Alteration of airway reactivity by mucus

In 11 beagles with permanent tracheostomies we investigated whether mucus hypersecretion alters airway reactivity to inhaled aerosols. Mucus was collected from the dogs while awake by resting a cytology brush on the lower tracheal mucosa; the mucus collection rate was used as an index of mucus flux. Mucus linear velocity was determined under light sedation by bronchoscopically observing the rate of particle clearance in the trachea. Mucus depth was then computed from the flux and velocity. On a separate occasion, under pentobarbital anesthesia, methacholine aerosols (1 min duration) were given at 10 min intervals in doubling doses up to at least 2 mg/ml. Pulmonary resistance RL was determined prior to and 2 min after each dose. After a 1 h pause, methacholine was infused at a constant rate of 40 micrograms X kg-1 X min-1 for 10 min. This dose produced a plateau in RL after approximately 3 min; the mean rise in RL was similar to that achieved with the 2 mg/ml aerosol. The infusion response Rinf was defined as the change in RL 4-5 min post infusion; the aerosol response Raer was defined as the change in RL 2 min post 2 mg/ml aerosol. There was no significant correlation between Rinf and Raer, nor between either Rinf or Raer and mucus flux. There was, however, a strong positive association between Rinf/Raer and mucus flux and a similar positive association between Rinf/Raer and mucus depth. These associations indicate that dogs with elevated secretion levels are relatively unresponsive to aerosolized as opposed to infused methacholine. Thus, to the extent that infusion reactivity reflects innate airway reactivity, the reactivity to inhaled aerosol may underestimate the true value when mucus hypersecretion occurs.