Acid aspiration-induced airways hyperresponsiveness in mice

Area of Science:

• Pulmonary Medicine
• Gastroenterology
• Immunology

Background:

• The link between gastroesophageal reflux, micro-aspiration, and airway hyperresponsiveness (AHR) in asthma patients remains debated.
• The direct impact of acidic reflux and aspiration on AHR in healthy individuals is not well understood.

Purpose of the Study:

• To investigate if aspiration of weak acid (pH 1.8) induces AHR in naive mice.
• To determine if reduced acidity (pH 4.0), mimicking gastric acid suppression therapy, prevents aspiration-induced AHR.

Main Methods:

• BALB/c female mice were exposed to saline with varying HCl acidity (pH 1.8, 4.0, 7.4) or sham aspiration.
• Respiratory impedance was measured via mechanical ventilation and forced oscillations following methacholine challenge.
• Airway lavage fluid was analyzed for inflammatory markers and protein content.

Main Results:

• Aspirating pH 1.8 significantly increased airway resistance and elastance at 2 and 24 hours compared to pH 4.0 and 7.4.
• No significant difference in AHR was observed between pH 7.4 and pH 4.0 aspirates.
• Mice aspirating pH 1.8 showed increased neutrophils, protein, and permeability in airway lavage fluid.

Conclusions:

• Acid aspiration is a direct trigger for acute AHR in mice.
• The mechanism involves the breakdown of airway epithelial barrier integrity.
• Gastric acid suppression therapy may play a role in mitigating aspiration-induced AHR.