{'fraction_non_alphanumeric': 0.03186558516801854, 'fraction_numerical': 0.03707995365005794, 'mean_word_length': 4.430817610062893, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
ACID ASPIRATION-INDUCED AIRWAYS HYPERRESPONSIVENESS 1 IN MICE 2

The role of gastroesophageal reflux and micro-aspiration as a trigger of airways 27 hyperresponsiveness (AHR) in patients with asthma is controversial. The role of acid 28 reflux and aspiration as a direct cause of AHR in normal subjects is also unclear. We 29 speculated that aspiration of a weak acid with a pH (1.8) equivalent to the upper range of 30 typical gastric contents would lead to AHR in naïve mice. We further speculated that 31 modest reductions in aspirate acidity to a level expected during gastric acid suppression 32 therapy (pH 4.0) would impede aspiration-induced AHR. BALB/c female mice were 33 briefly anesthetized with isoflurane and allowed to aspirate 75 μ L of saline with HCl (pH 34 1.8, 4.0, or 7.4) or underwent sham aspiration. Mice were re-anesthetized two or 24 hours 35 later, underwent tracheostomy, and were coupled to a mechanical ventilator. Forced 36 oscillations were used to periodically measure respiratory impedance ( Zrs ) following 37 aerosol delivery of saline and increasing doses of methacholine to measure for AHR. 38 Values for elastance ( H ), airways resistance ( R N ) and tissue damping ( G ) were derived 39 from Zrs . Aspirate pH of 1.8 led to a significant overall increase in peak R N , G , and H 40 compared to pH 4.0 and 7.4 at two and 24 hours. Differences between pH 7.4 and 4.0 41 were not significant. In mice aspirating pH 1.8 compared to controls, airway lavage fluid 42 contained more neutrophils, higher protein, and demonstrated higher permeability. We 43 conclude that acid aspiration triggers an acute AHR, driven principally by breakdown of epithelial barrier integrity within the airways.