Endotoxin responsiveness and subchronic grain dust-induced airway disease

Endotoxin is one of the principal components of grain dust that causes acut e reversible airflow obstruction and airway inflammation. To determine whet her endotoxin responsiveness influences the development of chronic grain du st-induced airway disease, physiological and airway inflammation remodeling parameters were evaluated after an 8-wk exposure to corn dust extract (CDE ) and again after a 4-wk recovery period in a strain of mice sensitive to ( C3H/HeBFeJ) and one resistant to (C3H/HeJ) endotoxin. After the CDE exposur e, both strains of mice had equal airway hyperreactivity to a methacholine challenge; however, airway hyperreactivity persisted only in the C3H/HeBFeJ mice after the recovery period. Only the C3H/HeBFeJ mice showed significan t inflammation of the lower airway after the 8-wk exposure to CDE. After th e recovery period, this inflammatory response completely resolved. Lung ste reological measurements indicate that an 8-wk exposure to CDE resulted in p ersistent expansion of the airway submucosal cross-sectional area only in t he C3H/HeBFeJ mice. Collagen type III and an influx of cells into the subep ithelial area participated in the expansion of the submucosa. Our findings demonstrate that subchronic inhalation of grain dust extract results in the development of chronic airway disease only in mice sensitive to endotoxin but not in mice that are genetically hyporesponsive to endotoxin, suggestin g that endotoxin is important in the development of chronic airway disease.