Asthma is a complex trait that is determined by both genetic and environmental factors. Evidence for genetic predisposition to asthma (and related phenotypes) is derived from family studies, twin studies, adoption studies, and segregation analyses (also see Burkart et al for a more recent review). There is also evidence that different genes influence asthma phenotypes of different racial/ethnic groups. Many candidate genes contributing to the development and expression of asthma have been proposed including gene variants associated with T-cell differentiation and related biological processes (eg, cytokine function and IgE production), genes related to drug response (eg, p-adrenergic receptor and glucocorticoid receptor), and genes important to the handling of environmental toxins (eg, cytochrome P450 and glutathione S-transferase genes). Genetic polymorphisms in the P2-adrenergic receptor have been linked to asthma severity, and the prevalence of functional polymorphisms in the p2-adrenergic receptor gene varies across race.
There are a number of key ideas to keep in mind when considering the genetic determinants of asthma disparities. This significant rise in asthma prevalence and severity over the past 2 to 3 decades, along with the widening disparities is too rapid to be explained by changes in genetic factors. Moreover, it needs to be kept in mind that genetic factors generally determine susceptibility to but not development of the disease. Racial-ethnic variability in the distribution of genetic polymorphisms can also modify the response to environmental exposures that are socially and economically patterned as well as the response to drug treatments. As we increasingly come to understand that the concept of “race” is not a true biological characteristic, we need to avoid simplistic interpretations of intergroup differences or genetic stratification. That is, although race/ ethnicity has been used as a proxy for biology and genetic risk in the past, researchers are increasingly viewing race as more of a social construct. Genetic studies that ignore interactions with broad environmental factors in ethnic minority populations would likely perpetuate the view of race as a biological construct. It is a known fact that you may buy ventolin inhalers online spending on it less time, money and energy.
It is unlikely then that genetic factors alone explain the rise in asthma prevalence or the observed disparities. It is more likely the case that gene-by-gene and gene-by-environment interactions are the crucial determinants of asthma occurrence and severity. Genetic variants that have causal effects but also modify the host response to social and physical environments may not be unique to minority populations and are likely to be common among the general population. Rather, differential exposure to relevant environmental exposures could explain disease disparities. The examination of the main effects of genes and interactions between genes and environmental factors will more likely inform the discernment of common final pathways to asthma disparities. From the perspective of health disparities, this means that both the environmental exposure and the genetic factor will be critical determinants in the causation pathway of the disease, Subjects who are exposed to toxins that are more highly prevalent in urban communities (eg, stress, smoking, aeroallergens, and diesel exhaust) and carry the genetic variants will have the greatest increased risk of disease, whereas subjects who are exposed to the toxins but do not have the genetic variant will have only a modestly increased risk of disease, Thus, applying genetic knowledge about asthma to reducing asthma disparities will require sophisticated strategies based on the role of both significant genetic and relevant social and physical environmental risk factors, No amount of progress in understanding the genetic factors underlying asthma etiology and response to treatment will help to reduce health disparities unless racial/ ethnic/SES disparities in exposure to risk-related social and environmental factors are concomitantly addressed.
Need for a Multilevel Perspective
The etiology of health problems is increasingly recognized as a result of the complex interplay of influences operating at several levels, including the individual, the family, and the community. As part of this growing complexity, evidence supports the notion that connections between health and economic well-being are embedded within the larger context of people’s lives,102Д03 The profound question, initially raised in the context of cancer, is, what gets asthma? Is it the cell, gene, organ, individual, household, population subgroup, or community? Indeed, the potential answers are rarely exclusive,> As reviewed above, more recently observed epidemiologic trends suggest that asthma may provide an excellent paradigm for understanding the role of community-level contextual factors in disease, Specifically, a multilevel approach that includes an ecological perspective may help to explain heterogeneities in asthma expression across socioeconomic and geographic boundaries that to date have remained largely unexplained (Fig 1).
Traditionally, asthma epidemiology has focused on individual-level risk factors and family factors, Far less attention has been given to the broader social context in which individuals live, Although it is beyond the scope of the current discussion given the space limitations, one also must consider the developmental timing of exposures over the course of a lifetime relative to specific asthma outcomes, whether individual or contextual factors are being considered. Factors leading to the onset, remission, or persistence of asthma across the course of a lifetime may be influenced by physical exposures and social experiences beginning in utero, a series of social and biological experiences initiated by early childhood exposure, or cumulative exposure to toxic biological or social factors over critical periods of development.
