Air Pollution and Child Lung Health: Critical Thresholds at Critical Times.

In September 2021, the World Health Organization (WHO) released updated global air quality guidelines (AQGs) for the first time since 2005. Incorporating a wealth of interim evidence demonstrating the adverse health effects of air pollution, the WHO tightened recommendations for target air pollution concentrations, including lowering the AQG for fine particulate matter (particulate matter ⩽2.5 μm in aerodynamic diameter [PM2.5]) from 10 μg/m3 to 5 μg/m3 (1). These updated guidelines not only emphasize the global urgency of improving air quality to prevent illness and death but also send the message that harmful effects occur even at lower concentrations of air pollution.

On the heels of these more stringent recommendations, in this issue of AnnalsATS, Takebayashi and colleagues (pp. 763–772) investigated the association between concurrent exposure to low concentrations of PM2.5 and lung function growth over 4 years in a large cohort of 1,466 pre- and early adolescent school children across 10 cities in Japan (2). Exposure measurements captured continuous ambient PM2.5, ozone (O3), and nitrogen dioxide (NO2) concentrations at or near each school and were characterized by relatively low overall annual mean PM2.5 concentrations of 13.5 μg/m3. Perhaps counter to the sense that air pollution—even at lower thresholds—is harmful to lung health, the authors found no significant associations between PM2.5 at these concentrations and lung function growth over the study period in models adjusted for confounders and copollutants.

These results are in contrast to previous literature demonstrating adverse effects of higher PM2.5 concentrations (>20 μg/m3) on longitudinal childhood lung function trajectories (3), as well as corresponding improvements in lung function with reduced exposure to air pollution during adolescence (4).

Despite its null findings, this study highlights an important paradigm of how environmental insults may alter the trajectory of human health and increase risk for future disease depending on the dose and timing of such exposures. Prior evidence for the presence of critical windows of susceptibility supports that, as early as the prenatal period, ambient air pollution exposures at specific weeks of gestation (with corresponding developmental milestones) have differential effects on lung function and respiratory disease risk during childhood (5–8). These and other data highlight the importance of examining the influence of environmental exposures on lung function trajectories during uniquely vulnerable points across the life course. In line with this concept, Takebayashi and colleagues present a unique snapshot of the impact of air pollutant exposures experienced at the verge of the accelerated lung growth of adolescence that ultimately contributes to the attainment of peak individual lung function in early adulthood. This inquiry is motivated by epidemiologic data from other cohorts that have linked environmental risk factors present at the preadolescent life stage to the development of chronic lung disease in middle age (9), emphasizing the importance of examining air pollutant exposures during critical windows of development that could have far-reaching consequences on lung health later in life. It remains to be seen what associations may exist between preadolescent low-dose PM2.5 exposures and the attainment of peak lung health in extended follow-up periods of this cohort.

Apart from its overall contribution to this framework, the study has several strengths. The authors enrolled a large number of participants over a broad geographic area, allowing for generalizability of findings across Japan. In addition, high spirometry completion rates captured lung function at repeated points along the growth curve within the pre/early adolescent life stage. Another strength of the study is the inclusion of other air pollutants (O3 and NO2) in multipollutant models and multiple other sensitivity analyses resulting in consistent findings. However, as the authors gathered exposure data contemporaneous to lung function measurements, one gap in our ability to interpret a lack of relationship lies in the absence of exposure data before preadolescence. In effect, early-life exposures not captured by the current study may have already “set the course” toward an altered lung health trajectory. Looking forward to future trajectories, we must also consider that lung function values at time of study entry are a function of the cumulative effects of exposures experienced before that point in childhood, contributing to the phenomenon described by Peto in 1981 as the horse-racing effect (10).

Given the study findings, is it safe to say, then, that lower concentrations of PM2.5 exposure during pre/early adolescence are benign for lifelong lung health? It is a comfort that we likely cannot take in good conscience, especially in the current environmental climate. Rather, a singular focus on physiologic measurements as the prime indicator of lung health is a gross overestimation and, more importantly, may miss opportunities for early intervention to preempt progression to disease. Instead, a greater focus on evaluating intermediate phenotypes of impaired lung health, such as respiratory symptoms and early changes on lung imaging, may help to identify altered respiratory status among individuals without established disease (11). For example, persistent respiratory symptoms in “healthy” young adult populations predict risk of future chronic lung disease, including accelerated lung function decline (12). Furthermore, detectable changes on chest computed tomography using objective analytic tools in otherwise visually normal-appearing lung have been associated with increased morbidity and mortality from chronic lung disease (13). This emerging evidence suggests that early markers of impaired lung health beyond spirometry may help to more precisely evaluate the harm associated with toxic exposures.

Until there is further evidence, the revised WHO AQGs serve as an impetus to continue to push the agenda for cleaner air. In these efforts, it is imperative to consider the unique vulnerability of developing children to the short- and long-term health effects of air pollution.