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Stephen H. Gavett,¹ Najwa Haykal-Coates,¹ Lisa B. Copeland,¹ Joachim Heinrich,² and M. Ian Gilmour¹

¹Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA; ²GSF - Research Center for Environment and Health, Institute of Epidemiology, Neuherberg, Germany

Abstract
Children living in Hettstedt in eastern Germany have been reported to have a higher prevalence of sensitization to common aeroallergens than another cohort living in the neighboring city of Zerbst ; these differences correlated with the presence of industrial air pollution. Samples of fine particulate matter (< 2.5 µm aerodynamic diameter ; PM_2.5) collected in Hettstedt in 1999 had several-fold higher levels of zinc, magnesium, lead, copper, and cadmium than samples from Zerbst. To determine if the results from epidemiologic studies could be repeated in an animal model, we administered PM_2.5 from Hettstedt and Zerbst to ovalbumin-allergic mice. In Balb/c mice, PM_2.5 from Hettstedt, but not PM_2.5 from Zerbst or control filter extract, caused a significant increase in immediate responses to ovalbumin challenge when aspirated 2 hr before challenge, but not when aspirated immediately before sensitization 2 weeks earlier. Antigen-specific IgE was increased by Hettstedt PM_2.5 whether administered before sensitization or challenge. Airway responsiveness to methacholine aerosol and lung inflammatory cell numbers were significantly increased only in allergic mice exposed to Hettstedt PM_2.5 before challenge. Both Hettstedt and Zerbst PM_2.5 significantly increased lung injury parameters and proinflammatory cytokines. These results are consistent with epidemiologic findings and show that metal composition of ambient PM_2.5 influences the severity of allergic respiratory disease. Key words: air pollution, airway hyperresponsiveness, allergic sensitization, asthma, epidemiology, inflammation, metals. Environ Health Perspect 111:1471-1477 (2003) . doi:10.1289/ehp.6300 available via http://dx.doi.org/ [Online 27 May 2003]