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Airway reactivity following repeated milk aspiration in rabbits
1Department of Pediatric Pulmonology, University of Nebraska Medical Center, Omaha, Nebraska 68198-5190, USA.
Abstract:
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.
Insights
Repeated milk aspiration in rabbits increased airway reactivity and inflammation, suggesting microaspiration may link gastroesophageal reflux (GER) and asthma. This study explored the connection between aspiration and airway hyperresponsiveness.
Area of Science:
- Pulmonary Medicine
- Gastroenterology
- Respiratory Physiology
Background:
- Asthma and gastroesophageal reflux (GER) are frequently comorbid conditions.
- Microaspiration is a potential pathophysiological link between GER and asthma.
- Understanding this connection is crucial for managing respiratory symptoms in GER patients.
Purpose of the Study:
- To investigate the effect of repeated small-volume aspiration, mimicking GER, on airway reactivity in a rabbit model.
- To correlate changes in airway reactivity with airway cytology following aspiration.
- To assess the long-term impact of aspiration on respiratory function and inflammation.
Main Methods:
- Rabbits underwent weekly intratracheal instillations of milk or saline (control) for five weeks.
- Airway reactivity was measured using methacholine challenge tests (PC50R).
- Bronchial washings were collected for cytological analysis (neutrophils, eosinophils).
Main Results:
- Milk aspiration led to significantly higher methacholine responsiveness compared to saline controls.
- This increased reactivity was observed both during the instillation period and at recovery.
- Cytological analysis revealed increased neutrophils and eosinophils in the airways of the milk-aspirated group.
Conclusions:
- Repeated small-volume milk aspiration induces persistent airway inflammation in rabbits.
- This inflammation is associated with increased airway reactivity, supporting the role of microaspiration in GER-related respiratory issues.
- Findings suggest a potential mechanism linking GER, microaspiration, and heightened airway responsiveness in asthma.