title: Effects of combined ozone and air pollution particle exposure in mice.
abstract: Epidemiologic studies indicate that ozone (O3*) and air pollution particles can exacerbate asthma symptoms. We investigated whether coexposure to inhaled particles and O3 causes a synergistic effect on airway responsiveness and allergic inflammation in a murine (BALB/c) model of ovalbumin (OVA)-induced asthma. Half of the mice were sensitized by intraperitoneal injection of OVA and then exposed to OVA aerosol on 3 successive days to create the asthmatic phenotype; the other half were sensitized to OVA and exposed to phosphate-buffered saline (PBS) to create the nonasthmatic control group. On the same 3 days that the OVA or PBS challenge was administered, mice were further divided into groups that were exposed for 5 hours to concentrated ambient particles (CAPs; mass values ranging from 63 to 1,569 microg/m3 for 1 day's exposure), 0.3 ppm O3, both, or neither (n > or = 61 total mice per exposure group for all 12 experiments). Whole-body plethysmography was used to measure airway responsiveness after challenge with aerosolized methacholine (MCh). Enhanced pause (Penh), an index that closely correlates with pulmonary resistance (Hamelmann et al 1997), was measured daily in each mouse immediately after pollutant exposure and, for 7 of the 12 experiments (n > or = 36/exposure group), beginning 24 hours after the final OVA or PBS challenge. Using several complementary statistical models, we found that exposure to CAPs alone caused a small but significant increase in Penh in both normal and asthmatic mice immediately after exposure (an increase of approximately 1% per 100-microg/m3 increase in CAPs). No increase in Penh was found in animals exposed to O3 alone or to filtered air. Compared with control animals, no combination of exposure atmosphere plus asthma produced a synergistic effect on Penh. By 24 hours after the last OVA or PBS challenge, any enhanced response induced by pollutant exposure had declined to control levels. The pollutant exposures did not significantly increase airway inflammation (assessed by bronchoalveolar lavage [BAL] fluid analysis beginning 24 or 48 hours after the final OVA or PBS challenge). Because CAPs are a heterogeneous mixture of particles, elemental analysis was conducted and associations between specific elemental groupings (present in daily samples) and airway responsiveness were analyzed. This analysis showed that increased Penh in asthmatic mice exposed to CAPs plus O3 was associated with the AlSi fraction of CAPs. No such association was found in control mice or in asthmatic mice not exposed to O3. We conclude that CAPs exposure causes an immediate, short-lived (< 24-hour), small increase in airway responsiveness in mice and that changes in airway physiology are correlated with specific elements found within the particle mixture.
authors.affiliation: Harvard School of Public Health, Department of Environmental Health, Boston, MA 02115-6021, USA.
authors.forename: L
authors.initials: L
authors.lastname: Kobzik
authors.forename: C A
authors.initials: CA
authors.lastname: Goldsmith
authors.forename: Y Y
authors.initials: YY
authors.lastname: Ning
authors.forename: G
authors.initials: G
authors.lastname: Qin
authors.forename: B
authors.initials: B
authors.lastname: Morgan
authors.forename: A
authors.initials: A
authors.lastname: Imrich
authors.forename: J
authors.initials: J
authors.lastname: Lawrence
authors.forename: G G
authors.initials: GG
authors.lastname: Murthy
authors.forename: P J
authors.initials: PJ
authors.lastname: Catalano
mesh_terms: D000393:Air Pollutants / Q000009:adverse effects*; D000403:Airway Resistance / Q000502:physiology; D000818:Animals; D001249:Asthma / Q000209:etiology* / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004391:Dust; D004781:Environmental Exposure / Q000009:adverse effects*; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D010126:Ozone / Q000009:adverse effects*; D010993:Plethysmography, Whole Body
chemical_list: D000393:Air Pollutants; D004391:Dust; D010126:Ozone