Clougherty and Kubzansky stress (Fugisawa 2005) or inflammatory cell [immunoglobulin E (IgE)] production (Diaz- Sanchez et al. 2000; Nel 2001). More studies have explored air pollution effect modification by socioeconomic status (SES) than by stress. Given other evidence of greater stress-related illness and susceptibility among persons with lower SES (Kubzansky et al. 2000; Miller and Chen 2007; Seeman et al. 2004), heightened air pollution responses with lower SES may be mediated through stress-related pathways. The American Cancer Society (ACS) studies reported stronger effects of air pollution on respiratory, cardiovascu- lar, and all-cause mortality among lower-SES persons (Krewski et al. 2000), supported by other studies reporting stronger air pollution– health associations among less-educated adults (Finkelstein et al. 2003; Hoek et al. 2002; Pope 2002). Time-series studies have indi- cated that lower-SES persons display stronger associations between short-term air pollution exposures and health (Jerrett et al. 2004; Lin et al. 2004; Martins et al. 2004), although not consistently (Zanobetti 2000). These stud- ies, however, have not explored specific com- ponents of SES that may be responsible for susceptibility effects, although stress has been proposed as a key component. Several theoretical perspectives suggest that social, economic, and psychological dis- advantage may cluster (Adler and Matthews 1994; Evans and English 2002; Link and Phelan 2000; Shonkoff and Phillips 2000). Fundamental causes theory, for example, describes social conditions (e.g., socioeconomic position) as determinants of resource access and psychological and behavioral experience, shaping disease risk (Link and Phelan 1995). Although applicable to combined social and physical exposures, these theories have not addressed methodologic issues (e.g., spatial cor- relation, confounding, measurement bias) or interpretation challenges arising in combining theory, methods, and data across disciplines. Like air pollution, low SES and stressors (e.g., noise) may be elevated in urban settings along highways and industrial areas, and methods are needed to disentangle effects of clustered social and physical stressors and to investigate poten- tial synergies. One model (Morello-Frosch and Shenassa 2006) captures our key constructs of interest: a) varied stressors at the individual and community level contribute to individual chronic stress; b) chronic individual stress is embodied as allostatic load, or physiologic wear and tear, influencing individual susceptibility; and c) stress-borne physiologic susceptibility may shape response to environmental expo- sures, including internal dose, resiliency, likeli- hood of developing a given illness, and ability to recover from it. Like other models combining social and physical exposures (deFur et al. 2007; Gee 1352 and Payne-Sturges 2004; O’Neill et al. 2003), the Morello-Frosch model acknowledges that some community-level stressors are also physical hazards (e.g., poor housing quality), complicating distinctions between effects of psychosocial and physical factors. This model frames our discussion, although it is outside the scope of our review to describe the myriad possible social, political, and economic forces that contribute to individual stress. Instead, we focus our attention on individual-level stress and pollution susceptibility, given that higher-level stressors need be individually embodied to modify pollution effects through stress-specific pathways. We build on conceptual models of social– environmental interaction by describing key methodologic and conceptual issues that arise when merging data and methods from across environmental and social science tra- ditions. We hope to foster more integrative approaches toward understanding combined health effects of social and physical environ- mental exposures. We attempt to synthesize the literature to date on the following: • Effects of stress on respiratory health and susceptibility • Epidemiologic and toxicologic evidence of synergistic effects of stress and pollution • Pathways through which stress may influ- ence pollution susceptibility • Methodologic challenges in merging data and methods from environmental and social sciences. We aim to provide a template for research- ers aiming to rigorously consider combined effects on health across disciplines. We hope to support the growing literature targeted at dis- entangling effects of spatially clustered social and environmental exposures and exploring potential synergies among these exposures. Physiologic Effects of Psychological Stress on Respiratory Health and Susceptibility A long history of research links psychological stress and respiratory health. In Treatise on Asthma, Maimonides (1135–1204) described the illness—“Whereas treatment of asthma is important, treatment of a patient as a whole is more important. For asthma the physi- cian must be a doctor in every sense”—and described the importance of clean air and its interplay with emotions and hormones (Muntner 1963). In the 1930s, Hans Selye recognized links between chronic stress in laboratory rats and nonspecific susceptibility to respiratory distress and death (Selye 1936). More recently, chronic stress has been linked to asthma symptoms in cross-sectional studies (Oh et al. 2004), and prospective studies link caregiver stress to infant wheeze (Wright et al. 2002). Among asthmatic adolescents, SES has been associated with stress-linked immune mediators [interleukin (IL)-5, interferon-γ], an association mediated by stress and con- trol beliefs (Chen et al. 2003). Acute stressors (e.g., violent events) may trigger asthma epi- sodes (Sandberg et al. 2000, 2004), and older individuals with greater psychological distress and anger display faster lung function decline over time (Kubzansky et al. 2002). Distinctions between acute (short-term, generally lasting days to weeks) and chronic (longer-term, lasting weeks to years) stress is not always clear. Some severe acute stressors (e.g., sexual violence, or combat) can pro- duce chronic stress effects (i.e., post-traumatic stress disorder). Assessing stress chronicity is important, however, as acute and chronic stress can produce substantively different physiologic sequelae, and the predominance of acute versus chronic stress experience in a given period may shape observed relationships between stress and susceptibility. Acute stress is linked to sympathetic innervation, includ- ing increased ventilation and bronchodilation, plausibly masking some short-term effects air pollution effects (e.g., acute irritation, bronchoconstriction). Conversely, chronic stress can produce wear and tear on bodily sys- tems, weaken immune function, and increase pollution susceptibility. Because of these very different physiologic sequelae, careful consid- eration of stress chronicity and of the relative chronicities of stress and pollution exposures is critical in accurately characterizing their inter- play and in interpreting interactions. Acute stress, sympathetic regulation, and the fight-or-flight response. Sympathetic ner- vous system activation under acute stress produces the immediate, short-term fight- or-flight response. Neural synapses produce catecholamines (e.g., epinephrine and nor- epinephrine or adrenaline and noradrenaline), and catabolic functioning breaks down metabolites for physical activity and energy expenditure. Glucocorticoids are produced, including cortisol, increasing heart rate, ventilation, myocardial contraction force, arterial vasodilation to working muscles, vaso- constriction to nonworking muscles, and dilat- ing pupils and bronchi. Under acute stress, parasympathetic nervous system–regulated activities subside (e.g., salivary and intestinal secretions for digestion and nutrient absorp- tion, growth and repair). Frequent sympa- thetic nervous system dominance under repeated acute stress may interfere with growth and repair, especially important for children’s development, and suggests one pathway through which childhood stress may shape lifelong health and susceptibility. Chronic stress, immune function, and inflammatory response. Chronic stress may be characterized by recurrent acute stress or an inability to moderate acute stress responses ovlume 117 | number 9 | September 2009 • Environmental Health Perspectives