Increased airway hyperresponsiveness and inflammation in a juvenile mouse model of asthma exposed to air-pollutant aerosol

Asthma and its exacerbation by air pollution are major public health proble ms. This investigation sought to more precisely model this disorder, which primarily affects children, by using very young mice. The study first attem pted to create allergic airway hypersensitivity in neonatal mice and to det ermine if physiologic testing of airway function was possible in these smal l animals. Neonatal mice were sensitized by ip injection of ovalbumin (OVA, 5 mu g) and alum (1 mg) at 3 and 7 d of age. One week later, mice were cha llenged by allergen nebulization (3% OVA in PBS, 10 min/d, d 14-16). OVA-ex posed mice showed: (1) increased airway hyperresponsiveness (AHR) to methac holine by whole-body plethysmography; (2) eosinophilia in bronchoalveolar l avage (BAL) fluid; (3) airway inflammation using histopathology techniques; and (4) elevated serum anti-OVA immunoglobulin E. Hence, these neonatal mi ce were successfully sensitized and manifested "asthmatic" responses after allergen challenge. Experiments were conducted to investigate the effect of one surrogate for ambient air particles, residual oil fly ash (ROFA), on t his juvenile asthma model. Aerosolized ROFA leachate (super-natant of 50 mg /ml, 30 min, on d 15) had no marked effect alone, bur caused a significant increase in AHR and airway inflammation in OVA-sensitized and challenged mi ce. This synergistic effect was abrogated by the antioxidant dimethylthiour ea (DMTU, 3 mg/kg mouse, ip). This model may be useful to study air polluti on-mediated exacerbation of asthma in children.