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

Using State-of-the-art Rheological Methods to Characterize CF Sputum and the Effects of Mucoactive Agents: A Pilot Study

The purpose of this study is to characterize the rheological properties of cystic fibrosis (CF) and healthy sputum and to examine the effects of mucoactive agents on the rheology of CF and healthy sputum. By collaborating with Genentech, the investigators (scientists at UCSF) plan to incorporate the latest scientific findings into our work to discover and develop new treatments for CF.

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.

Inclusion Criteria:

• Healthy control subjects:

  • Age 18-65
  • No history of lung disease or cardiac disease

• Cystic fibrosis subjects:

  • Age 18-65
  • Diagnosis of CF - sweat chloride values > 60 mM on pilocarpine iontophoresis sweat tests and/or 2 allelic CF-producing mutations by genetic analysis

Exclusion Criteria:

• Use of recreational drugs within 1 year prior to enrollment
• Use of tobacco within 1 year prior to enrollment, or > 10 pack-year tobacco history
• Upper respiratory tract infection in the 4 weeks prior to enrollment in the study
• Current use of antihistamines to treat allergies