TY - JOUR A1 - Wagner, Ulrich A1 - Staats, Petra A1 - Fehmann, Hans-Christoph A1 - Fischer, Axel A1 - Welte, Tobias A1 - Groneberg, Jan David Alexander T1 - Analysis of airway secretions in a model of sulfur dioxide induced chronic obstructive pulmonary disease (COPD) T2 - Journal of occupational medicine and toxicology N2 - Hypersecretion and chronic phlegm are major symptoms of chronic obstructive pulmonary disease (COPD) but animal models of COPD with a defined functional hypersecretion have not been established so far. To identify an animal model of combined morphological signs of airway inflammation and functional hypersecretion, rats were continuously exposed to different levels of sulfur dioxide (SO2, 5 ppm, 10 ppm, 20 ppm, 40 ppm, 80 ppm) for 3 (short-term) or 20–25 (long-term) days. Histology revealed a dose-dependent increase in edema formation and inflammatory cell infiltration in short-term-exposed animals. The submucosal edema was replaced by fibrosis after long-term-exposure. The basal secretory activity was only significantly increased in the 20 ppm group. Also, stimulated secretion was significantly increased only after exposure to 20 ppm. BrdU-assays and AgNOR-analysis demonstrated cellular metaplasia and glandular hypertrophy rather than hyperplasia as the underlying morphological correlate of the hypersecretion. In summary, SO2-exposure can lead to characteristic airway remodeling and changes in mucus secretion in rats. As only long-term exposure to 20 ppm leads to a combination of hypersecretion and airway inflammation, only this mode of exposure should be used to mimic human COPD. Concentrations less or higher than 20 ppm or short term exposure do not induce the respiratory symptom of hypersecretion. The present model may be used to characterize the effects of new compounds on mucus secretion in the background of experimental COPD. Y1 - 2006 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/25655 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-256551 SN - 1745-6673 VL - 1 IS - 12 PB - BioMed Central CY - London ER -