residents, with negative health consequences (Forsberg et al. 1997), although perceived air quality can also be influenced by disease status (Piro et al. 2008). Indeed, it can be dif- ficult to distinguish health effects produced by the physical aspects of air pollution from its psychosocial health effects in communities near toxic sites (Elliot et al. 1993; Eyles et al. 1993), to separate both pollution-derived effects from those of other spatially correlated stressors, or to establish directionality. To better elucidate this complex synergy among exposure pathways, environmental expo- sure assessment and risk management may ultimately consider both tangible physical and psychosocial effects of pollution to fully understand the mechanisms linking air pollu- tion, stress, and susceptibility. Additional Questions to be Explored Many questions about stress-related pollution susceptibility remain. We raise several here, describing each only briefly, and hope these issues will be explored in detail in coming years. To which pollutants and health out- comes is stress-related susceptibility relevant? A few studies demonstrate significant stress- related modification in air pollution effects on respiratory health, particularly asthma onset (Clougherty et al. 2007) and exacer- bation (Chen et al. 2008; Clougherty et al. 2006). Stress may also modify relationships between bone lead and cardiovascular out- comes (e.g., hypertension) (Peters et al. 2007) and, in the same data set, heart rate variabil- ity (Clougherty JE, Peters JL, Schwartz J, Kubzansky L, unpublished data). A growing toxicology literature demonstrates stress-re- lated susceptibilities to neurocognitive effects of lead and polychlorinated biphenyls, includ- ing neurologic damage and hippocampal func- tion (Cory-Slechta et al. 2004). These vastly different exposures and outcomes demonstrat- ing stress–pollutant interactions and the many physiologic systems affected by stress (e.g., sympathetic regulation, immune function, glucocorticoid production) suggest potential stress-related modifications in a wide range of pollutant exposures on health outcomes. Are these interactions different in illness onset than in exacerbation? For preexisting illness, many factors may modify stress effects on illness severity and chronicity, including current medical treatment and comorbidi- ties. The progression of preexisting illness, if influenced by stress, may also change the relevant temporalities, as later stress could plausibly modify recovery from environmen- tally derived illness. Thus, stress–pollution interactions may be even more complicated for existing illness, and careful attention to temporality and confounding (e.g., by medi- cal treatment) is even more important. Some evidence suggests that stress may modify pollution effects in exacerbating preexisting asthma (Chen et al. 2008; Clougherty et al. 2006), although both studies produced associ- ations opposite to hypotheses (stronger pollu- tion effects with lower stress). More generally, attention to distinguishing processes related to illness onset from illness progression or exac- erbation will be critical in assessing whether interactions are robust or should be expected in healthy populations. Are there critical periods for stress and pollution exposures across the life course? Different diseases are relevant at different life stages. Asthma is among the most preva- lent chronic illnesses of childhood, whereas cardiovascular illness generally afflicts older persons. Because the life-course distribution of illness varies considerably, relationships among stress, susceptibility, and illness likely also vary with age. Although stress can be toxic at any age, there may be critical periods, such as during early immune development, when it is particularly influential in shaping future susceptibility and disease risk (Evans and English 2002). Parental stress has been used to exam- ine stress exposures in young children, and research supports inverse associations for both mother’s SES and depressive states on chil- dren’s stress hormone levels (Lupien et al. 2000). Prospective studies have linked care- giver stress to infant wheeze (Wright et al. 2002), and maternal stress during pregnancy may influence immune function and health in neonates (Weiss and Bellinger 2006). Maternal air pollution exposures associated with low birth weight (Gouveia et al. 2004) may increase later childhood respiratory dis- ease risk. Stress exposures during development may produce broad biological and psychologi- cal vulnerabilities, affecting neuroendocrine, immune, metabolic, and growth processes (Viltart and Vanbesien-Maillot 2007). Although not entirely immutable, these effects may have permanent and compounding con- sequences, especially if not addressed early (Cicchetti and Walker 2001; McEwen 2008). What are the roles of gender/sex and race/ ethnicity in shaping stress-related susceptibil- ity to pollution? It is beyond the scope of this review to describe the myriad societal-level sources of stress. However, ongoing research in this area will be informed by the growing literatures on racism as a prevalent stressor, and on sex and gender differences in psycho- logical and physiologic responses to stress and susceptibility. Racial and ethnic minority groups in the United States are often differentially exposed to psychosocial stressors and physi- cal contaminants in their homes, neighbor- hoods, and workplaces (Bullard 1990). The environmental justice movement has drawn Environmental Health Perspectives • volume 117 | number 9 | September 2009 Stress and air pollution susceptibility attention to disproportionate pollution expo- sures in minority and low-income commu- nities (Krieger 1990), but only recently has attention been directed to combined pollu- tion exposures and greater susceptibility in these communities (Clougherty et al. 2007; Evans and English 2002; Morello-Frosch and Shenassa 2006; National Environmental Justice Advisory Council 2004). Experiences of racism as a stressor have been associated with negative physical and emotional health effects (Borrell et al. 2006; Clark et al. 1999; Krieger and Sidney 1996; Kwate et al. 2003; Landrine and Klonoff 1996; Thompson 1996) modified by coping practices and social support (Kwate et al. 2003). Experiences of racial discrimina- tion predicted poorer birth outcomes among women with Arabic names in California after 11 September 2001 (Lauderdale 2006). There is also evidence of poorer health, including mortality, for U.S. persons than for foreign- born persons of the same ethnicity, especially Hispanics (Singh and Hiatt 2006). Effects of race and racism are not fully mediated through social class (Kwate et al. 2003) and are not gen- erally attributable to genetic variation (Krieger 2005). Race-related stressors may contribute to “weathering” or physiologic wear and tear (Geronimus 1992; Goodman et al. 2005; Merritt et al. 2004). Hypertension onset, for example, may be four to seven times higher among low-SES than among high-SES African- American men (James et al. 2006). African Americans also have higher rates of cardiovas- cular illness (Pappas et al. 1993) and low birth weight (David and Collins 1997) relative to Caucasians with comparable education. Sex and gender differences in stress and susceptibility may be significant. The distinction between gender (socially influ- enced behaviors) and sex (biology, includ- ing hormonal composition, sex organs, and anthropometric measures) is comparable with that between exposure and susceptibil- ity. Sex differences have been observed in air pollution–health associations. After early childhood, more studies report greater risks among women and girls (Luginaah et al. 2005; Oftedal et al. 2008; Rojas-Martinez et al. 2007; Rosenlund et al. 2008), possi- bly explained, in part, by biological sex dif- ferences in lung capacity, hormonal status, inflammation, or airway particle deposition (Kim and Hu 1998; Kohlhaufl et al. 1999). Gendered social and behavioral patterns also matter. Sex stratification in the workforce and work-related exposures are well documented (Arbuckle 2006; Messing and Stellman 2006). Among children, play activities may influ- ence ventilation rate, creating exposure dif- ferences between boys and girls (McConnell et al. 2002). Common pollution exposures metrics may be differently accurate by gen- der; residential exposures may better capture 1355