Clearance of intrapulmonary mucus by the high-velocity airflow generated by cough is the major rescue clearance mechanism in subjects with mucoobstructive diseases and failed cilial-dependent mucus clearance, e.g., subjects with cystic fibrosis (CF) or chronic obstructive pulmonary disease (COPD). Previous studies have investigated the mechanical forces generated at airway surfaces by cough but have not considered the effects of mucus biophysical properties on cough efficacy. Theoretically, mucus can be cleared by cough from the lung by an adhesive failure, i.e., breaking mucus-cell surface adhesive bonds and/or by cohesive failure, i.e., directly fracturing mucus. Utilizing peel-testing technologies, mucus-epithelial surface adhesive and mucus cohesive strengths were measured. Because both mucus concentration and pH have been reported to alter mucus biophysical properties in disease, the effects of mucus concentration and pH on adhesion and cohesion were compared. Both adhesive and cohesive strengths depended on mucus concentration, but neither on physiologically relevant changes in pH nor bicarbonate concentration. Mucus from bronchial epithelial cultures and patient sputum samples exhibited similar adhesive and cohesive properties. Notably, the magnitudes of both adhesive and cohesive strength exhibited similar velocity and concentration dependencies, suggesting that viscous dissipation of energy within mucus during cough determines the efficiency of cough clearance of diseased, hyperconcentrated, mucus. Calculations of airflow-induced shear forces on airway mucus related to mucus concentration predicted substantially reduced cough clearance in small versus large airways. Studies designed to improve cough clearance in subjects with mucoobstructive diseases identified reductions of mucus concentration and viscous dissipation as key therapeutic strategies.
In health, the high-speed airflow associated with cough represents a vital backup mechanism for clearing accumulated mucus from our airways. However, alterations in the mucus layer in cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) leads to the mucus layer adhered to the airway surfaces, representing the nidus of chronic lung infection. To understand what is different about diseased mucus and why cough clearance is defective, there is a need for techniques to quantify the strength of the interactions limiting the ability of airflow to strip mucus from the airway surface (i.e., adhesive strength) or tear mucus apart (i.e., cohesive strength). To overcome the issues with measuring these properties in a soft (i.e., low elastic modulus) mucus layer, we present here novel peel-testing technologies capable of quantifying the mucus adhesive strength on cultured airway cells and cohesive strength of excised mucus samples. While this protocol focuses on measurements of airway mucus, this approach can easily be adapted to measuring adhesive/cohesive properties of other soft biological materials.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.