Could Neighborhood Context Be a Source in Producing Social Disparities in Asthma?
There is evidence that the risk factors associated with asthma, which were outlined earlier, are unevenly distributed across communities and neighborhoods. The failure to view these risk factors within its context can be limiting. Neighborhood contexts, defined by their characteristics related to socioeconomic disadvantage, physical conditions, and social processes, may play a critical role in accounting for the social disparities in asthma. Indeed, each of the risk factors (eg, exposure to indoor allergens, outdoor pollution, and smoking) that were discussed in the previous sections is likely to be distributed disproportionately across populations as well as communities and neighborhoods. At the same time, there has been growing interest in the potential role of the social environment in both health and psychological processes. This is a useful way to conceptualize environmental influences on health whether one operationalizes the environment as a social or a physical construct. Both physical and social factors can be a source of environmental demands that contribute to the stress experienced by populations living in a particular area. Bridging such theoretical constructs with research into asthma disparities is timely, given the convergence with advances in understanding the influences of psychological stress on the development and expression of asthma. Structurally disadvantaged neighborhoods may not only generate clustering of physical risk factors but may also act as a stressor inducing, for instance, individuals to smoke. Neighborhood structural disadvantage may also contribute to the level of sociophysical disorder in the community, including violence, which may, in turn, influence asthma, as reviewed in more detail below.
The potential import of such a framework stems from a number of observations. Notably, asthma trends are consistent with an inverse association between SES and adverse health outcomes found for many diseases. Explanations of such a ubiquitous socioeconomic gradient in health together with the observation that it is capable of replicating itself on new disease processes as they emerge in society calls for an understanding of how humans can become generally vulnerable or resilient to disease over time. This argues for the consideration of not only physical factors that alter biological processes but also how psychosocial conditions get into the body. Chronic stress may be a pervasive environmental factor imposed on already vulnerable popu-lations, resulting in an enhanced biological response to known physical environmental exposures. Mechanisms linking psychological stress, personality, and emotion to atopic disease continue to be elucidated and have been reviewed elsewhere. Moreover, the effects of environmental toxins (ie, air pollution and tobacco smoke) on atopy and asthma may be mediated by the common pathway of oxidative stress, a process that may be potentiated by chronic psychological stress. Further research is needed to examine these relationships.
Ecological views on health recognize that individual-level health risks and behaviors have multilevel determinants, which are in part influenced by the social context within which subjects live. Emerging scholarship on how social environments “get under the skin” to influence health suggests that psychological factors play a key role. That is, the degree of chronic stress is significantly influenced by the characteristics of the families, homes, and communities in which we live. Indicators of neighborhood disadvantage (ND) that may lead to chronic stress have been investigated in relation to urban children’s development. ND, characterized by the presence of a number of area-level stressors including poverty, unemployment/underemployment, percentage of unskilled laborers, limited social capital or social cohesion, substandard housing, and high crime/violence exposure rates. Such stress is chronic and can affect all subjects in a given environment regardless of their individual-level risks. In the United States, many urban communities are characterized by high ND levels. Evidence from social epidemiology on the determinants of health disparities among racial and ethnic minorities and low-SES populations points to the powerful influence of community characteristics in promoting health and well-being. One potential mediating feature of community life that has generated considerable attention is the concept of “social capital.” Social capital, and related constructs such as social cohesion, have been to linked to economic development, investment in public goods such as education, and crime/violence rates in a community.
Our previous work has identified violence exposure as a prevalent factor that concerns residents of Boston communities and, in turn, has linked violence exposure to asthma morbidity.> Violence serves as a good example of these social processes that may be impacting health. Social capital is strongly correlated with violent crime rates, which impacts community resilience by undermining social cohesion. Thus, crime and violence (or the lack of it) can be used as indicators of collective well-being, social relations, or social cohesion within a community and society. Violent victimization is a major cause of childhood morbidity in urban America. The rates of experiencing and witnessing serious and lethal violence among inner-city youth are also high.135 A prevalence study in a pediatric primary care clinic at Boston City Hospital found that 10% of children had witnessed a knifing or shooting before the age of 6 years; 18% had witnessed shoving, kicking, or punching; and 47% had reported hearing gunshots in their neighborhood. In a preadolescent sample in Boston, our group found that 61% had witnessed shoving, kicking, or punching; 8% had witnessed a stabbing or shooting; and 21% reported hearing gunshots in their communities.
Figure 1. A multilevel approach including an ecological perspective to explain heterogeneities in asthma expression across socioeconomic and geographic boundaries.