Metal-rich Ambient Particles (Particulate Matter2.5) Cause Airway Inflammation in Healthy Subjects

Abstract

Epidemiologic studies have shown an increased prevalence of aller- gic asthma in children living in a German smelter area (Hettstedt) compared with a cohort who live in a nonindustrialized area (Zerbst). However, it is not known whether ambient particles (par- ticulate matter2.5 (PM2.5)) from these areas induce distinct lung in- flammation, which might be an explanation for this difference. Therefore, 100 go f PM 2.5 suspensions, collected simultaneously in the two areas, were instilled through a bronchoscope into contra- lateral lung segments of 12 healthy volunteers. PM2.5 from both Hettstedt and Zerbst increased the number of leukocytes in the bronchoalveolar lavage performed 24 hours later. PM2.5 from Hett- stedt, but not Zerbst, induced a significant influx of monocytes (Hett- stedt: 7.0% vs. Zerbst: 4.3%) without influencing the expression of surface activation markers on monocytes and alveolar macrophages. Oxidant radical generation of bronchoalveolar lavage cells and cyto- kine concentration (interleukin-6 and tumor necrosis factor- )i n bronchoalveolar lavage fluid was significantly increased after instilla- tion of Hettstedt PM2.5. We conclude that environmentally relevant concentrations of PM2.5 from the smelter area induced distinct airway inflammation in healthy subjects with a selective influx of monocytes and increased generation of oxidant radicals. The higher concentra- tion of transition metals in PM2.5 from Hettstedt might be responsible for this increased inflammation. Cross-sectional epidemiologic studies in eastern Germany have clearly shown that regional differences in ambient particulate matter (PM) concentration are associated with differences in the prevalence of respiratory and allergic diseases. School children living in the smelter area of Hettstedt, which was strongly im- pacted by PM during the 1980s and in the early 1990s, had a significantly higher prevalence of allergies and bronchitis com- pared with children living in the rural control area of Zerbst (1). After the German reunification, levels of total PM were reduced and PM concentrations converged between different areas throughout the 1990s. The differences in the prevalence rates of nonallergic respiratory symptoms between the two cities de- creased and lung function impairment improved along with im- proved air quality (2-4). However, the difference in the prevalence of allergies remained (4), which indicates that the composition of Hettstedt PM may contribute to the higher prevalence of allergies in that area independently of particle mass. This ques- tion has been investigated by Gavett and coworkers, who applied