Evidence suggests an etiologic role for both physical toxins (1) and social determinants (2, 3) in the evolution and trajectory of children's lung function growth and development. Traffic-related air pollution is a global public health problem (4), and children may be most vulnerable (5). The adverse effects of air pollution on respiratory development in children have been extensively documented (6). In parallel, a growing body of literature suggests that psychological factors influence the programming of neuroendocrine, autonomic, and immune inflammatory processes implicated in respiratory development, suggesting they too play a role in lung development, although studies in humans remain scarce (2, 7).
Whereas traditional research has focused on the main effects of social and physical environmental factors, evolving research underscores the importance of interactions among these factors (8). Although a number of theoretical models have been put forth to explain how social conditions “get into the body” to impact health, the psychosocial stress model has been increasingly adopted. Psychological stress is conceptualized as a social pollutant that, when “breathed” into the body, disrupts biological systems overlapping with those altered by physical pollutants and toxicants (e.g., immune and nonimmune inflammatory processes). It is thus plausible that biologically compromised systems related to earlier life stress may be more vulnerable to subsequent environmental toxins and vice versa.
In general, stress may result in long-lasting physiological effects that influence disease risk (9). Under stress, physiological systems may operate at higher or lower levels than in normal homeostatic conditions. Disturbed regulation of stress systems (e.g., hypothalamic-pituitary-adrenal [HPA] axis, autonomic nervous system) may modulate immune function leading to increased airway inflammation, remodeling, and altered airway reactivity. Air pollution exposures have also been linked to disruption of neuroimmune responses (10) and autonomic reactivity, even in young healthy subjects (11). Moreover, air pollutants may generate oxidative species activating pathways similar to psychological stressors (9, 12). Consequent aberrant or excessive proinflammatory immune responses as well as oxidant-induced changes and sympathovagal imbalance, are determinants of lung structure–function changes during development.
Data presented by Islam and coworkers (13) in this issue of the Journal (pp. 822) builds on growing literature demonstrating interactive effects between psychosocial stress and ambient air pollution on respiratory morbidity (14–16). These data are first to suggest a synergistic relationship between stress and subsequent ambient air pollution effects on childhood lung function (13).
However, when interpreting the findings it is important to understand the stress measure being used. Stress has been conceptualized in a number of different ways with noted advantages and disadvantages as recently summarized (17). Islam and colleagues (13) used the Perceived Stress Scale (PSS), a brief self-report questionnaire that measures one's subjective perception of how stressful they find their life to be over the preceding month. This conceptualization taps into the individual's appraisal of whether the events they encounter are threatening, taxing, or potentially overwhelming to their existing coping resources. The measure may be tapping into the extent of the environmental demands the child's caregiver was under at the time the questionnaire was administered, stable individual differences in how caregivers in the study evaluate events in the world, or their ability to cope for example. The authors used a one-time PSS measure at enrollment. This then was used as an index of chronic stress to predict lung function in relation to air pollution exposures assessed approximately 6 years later when children were on average 11.2 years of age. This assumes that perceived stress is stable over time in these caregivers, an assumption that may not hold true, particularly if the environment is not stable (i.e., the stressors and life events they experience are likely dynamic) or their approach to stress appraisal changes depending on the challenges being faced. Thus a single assessment using the PSS may reflect more contemporaneous stress rather than chronic, ongoing experiences. Studies that incorporate repeated assessments of stress appraisal over time or more comprehensive measurements of life events and chronic stressors that these families may be experiencing over time will address this more definitively. Stressors may be experienced across a number of life domains and social structures (e.g., household, work, community), and knowing more about the sources of stress leading to adverse effects will better inform intervention and prevention strategies (18). As the authors point out, more direct assessment of stress experienced by the children when age appropriate, rather than their caregivers, will be important. Additional prospective studies examining stress effects on lung function and enhanced environmental vulnerability are needed. Incorporation of biomarkers to assess underlying mechanisms that may be operating in the additive and/or synergistic effects of stress and air pollution on lung function is also needed.
Another area of particular interest in children's environmental health is the search for mechanisms responsible for disparities across economic and ethnic groups. There are well-documented negative correlations between lung function measures and socioeconomic status (SES) (3). Lower SES during childhood has been associated with lower maximally attained lung function in young adulthood, as well as a more accelerated lung function decline (19). Populations living in more impoverished urban neighborhoods are disproportionately exposed to air pollutants and may also be more likely to experience stress (20, 21). The authors noted a number of social and economic correlates of the PSS scores in this cohort (e.g., caregiver education level, household income, health insurance status, and ethnicity-related factors, such as language). Analysis suggested that the interaction between baseline PSS in these caregivers and ambient pollution measures on lung function were not explained by insurance status. It was not clear whether similar adjustments were made for other SES indicators to determine residual confounding by SES. One can argue that psychological stress should be considered as a mediator of the relationships among SES, air pollution exposure, and lung function outcomes, and thus should not be controlled for at all. Rather, alternative statistical approaches (e.g., structural equation modeling) could be implemented to formally test mediation. Smoking can also be considered as a mediator of stress-health effects. Thus, another question that arises is whether the enhancing effect due to stress reported here may, at least in part, be due to environmental tobacco smoke exposure related to caregiver stress in the home. Such pathways should be explored more directly in future research.
Because social stress and other environmental toxins (e.g., air pollutants) are often concurrent and may influence common physiological pathways, understanding the potential synergistic effects and how they may be operating across sociodemographic factors promises to more completely inform respiratory disease risk in children. We need to better understand how the physical and psychological demands of living in a disadvantaged environment may potentiate an individual's susceptibility to environmental exposures across these domains. Conducting this work in childhood and adolescence is critical, given that these early effects may persist into adult life, magnifying the public health impact.