Research

Analysis of airway secretions in a model of sulfur dioxide induced chronic obstructive pulmonary disease (COPD)

Ulrich Wagner^1,2 , Petra Staats¹ , Hans-Christoph Fehmann¹ , Axel Fischer³ , Tobias Welte⁴ and David A Groneberg^4,5

¹  Department of Medicine, Pulmonary and Critical Care Division, Philipps-University, Baldingerstr., D-35043 Marburg, Germany

²  Department of Medicine/Respiratory Medicine, Klinik Löwenstein, Geißhölzle 62, D-74245 Löwenstein, Germany

³  Allergy-Centre-Charité, Otto-Heubner-Centre, Pneumology and Immunology, Charité – Universitätsmedizin Berlin, Free and Humboldt-University Berlin, Augustenburger Platz 1 OR-1, D-13353 Berlin, Germany

⁴  Department of Respiratory Medicine, Hannover Medical School, Carl-Neuberg-Str. 1 OE 6870, D-30625 Hannover, Germany

⁵  Institute of Occupational Medicine, Charité – Universitätsmedizin Berlin, Free and Humboldt-University Berlin, Ostpreussendamm 111, D-12207 Berlin, Germany

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Journal of Occupational Medicine and Toxicology 2006, 1:12doi:10.1186/1745-6673-1-12

Published:	7 June 2006

Abstract

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.