Early-Life Ozone Exposure and 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.

Figure 1.. Inclusion Diagram

Depicts the full potential sample in the ECHO prenatal and early childhood pathways to health consortium (ECHO-PATHWAYS) and reasons for exclusion from the analytic sample.

Figure 2.. Association Between Early-Life Ozone (O₃) and Current Asthma and Wheeze at Age 4 to 6 Years

Odds ratios (ORs) and 95% CIs of 2 ppb higher early-life O₃ are depicted. Minimal models were adjusted for child sex, age, birth year, and site. Primary models were additionally adjusted for maternal education, maternal asthma status, postnatal secondhand smoke exposure, and Neighborhood Deprivation Index. Extended models were additionally adjusted for household income interacted with household size, furry pet ownership, maternal prenatal smoking, and duration of breastfeeding.

Figure 3.. Probit Bayesian Kernel Machine Regression Exposure-Response Function of Each Pollutant When Other Pollutants Are Held to Their Median Value

This figure represents the change in the predicted outcome probability z score as 1 pollutant increases in concentration while the other 2 pollutants are held to their median. A-C, Current asthma at age 4 to 6 years, and D-F, current wheeze at age 4 to 6 years. A rug plot depicting pollutant concentrations can be found along the x-axis. NO₂ indicates nitrogen dioxide; O₃, ozone; PM_2.5, fine particulate matter; ppb, parts per billion.