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1 School of Pharmacy, University of Wisconsin, Madison, Wisconsin, United States; Medicine, University of Wisconsin, Madison, Wisconsin, United States; Pediatrics, Unversity of Wisconsin, Madison, Wisconsin, United States; Morris Institute for Respiratory Research, University of Wisconsin, Madison, Wisconsin, United States
2 School of Pharmacy, University of Wisconsin, Madison, Wisconsin, United States
3 Medicine, University of Wisconsin, Madison, Wisconsin, United States
4 Department of Medicine and Pediatrics, University of Wisconsin Hospital, 600 Highland Avenue-H4/432, Madison, Wisconsin, 53792-3244, United States; Morris Institute for Respiratory Research, University of Wisconsin, Madison, Wisconsin, United States
5 Medicine, University of Wisconsin Medical School, 600 Highland Avenue, K4-948 CSC-9988, Madison, Wisconsin, 53792, United States; Morris Institute for Respiratory Research, University of Wisconsin, Madison, Wisconsin, United States
* To whom correspondence should be addressed. E-mail: rlsorkne{at}wisc.edu.
While both asthmatics and allergic rhinitics develop an acute inflammatory response to lower airway allergen challenge, only asthmatics experience airway obstruction resulting from chronic environmental allergen exposure. Hypothesizing that asthmatic airways have an altered response to chronic allergic inflammation, we compared the effects of repeated low-level exposures to inhaled Alternaria extract in sensitized rats with preexisting chronic postbronchiolitis airway dysfunction versus sensitized controls with normal airways. Measurements of airspace (bronchoalveolar lavage) inflammatory cells, airway goblet cells, airway wall collagen, airway wall eosinophils, airway alveolar attachments, and pulmonary physiology were conducted after 6 weekly exposures to aerosolized saline or Alternaria extract. Postbronchiolitis rats, but not those starting with normal airways, had persistent increases in airway wall eosinophils, goblet cell hyperplasia in small airways, and loss of lung elastic recoil after repeated exposure to aerosolized Alternaria extract. Despite having elevated airway wall eosinophils, the postbronchiolitis rats had no eosinophils in bronchoalveolar lavage at 5 days after the last allergen exposure, suggesting altered egression of tissue eosinophils into the airspace. In conclusion, rats with preexisting airway pathology had altered eosinophil trafficking, and allergen-induced changes in airway epithelium and lung mechanics that were absent in sensitized control rats that had normal airways prior to the allergen exposures.
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