Asthma is a multifactorial airway disease that arises from a relatively common genetic background interphased with exposures to allergens and airborne irritants. The rapid rise in asthma over the past three decades in Western societies has been attributed to numerous diverse factors, including increased awareness of the disease, altered lifestyle and activity patterns, and ill-defined changes in environmental exposures. It is well accepted that persons with asthma are more sensitive than persons without asthma to air pollutants such as cigarette smoke, traffic emissions, and photochemical smog components. It has also been demonstrated that exposure to a mix of allergens and irritants can at times promote the development phase (induction) of the disease. Experimental evidence suggests that complex organic molecules from diesel exhaust may act as allergic adjuvants through the production of oxidative stress in airway cells. It also seems that climate change is increasing the abundance of aeroallergens such as pollen, which may result in greater incidence or severity of allergic diseases. In this review we illustrate how environmental tobacco smoke, outdoor air pollution, and climate change may act as environmental risk factors for the development of asthma and provide mechanistic explanations for how some of these effects can occur.

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Emerging evidence suggests environmental chemical exposures during critical windows of development may contribute to the escalating prevalence of obesity. We tested the hypothesis that prenatal air pollution exposure would predispose the offspring to weight gain in adulthood. Pregnant mice were exposed to filtered air (FA) or diesel exhaust (DE) on embryonic days (E) 9-17. Prenatal DE induced a significant fetal brain cytokine response at E18 (46-390% over FA). As adults, offspring were fed either a low-fat diet (LFD) or high-fat diet (HFD) for 6 wk. Adult DE male offspring weighed 12% more and were 35% less active than FA male offspring at baseline, whereas there were no differences in females. Following HFD, DE males gained weight at the same rate as FA males, whereas DE females gained 340% more weight than FA females. DE-HFD males had 450% higher endpoint insulin levels than FA-HFD males, and all males on HFD showed decreased activity and increased anxiety, whereas females showed no differences. Finally, both DE males and females fed HFD showed increased microglial activation (30-66%) within several brain regions. Thus, prenatal air pollution exposure can "program" offspring for increased susceptibility to diet-induced weight gain and neuroinflammation in adulthood in a sex-specific manner.

We tested the hypothesis that particulate air pollutants are associated with metals that have a capacity to transport electrons and that biologic activity of the particulates can correlate with the concentrations of these metals. The metals studied were titanium, vanadium, chromium, manganese, iron, cobalt, nickel, and copper. Measurements included ( 1 ) oxidized products of deoxyribose catalyzed by particulates, (2) induction of a neutrophilic alveolitis after particdate instillation, (3) increments in airway reactivity after particulate instillation, and (4) mortality after exposures to both dusts and a microbial agent. Employing 10 different dusts of either natural or anthropogenic origin, in vitro generation of oxi- ~ dized products of deoxyribose increased with ionizable concentrations of all metals, except for titanium, associated with the particles. After tracheal instillation of dust into rats, both the neutrophil influx and lavage protein increased with ionizable concentrations of these same metals. Changes in airway reactivity following instillation of dusts in rats alsoappeared to be associated with the ionizable concentrations of these metals. Similarly, mortality after injection of particles in mice with subsequent exposure to aerosolized Streptococcus zooepidemicus reflected metal concentrations. We conclude that particulate air pollutants are associated with metals which have a capacity to catalyze electron transfer. An in vitro measure of oxidant production increased with ionizable concentrations of the metals. Indices of in vivo lung injury also corresponded to concentrations of these same metals.