after delivery, such as young, single mothers with limited education. It has been suggested that effective secondary prevention could take place during doctor visits due to child’s respira- tory problems. The most important issue for future research is how to eliminate (or at least reduce) ETS exposure effectively both in child- hood and adulthood. Ambient Air Pollution and Asthma Induction Although extensive evidence shows that ambient air pollution exacerbates existing asthma, a link with the development of asthma is less well established. This is primarily because few prospective studies with extensive exposure data have been conducted. However, in the past few years, some limited data sets have emerged to support associations between air pollution and incidence of asthma. The ambient air pollutants studied have included particulate matter (PM), nitrogen dioxide (NO2), sulfur dioxide (SO2), and ozone (O3). The epidemiologic data on whether ambi- ent air pollution contributes to the incidence of asthma are from ﬁve studies—three in children and two in adults. Of the childhood studies, one was a birth cohort from the Netherlands, the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) study (Brauer et al. 2002), in which > 4,000 children were enrolled at birth and followed up to 2 years of age. Trafﬁc-related air pollution was assessed on the basis of geographic information system models that were validated by a network of 40 moni- toring stations at which NO2, PM2.5 (PM with aerodynamic diameter ≤ 2.5 µm), and reﬂectance measures for “soot” were assessed at four 2-week periods throughout a calendar year. The outcomes were parental reports of several phenotypes relevant to asthma; doctor- diagnosed asthma, bronchitis, ENT (ear, nose, and throat) infections, serious colds, or ﬂu; and symptoms of wheeze and dry night cough. Small but statistically signiﬁcant associations [relative risk (RR), 1.11–1.20] were found between traffic-related air pollution and wheeze, doctor-diagnosed asthma, ENT infec- tions, and serious colds or ﬂu. An international collaborative study involving the Netherlands, Germany, and Sweden was established to examine traffic- related air pollution and childhood asthma (Gehring et al. 2002). Preliminary results pub- lished for 1,756 infants in Germany with fol- low-up through 2 years of age showed signiﬁcant associations between dry cough at night in the ﬁrst year of life and three meas- ures of pollution—NO2, PM2.5, and soot, with ORs of 1.32–1.40. The associations persisted but were weaker in the second year of life (ORs 1.16–1.24). No association was found with wheezing, respiratory infections, or bronchitis. The Children’s Health Study (CHS) includes > 6,000 children enrolled in 1993 and 1996 in 12 communities throughout southern California and provides a maximum range in exposure to ambient ozone, particles, acids, and oxides of nitrogen (McConnell et al. 2002). This report included 3,535 chil- dren without asthma at baseline and at least 1 year of follow-up during which 259 new cases of asthma diagnosis were reported. Air pollution was defined in this analysis by whether the community in which the child lived was in the bottom or top half of expo- sure for a given pollutant. The communities divided the same way for PM, NO2, and acids, but the high- and low-ozone communi- ties were different. When ozone levels were examined alone, there was no increased risk of asthma with high exposure, and the peak level was actually related to significantly dimin- ished risk. When children who participated in sports activities were examined, those who played three or more sports had an increased risk of asthma (RR = 1.8; 95% CI, 1.2–2.8). When the sports variable was further stratiﬁed by high/low air pollution status, there was no difference for particles, NO2, or acids, but an effect of three or more sports was strongly seen in the high-ozone communities. It should be noted that this finding was based on taking a very small category and dividing it into two subsets; only 9 of the 29 cases were in the low-ozone communities (RR = 0.8), versus 20 in the high-ozone communities (RR = 3.3; 95% CI, 1.9–5.8). The evidence on air pollution and asthma incidence in adults comes from a cohort study of Seventh-day Adventists in California, known as the ASHMOG study. Investigators analyzed air pollution exposure in residentially stable nonsmokers in 1977 and followed up in 1982 and 1992. Exposure was based on the nearest monitoring station to the work and home addresses. In the ﬁrst study, Abbey et al. (1995) examined incident asthma (79 cases) in relation to PM and reported a relative risk of 1.30 (95% CI, 0.97–1.73) for 1,000 hr/year exposure to concentrations of PM10 (PM with aerodynamic diameter ≤ 10 µm) that exceeded 100 µm/m3. A later study on ozone that included 115 incident cases of asthma (McDonnell et al. 1999) reported an increased risk in men for a 27 ppb (interquartile range) increase in ozone (RR = 2.09; 95% CI, 1.03–4.16) but no association in women. In summary the results from the five prospective studies support a modest increase in risk for air pollution in relation to pheno- types relevant to asthma. The three studies of subjects old enough to have a ﬁrm diagnosis of asthma share limitations of uncertainty about when asthma started. This is a caveat for any prospective study of chronic disease, however, where it is difficult to distinguish Environmental Health Perspectives • VOLUME 114 | NUMBER 4 | April 2006 Environmental exposures and asthma possible exacerbation of preclinical symptoms from incidence of new asthma. The children’s studies are still quite small in scope, and activ- ity patterns such as number of outdoor sports may also reﬂect other unrealized confounders. Numerous large-scale initiatives [e.g., the National Children’s Study (NCS 2005)] designed to track disease incidence and sever- ity from before birth and relate those effects to environmental exposures will be able to more clearly deﬁne risk factors for the devel- opment of diseases such as asthma. Role of Prooxidative DEP Chemicals in Airway Inﬂammation and Allergic Adjuvancy Four key questions [National Research Council (NRC) 1998) regarding the adverse health effects of PM on asthma are a) What is the mechanism by which PM affects car- diorespiratory morbidity and mortality? b) What are the PM components responsible for adverse health effects? c) What are the types and sizes of PM that are most potent? and d) Who in the population is more prone to adverse health effects? The impact of PM on the genesis and exacerbation of asthma is a good disease model to probe these questions (Nel et al. 1998). Atopic asthma is a disease of allergic airway inflammation, which from an ambient particle perspective could be approached by studying how PM pollutants in combination with common aeroallergens lead to a) the genesis of asthma, b) T-helper 2 (TH2) immune deviation by acting as adju- vants for allergic inflammation, and c) acute exacerbation of existing disease through an effect on AHR (Li et al. 2003a, 2003b). To approach the questions listed above from an investigative perspective, reseachers have used DEPs as a model PM pollutant for in vitro and in vivo experiments (Nel et al. 1998). Several groups have demonstrated that DEPs can act as an adjuvant when combined with an experimental allergen, ovalbumin, resulting in enhanced IgE antibody produc- tion and increased allergic inﬂammation and AHR in mice (Miyabara et al. 1998; Whitekus et al. 2002; Xiao et al. 2003). To define the mechanistic basis for the proinflammatory effects of DEPs, Li et al. (2000, 2004) approached the problem from the premise that DEPs contain a large number of chemi- cals that play a role in inflammation. This includes transition metals as well as a host of organic chemical compounds. Among the organic chemicals, there is good evidence for the role of polycyclic aromatic hydrocarbons (PAHs) and quinones as toxicologically rele- vant compounds that give rise to reactive oxygen species (ROS) (Li et al. 2003a, 2003b; Monks et al. 1992; Penning et al. 1999; Xia 629