal respiratory distress syndrome (Rubin et al., 1992). Using measurements of sputum-substrate contact angle and interfacial tension, cystic fibrosis (CF) sputum had been shown to have an abnormally high adhesion tension, (Girod et al., 1992). We assessed the in vitro effects of synthetic surfactant (Exosurf, Burroughs-Wellcome, Research Triangle Park, NC) on the physical and transport properties of sputum from 15 patients with CF and 30 patients with stable chronic bronchitis (CB). The concentration of ExosurfTM used was 13.5 mg of DPPC/ml corresponding to the reconstituted concentration for aerosol administration. The sputum was divided so that aliquots each were treated with Exosurf and amphibian Ringer's solution layered on the sputum at a concentration of 1:5 v/v for 15 min at 24 degrees C. There was a reduction in spinnability (p < 0.0001) in CF sputum from baseline and a fall in adhesion tension (0.05 < p < 0.1) with Exosurf treatment. Potentially important increases in both mucociliary and cough clearability were noted without associated changes in sputum rheology. In bronchitis sputum, surfactant reduced adhesiveness (p < 0.01), but this was not associated with improved clearability. Adhesive forces are involved in ciliary coupling and cough transport. This raises the possibility of using surfactant as a mucokinetic agent in the therapy of chronic suppurative lung disease.