Prolonged allergen exposure induces structural airway changes in sensitized rats

The pathogenesis and functional consequences of airway remodeling in asthma remain to be fully established. In the present study we evaluated the effe ct of prolonged allergen exposure on airway function and structure in rats. Sensitized Brown Norway rats were repeatedly exposed for periods of 2 4, o r 12 wk to aerosolized ovalbumin (OA) or phosphate-buffered saline (PBS). O A exposure induced a persistent increase in OA-specific serum IgE and in th e number of peribronchial eosinophils. After 2 wk of OA exposure, airway hi stology revealed goblet-cell hyperplasia, an increase in bromodeoxyuridine- positive cells in airway epithelium, increased fibronectin deposition, and a thickening of the airway inner wall area. This coincided with airway hype rresponsiveness (AHR) to aerosolized carbachol. After OA exposure for 12 wk , increased fibronectin (p < 0.05 versus PBS) and collagen deposition (p < 0.05 versus PBS) were observed in the submucosa. After 12 wk of exposure, n either total nor inner wall area or airway responsiveness to carbachol were any longer significantly different from those of PBS-exposed animals. In c onclusion, prolonged OA exposure in rats induces structural airway changes that bear similarities to airway remodeling in asthma. The study data furth er indicate that depending on the extent and distribution of remodeling, ch anges in the extracellular matrix can enhance or protect against AHR.