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Wednesday, November 5, 2014

Environmental impacts on immune responses in atopy and asthma

Despite the improvement of air quality in the U.S. since the enhancement of the Clean Air Act in 1990, exposures to outdoor and indoor air pollution remain a significant risk factor for both the development of asthma and the triggering of asthma symptoms.   Clinical studies have shown that significant asthma exacerbations were attributable to air pollution exposure, as a result of living in densely populated cities with elevated ambient fine particulate matter (PM2.5) and ozone (O3). In their review, Miller and Peden highlight new data on the effects of pollutant exposure on the innate and adaptive immune responses, genetic and epigenetic modifiers of response to pollutants, and potential interventions to mitigate these effects (J Allergy Clin Immunol 2014; 134(5): 1001-1008).

Several studies have determined that the effects of air pollution are heightened during the prenatal period.  This suggests that there is greater vulnerability of the growing lungs and the developing immune system, thus predisposing towards more airway inflammation later in life.  Similarly, studies suggest that factors such as chronic low-grade inflammation associated with obesity and stress may predispose towards asthma. Furthermore, the authors describe evidence that the mechanism behind these effects alter the innate and adaptive immunity, inducing a heightened immune response. Another emerging area of investigation is the effects of the environment on oxidative stress genes such as glutathione S-transferase (GST) genes as well as genes associated with Toll-like receptors of the innate immune system. Newer mechanistic lines of investigation focus on epigenetic regulation, and identifying asthma genes whose imprinting may be disrupted by environmental exposures.

Pollutant induced asthma exacerbations are less frequent in patients that use inhaled corticosteroids, suggestive that interventions that target acute inflammatory responses are beneficial, however future studies are required to test the efficacy of interventions in this population. Actively minimizing both indoor and outdoor pollutants and government air care regulations could decrease pollutant impacts on allergic lung disease.

Question for the authors:
How has the improved air quality over recent decades relate to the incidence of pollution related asthma exacerbations? 

In studies of both the Atlanta and Beijing Olympic Games, interventions that decreased automotive and point-source combustion were associated with decreased asthma morbidity. Future studies are needed to investigate more thoroughly whether improvements in air quality contribute to fewer asthma exacerbations.   This remains a difficult challenge to show as even the best designed epidemiological studies are unable to prove causality.

Stress and asthma: novel insights on genetic, epigenetic and immunologic mechanisms

In the U.S., ethnic minorities and the economically disadvantaged are disproportionately exposed to chronic psychological stressors such as poverty, discrimination and violence. Recent findings support a causal link between exposure to these stressors at the individual or community level and asthma morbidity. Moreover, current evidence suggests that the relation between stress and asthma is complex and partially mediated or modified by environmental exposures, adherence with treatment, co-morbidities and coping mechanisms.

In a review article, Rosenberg et al discuss recent findings suggesting potential biologic mechanisms for stress-related asthma, including changes in the methylation and expression of genes that regulate behavioral, autonomic, neuroendocrine, and immunologic responses to stress (J Allergy Clin Immunol 2014; 134(5): 1009-1015). For example, there may be susceptibility genes that predispose chronically stressed youth to both post-traumatic stress disorder and asthma. Moreover, recent studies show that low socioeconomic status in early life may program sustained resistance to glucocorticoid signaling, which could undermine the efficacy of steroid therapy in subjects who develop asthma.

The authors emphasize that the development of novel indicators or biomarkers of chronic stress is imperative, given that current stress measures cannot be used in young children or are difficult to implement in large studies. In addition, adequate phenotypic assessment of asthma, accounting for mediators and modifiers of the effects of stress on asthma, and studying the role of stress on treatment responses in vivo are key elements of future longitudinal studies of stress and asthma. Ultimately, further mechanistic insights on stress-related asthma should improve the prevention and treatment of asthma, particularly in vulnerable populations.