Excessive airway mucus can alter both the mass and site of aerosol deposition, which, in turn, may affect airway responsiveness to inhaled materials. In six prone sheep, we therefore measured pulmonary airflow resistance (RL) and cumulative aerosol deposition during five standard breaths (AD5) at base line and 3 min after inhalation challenge with 2% carbachol in buffered saline (10 breaths, tidal volume = 500 ml) or after an intravenous loading dose of carbachol (3 μg/kg) followed by a constant infusion of 0.3 μg · kg-1 · min-1 with and without instillation of 20 ml of a mucus simulant (MS) into the distal end of each of the main bronchi or 30 ml of MS into the right main bronchus only by means of a flexible fiber-optic bronchoscope. Before carbachol challenge, RL did not change with MS into either both lungs or one lung only. AD5 increased from 36 ± 2% (SE) before to 42 ± 2% after MS instillation into both lungs (P < 0.05) but remained unchanged after MS into one lung. After carbachol inhalation, RL increased significantly by 154 ± 20 before and 126 ± 25% after MS into both lungs and 162 ± 24 before and 178 ± 31% after MS into one lung (P < 0.05). When the percent increase in RL was normalized for total aerosol deposition (%ΔRL/AD5), the normalized values were lower after MS (3.0 ± 0.5) than before MS (4.4 ± 0.3) into both lungs (P < 0.05) but were not significantly different before and after MS into the right lung only. After intravenous carbachol, RL increased significantly by 211 ± 71 before and 183 ± 32% after MS into both lungs (P < 0.05). However, the two values were not significantly different from each other. These results indicate that excessive airway mucus may have at least two effects on airway responsiveness to an inhaled bronchoconstrictor agent: reduction in airway responsiveness by providing a protective layer over the mucosa and an increase in airway responsiveness due to enhanced aerosol deposition.
ASJC Scopus subject areas
- Physiology (medical)