Mechanistic insights into ozone-induced asthma exacerbation: role of oxidative stress and IL-33

Short-term exposure to ozone is linked to the onset and exacerbation of asthma, yet the underlying mechanisms remain unclear. This study aims to elucidate the molecular pathways and key mediators involved in ozone-induced asthma exacerbation. In a longitudinal epidemiological study, each 10 µg/m³ increase in ozone is associated with decreases in forced vital capacity (FVC), forced expiratory volume in one second (FEV₁), and peak expiratory flow (PEF) of 26.24 ml (95 % confidence interval [CI]: 11.16 ml, 41.33 ml), 19.10 ml (95 % CI: 6.96 ml, 31.24 ml), and 41.65 ml/s (95 % CI: 3.87 ml/s, 79.43 ml/s), respectively. In asthmatic mice, ozone exposure induces oxidative stress and worsens pulmonary dysfunction, lung tissue damage, and inflammation, disrupting the balance of type 2 innate lymphoid cells (ILC2s), T helper type 2 (Th2), and T helper type 17 (Th17) cells. These effects are partially mitigated by N-acetylcysteine (NAC). Furthermore, ozone exposure significantly increases the interleukin (IL)-33 level, while treatment with an IL-33 neutralizing antibody markedly improves lung dysfunction, inflammatory cell infiltration, and immune response dysregulation. In conclusion, this study highlights that short-term exposure to ozone has deleterious effects on asthmatic patients and animals by inducing oxidative stress in lungs and disrupting immune function via IL-33.