Using Rheological Methods to Characterize Cystic Fibrosis (CF) Sputum and the Effects of Mucoactive Agents

There are two major mechanisms for mucus clearance in the airway, both of which are
dependent upon optimal mucus viscosity and elasticity. These mechanisms are severely
impaired in cystic fibrosis. The physical properties of sputum can be measured using
rheological methods, enabling comparison between mucus in health and in disease. Therapies
which enhance mucus clearance from the airway and decrease the volume of airway secretions
are collectively called "mucoactive agents." Therapies which specifically disrupt innate
mucus architecture by breaking intermolecular entanglements and bonds are called mucolytic
agents. Mucolytic drugs can be considered in three general categories: classic mucolytics
(n-acetylcysteine), peptide mucolytics (Pulmozyme®), and non-destructive mucolytics
(hypertonic saline). Using state-of-the-art rheological methods, we can characterize the
physical properties of CF mucus and measure the rheologic effects of mucoactive drugs more
accurately and reproducibly than what has been previously done in the literature. In this
way, we will determine which of the current mucoactive agents are most effective in
normalizing sputum rheology in CF, and we will gain important insights about the limitations
of current mucoactive drugs.