Bronchial hyperresponsiveness: animal models and clinical aspects

The environmental disaster following flooding by red sludge in the Ajka region in Hungary poses a seriouspublic health threat with particular concern regarding the potentially adverse respiratory effects of theinhalation of red sludge dust (RSD). The respiratory consequences of the inhalation of RSD obtained fromfield samples were investigated in rats. Rats were either exposed to RSD at a high concentration (2 weeks,8 h/day), or kept in room air. After the exposures, the airway resistance (Raw) and the respiratory tissuesmechanics were measured under baseline condition, and following methacholine (MCh) challenges withthe aim of establishing airway hyper-responsiveness (AH). Histopathology was performed to assess lungmorphologic alterations. The physical properties and the chemical composition of the RSD were alsocharacterized. The size distribution, chemical composition and topology of the RSD particles applied inour experiments were similar to those observed at the site of the disaster. The inhalation of RSD did notalter the basal respiratory mechanics, whereas it led to greater MCh-induced responses in Raw, demon-strating the progression of mild AH. Histopathological investigations revealed fine, granular particles inthe alveolar macrophages, as evidence that RSD had reached the lower respiratory tract and inducedmild inflammation around the alveoli and the pulmonary vasculature. The mild respiratory symptomsthat developed following short-term exposure of healthy individuals to high concentrations of airborneRSD do not appear to pose a greater respiratory hazard than the inhalation of urban dust at a comparableconcentration.© 2011 Elsevier Ireland Ltd. All rights reserved.