Ozone gas has been widely used as an infection control including COVID-19. Safety standard level (0.1 ppm) is set in most developed countries according to the results of preclinical and clinical studies in a healthy donor. Therefore, another safety standard level of ozone gas for the patient with respiratory disorders assumed to exist in a medical facility is required. The objective of this study is to investigate the detail adverse effects of 0.1 ppm ozone gas exposure in a mouse model of allergic asthma by focusing on both antigen-dependent and -independent immune responses including type 2 helper T cells (Th2) and type 2 innate lymphoid cells (ILC2). A mouse model of asthma was generated by repetitive intranasal sensitization and challenge of dermatophagoides farinae (Df) in female BALB/c mice. Ozone gas (0.1 ppm) was inhaled for continuous 5 days (6 hours/day) just before the end of the experiment. Ozone gas exposure significantly decreased the percutaneous oxygen saturation (SpO2). Inflammatory responses (related Th2 cytokine) and gene expression (IL13, IL33) in lung tissue, more over serum IgE levels were enhanced. This data indicates the safety standard level ozone gas (0.1ppm) has toxic effects for asthma patients. In the next step, reversibility of adverse effects of ozone gas was evaluated in a group with 2 weeks recovery phase after the final exposure to ozone gas. There was no impact of ozone gas exposure on SpO2, Th2 immune reactions (IL-4 and IL-5 production by T cells), and gene expression of lung tissue. Taken together, exposure to 0.1 ppm ozone gas significantly worsened the antigen-dependent and -independent asthma symptoms, however, the adverse effects of 0.1 ppm of ozone gas was temporary and 2 weeks recovery terms can alleviate the these symptoms to the normal.
