Toxic responses of the lung to inhaled pollutants: benefits and limitations of lung-disease models.
The widely accepted notion that certain individuals are more susceptible to air pollutants than others has been revitalized by recent epidemiology that strongly suggests that the elderly, particularly those with underlying cardiopulmonary diseases (e.g. chronic obstructive pulmonary disease (COPD), infection), and children with asthma are more susceptible to the adverse outcomes associated with ambient particulate matter (PM). Pulmonary toxicologists have adopted 'susceptibility' as an issue that can be approached experimentally and have begun to develop as well as study more relevant animal models. These models may have specific genetic traits or cardiopulmonary impairments analogous to human diseases. The goal is to identify potential susceptibility characteristics and elucidate whether responsiveness is due to impair compensation or some unique mechanisms. Several rodent models have been used with PM: pulmonary vasculitis, bronchitis, COPD, allergic asthma, infectious lung diseases, systemic hypertension, and congestive heart disease. Transgenic and knockout mice are of growing interest but have seen limited use in air pollutants studies, with primary interest being directed to specific mechanistic questions. No model should be used without careful consideration of its strengths and limitations. However, when interpreted in the context of field and epidemiology findings, they may reveal generic susceptibility attributes or useful biomarkers.
Costa
Daniel L
DL
Pulmonary Toxicology Branch, MD 82, Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA. costa.dan@epa.gov
Kodavanti
Urmila P
UP
D000280:Administration, Inhalation; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology; D006801:Humans; D008171:Lung Diseases / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D023421:Models, Animal; D012377:Rodentia
D000393:Air Pollutants