Abstract
Fine particulate matter 2.5 (PM(2.5)) is a prevalent atmospheric pollutant that is closely associated with asthma. Elderly patients have a high incidence of asthma with a long course of illness. Our previous studies revealed that exposure to PM(2.5) diminishes lung function and exacerbates lung damage in elderly rats. In the present study, we investigated whether PM(2.5) exposure influences susceptibility to allergic asthma in elderly rats. Brown-Norway elderly rats were treated with ovalbumin (OVA) for different durations before and after PM(2.5) exposure. The results from pulmonary function tests and histopathology indicated that early exposure to allergens prior to PM(2.5) exposure increased susceptibility to airway hyperresponsiveness and led to severe lung injury in elderly asthmatic rats. Cytokine microarray analysis demonstrated that the majority of cytokines and chemokines were upregulated in OVA-treated rats before and after PM(2.5) exposure. Cytological examination showed no change in eosinophil (EOS) counts, yet the amounts of neutrophils (NEU), white blood cells (WBC), lymphocytes (LYM), and monocytes (MON) in the lung lavage fluid of OVA-treated rats were significantly higher than those in control rats before and after PM(2.5) exposure, suggesting that PM(2.5) affects noneosinophilic asthma in elderly rats. ELISA results from the plasma and lung lavage fluid revealed that the levels of IgG1, IgE, IgG2a and IgG2b were significantly elevated in OVA-treated rats, whereas the level of IgG2b in the lung lavage fluid was significantly lower in rats treated with OVA prior to PM(2.5) exposure compared to those treated afterward. A non-targeted metabolomic analysis of plasma identified 202 metabolites, among which 31 metabolites were differentially abundant. Ten metabolites and 11 metabolic pathways were uniquely detected in OVA-treated rats before PM(2.5) exposure. Specifically, there were positive or negative correlations between the levels of Th2-associated cytokines (IL-4, IL-5, and IL-13) and six metabolites in the OVA-treated group before PM(2.5) exposure, whereas the levels of IL-4 and IL-5 were negatively correlated with five metabolites in the OVA-treated group after PM(2.5) exposure. Our findings suggest that PM(2.5) exposure could influence the susceptibility of allergic asthma in response to allergens in elderly rats, potentially through changes in plasma metabolites.