Metal Composition of Ambient P[M.Sub.2.5] Influences Severity of Allergic Airways Disease in Mice
Gavett, Stephen H., Haykal-Coates, Najwa, Copeland, Lisa B., Heinrich, Joachim, Gilmour, M. Ian, Environmental Health Perspectives
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 [micro]m aerodynamic diameter; P[M.sub.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 P[M.sub.2.5] from Hertstedt and Zerbst to ovalbumin-allergic mice. In Balb/c mice, P[M.sub.2.5] from Hettstedt, but not P[M.sub.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 P[M.sub.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 P[M.sub.2.5] before challenge. Both Hettstedt and Zerbst P[M.sub.2.5] significantly increased lung injury parameters and proinflammatory cytokines. These results are consistent with epidemiologic findings and show that metal composition of ambient P[M.sub.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]
Recent cross-sectional epidemiologic studies examined whether regional differences in air pollution could account for differences in prevalence rates of respiratory and allergic diseases in school-age children living in different cities in eastern Germany (Heinrich et al. 1999, 2000, 2002a, 2002b). The city of Hettstedt was strongly impacted by particulate matter (PM) and other air pollutants from industrial (metal mining and smelting) and domestic (burning of brown coal) sources, whereas the city of Zerbst had minimal industrial emissions and was a center of agriculture and administration. After controlling for medical, demographic, and indoor factors, children living in Hettstedt in the early 1990s had a 50% higher lifetime prevalence of allergies, eczema, and bronchitis compared to children from Zerbst and about twice the level of respiratory symptoms including wheeze, shortness of breath, and cough (Heinrich et al. 1999). Sensitization to common aeroallergens (e.g., dust mite, cat, mixed grasses, birch) and specific IgE levels were also significantly greater in children from Hettstedt than in children from Zerbst. These results suggested that exposure to air pollutants, including P[M.sub.2.5] (PM < 2.5 [micro]m aerodynamic diameter), could promote sensitization to common aeroallergens and promote the development or exacerbation of allergic and respiratory diseases. After German reunification, levels of total PM and sulfur dioxide in eastern Germany decreased throughout the 1990s, and regional differences in the prevalence of bronchitis, sinusitis, and frequent colds declined (Heinrich et al. 2000, 2002a). However, the difference in the prevalence of allergies between the two cities continued, despite the convergence of ambient PM concentrations (Heinrich et al. 2002b), suggesting that the composition of Hettstedt PM may also contribute to the higher prevalence of allergies in that area.
In the present study, our objective was to determine if the results observed in these epidemiologic studies could be replicated in an animal model and identify P[M.sub.2.5] composition as a causative factor in the increased prevalence and severity of allergic diseases in Hettstedt compared with Zerbst. …