Intermittent ozone inhalation during house dust mite-induced sensitization primes for adverse asthma phenotype

The ability of air pollution to induce acute exacerbation of asthma is well documented. However, the ability of ozone (O-3), the most reactive gaseous component of air pollution, to function as a modulator during sensitization is not well established. C57BL/6 J male mice were intranasally sensitized to house dust mite (HDM) (40 mu g/kg) for 3 weeks on alternate days in parallel with once-a-week O-3 exposure (1 ppm). Mice were euthanized 24 h following the last HDM challenge. Lung lavage, histology, lung function (both forced oscillation and forced expiration-based), immune cell profiling, inflammation (pulmonary and systemic), and immunoglobulin production were assessed. Compared to HDM alone, HDM + O-3 leads to a significant increase in peribronchial inflammation (p < 0.01), perivascular inflammation (p < 0.001) and methacholine-provoked large airway hyperreactivity (p < 0.05). Serum total IgG and IgE and HDM-specific IgG1 were 3-5 times greater in HDM + O-3 co-exposure compared to PBS and O-3-exposed groups. An increase in activated/mature lung total and monocyte-derived dendritic cells (p < 0.05) as well as T-activated, and T memory lymphocyte subset numbers (p < 0.05) were noted in the HDM + O-3 group compared to HDM alone group. Concurrent O-3 inhalation and HDM sensitization also caused significantly greater (p < 0.05) lung tissue interleukin-17 pathway gene expression and mediator levels in the serum. Redox imbalance was manifested by impaired lung antioxidant defense and increased oxidants. O-3 inhalation during allergic sensitization coalesces in generating a significantly worse T(H)17 asthmatic phenotype.