Airway reactivity following repeated milk aspiration in rabbits.

Asthma and gastroesophageal reflux (GER) are commonly associated disorders. Microaspiration is one possible link between these processes. The purpose of this study was to assess methacholine reactivity following repeated small-volume aspiration such as may occur with GER. This was also correlated with airway cytology. Five weekly intratracheal instillations of either milk (N = 8) or saline sham controls (N = 7) in volumes of 0.25 mL/kg were performed in anesthetized rabbits. Transpulmonary pressure, flow, tidal volume, central airways resistance, and dynamic lung compliance were measured in anesthetized and paralyzed animals at baseline, after 2 and 5 weeks of instillation, and 3 weeks after the last instillation. Doubling concentrations of methacholine were given until a 50% or greater increase in resistance occurred (PC50R). Bronchial washings for cytological evaluation were performed after the physiologic measurements and before each instillation. There were no significant differences in airway reactivity between baseline and all subsequent observation points within each of the two groups. However, methacholine responsiveness was significantly higher in the milk group before the final instillation (PC50R = 5.84 vs. 12.97 mg/mL, P = 0.03) and at recovery (PC50R = 6.40 vs. 10.56 mg/mL, P = 0.047) when compared to saline controls. This was associated with a higher neutrophil percentage (P = 0.01) at 5 weeks, and eosinophil percentage (P = 0.05) at recovery in the bronchial wash specimens from the milk group. These results show that repeated small-volume aspiration of milk in rabbits causes persistent inflammation and is associated with greater airway reactivity when compared to sham controls. This inflammation was accompanied by either increased neutrophils or eosinophils in bronchial lavage specimens. These findings lend support to a possible role of microaspiration in association with increased airway reactivity in patients with GER. Copyright 2000 Wiley-Liss, Inc.