Short-term effects of air pollutants on acute asthma exacerbation among children with persistent asthma: A nationwide case-crossover study in Japan

• We evaluated short-term effects of air pollution on acute asthma exacerbation. • The study population comprised children with persistent asthma aged 4–5 years. • Single-pollutant and multi-pollutant models were employed. • Various air-pollutant exposures triggered acute asthma exacerbation. • NO 2 had the greatest effect size. Although numerous studies have suggested short-term effects of air pollutants on acute asthma exacerbation, no study has yet specifically focused on children with persistent asthma, a particularly vulnerable population. In addition, several important aspects remain unclear: the potential harm caused by inhaled corticosteroids (ICS) and the disentangling of impacts from multiple pollutants. This case-crossover study utilized data from the Japan Medical Data Center between 2005 and 2022. The study population included children with persistent asthma aged 4–5 years. A date of acute asthma exacerbation was selected as the focal window, with two corresponding reference windows at -7 and -14 days. The exposures were ambient particulate matter 2.5, nitrogen dioxide (NO 2 ), carbon monoxide, photochemical oxidants, sulfur dioxide, total hydrocarbons, and non-methane hydrocarbons. For multi-pollutant models, we incorporated all air pollutants by using principal component analysis. Conditional logistic regression models were applied, adjusting for temperature, humidity, and air pressure. An interaction term with ICS use was included. In total, 142,947 acute asthma exacerbation cases were identified, with 20,724 children having persistent asthma. In single-pollutant models, higher levels of air pollutants, except for photochemical oxidants, were associated with increased risks. No significant interaction effects of ICS were observed. Multi-pollutant models suggested that NO 2 had the greatest impact (odds ratio among non-ICS users: 1.23 [95 % confidence interval: 1.17–1.29]). Most air pollutants, particularly NO 2 , were associated with higher risks of acute asthma exacerbation. Physicians may not need to be overly concerned about harmful interactions of ICS.