Rodent models of susceptibility: what is their place in inhalation toxicology?

There is renewed interest in inhalation toxicology regarding ‘susceptibility’ as associated with host variables, including genetics, age, diet, and disease. This interest derives from epidemiology that shows air pollution-related human mortality/morbidity, especially among individuals with cardiopulmonary disease. Several animal models with experimental or genetically-based cardiopulmonary diseases are now being incorporated into inhalation toxicology studies to investigate mechanisms that underlie host susceptibility. However, current models have strengths and limitations as to how they mimic the essential features of human diseases. To date, animal models of pulmonary hypertension, bronchitis, asthma, and cardiovascular disease, but not emphysema, appear to exhibit greater susceptibility to air pollution particulate matter. As in humans, host susceptibility appears to involve multiple genetic and environmental factors, and is poorly understood, but the database of information is growing rapidly. As existing models gain wider use, our understanding of the models will improve and encourage refinements/development of models that integrate both genetic and environmental factors to better mimic the human condition.