The relationship of mucus concentration (hydration) to mucus osmotic pressure and transport in chronic bronchitis

RATIONALE: Chronic bronchitis (CB) is characterized by persistent cough and sputum production. Studies were performed to test whether mucus hyperconcentration and increased partial osmotic pressure, in part due to abnormal purine nucleotide regulation of ion transport, contribute to the pathogenesis of CB. OBJECTIVES: We tested the hypothesis that CB is characterized by mucus hyperconcentration, increased mucus partial osmotic pressures, and reduced mucus clearance. METHODS: We measured in CB subjects as compared to normal and asymptomatic smoking controls: 1) indices of mucus concentration (hydration), i.e., % solids; and 2) sputum adenine nucleotide/nucleoside (NT/NS) concentrations. In addition, sputum partial osmotic pressures and mucus transport rates were measured in CB subjects. MEASUREMENTS AND RESULTS: CB secretions were hyperconcentrated as indexed by an increase in % solids and total mucins, in part reflecting decreased extracellular NT/NS concentrations. CB mucus generated concentration-dependent increases in partial osmotic pressures into ranges predicted to reduce mucus transport. Mucociliary clearance (MCC) in CB subjects was negatively correlated with mucus concentration (% solids). As a test of relationships between mucus concentration and disease, mucus concentrations and MCC were compared to FEV1 and both were significantly correlated. CONCLUSIONS: Abnormal regulation of airway surface hydration may slow MCC in CB and contribute to disease pathogenesis.