Breaking patterns of environmentally influenced disease for health risk reduction: immune perspectives

Abstract

Background: Diseases rarely, if ever, occur in isolation. Instead, most represent part of a more complex web or "pattern" of conditions that are connected via underlying biological mechanisms and processes, emerge across a lifetime, and have been identified with the aid of large medical databases.

Objective: We have described how an understanding of patterns of disease may be used to develop new strategies for reducing the prevalence and risk of major immune-based illnesses and diseases influenced by environmental stimuli.

Findings: Examples of recently defined patterns of diseases that begin in childhood include not only metabolic syndrome, with its characteristics of inflammatory dysregulation, but also allergic, autoimmune, recurrent infection, and other inflammatory patterns of disease. The recent identification of major immune-based disease patterns beginning in childhood suggests that the immune system may play an even more important role in determining health status and health care needs across a lifetime than was previously understood.

Conclusions: Focusing on patterns of disease, as opposed to individual conditions, offers two important venues for environmental health risk reduction. First, prevention of developmental immunotoxicity and pediatric immune dysfunction can be used to act against multiple diseases. Second, pattern-based treatment of entryway diseases can be tailored with the aim of disrupting the entire disease pattern and reducing the risk of later-life illnesses connected to underlying immune dysfunction. Disease-pattern-based evaluation, prevention, and treatment will require a change from the current approach for both immune safety testing and pediatric disease management.

Figure 1

The adverse outcomes of developmental and adult immunotoxicity. The detection of immune suppression is useful, but it is the remaining adverse immune outcomes (boxed) that appear to be the more important public health risks when one considers prevalence of chronic disease and significant patterns of immune-based disease.

Figure 2

Prototype pattern of disease for health risk reduction connected to metabolic syndrome. Environmental exposures elevating the risk of metabolic syndrome are on the far left. Diseases and conditions with elevated risk associated with metabolic syndrome are on the far right. The first window on the left illustrates the opportunity to prevent initiation of metabolic syndrome by identifying and protecting against problematic environmental exposures that increase the risk of metabolic syndrome. The second window shows the opportunity to intervene in the metabolic syndrome pattern and reduce the risk for progression to associated diseases. Prompt intervention focused on the entire metabolic syndrome disease pattern may be more effective than treatment begun much later in life (as indicated by the diminishing triangle). Both the prevention and intervention strategies are important components of overall health risk reduction. The focus on patterns of disease deviates from the traditional single-disease approach.

Figure 3

Early-life risk factors for metabolic syndrome: a timeline of human development from conception to 4 years of age. Abbreviations: GALT, gut-associated lymphoid tissue; MO, macrophage. Categories of different risk factors for metabolic syndrome are shown across the top. Below the timeline, windows of immune maturation are indicated that appear to be most relevant to environmental risk of metabolic syndrome. Combined, these factors and the critical windows are useful to further investigate the connection of an immune dysfunction–metabolic syndrome in early life. The dashed line indicates that immune maturation may continue after birth. Information derived from Dietert and Zelikoff (2008), Dietert and Dietert (2010), and DeWitt and Dietert (2010).

Figure 4

Venn diagram showing six patterns of immune-related diseases and the interactions among the patterns. Designated entryway diseases are shown in bold type within each pattern. Reported comorbid diseases or conditions are included for each pattern and those shared among multiple patterns fall within the intersections of the patterns.

Figure 5

Strategies for breaking a pattern of immune-dysfunction–based disease using childhood asthma as the entryway condition. Diseases and conditions with reported elevated risk among asthmatics are shown on the far right. The first window on the left illustrates the opportunity to prevent the initiation of this disease pattern by blocking DIT-induced immune dysfunction and elevated risk of childhood asthma. The second window shows the opportunity to intervene in the pattern and reduce the risk for progression to associated diseases beyond childhood asthma. Prompt intervention focused on this pattern may be more effective than treatments that are begun just before the onset of additional diseases. The importance of timing of appropriate intervention for likelihood of success in breaking the pattern is depicted using a diminishing triangle. Both the prevention and intervention strategies are important components of overall health risk reduction. Data from Dietert and Zelikoff (2008, .