
Dearborn LC, Hazlehurst MF, Sherris AR, et al. JAMA Netw Open. 2025;8(4):e254121. doi:10.1001/jamanetworkopen.2025.4121
Key Points
Question Is early-life ozone (O3) exposure associated with asthma and wheeze in children independently and within mixtures of other air pollutants?
Findings In this multisite cohort study of 1188 children, higher mean O3 exposure between birth and age 2 years was associated both independently and within mixtures of fine particulate matter and nitrogen dioxide with higher odds of caregiver-reported asthma and wheeze at ages 4 to 6 years but not ages 8 to 9 years.
Meaning These findings suggest that in areas of low ambient O3 pollution, early-life O3 exposure was associated with asthma and wheeze in children.
Abstract
Importance Ozone (O3) is the most frequently exceeded air pollutant standard in the US. While short-term exposure is associated with acute respiratory health, the epidemiologic evidence linking postnatal O3 exposure to childhood asthma and wheeze is inconsistent and rarely evaluated as a mixture with other air pollutants.
Objectives To determine associations between ambient O3 and subsequent asthma and wheeze outcomes both independently and in mixture with fine particulate matter and nitrogen dioxide in regions with low annual O3 concentrations.
Design, Setting, and Participants This cohort study consisted of a pooled, multisite analysis across 6 US cities using data from the prospective ECHO-PATHWAYS consortium (2007-2023). Included children had complete airway surveys, complete address histories from age 0 to 2 years, and a full term birth (≥37 weeks). Logistic regression and bayesian kernel machine regression (BKMR) mixture analyses were adjusted for child anthropomorphic, socioeconomic, and neighborhood factors.
Exposures Exposure to ambient O3 in the first 2 years of life derived from a validated point-based spatiotemporal model using residential address histories.
Main Outcomes and Measures The primary outcome was asthma and wheeze at ages 4 to 6 years; the secondary outcome was asthma and wheeze at ages 8 to 9 years. Outcomes were based on caregiver reports derived from a validated survey.

Results The analytic sample of 1188 participants had a mean (SD) age of 4.5 (0.6) years at the age 4 to 6 years visit and consisted of 614 female participants (51.7%) and 663 mothers who had a bachelor’s degree or higher (55.8%). The mean (SD) O3 concentration was 26.1 (2.9) parts per billion (ppb). At age 4 to 6 years, 148 children had current asthma (12.3%) and 190 had current wheeze (15.8%). The odds ratio per 2 ppb higher O3 concentration was 1.31 (95% CI, 1.02-1.68) for current asthma and 1.30 (95% CI, 1.05-1.64) for current wheeze at age 4 to 6 years; null associations were observed for outcomes at age 8 to 9 years, and for sensitivity covariate adjustment. BKMR suggested that higher exposure to O3 in mixture was associated with current asthma and wheeze in early childhood.
Conclusions and Relevance In this cohort study with relatively low ambient O3 exposure, early-life O3 was associated with asthma and wheeze outcomes at age 4 to 6 years and in mixture with other air pollutants but not at age 8 to 9 years. Regulating and reducing exposure to ambient O3 may help reduce the significant public health burden of asthma among US children.