Recurrent milk aspiration produces changes in airway mechanics, lung eosinophilia, and goblet cell hyperplasia in a murine model

Recurrent aspiration of milk into the respiratory tract has been implicated in the pathogenesis of a variety of inflammatory lung disorders including asthma. However, the lack of animal models of aspiration-induced lung injur y has limited our knowledge of the pathophysiological characteristics of th is disorder. This study was designed to evaluate the effects of recurrent m ilk aspiration on airway mechanics and lungs cells in a murine model. Under light anesthesia, BALB/c mice received daily intranasal instillations of w hole cow's milk (n = 7) or sterile physiologic saline (n = 9) for 10 d. Res piratory system resistance (Rrs) and dynamic elastance (Edyn,rs) were measu red in anesthetized, tracheotomized, paralyzed and mechanically ventilated mice 24 h after the last aspiration of milk. Rrs and Edyn,rs were derived f rom transrespiratory and plethysmographic pressure signals. In addition, ai rway responses to increasing concentrations of i.v. methacholine (Mch) were determined. Airway responses were measured in terms of PD100 (dose of Mch causing 100% increase from baseline Rrs) and Rrs,ma-v (% increase from base line at the maximal plateau response) and expressed as % control (mean +/- SE). We found recurrent milli aspiration did not affect Edyn and baseline R rs values. However, airway responses to Mch were increased after milk aspir ation when compared with control mice. These changes in airway mechanics we re associated with an increased percentage of lymphocytes and eosinophils i n the bronchoalveolar lavage, mucus production, and lung inflammation. Our findings suggest that recurrent milk aspiration lends to alterations in air way function, lung eosinophilia, and goblet cell hyperplasia in a murine mo del.