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 injury has limited our knowledge of the pathophysiological characteristics of this disorder. This study was designed to evaluate the effects of recurrent milk aspiration on airway mechanics and lung cells in a murine model. Under light anesthesia, BALB/c mice received daily intranasal instillations of whole cow's milk (n = 7) or sterile physiologic saline (n = 9) for 10 d. Respiratory system resistance (Rrs) and dynamic elastance (Edyn,rs) were measured in anesthetized, tracheotomized, paralyzed and mechanically ventilated mice 24 h after the last aspiration of milk. Rrs and Edyn,rs were derived from transrespiratory and plethysmographic pressure signals. In addition, airway responses to increasing concentrations of i.v. methacholine (Mch) were determined. Airway responses were measured in terms of PD(100) (dose of Mch causing 100% increase from baseline Rrs) and Rrs,max (% increase from baseline at the maximal plateau response) and expressed as % control (mean +/- SE). We found recurrent milk aspiration did not affect Edyn and baseline Rrs values. However, airway responses to Mch were increased after milk aspiration when compared with control mice. These changes in airway mechanics were associated with an increased percentage of lymphocytes and eosinophils in the bronchoalveolar lavage, mucus production, and lung inflammation. Our findings suggest that recurrent milk aspiration leads to alterations in airway function, lung eosinophilia, and goblet cell hyperplasia in a murine model.
Janahi
I A
IA
Department of Pediatrics, Section of Pediatric Pulmonology, Baylor College of Medicine, Houston, Texas 77030, USA.
Elidemir
O
O
Shardonofsky
F R
FR
Abu-Hassan
M N
MN
Fan
L L
LL
Larsen
G L
GL
Blackburn
M R
MR
Colasurdo
G N
GN
D000281:Administration, Intranasal; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002417:Cattle; D005260:Female; D006965:Hyperplasia; D007322:Instillation, Drug; D051379:Mice; D008807:Mice, Inbred BALB C; D008892:Milk / Q000633:toxicity*; D023421:Models, Animal; D011015:Pneumonia, Aspiration / Q000209:etiology / Q000473:pathology*; D011657:Pulmonary Eosinophilia / Q000209:etiology*; D015656:Respiratory Mechanics; D020545:Respiratory Mucosa / Q000473:pathology*